OBJECTIVE: To investigate antiviral mechanism of bromhexine for the treatment of COVID-19. METHODS: Based on the existing literature, the infection pathways of new coronavirus(SARS-CoV-2) were systematically summarized by us, and used the SWISSDOCK molecular simulation method to carry out virtual screen systematically for key targets and marketed drugs. RESULTS: TMPRSS2/ACE2 pathway was found to be the most efficient and probably the major pathway for SARS-CoV-2 virus to infect the lung and other tissue by us. Bromhexine, an expectorant, can strongly inhibit TMPRSS2 protease (EC50:0.75 μmol•L-1) in vitro. Bromhexine has few adverse effects and also has the beneficial effects of promoting the release and maintenance of endogenous active substances in the lung, alveolar function, and promoting sputum excretion, which is suitable for use together with other COVID19 medication and therapies. CONCLUSION: Bromhexine has a unique potential antiviral mechanism, and clinical research should be conducted to play its role in the prevention, treatment and prognosis of COVID19.

Clinical comprehensive evaluation of drugs is an important technical tool for drug supply assurance decision - making，which requires evaluation subjects to use multiple evaluation methods and tools to carry out a comprehensive evaluation of multi-dimensional and multi -level evidence for drugs . Multi-criteria decision analysis （MCDA）is an important method for clinical comprehensive evaluation of drugs ，including weight assignment and comprehensive evaluation . Step-wise weight assessment ratio analysis（SWARA）is a weighting method for MCDA ，which can determine indicator weight concisely and accurately compared to other methods . This paper introduces the method of SWARA ，and systematically reviews the application of SWARA in the comprehensive clinical evaluation of drugs . Currently，the SWARA method is used in various research areas . Within the field of pharmaceuticals，researchers use the SWARA method to build MCDA models and calculate specific weight values for each drug evaluation criterion by consulting a team of experts . The advantage of SWARA is that it provides a brand -new way of assigning the weight of drug evaluation criterion by consulting experts ’opinions or judgments according to corresponding steps to solve the MCDA problem in the medical field ；however，it has certain subjectivity and uncertainty in solving complex decision -making problems，and there may also be problems such as insufficient screening of evaluation criterion and incomplete coverage of topics ， which should be paid attention to in application .

OBJECTIVE To evaluate the safety of fondaparinux in pregnancy and provide reference for its rational clinical application. METHODS A search was conducted in databases including CNKI， Wanfang， PubMed， Embase， and Elsevier （the search time was from the construction of the database to December 17， 2024） to collect case report literature on fondaparinux use during pregnancy. Patient demographic information， fondaparinux use during pregnancy， concomitant medications， clinical manifestations， and treatment details were extracted for descriptive statistical analysis. RESULTS A total of 17 case reports regarding the use of fondaparinux during pregnancy were collected， involving 42 patients from 11 countries and 47 pregnancy records. Among these， 20 cases involved the use of fondaparinux for the prevention of pregnancy-related venous thromboembolism （VTE）， while 27 cases were fondaparinux treatment due to related conditions. A total of 29 occurrences of the patients were treated with fondaparinux due to a （family） history of VTE. Nine occurrences of complicated pregnancies were reported， and 35 patients had records of comorbidities or relevant medical histories. The adverse events that occurred during pregnancy with the use of fondaparinux include postpartum hemorrhage （7 cases） and excessive anticoagulation caused by inappropriate dosage （1 case）. Among the 7 cases of postpartum hemorrhage， 3 cases had a blood loss of no less than 1 000 mL （including 2 cases with uterine atony）， 3 cases had a drug discontinuation time of ≤12 h. CONCLUSIONS Based on the existing literature， the safety of fondaparinux during pregnancy is generally manageable， with the main adverse event being postpartum hemorrhage. The dosage， interval between discontinuation，comorbidities/medical history， and concomitant medications of fondaparinux may be the main causes of its adverse events.

