The development of novel biologics provides a new therapeutic strategy for immune-related kidney diseases. Novel biologics such as anti-leukocyte differentiation antigen 20 monoclonal antibody, B lymphocyte stimulator/ a proliferation-inducing ligand-targeting drugs, and complement inhibitors provide more precise treatment for immunerelated kidney diseases by targeting specific molecules or receptors. However, further studies are needed in terms of therapeutic efficacy, safety, optimal dosage and applicability in different kidney diseases. This article reviewed the application progress of various novel biologics in immune-related kidney diseases, and aimed to discuss their therapeutic potential, existing evidence and future research direction.

Objective To study the effects of levetiracetam combined with perampanel on the discharge index and electroencephalogram(EEG) manifestations of benign childhood epilepsy with centrotemporal spikes(BECT). Methods A total of 95 children with admitted to the department of pediatric neurorespiratory in our hospital were selected as the research subjects and randomly divided into the control group(n＝47) and the study group(n＝48). The control group was treated with levetiracetam, while the study group was treated with perampanel in combination on the control group. The clinical effects after treatment, the discharge index during the episode of electroencephalogram, the differences in the α, θ, and δ bands of EEG, and the differences between language intelligence quotient and operational intelligence quotient were compared between the two groups. The occurrence of adverse reactions during the treatment period was also monitored. Results After treatment, the total effective rate of the control group was lower than that of the study group(78.72% vs. 95.83%, P＜0.05). The difference in discharge index of the study group was greater than that of the control group(P＜0.05). The improvement rate of the study group was higher than that of the control group(91.67% vs. 70.21%, P＜0.05). The differences in the α, θ and δ bands of EEG activity in the study group were all higher than those in the control group(P＜0.05). The differences in language intelligence quotient scores and operational intelligence quotient scores of the study group were both higher than those of the control group(P＜0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05). Conclusion Levetiracetam combined with perampanel can effectively improve the discharge index of children with , enhance the improvement effect of EEG, promote the recovery of cognitive function, and has good safety.

Non-alcoholic steatohepatitis(NASH), as a chronic metabolic disease, is closely related to obesity, diabetes mellitus type 2, hyperlipidemia and other metabolic syndromes. Its pathogenesis involves multiple factors such as genetics, environment and lifestyle, especially metabolic disorders as the core driving force, which promote disease progression through oxidative stress, endoplasmic reticulum stress and inflammatory pathway activation. For the treatment of NASH, multiple potential therapeutic targets have been identified, such as metabolic regulation, blocking of inflammatory pathways, and anti-fibrosis. NASH may also progress to severe diseases such as cirrhosis and liver cancer, which poses a major threat to human health. In addition, NASH is often accompanied by other metabolic diseases, forming a vicious cycle that further increases the difficulty of treatment and the burden on patients. This article aims to comprehensively review the pathogenesis, therapeutic targets and drug research progress of NASH, and discuss its harm to humans, so as to provide reference for future research and clinical practice.

Atopic dermatitis(AD) is a common chronic inflammatory skin disease that seriously affects the quality of life of patients. Traditional treatments such as topical steroids and immunosuppressants have limited efficacy in some patients and are accompanied by adverse reactions. In recent years, biologics have provided new treatment options for patients with moderate to severe AD by targeting key inflammatory factors. Dupilumab, as the first approved biologic, significantly improved patients' skin symptoms and pruritus. Subsequently, drugs such as tralokinumab, lebrikizumab, and nemolizumab further expanded the options for targeted therapy. Biologics have shown promising prospects in improving the treatment outcomes of patients with moderate to severe AD, and are expected to further improve efficacy and affordability through personalized medicine, optimized dosing strategies, and cost control. This article reviewed the targets, mechanisms of action, and clinical research progress of major biological agents, in order to provide reference for the clinical treatment of AD patients.

Iron metabolism disorder is common disorder in patients with chronic kidney disease, which leads to renal anemia(RA). Intravenous iron is an important treatment for RA, and commonly used drugs include ferric carboxymaltose, ferumoxytol and ferric derisomaltose. Based on the previous research results, this article reviewed the application progress of intravenous iron in RA, in order to provide some ideas for individualized iron therapy

我国药品集中采购 ( 以下简称“集采”) 政策形成于经济市场化改革和医药卫生体制改革的重要时期，走过了从计 划采购、医院联合采购试点、地 ( 市 ) 扩大试点，省为单位、省际联合、国家组织六个不同阶段与药品集采政策变革、初 创、调整、拓展、融合、完善的发展历程相对应，政策发展以问题、需求为导向，从部门碎片化、局部效应，逐步向整体 性、系统化、综合成效转变。文章梳理了我国药品集采发展的历程，总结不同时期药品集采政策的特点，显示我国经济改 革和医药卫生体制改革相关政策与药品集采政策发展互为因果、相互协调，推动了药品供应保障治理体系现代化进程。

Chronic kidney disease(CKD) has long been an important global health problem, and renal anemia(RA) is one of the important complications of CKD, which is closely related to the increase of all-cause mortality and cardiovascular mortality in patients. The occurrence of RA is related to the deficiency of erythropoietin(EPO) production. EPO related drugs are an important treatment for RA and affect the prognosis of patients with CKD. This article reviewed the application progress of EPO related drugs in RA in recent years, in order to provide some reference for clinic.

