Objective To introduce the contents, significance of the policy on ''Notice on Establishing Initial Launching Market Price Formation for Newly Original Chemicals and Encouraging High-Quality Innovation'' issued by the China Healthcare Security Administration in 2024 and put forward suggestions for improvement. Methods The contents and requirements of economic analysis of new drugs with high, middle and low innovative degrees were summarized through policies analysis and literature review, the classification of added benefits of innovative drugs in America, Germany, France and Canada was compared. Results Great progress has been made in the research and development of innovative drugs in China in recent years. We should adhere to the basic principle that drug prices should be determined by the market, and give full play to the role of the government in supporting and guiding the prices of newly listed drugs. The innovation degree of new drugs is evaluated from three dimensions: pharmaceutical basis, clinical value and evidence-based information. The evaluation system consists of 3 first-grade indexes, 13 second-grade indexes and 34 third-grade indexes, which are classified into high(90—150 scores), middle(50—90 scores) and low(below 50 scores) categories according to the scores value, to guide pharmaceutical companies to self-evaluating the innovation degree of newly listed chemicals. Conclusion The new policy encourages the development of high-quality innovative drugs, and takes the clinical value as the priority, paying attention on the added therapeutic benefit assessment. The new policy clarifies the composition of the ''basket'' and ''initial price'' of countries and regions of external reference pricing that has been established in China. The composition including 5 parts, the manufacturing costs, production period costs, sales profits, taxes, and distributor/wholesaler's mark-up. It should fully mobilize the initiative of free-pricing system by the pharmaceutical enterprises, recommendation from trade associations, clinical professional opinions issued by medical institutions, mobilize the enthusiasm of health technology assessment agencies and multi-disciplinary experts, finally conduct the social co-governance of drug prices in China.

Cancer patients are more likely to develop venous thromboembolism than the general population, and venous thromboembolism is the second leading cause of death in cancer patients after the primary cause of cancer itself. Lung cancer is one of the cancer types with the highest risk of venous thrombosis. Among venous thromboembolism, pulmonary embolism is the most dangerous and has a significant impact on the treatment, condition and prognosis of lung cancer patients. This paper discussed the pathogenesis, risk factors and current predictive models of pulmonary embolism in patients with lung cancer.

Chronic obstructive pulmonary disease(COPD) is a heterogeneous lung disease characterized by chronic respiratory symptoms(dyspnea, cough, sputum production, and/or exacerbation) due to airway(bronchitis, bronchiolitis) and/or alveolar abnormalities(emphysema) that cause persistent, often progressive airway obstruction. The degree of airflow limitation can be improved with standard treatment, due to its long duration and ease of recurrence, COPD can gradually lead to progressive decline in lung function and worsening symptoms such as dyspnea and reduced exercise tolerance, which seriously affect patients' daily life and quality of life. With the deepening of clinical research, in addition to pharmacotherapy, respiratory therapy has been found to be important in improving lung function, prognosis and quality of life in patients with COPD. This article simply summarized the respiratory therapy in the stable phase and acute exacerbation/combined respiratory failure of COPD.

Objective To evaluate the effect of virtual reality technology on the rehabilitation of patients with chronic obstructive pulmonary disease(COPD) by meta-analysis. Methods PubMed, Cochrane Library, Web of Science, Embase, CNKI, Wanfang database and VIP Chinese journal full-text database were searched to collect clinical trials on the application of virtual reality technology to the rehabilitation of COPD patients, and the search time was from the establishment of the database to July 2023. RevMan 5.4 software was used for data processing. Results A total of 15 literatures were included, including 1 058 subjects. The results of meta-analysis showed that virtual reality rehabilitation training could increase the 6-minute walking distance of COPD patients[mean difference(MD)＝21.48, 95% confidence interval(CI): 16.01—26.95, P＜0.01], and improve pulmonary function, including blood oxygen saturation(MD＝1.16, 95%CI: 0.67—1.65, P＜0.01), forced expiratory volume in the first second(MD＝0.27, 95%CI: 0.22—0.32, P＜0.01), and the ratio of forced expiratoryvolume to forced vital capacity in the first second(MD＝4.51, 95%CI: 3.34—5.67, P＜0.01) in COPD patients. Symptom control was improved(MD＝-3.05, 95%CI: -3.27 — -2.83, P＜0.01). There was no significant difference in improving hypoxia[standardized mean difference(SMD)＝0.11, 95%CI: -0.22 — 0.45, P＝0.51] and quality of life(SMD＝-0.28, 95%CI: -0.62—0.07, P＝0.12). Conclusion Virtual reality technology can improve the exercise endurance, lung function, symptom control of COPD patients, and the application effect is good.