At present， there is a lack of unified and standardized management for the rational use of national key monitoring drugs. According to the relevant requirements of the state， based on the relevant literature published at home and abroad in recent years and combined with the management practice of many medical institutions across the country on the national key monitoring drugs， in order to make the national key monitoring drugs more reasonable use and standardized management in medical institutions at all levels， the Clinical Pharmacy Branch of the Chinese Medical Association， the Pharmaceutical Epidemiology Special Committee of the Chinese Pharmaceutical Association and the Pharmaceutical Epidemiology Special Committee of the Sichuan Pharmaceutical Association organized experts to fully discuss， and to form this management standard. This standard mainly provides relevant opinions and suggestions on the basic principles of rational use of key monitoring drugs and the regulatory measures for key monitoring drugs， especially on how to strengthen the pharmaceutical management and use management of key monitoring drugs， further promoting the standardized use of key monitoring drugs.

Autophagy is a process that delivers cytoplasmic components to lysosome for degradation, which plays an important role in intracellular homeostasis and achieving self-renewal.Recent studies have shown a close relation between autophagy and renal cystogenesis in ADPKD.Further studies show that there are two phenomena of autophagy impairment and autophagy enhancement in the ADPKD disease model.Autophagy disorders influence the occurrence and development of ADPKD.Therefore, the regulation of autophagy may be a new strategy for ADPKD treatment.Medicines that regulate autophagy through mTOR-dependent and mTOR-independent pathways also show a positive effect in alleviating ADPKD symptoms.This paper reviews the progress of the role of autophagy in ADPKD and provides reference for further research of autophagy in ADPKD and its medicine regulation.

Objective In order to improve the rationalization of medication use for thrombosis prevention and treatment in children,the guideline aims to develop a comprehensive and practical guideline for pharmacy practice in the prevention and treatment of thromboembolic diseases in children.Through a systematic review of the available evidence-based medical evidence,specific recommendations for drug prevention and treatment are presented.Methods The World Health Organization(WHO)guideline development manual was used for the study design of the guideline.A systematic search and extensive collection of common medication problems for the prevention and treatment of thrombosis in children existed nationwide,and the Delphi method was used to research experts and determine the final clinical problems to be included.Then,a systematic literature search was conducted to comprehensively assess the existing original studies,systematic evaluations,and guidelines or consensus of professional organizations.Quality evaluation was conducted according to the grades of recommendations assessment,development and evaluation(GRADE)method,and consensus on the recommendations and level of evidence was reached again through the Delphi method,which ultimately led to the formation of the pharmacy practice guidelines for the prevention and treatment of thromboembolic diseases in children.Results A total of 29 clinical problems assessed by 74 experts in clinical pharmacy and clinical medicine were collected during the development of the guideline;15 clinical problems were screened through two rounds of questionnaires;and 15 clinical medication recommendations were developed under the supervision of two methodologists.Conclusion By comprehensively evaluating the feasibility and safety of clinical practice,the guideline will provide specific antithrombotic medication recommendations for pediatric healthcare professionals,which will help improve the prevention and treatment of thrombosis in children and promote more standardized and effective medical practice.

OBJECTIVE： To evaluate therapeutic efficacy of reteplase versus alteplase in the treatment of acute myocardial infarction in China， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from Cochrane library， PubMed， Embase， Medline， CJFD， CSJD， Wanfang database by computor， etc.， also by manual search， RCTs about therapeutic efficacy （recanalization rate of thrombolysis） of reteplase （trial group） versus alteplase （control group） in the treatment of acute myocardial infarction in China were collected from Jan. 1995 to Sept. 2018. After data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0， Meta-analysis was performed for recanalization rate of thrombolysis by using Rev Man 5.3 software. RESULTS： A total of 23 RCTs were included， involving 1 742 patients. Results of Meta-analysis showed that recanalization rate of thrombolysis in trial group was significantly higher than control group， with statistical significance [OR＝0.61，95％CI（0.50，0.73），P＜0.001]. Sub-group Meta-analysis was performed according to the successful time of thrombolysis. Results of Meta-analysis showed that recanalization rate of thrombolysis in trial group 1 h [OR＝0.38，95％CI（0.25，0.58），P＜0.001]， 1.5 h [OR＝0.44，95％CI（0.25，0.79），P＝0.006] and 2 h [OR＝0.62，95％CI（0.42，0.92），P＝0.02] after thrombolysis were significantly higher than control group， with statistical significance. CONCLUSIONS： The recanalization rate of thrombolysis by reteplase in Chinese patients with acute myocardial infarction in better than by alteplase.