Glucagon-like peptide-1 receptor agonist(GLP-1RA) has been widely used in the treatment of patients with type 2 diabetes mellitus. GLP-1RA can also help improve renal outcomes in patients with diabetic nephropathy(DN). GLP-1RA plays a renal protective role by inhibiting inflammatory response, reducing oxidative stress, alleviating damage induced by advanced glycosylation end products and improving metabolic abnormalities, and has great potential in preventing and slowing down the occurrence and development of DN. This article reviewed the clinical evidence and mechanism of GLP-1RA in DN, so as to provide reference for clinical use.

With the widespread use of antibiotics, the ongoing development of microbial resistance poses a significant threat to global health. Therefore, the search for new antibiotics or other antimicrobial resources has become the focus of global scientific research. Antimicrobial peptides(AMPs) have attracted much attention as excellent candidates for overcoming antibiotic resistance. AMPs are small molecular proteins that are naturally produced by all living organisms and play a crucial role in the host's innate immunity against a variety of microorganisms, including bacteria, fungi, and viruses. AMPs are widely found in various organisms such as microorganisms, plants, insects, and mammals. AMPs exert biological activity by targeting key molecules such as cell membranes, cell walls, DNA and proteins within cells. The wide range of sources and complex and diverse mechanisms provide a solid foundation for the wide application of AMPs. This article reviewed the classification of AMPs based on animal origin, the mechanisms and applications in pharmaceutical field, in order to provide professional reference for further research in related fields.

Rheumatoid arthritis(RA), a common chronic autoimmune disease. In addition to glucocorticoids, nonsteroidal anti-inflammatory drugs, and herbal medicines, the treatment drugs for this disease also include disease - modifying anti-rheumatic drugs(DMARDs). DMARDs include traditional DMARDs, biological disease-modifying antirheumatic drugs(bDMARDs) and targeted synthetic disease-modifying anti-rheumatic drugs(tsDMARDs). The latter two are also breakthrough therapeutic drugs for RA in recent years. This article provided a detailed introduction to bDMARDs and tsDMARDs, and briefly described other potential therapeutic drugs, to provide new ideas and directions for clinical medication.

Vitiligo is a common acquired skin mucosal pigment loss disease, and there is no cure. The pathogenesis of vitiligo is complex, involving multiple factors such as genetics, autoimmunity, and oxidative stress. With the deepening research on the pathogenesis of vitiligo, biologics targeting specific sites have been continuously developed, especially targeted treatments for immune regulation and anti-inflammatory response, which provide new ideas for the treatment of vitiligo. This article focused on the feasibility of using biologics as a new treatment method for vitiligo, in order to provide reference for exploring better treatment options.

Objective To explore the role and existing problems of centralized drug procurement policies in balancing medical, pharmaceutical, and medical insurance costs, ensuring safe and rational use of drugs by the public, and promoting the healthy development of the pharmaceutical industry. Method The relevant policies, literature, cases, and data were analyzed, and the impact and response of policies on various stakeholders and their reactions were interpreted from multiple dimensions. Result The policy of centralized drug procurement was formed during the period of China's economic marketization reform and medical and health system reform. While promoting the construction of the drug supply guarantee system, the policy has promoted the reform of the compensation mechanism of public hospitals and the medical service prices, promoted the balance of medical insurance funds and the modernization of the medical and health governance system. At present, centralized drug procurement has problems in policy implementation, quality improvement and expansion, slow adjustment of medical service prices, and increased difficulty in balancing the interests of the public, medicine, medical development, and fund security. It is necessary to improve the unified and efficient policy linkage and management coordination mechanism of medical insurance, healthcare, and medicine, and promote "value medicine". Conclusion The policy of centralized drug procurement and the reforms related to medicine, healthcare, and medical insurance are mutually causal and synergistic, promoting the modernization process of the governance system and governance capacity of the medicine, healthcare, and medical insurance.

Objective To observe the effect of modified Buyang Huanwu decoction combined with sacubitril valsartan on chronic cardiac failure(CHF). Methods A total of 120 CHF patients with Qi deficiency and blood stasis admitted to Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from November 2021 to June 2023 were randomly divided into western medicine group(n＝60) and Chinese and western medicine combined group(n＝60). The western medicine group was treated with sacubitril valsartan on the basis of conventional treatment, and the Chinese and western medicine combined group was treated with modified Buyang Huanwu decoction on the basis of western medicine group, with a course of 3 months. Results After treatment, the traditional Chinese medicine syndrome score, quality of life score, N-terminal brain natriuretic peptide precursor, myocardial troponin T level and left ventricular mass index in the two groups were decreased compared with before treatment(P＜0.05), the left ventricular ejection fraction and 6 min walking test were higher than those before treatment(P＜0.05), and the above indexes in Chinese and western medicine combined group were better than those in western medicine group(P＜0.05). The total effective rate of the combined group was obviously higher than that of the western medicine group(91.67% vs 76.67%, P＜0.05). There was no significant difference in the incidence of adverse reactions between the combined group and western medicine group(8.33% vs 13.33%, P＞0.05). Conclusion Modified Buyang Huanwu decoction combined with sacubitril valsartan has high curative effect on CHF, and can improve the heart function and quality of life of patients.