Objective To evaluate the effect of long-term oxygen therapy combined with exercise rehabilitation on chronic obstructive pulmonary disease(COPD) patients by meta-analysis. Methods PubMed, Cochrane Library, Web of Science, CNKI, Wanfang Database and VIP Chinese journal full-text database were searched to collect clinical trials on the effects of long-term oxygen therapy combined with exercise rehabilitation on COPD patients. The retrieval time was from the establishment of the databases to July 2023. Review Manager 5.4 software was used for data processing. Results A total of 11 literatures were included, including 403 subjects(201 subjects in experimental group and 202 subjects in control group). The results of meta-analysis showed that long-term oxygen therapy combined with exercise rehabilitation had nostatistical significance in improving cardiopulmonary function and exercise endurance compared with exercise alone. Longterm oxygen therapy combined with exercise rehabilitation could reduce blood lactate level[standardized mean difference (SMD)＝-0.51, 95% confidence interval(CI): -0.93 — -0.09, P＝0.02]. The partial pressure of oxygen was improved [mean difference(MD)＝10.55, 95%CI: 9.62—11.49, P＜0.01], and the partial pressure of carbon dioxide was decreased (MD＝-5.15, 95%CI: -5.67 — -4.64, P＜0.01). In terms of quality of life, both St. George's respiratory questionnaire evaluation(MD＝-8.22, 95%CI: -9.32 — -7.13, P＜0.01) and BODE index evaluation indicated improvement(MD＝ 0.51, 95%CI: 0.04 — 0.98, P＝0.03). Conclusion Long-term oxygen therapy combined with exercise rehabilitation has no significant changes in exercise tolerance, cardiopulmonary function and other aspects of COPD patients compared with exercise alone, and can improve the quality of life. It can be applied to clinical rehabilitation treatment according to the specific situation of patients.

Objective To explore the mechanism of kaempferol on adriamycin resistance sensitivity of lung cancer cells based on transforming growth factor β1/Ras related C3 botox substrate 1(TGF-β1/Rac1) signaling pathway. Methods H1299/R cells were divided into negative control group(NC), kaempferol low, medium and high-dose groups, TGF-β1 inhibitor group, Rac1 inhibitor group, kaempferol high-dose＋TGF-β1 inhibitor group, kaempferol high-dose＋Rac1 inhibitor group, and kaempferol high-dose＋TGF-β1 inhibitor＋Rac1 inhibitor group. MTT assay was used to detect the cell growth inhibition rate and drug resistance sensitivity. Flow cytometry was used to detect the cell apoptosis. Transwell chamber was used to detect the cell invasion. Western blotting was used to detect the expression of TGF-β1 and Rac1 protein. Results Compared with NC group, the half inhibitory concentration(IC50), cell invasion ability in kaempferol low, medium and high-dose groups, TGF-β1 inhibitor group, Rac1 inhibitor group were significantly decreased, while the cell apoptosis rate was increased, and the expression of TGF-β1 and Rac1 protein were significantly decreased(P＜0.05). Compared withthe kaempferol high-dose group, the IC50, cell invasion ability, TGF-β1 and Rac1 protein expression of H1299/R cells in kaempferol high-dose＋TGF-β1 inhibitor group, kaempferol high-dose＋Rac1 inhibitor group, and kaempferol high-dose＋ TGF-β1 inhibitor＋Rac1 inhibitor group were significantly decreased, while the cell apoptosis rate was significantly increased(P＜0.05). Conclusion Kaempferol can reverse adriamycin resistance in lung cancer cells, inhibit the invasion of adriamycin resistant cells and promote apoptosis, the mechanism may be related to the inhibition of TGF-β1/Rac1 signaling pathway.