OBJECTIVE： To study the relationships of polymorphism of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus with drug concentration of methotrexate （MTX） and high-dose MTX （HD-MTX）-induced ADR in acute lymphoblastic leukemia （ALL） children. METHODS： From Oct. 2015 to Sept. 2018， 70 ALL hospitalized children of Han nationality in Sichuan area who received HD-MTX treatment and were in consolidation chemotherapy were selected retrospectively from Sichuan People’s Hospital. The blood concentration of MTX at 48 and 72 hours after administration was measured by EMIT. The genetic typing of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus were detected with real-time PCR. The relationships of the polymorphism of MTRR gene and SLCO1B1 gene with MTX blood concentration [dose-corrected concentration （c48 h/D，48 h）， the proportion of children with different concentration of MTX （≤0.1， ＞0.1 μmol/L）] and ADR （such as myelosuppression， liver function damage， gastrointestinal response， mucosal damage， rash， etc.） were analyzed. Binary Logistic regression analysis for the correlation of ADR with different influencing factors （gene polymor- phism， blood concentration of MTX， immunophenotyping， body mass index， etc.） was carried out by Wald method. RESULTS： Totally 31， 32， 7 children with MTRR gene AA， AG and GG genotype， while 23， 37， 10 children with SLCO1B1 gene TT， TC and CC genotype were detected. The distribution of each genotype in 70 children conformed to Hardy-Weinberg equilibrium （P＞0.05）. There was no significant difference in c48 h/D（48 h） of children and the proportion of children with different concentration of MTX （72 h） among difterent genotypes of MTRR and SLCO1B1 gene （P＞0.05）. There was statistical significance in the incidence of liver function injury in children with different genotypes of MTRR gene （P＜0.05）， and the AA genotype was significantly higher than the AG+GG genotype （P＜0.05）. There was no correlation of MTRR gene polymorphism with the incidence of other ADR， neither SLCO1B1 gene polymorphism with the incidence of ADR （P＞0.05）. The results of Binary Logistic regression analysis showed that liver function damage in ALL children was related to the gene polymorphism of MTRR； gastrointestinal reaction was related to whether the plasma concentration was more than 0.1 μmol/L at 72 h； mucosal damage was related to the immune type and BMI of children； the occurrence of skin allergy was correlated with body weight of children（P＜0.05）. CONCLUSIONS： Gene polymorphism of MTRR rs1801394 locus may associated with the occurrence of HD-HTX-induced liver function injury in ALL children， but its polymorphism and gene polymorphism of SLCO1B1 rs11045879 locus are not related to MTX blood concentration in ALL children.

ProBiotic-4 is a probiotic preparation composed of , , , and . This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor- at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-B (NF-B) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of -H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-B signaling pathway and inflammatory responses.

The sodium taurocholate co-transporting polypeptide(NTCP),a bile acids transporter,has been identi-fied as a new therapeutic target for the treatment of liver disease.This paper thoroughly investigates the function of NTCP for regulating bile acid regulation,its correlation with hepatitis B and D infections,and its association with various liver diseases.Additionally,in this review we examine recent breakthroughs in creating NTCP inhibitors and their prospective applications in liver disease treatment.While this review emphasizes the promising potential of targeting NTCP,it concurrently underscores the need for broader and more detailed research to fully understand the long-term implications and potential side effects associated with NTCP inhibition.