Objective To explore the clinical efficacy of Siwanfeng decoction in treating atopic dermatitis(AD) in children with heart fire and spleen deficiency syndrome. Methods A total of 70 patients with AD who met the inclusion criteria were randomly divided into treatment group and control group, with 35 cases in each group. The treatment group was given Siwanfeng decoction orally, while the control group was given levocetirizine hydrochloride oral liquid orally. The treatment course was 6 weeks. The changes in scoring AD(SCORAD) scores and clinical efficacy were compared between two groups. Results The total effective rate of the treatment group was 97.14% and 40% in the control group, and the total effective rate of the treatment group was significantly higher than that of the control group(P＜0.001). After treatment, the SCORAD score in the treatment group was decreased than before treatment and the control group, and the difference was statistically significant(P＜0.001). Conclusion Siwanfeng decoction has a good clinical efficacy in treating children with AD with heart fire and spleen deficiency syndrome

The clinical use of targeted agents has revolutionized treatment strategies for non-small cell lung cancer(NSCLC) patients carrying targetable mutations for two decades, and has resulted in significant survival benefits. In recent years, the types and clinical use of targeted agents have expanded, with breakthroughs in the treatment of advanced to locally advanced unresectable patients and perioperative adjuvant treatment of resectable patients. In advanced patients, the combination of targeted drugs with chemotherapy or dual-antibody drugs has also provided new options for first-line and subsequent treatment. Meanwhile, antibody-drug conjugates have made positive progress in the subsequent treatment of advanced patients. This article aimed to review the research progress of targeted drugs in the clinical application of intermediate and advanced NSCLC.

Secondary hyperparathyroidism(SHPT) is one of the most important complications of chronic kidney disease-mineral and bone disorder(CKD-MBD), which can significantly increase the risk of bone deformities, cardiovascular events, and death. In the current treatment of CKD-MBD SHPT, phosphorus binders, calcium-like agents, polynuclear iron-hydroxide and tenapanor have shown advantages. Novel active vitamin D analogues can effectively reduce the level of intact parathyroid hormone(iPTH). This article reviewed the recent progress of IPTH-decreasing CKD-MBD drugs in order to provide reference for clinical use.

Objective To systematically review the literature on the accessibility of national medicare negotiated drugs and summarize its improvement. Methods CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science were searched to collect published literature about national medicare negotiated drugs accessibility, and analyze the content of the literature. Results 25 literatures were included, of which 17 focus on the impact of national medicare negotiated drugs accessibility, while the remaining 8 research the current status of national medicare negotiated drugs accessibility after the policy. Regarding availability, all of the literature found that the policy had a significant positive effect on the uptake of drugs, while 40%(10/25) found that there were some regional or institutional differences in the availability. Regarding affordability, only 60%(15/25) of the literature noted a sharp decrease in the price of national medicare negotiated drugs after the policy. However, 27%(4/15) mentioned that the out-of-pocket costs of most anticancer drugs were still high. Conclusion The National Price Negotiation policy has effectively improved drug accessibility, but it is still necessary to continuously promote the use of national medicare negotiated drugs and to improve the treatment of medicines in health insurance.

Biological agents and oral small molecule(OSM) drugs provide a new approach for the treatment of pediatric skin diseases, such as atopic dermatitis, psoriasis, alopecia areata, and hidradenitis suppurativa. Although most biological agents and OSM drugs have only been approved for use in adult patients, with the continuous strengthening of their clinical safety evaluations and the gradual approval of their use in adolescents and children, biological agents and OSM drugs are expected to become new choices for pediatric skin disease medication in the future. This article comprehensively reviewed the biological agents and OSM drugs that have been approved by the US Food and Drug Administration in recent years or have potential for treating atopic dermatitis, psoriasis, alopecia areata, and hidradenitis suppurativa in children, in order to provide reference for the treatment of related diseases.

Objective To investigate the therapeutic effect of calcium and zinc gluconate oral solution on osteoporosis in ovariectomized rats. Methods 72 SD rats were randomly divided into sham operation group, model group, positive control group and low, medium and high doses of Xingaite groups(3, 6, 12 ml/kg), with 12 rats in each group. Except for the sham operation group, the ovaries were removed to establish the osteoporosis model. The positive control group was given estradiol 0.1 mg/kg, and the sham operation group and the model control group were given the same volume of purified water by gavage for 99 days. The body mass of the rats was observed every 3 days. After treatment, bone mineral density(BMD), bone volume relative to tissue volume(BV/TV) and bone surface relative to tissue volume(BS/TV) were analyzed by micro-CT. Calcium, zinc and bone metabolism were detected by enzyme linked immunosorbent assay. Results Compared with the model group, the zinc-calcium group significantly inhibited the growth of body mass, increased the level of zinc, improved the bone loss of femur, increased trabecular number and connection and BMD, increased BV/ TV and BS/TV, and decreased the levels of osteocalcin and procollagen type Ⅰ carboxy-terminal peptide. Conclusion Xingaite can improve the microstructure of bone trabecular in ovariectomized rats, increase bone density, slow down the osteoporosis process in ovariectomized rats, and has a good effect on ovariectomized rats with osteoporosis.