Objective To investigate the inhibitory effect of β-sitosterol on quercetin in A549 cells and its mechanism. Methods The A549 cells were divided into control group, quercetin group, quercetin＋β-sitosterol group, estradiol group, estradiol＋quercetin group, and estradiol＋quercetin＋β-sitosterol group. The cell survival rate the inhibitory effects of A549 cell. The flow cytometry and immunofluorescence methods were used to determine the pro-apoptotic effect of on lung cancer cells. Western blotting was used to the regulatory effects of phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/ mammalian target of rapamycin(mTOR) signaling pathway. Results Quercetin could inhibit the survival rate of A549 cells with dose-response relationship(P＜0.05).Estradiol promoted the growth of A549 cells. Compared with quercetin group or quercetin＋β-sitosterol group, estradiol＋quercetin＋β-sitosterol group more inhibited the proliferation of A549 cells, increased the proportion of apoptosis and the expression level of caspase-3(P＜0.05), promoted the phosphorylation of mTOR and AKT, and decreased the phosphorylation of PI3K. Conclusions Under the intervention of estradiol, β-sitosterol combined with quercetin inhibited A549 cells, the mechanism of which may be through the PI3K/Akt/mTOR pathway of apoptosis.

Objective To investigate the effects of ophiopogonin B on epithelial mesenchymal transformation(EMT), chemotherapy resistance and sonic hedgehog(Shh)/glioma associated oncogene homolog(Gli)1 pathway in hepatocellular carcinoma. Methods Screening suitable concentration of ophiopogonin B. The HepG2 cells were divided into control group, ophiopogonin B low(group A), medium(group B), high concentration group(group C) and ophiopogonin B high concentration＋Shh agonist group(group D). The HepG2/adriamycin(ADM) cells were divided into HepG2/ADM group, ADM group, ophiopogonin B group and ADM＋ophiopogonin B group. HepG2 cell proliferation, apoptosis, EMT, Shh/ Gli1 pathways and related protein expression were detected. HepG2/ADM cells were treated to detect cell proliferation, apoptosis, Shh and Gli1 proteins. Results Compared with the control group, 5-ethynyl-2'-deoxyuridine(EdU) positive rate, the expressions of Ki67, B cell lymphoma(Bcl)-2, neural cadherin, vimentin, Shh and Gli1 in groups A, B and C decreased successively, while the apoptosis rate, Bcl-2 associated X protein(Bax) and cadherin expression in epithelial cells increased successively(P＜0.05). Compared with group C, Edu positive rate, Ki67, Bcl-2, neural cadherin, vimentin,Shh and Gli1 expressions in group D were increased, while apoptosis rate, Bax and cadherin expression in epithelial cells were decreased(P＜0.05). Compared with HepG2/ADM group, EdU positive rate, Shh and Gli1 expressions in ADM and ophiopogonin B group decreased, and apoptosis rate increased(P＜0.05). Compared with ADM and ophiopogonin B groups, Edu positive rate, Shh and Gli1 expressions were decreased in ADM＋ophiopogonin B group, and apoptosis rate was increased(P＜0.05). Conclusion Ophiopogonin B inhibits EMT of HepG2 cells by inhibiting Shh/Gli1 pathway and reducing chemotherapy resistance.

Objective To investigate the effects of stanozolol combined with conventional therapy on predicting adult height(PAH) and gonadal development in children with idiopathic central precocious puberty(ICPP). Methods A total of 80 ICPP children admitted to our hospital from June 2018 to June 2020 were randomly divided into control group(routine regimen) and observation group(routine regimen＋stanozolol), with 40 cases in each group. The results of PAH and gonad development in the two groups were compared. Results After treatment, the growth rate and PAH in observation group were higher than those in control group(P＜0.05). Tanner stage and pubic hair stage were better than control group (P＜0.05). The volume of left and right ovary was lower than that of control group(P＜0.05). In the observation group, the effect of children with large bone age(11 - 14 years old) to achieve PAH was better than that of children with small bone age(8 - 11 years old) (P＜0.05). No serious drug-related adverse reactions occurred in the two groups during treatment. Conclusion Stanozolol is effective in the treatment of ICPP in children, can significantly improve the prediction of PAH, improve symptoms, inhibit gonadal development, and has good safety, especially for growth promotion in children with large bone age.