Fatty liver is a disease characterized by abnormal accumulation of fat in liver cells, the incidence of which is increasing year by year, and has become an urgent public health problem in the world. The pathogenesis of fatty liver is complex, including alcoholic and non-alcoholic factors, metabolic disorders and drug effects. In recent years, traditional Chinese medicine and its active ingredients have been widely concerned by researchers because of their unique multitarget characteristics and overall conditioning effects. This article reviewed the research progress of some Chinese herbal compounds and their effective components in the treatment of non-alcoholic fatty liver disease.

Diagnosis-intervention packet(DIP) is a payment method with Chinese characteristics proposed by combining payment by disease with regional total budget and points. It is currently one of the hospitalization payment methods being promoted in China. This study collected literature on the practical effects of DIP, and used literature hotspot analysis and system review method to summarize the trend of DIP research hotspots and the comparison of effects before and after policy implementation, and put forward the relevant suggestions to improve the research on DIP

Systemic lupus erythematosus(SLE) is is a chronic autoimmune disease characterized by multi-system involvement. The disease recurs repeatedly, often accompanied by infections and organ damage, which seriously threaten the quality of life of patients. With the breakthroughs of molecular immunology research, important progress has been made in the targeted treatment strategies for SLE. Based on evidence-based medical evidence, this paper systematically reviewed current drug treatment regimens for SLE, mainly including the optimized application of traditional drugs, as well as the clinical value of innovative therapies such as biological agents like belimumab and telitacicept, and novel treatment approaches such as chimeric antigen receptor T-cell immunotherapy, in order to provide evidence-based basis for individualized treatment decisions.

Psoriasis is a chronic, recurrent, immune-mediated systemic inflammatory skin disease that significantly impairs patients' physical and mental health as well as the quality of life of patients. With the widespread application of treatment methods such as biological agents, the therapeutic effect of psoriasis has significantly improved, but the problem of recurrence remains prominent. Immune abnormalities(such as tissue resident memory T cells, cytotoxic T cell 17), genetic susceptibility, infectious factors, environmental changes, and unhealthy lifestyles are important triggers for psoriasis recurrence. Meanwhile, there are differences in the recurrence time of different types of biologics after discontinuation, and the risk of recurrence is closely related to patient's compliance and comorbidity status. The article systematically reviewed the relevant mechanisms, influencing factors, and intervention strategies for psoriasis vulgaris recurrence, and proposed multidimensional prevention and intervention strategies for recurrence issues, including optimizing biological agent management, combination therapy regimens, improving lifestyle, and long-term follow-up mechanisms, providing reference for clinical treatment.

nkylosing spondylitis(AS) is an autoimmune disease mainly characterized by chronic inflammation of the axial spinal joints, and its onset is significantly correlated with genetic markers such as human leukocyte antigen B27. AS has the characteristics of multi-system involvement and can cause extra-articular manifestations such as gastrointestinal dysfunction, renal damage and skin and mucosal lesions. The clinical treatment drugs for AS mainly include three categories: non-steroidal anti-inflammatory drugs, glucocorticoids and antirheumatic drugs for improving the condition. With the breakthrough of biological targeted therapy, biological agents such AS tumor necrosis factor inhibitors and interleukin-17 inhibitors have become a new paradigm for the treatment of AS. This paper systematically reviewed the latest research on AS biological agents combined with AS physical rehabilitation, exercise therapy and other non-pharmaceutical intervention methods, aiming to provide evidence-based basis for optimizing the comprehensive management plan of AS.

Objective To investigate the effect of remimazolam on cognitive dysfunction induced by sevoflurane in rats by regulating Toll-like receptor(TLR)4/myeloid differentiation factor(MyD)88/nuclear transcription factor(NF)-κB pathway. Methods A total of 72 male SD rats were divided into A to F groups, 12 rats in each group. A group(50% air and oxygen mixture, 2 L/min) and other groups were treated with A group＋2% sevoflurane to construct aged postoperative cognitive dysfunction rat model. After successful modeling, C groups to E were given(1.5 mg/kg, 3 mg/kg and 6 mg/ kg remimazolam＋intraperitoneal injection of the same amount of 0.9% sodium chloride injection), respectively, F group was given(6 mg/kg remimazolam＋intraperitoneal injection of 75 μg RS09). The rats in A group and B group were injected with the same amount of 0.9% sodium chloride injection in the tail vein and abdominal cavity. The escape latency,the number of crossing platforms and the histopathology of hippocampus were observed. The expression of ionized calcium-binding adapter molecule(IBA)-1 was detected by immunofluorescence staining. Enzyme-linked immunosorbent assay was used to detect the levels of neuron-specific enolase(NSE), interleukin(IL)-6 , central nervous system specific protein S-100β, and tumor necrosis factor(TNF)-α in hippocampus. Terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to detect neuronal apoptosis. TLR4, MyD88, Cleaved caspase-3 and p-NF-κB p65 proteins were detected by immunoblotting. Results Compared with B group, the disordered arrangement of neurons and cell morphological changes of rats in C ~ E group were improved, the escape latency was shortened, and the number of crossing platforms was increased. Levels of NSE, S-100β, IL-6, TNF-α, the number of IBA-1 positive cells, neuronal apoptosis rate, and the proteins levels of TLR4, MyD88, Cleaved Caspase-3, and p-NF-κB p65 were significantly decreased(P＜0.05). Conclusion Remimazolam may improve sevoflurane-induced cognitive dysfunction in aged rats by inhibiting the TLR4/MyD88/NF-κB pathway.