Objective To analyze the effects of self-designed Qufeng Yangxue Runfu liquid bath combined with levocetirizine hydrochloride on itchy scratching behavior and calcium and phosphorus metabolism in patients with maintenance hemodialysis(MHD). Methods A total of 80 patients with regular MHD and blood vacuity and wind-driness in our hospital from January 2021 to August 2022 were selected and divided into control group(conventional treatment＋ levocetirizine hydrochloride) and observation group(conventional treatment＋levocetirizine hydrochloride＋self-designed Qufeng Yangxue Runfu liquid bath) by random number table method, with 40 cases in each group. Pruritus score, blood calcium, blood phosphorus, parathyroid hormone(PTH), hypersensitive C-reactive protein(hs-CRP), interleukin(IL)-6 and clinical efficacy were compared between the two groups before and after treatment. Results After treatment, the levels of pruritus score, blood phosphorus, PTH, hs-CRP and IL-6 in both groups were decreased(P＜0.05), and the observation group was lower than the control group(P＜0.05). The serum calcium level in both groups were higher than before(P＜ 0.05), and the observation group was higher than the control group(P＜0.05). The curative effect of observation group was significantly higher than that of control group(87.50% vs 67.50%, P＜0.05). Conclusion Self-designed Qufeng Yangxue Runfu liquid bath combined with levocetirizine hydrochloride has a better effect on skin pruritus in MHD patients, which caneffectively relieve pruritus, improve calcium and phosphorus metabolism, and reduce inflammation in vivo.

Objective To analyze the effects of Qinxitong tablets combined with tripterygium glycosides on platelet aggregation and B cell expression in patients with rheumatoid arthritis(RA). Methods A total of 100 RA patients admitted to our hospital from January 2021 to February 2022 were selected and divided into study group(tripterygium glycosides＋ methotrexate＋Qinxitong tablets, n＝49) and control group(tripterygium glycosides＋methotrexate, n＝51) according to simple sorting random method. The efficacy, clinical symptom score, helper T cell(Th)17/regulatory T cell(Treg) and C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), cyclic citrullinated peptide(CCP), soluble growth stimulation expressed gene 2 protein(sST2), matrix metalloproteinases(MMP)3, rheumatoid factor(RF), human platelet α granule membrane glycoprotein(CD62p), CD41, chemokine C-X-C motif ligand(CXCL)13 and the incidence of complications were compared between the two groups. Results After treatment, the total effective rate of the study group was higher than that of the control group(95.92% vs 74.51%, P＜0.05). The scores of morning stiffness, joint pain, joint swellingand joint tenderness were lower than those of control group(P＜0.05). The levels of Th17/Treg, CRP and ESR were lower than those of control group(P＜0.05). The levels of sST2, MMP3 and RF were lower than those of control group(P＜0.05). Serum levels of CD62p and CD41 were lower than those of control group(P＜0.05). The level of CXCL13 was lower than that of control group(P＜0.05). The total complication rate was lower than that of control group(P＜0.05). Conclusion Qinxitong tablets combined with tripterygium glycosides can effectively relieve the clinical symptoms of RA patients, inhibit platelet aggregation, reduce the expression of inflammatory cells and B cell, and control the levels of sST2, MMP3 and RF, which is safe and effective.

Objective To perform a rapid health technology assessment(rHTA) on the safety, effectiveness, and economy of pertuzumab in human epidermal growth factor receptor(HER)2-positive breast cancer, and to provide an evidencebased basis for clinical drug decision. Methods Pubmed, Cochrane Library, Embase, CNKI, Wanfang, official HTA websites were systematically searched. References were screened according to the inclusion and exclusion criterion. And the results were analyzed by data extraction and quality evaluation. Results 20 systematic review/meta-analysis, 12 economic studies and 4 HTA were included in our study. The results of the study showed that in terms of effectiveness, pertuzumab can improve the pathologic conplete remission(pCR) and objective remission rate(ORR) of trastuzumab, pCR and disease free survival(DFS) of trastuzumab plus chemotherapy for neoadjuvant breast cancer patients. For the patients with metastatic breast cancer, pertuzumab can improve the progression-free survival(PFS) of trastuzumab, PFS, ORR, 1-year, 2-year and median overall survival(OS) of trastuzumab plus taxol, the OS of trastuzumab plus capecitabine. In terms of safety,pertuzumab had mild side effects and good safety. In terms of economy, the combination of pertuzumab was not economical both in abroad and at home. Conclusion Pertuzumab was effective and safe in the treatment of HER2-positive breast cancer, but the economy was poor.