Objective To systematically introduce how to calculate the 50% effective concentration(EC50) of drugs using the Probit module in SPSS27.0 based on clinical research data, tproviding a reference for clinical researchers. Methods Taking a set of clinical data as an example, this study elucidates the specific steps of calculating the EC50 of drugs using SPSS27.0 and interprets the main output results. Additionally, the EC50 obtained by this method are compared and validated with those calculated by GraphPad Prism9.5. Results The EC50 calculated and analyzed by SPSS software are consistent with those obtained by GraphPad Prism9.5. Moreover, SPSS27.0 features simple steps and quick operations. Conclusion SPSS27.0 can be used to calculate and analyze EC50, which is convenient and fast in operation and is an ideal choice for clinical researchers who are not specialized in statistics.

Objective To explore the effect of Guifu Dingchuan granules as an adjuvant treatment of cough and asthma in the middle and advanced non-small cell lung cancer(NSCLC) with kidney Qi deficiency syndrome. Methods A total of 100 patients with cough and asthma in the middle and advanced NSCLC with kidney Qi deficiency syndrome in our hospital from December 2022 to January 2024 were selected and divided into control group(western medicine) and study group(Guifu Dingchuan granules combined with western medicine) according to simple sequencing random method, with 50 cases in each group. The clinical effect of the two groups was observed. The traditional Chinese medicine syndrome score, forced expiratory volume in one second(FEV1), peak expiratory flow(PEF), forced vital capacity(FVC), serum micro RNA(miR)-200a, miR-375, Leicester cough questionnaire(LCQ), quality of life questionnaire-core 30(QLQ-C30) and incidence of adverse reactions were compared before and after treatment. Results The total effective rate of the study group was higher than that of the control group(92.00% vs. 76.00%, P＜0.05). After treatment, LCQ and QLQ-C30 scores in the study group were lower than those in the control group(P＜0.05). The levels of FEV1, PEF, FVC, serum miR-200a and miR-375 in the study group were higher than those in the control group(P＜0.05). There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05). Conclusion Guifu Dingchuan granules can effectively improve the curative effect, improve lung function and quality of life in the adjuvant treatment of cough and asthma in the middle and advanced NSCLC patients with kidney Qi deficiency syndrome, and up-regulate the levels of serum miR-200a and miR-375 with high safety.

Objective To investigate the effects of lipopolysaccharide(LPS) on organoid growth, stem cells and related pathways. Methods The intestinal crypts of C57BL/6J mice were aseptically isolated and collected in vitro, and the threedimensional small intestinal organoids with multi-bud structure were cultured. Immunofluorescence staining was used to identify the cell composition of small intestinal organoids. After passage, small intestinal organoids were randomly divided into control group(LPS 0 μg/ml) and different concentrations of LPS groups(30、100 and 300 μg/ml). The growth and morphological characteristics of organoids, and the changes of stem cells and proliferating cells induced by LPS were observed. Comparative RNA sequencing and bioinformatics analysis were used to characterize the changes in genes and pathways induced by LPS. Results In D6 culture, small intestinal crypts formed stereoscopic intestinal organoids with multiple budding structures accompanying the intestinal lumen. After modeling, LPS inhibited the formation of intestinal organoid sprout structure, and the area of intestinal organoids was significantly reduced in a dose-dependent manner. IF staining results showed that the expression of intestinal cells and proliferating cells was increased. The comparative RNA sequencing showed that the expression of stem cells and proliferation-related genes was significantly increased, and the stem cells pathway was enriched. Conclusion The LPS-induced intestinal organoid injury model was initially constructed in vitro, and the mechanism and pathway of stem cell enhancement after injury were revealed, providing a reliable research platform for the mechanism research of intestinal diseases and the screening of effective drugs

Objective To evaluate the budget impact of the combination therapy of nivolumab and ipilimumab for the treatment of unresectable malignant pleural mesothelioma after its inclusion in the China's National Reimbuirsement Drug List(NRDL). Methods This study constructed a 5-year(2024—2028) budget impact analysis model from the perspective of the Chinese government health insurance authority to simulate the budget changes after the combination therapy of nivolumab and ipilimumab was included in the NRDL. The model analyzed factors such as the target population, drug market share, and treatment costs, comparing healthcare expenditures in scenarios with and without insurance coverage. One-way sensitivity analysis was performed to assess model robustness. Results After inclusion in the NRDL, the incremental expenditure from 2024 to 2028 mainly stems from health insurance payment portion of drug costs, with a cumulative increase of 66.645 million yuan. However, the overall financial impact on the insurance fund remains minimal. Sensitivity analysis showed that drug prices, reimbursement rates, and insurance coverage rates were the key factors affecting budget changes. Conclusion Although the combination therapy of nivolumab and ipilimumab included in the NRDL will increase expenditure, the impact on the overall fund burden is limited.

Proteolysis-targeting chimera(PROTAC) is a new technology for targeting protein degradation that has received great attention in the biomedical science community. PROTAC molecules can quickly and efficiently deplete target proteins by inducing degradation of target proteins using the ubiquitin-protease system, and can bind to substrates again to achieve multiple ubiquitination reactions, optimizing the dose dependence and drug resistance of traditional small molecules to a certain extent. However, this unique chemical structure and mechanism of action also brings many challenges to its in vivo and in vitro pharmacokinetic studies, mainly including poor solubility, poor permeability, poor oral absorption, and low bioavailability. Starting from the analysis of the physicochemical properties of PROTAC molecules, this article analyzed the pharmacokinetic characteristics and summarized the bioanalysis methods of such drugs. It also discussed the challenges and prospects of PROTAC technology, providing a reference for innovative research and breakthroughs in the field of PROTAC drugs.

Autoimmune disease(AID) is a class of diseases characterized by excessive inflammatory response to autoantigens, B lymphocytes are the core of the pathogenesis of AID, and cluster of differentiation(CD)20 monoclonal antibodies targeting at B lymphocytes depletion are widely used in the treatment of AID. Obinutuzumab, a type Ⅱ humanized anti-CD20 monoclonal antibody, can significantly reduce the number of B lymphocytes and inhibit the production of autoantibodies, and can be used to treat AID. This article reviewed the application progress of obinutuzumab in AID, aiming to provide some reference for clinical use.

Objective To observe the clinical efficacy of Bushen Huoxue decoction in treating carotid atherosclerosis(CAS) with kidney deficiency and blood stasis, and its influence on blood lipid, inflammation, complement activation and carotid ultrasound. Methods A total of 90 CAS patients with kidney deficiency and blood stasis who visited our hospital were included and randomly divided into control group and experimental group, 45 cases in each group. The control group was treated with conventional Western medicine, and the experimental group was treated with Bushen Huoxue decoction on the basis of the control group. The course of treatment was 12 weeks. The therapeutic efficacy, the traditional Chinese medicine(TCM) syndrome scores, lipid levels, carotid intima-media thickness, pulse wave conduction velocity, maximum plaque area, safety indicators (blood routine, electrocardiogram, liver and kidney function) of the two groups were recorded and compared before and after treatment. The serum levels of ficolin(FCN)3, MBL-associated serine protease(MASP)-1, tumor necrosis factor(TNF)-α, interleukin(IL)-6, complement C3 and C4 were detected by enzyme-linked immunosorbent assay. Results The total effective rate of the experimental group was higher than that of the control group(82.05% vs. 52.78%，P＜0.05). After treatment, compared with the control group, the levels of total cholesterol, low density lipoprotein cholesterol, FCN3, MASP-1, complement C4, TNF-α in the experimental group were decreased(P＜0.05), TCM syndrome scores and high density lipoprotein cholesterol level were increased(P＜0.05), and pulse wave conduction velocity was decreased(P＜0.05). During treatment, no significant adverse reactions or adverse events occurred in both groups. Conclusion Bushen Huoxue decoction can effectively improve the clinical symptoms of patients with CAS, improve the levels of blood lipids, inflammation and carotid ultrasound indexes, and the mechanism may be related to complement activation.

Objective To observe the efficacy of high-dose dexamethasone(DXM) combined with rafutrombopag in the treatment of newly diagnosed primary immunologic thrombocytopenic purpura(ITP). Methods A total of 80 newly diagnosed primary ITP patients in our hospital from June 2020 to June 2023 were enrolled and divided into control group(high-dose DXM) and study group(high-dose DXM＋rafutrombopag) by district randomization method, with 40 cases in each group. Platelet count(PLT) levels, the distribution of T lymphocyte subsets, efficacy and the occurrence of adverse reactions were compared between the two groups before treatment and at D7, D14, D30 and D60 of treatment. Results At D7, D14, D30 and D60 of treatment, the PLT levels in both groups were higher than before(P＜0.05), and the PLT levels of the study group were higher than those in the control group at D7, D14 and D30(P＜0.05). After treatment, cluster of differentiation(CD)3＋, CD4＋, CD4＋/CD8＋, complement C3, complement C4 and interleukin(IL)-4 in both groups were increased compared with those before treatment(P＜0.05), and the study group was higher than the control group(P＜0.05). The levels of CD8＋, IL-2, IL-10 and interferon in both groups were lower than before treatment(P＜ 0.05), and the study group was lower than the control group(P＜0.05). The total effective rate of the study group was higher than that of the control group(85.00% vs. 65.00%, P＜0.05), the rate of DXM secondary administration(10.00% vs. 30.00%, P＜0.05) and the incidence of adverse reactions(25.00% vs. 52.50%, P＜0.05) were lower than those of the control group. Conclusion High-dose DXM combined with rafutrombopag in the treatment of newly diagnosed primary ITP can effectively up-regulate PLT level, improve the distribution of T lymphocyte subsets, improve efficacy, and reduce the rate of DXM secondary administration and the incidence of adverse reactions.