Objective To evaluate the safety, efficacy and economy of lorlatinib as the first-line treatment in patients with anaplastic lymphoma kinase(ALK)-positive non-small cell lung cancer(NSCLC) by rapid health technology assessment(rHTA), and to provide evidence for clinical decision makers. Methods Domestic and foreign databases and other major official HTA websites were used, and the related literatures about lorlatinib as first-line treatment for ALK mutationpositive NSCLC patients were included and comprehensively analyzed. Results A total of 9 systematic/meta-analyses and 4 economic studies were included. Efficacy results showed that objective response rate and progression-free survival of lorlatinib were significantly better than other ALK-tyrosine kinase inhibitors and chemicals, but overall survival was not significantly different. Safety results showed that the incidence of adverse events of lorlatinib≥3 was only lower than ceritinib, but controllable. Economic results did not show a significant cost-effectiveness advantage. Conclusion Lorlatinib has efficacy and safety advantages in the first-line treatment of ALK mutation-positive NSCLC patients, but its economic advantages need to be further studied. More safety, effectiveness and economic studies focusing on intuitive comparison and multi-subgroup are necessary.

Ceftazidime/avibactam is a combination of third-generation ceftazidime and novel non-beta-lactamase inhibitors. At present, it has been approved for the clinical treatment of severe infections with limited therapeutic drugs such as hospital-acquired pneumonia, ventilator-associated pneumonia, and complex abdominal infection, and it also has been gradually applied in the clinical treatment of complex urinary tract infection and intracranial infection, and has shown obvious advantages. This article summarized the pharmacological action, pharmacokinetics, clinical application and drug use methods of ceftazidime/avibactam, in order to provide some reference for clinical drug selection and promote rational drug use.

Sepsis is a systemic inflammatory response syndrome induced by infection, and the pathophysiological changes are accompanied by metabolic disorders and abnormal inflammatory responses. However, the clinical characteristics and related molecular mechanisms of inflammation-metabolic reprogramming are still unclear. Recent studies have reported that dichloroacetate(DCA) can reverse the metabolic reprogramming secondary to sepsis, participate in cell metabolism, mitochondrial function, oxidative stress response, glucose and lipid metabolism, protein metabolism, and immune regulation, but the possible mechanism of action has not been fully clarified. To further study the effects of DCA on sepsis, this article reviewed the current application of DCA in sepsis and its possible molecular mechanisms, providing new targets, new ideas, and new methods for the prevention and treatment of sepsis.

Selective estrogen receptor degrader(SERD) is commonly used in the endocrine therapy of estrogen receptor(ER) positive advanced breast cancer. Elacestrant is a novel oral SERD that is for the treatment of advanced breast cancer with ER-positive and human epidermal growth factor receptor(HER)2-negative. It is more effective than other endocrine therapies and can significantly improve the median progression free survival of patients, and is also effective for breast cancer patients with ER gene α mutations. The launch of elacestrant will provide a more effective treatment option for patients with ER-positive, HER2-negative advanced breast cancer.

Through national negotiations on innovative drugs and the update of drug catalogue, more and more effective therapeutic drugs have been included in the medical insurance fund, which reduces the burden of medical expense while meeting the drug needs of insured patients. However, some violations of laws and regulations of clinical drug use in the supervision of medical insurance fund have been found. At the same time, with the implementation of new policies such as centralized drug procurement policy, "dual channel drugs" and reform of medical insurance payment methods, as well as the development of new medical forms such as "internet＋health care", some new problems and phenomena have also been found in the supervision. Based on the typical cases in the supervision of medical insurance, this paper summarized the common violations of clinical drug use.