Objective To investigate the therapeutic effect of idebenone combined with dopamine on Parkinson's disease(PD) and its effects on serum neurocytokines and oxidative stress indexes. Methods A total of 130 PD patients in our hospital from June 2022 to December 2023 were selected and divided into observation group and control group according to simple ordering random method, with 65 cases in each group. On the basis of conventional treatment, the control group was treated with levodopa and benserazide hydrochloride tablets, and the observation group was treated with idebenone on the treatment regimen of the control group. The course of treatment of both groups was 3 months. The clinical efficacy, the unified PD rating scale(MDS-UPDRS)Ⅲ, non-motor symptoms scale(NMSS), mini mental status examination(MMSE) score, and nerve growth factor(NGF), brain-derived neurotrophic factor(BDNF), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px) and catalase(CAT) were compared between the two groups. Results The overall response rate of observation group was higher than that of control group (84.62% vs. 67.69%, P＜0.05). The MDS-UPDRS III, NMSS score and serum MDA level in the observation group were lower than those in the control group(P＜0.05). The MMSE score, serum NGF, BDNF, SOD, GSH-Px and CAT levels in observation group were higher than those in control group(P＜0.05). Conclusion Idebenone combined with dopamine is effective in the treatment of PD, which can improve the symptoms and cognitive function of patients, and its mechanism may be related to the regulation of serum neurocytokines and oxidative stress response.

The BXD recombinant inbred mouse strains, developed through the hybridization of female C57BL/6J and male DBA/2J mice, followed by over 20 generations of brother-sister matings, represent the largest and most genetically characterized group of recombinant inbred strain populations of mammals globally, with over 150 strains. These mice exhibit significant genetic diversity and extensive phenotypic variation, alongside a wealth of genotype, phenotype, and omics data. These characteristics make BXD mice a valuable resource for studying complex traits and diseases, which can be used for the construction of disease models, the study of disease mechanisms, drug target discovery, and preclinical drug evaluation. The application of BXD mice is crucial in advancing biomedical research, promoting disease prevention and treatment, and achieving precision medicine. With the deepening of research, BXD mice are poised to play a greater role across various fields.

Objective To explore the clinical efficacy of modified Shenling Baizhu powder combined with mesalazine in the treatment of mild to moderate ulcerative colitis(UC) with spleen deficiency and dampness accumulation syndrome. Methods A total of 70 patients with mild to moderate UC with spleen deficiency and dampness accumulation syndrome admitted to the outpatient and ward of the department of spleen and stomach diseases of Jiangyin Hospital of Traditional Chinese Medicine and Jiangsu Province Hospital of Traditional Chinese Medicine from October 2023 to December 2024 were selected and divided into control group and treatment group according to the random number table method, with 35 cases in each group. The control group was treated with mesalazine, while the treatment group was treated with the modified formula of Shenling Baizhu Powder in addition to the treatment of control group. Both groups were treated for 24 weeks. The total effective rate, symptom score, colonoscopy mucosal lesion scores, and iron death related factors were compared between the two groups. Results The total effective rate of the treatment group was better than that of the control group(94.29% vs. 82.86%, P＜0.05). After treatment, the average symptom scores, colonic mucosal lesion scores and serum ferrous ion of the two groups decreased significantly(P＜0.05). The levels of serum superoxide dismutase, glutathione and glutathione peroxidase 4 increased significantly(P＜0.05). The improvement of diarrhea, abdominal distension, abdominal pain, limb drowsiness and anorexia in the treatment group were better than those in the control group(P＜0.05). There was no statistically significant difference in the improvement of purulent bloody stool and colonic mucosal lesions between the two groups(P＞0.05). No significant adverse reactions were observed in the two groups during treatment. Conclusion The modified Shenling Baizhu powder has a remarkable therapeutic effect on patients with mild to moderate UC with spleen deficiency and dampness accumulation syndrome, and it has good safety and high clinical application value.

Objective To explore the clinical effect of tirofiban combined with ginkgo biloba diterpene lactone in the treatment of acute cerebral infarction(ACI), and its influence on nerve function and hemorheology. Methods A total of 150 patients with ACI who received treatment in our hospital from June 2021 to June 2023 were selected, and divided into the control group and combined medication group by simple randomization method, with 75 patients in each group. Both groups received conventional treatment and were also given tirofiban, while the combined group received ginkgo biloba diterpene lactone in addition to the control group. Observe and compare The clinical efficacy, the changes in neurological deficits, daily living abilities, serum inflammatory factor levels, coagulation function indicators, hemorheological indicators and the occurrence of adverse reactions in the two groups were observed and compared. Results The total effective rate of the combined medication group was higher than the control group(94.67% vs. 80.00%, P＜0.05). After treatment, the scores of the National Institutes of Health Stroke Scale, serum C-reactive protein, interleukin-6, and tumor necrosis factor alpha levels in both groups decreased compared to before treatment, and the combined medication group was lower than the control group(P＜0.05). The scores of activities of daily living in both groups improved compared to before treatment, and the combined medication group was higher than the control group(P＜0.05). After treatment, the fibrinogen, D-dimer, whole blood low-shear viscosity, whole blood high-shear viscosity, and plasma viscosity in both groups decreased compared to before treatment, and those in the combined medication group were lower than the control group(P＜0.05). The prothrombin time and activated partial thromboplastin time increased compared to before treatment, and those in the combined medication group were higher than the control group(P＜0.05). There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05). Conclusion Tirofiban combined with ginkgo biloba diterpene lactone in the treatment of ACI can significantly improve the clinical efficacy, effectively improve the neurological impairment and daily living ability of patients, reduce the level of serum inflammatory factors, optimize the coagulation function and hemorheological indexes, and has high safety.

Objective To observe the clinical effect of calcium polycarbophil in the treatment of opioid-induced constipation(OIC). Method A total of 204 OIC patients treated in our hospital from June 2022 to December 2023 were selected and divided into control group and study group according to a simple randomization method, with 102 cases in each group. They were respectively treated with glycerin enema for rectal administration and oral administration of calcium polycarbophil tablets for 2 weeks. The average number of completely spontaneous bowel movement(CSBM) per week, Bristol stool form scale(BSFS), bowel function index(BFI), numerical rating scale(NRS) for pain, patient assessment of constipation-quality of life(PAC-QOL) and serum inflammatory factor levels were compared between the two groups before and after treatment. Result After treatment, the proportion of patients with CSBM≥3 times per week or an increase of ≥1 time compared with the baseline in the study group was significantly higher than that in the control group(50.0% vs. 31.4%，P＜0.05). The number of patients with BSFS types 3～4 in the study group was significantly higher than that in the control group(57.8% vs. 40.2%，P＜0.05). After treatment, BFI and PAC-QOL scores, IL-6 and hs-CRP levels in both groups were lower than before treatment(P＜0.05), and the study group was lower than the control group. There was no significant difference in NRS score between the two groups before and after treatment(P＞0.05). Conclusion Calcium polycarbophil can effectively improve the symptoms of constipation and quality of life in OIC patients, and reduce the level of serum inflammatory factors, which is worthy of clinical promotion.

Objective To investigate the effect of citalopram combined with pregabalin on pain degree and negative emotions in patients with postherpetic neuralgia. Methods A total of 103 patients with postherpetic neuralgia treated in our hospital from September 2022 to March 2023 were selected as the study objects. They were randomly divided into the observation group(n＝52) and the control group(n＝51). The observation group received pregabalin combined with citalopram, while the control group received pregabalin. The clinical efficacy, pain degree, anxiety, depression and cytokine changes were compared between the two groups. Results The clinical efficacy rate of the observation group was higher than that of the control group(94.23% vs 64.71%, P＜0.05). After treatment, the visual analogue scale, Hamilton Anxiety Scale, Hamilton Depression Scale, the levels of interleukin-6 and tumor necrosis factor-α in the both groups were decreased than those before treatment, and the observation group was lower than the control group(P＜0.05). Conclusion Pregabalin combined with citalopram can improve the clinical efficacy, effectively alleviate the pain, ameliorate the anxiety and depression, and attenuate the inflammation response in patients with postherpetic neuralgia.

Objective To explore the effect of Tingli Dazao Xiefei decoction as an adjuvant treatment for children with severe pneumonia(SP) of phlegm-heat obstructing lung syndrome, and its effect on receptor for advanced glycation end products(RAGE) and diamine oxidase(DAO) levels. Methods A total of 104 children with SP in our hospital from March 2022 to March 2024 were selected and randomly divided into the control group and the study group, with 52 cases in each group. All children were given conventional oxygen inhalation and anti-infection treatment. The control group was treated with phentolamine, and the study group was treated with phentolamine combined with Tingli Dazao Xiefei decoction. Both groups were treated for one week. The therapeutic effects, the traditional Chinese medicine(TCM) syndrome scores, arterial blood gas indicators[arterial partial pressure of oxygen(PaO2), arterial carbon dioxide(PaCO2), blood oxygen saturation(SpO2)], inflammatory factors[C-reactive protein(CRP), tumor necrosis factor(TNF)-α, interleukin(IL)-6], lung function, RAGE, and DAO levels between two groups were compared. The occurrence of adverse reactions of the two groups during the treatment process were recorded. Results After treatment, the clinical efficacy, PaO2, SpO2 and pulmonary function indexes of the study group were all better than those of the control group(P＜0.05), the TCM syndrome scores, PaCO2, CRP, TNF-α, IL-6, RAGE and DAO levels were all lower than those of the control group(P＜ 0.05). There was no statistically significant difference in the occurrence of adverse reactions between the two groups(P＞ 0.05). Conclusion Tingli Dazao Xiefei decoction has a better adjuvant therapeutic effect on children with SP of phlegmheat obstructing lung syndrome. It can effectively improve clinical symptoms and arterial blood gas indicators, and reduce the levels of serum RAGE and DAO.