OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

OBJECTIVE To construct the research questions and topic selection evaluation index system of the Guideline for Topic Selection for Comprehensive Clinical Evaluation of Drugs （hereinafter referred to as the Guideline）， so as to provide the basis for the formulation of the Guideline. METHODS Through literature research， an expert questionnaire on the research questions and evaluation index system of the Guideline was initially constructed. Experts were selected according to relevant requirements of the guideline formulation and Delphi method； the research questions and evaluation indicators of the Guideline were screened by electronic questionnaire communication， and the weights of evaluation index system of topic selection were assigned by the analytic hierarchy process. RESULTS Five research questions of the Guideline were constructed， including the organization and management of theme selection， evaluation process， evaluation methods， evaluation index system， and index weight assignment. And a theme selection and evaluation index system， including 5 primary indexes， 9 secondary indexes and 17 tertiary indexes， was constructed. Kendall coefficients of the research questions and all indexes were ＞0.4， and the P values of χ2 test were＜0.05， which meant the evaluation results were consistent. The weights of all levels of the evaluation index system were assigned by analytic hierarchy process with consistency ratio of 0.007 6 （＜0.1）， and the model matrix passed the consistency test. CONCLUSIONS The research questions and topic selection evaluation index system of the Guideline established in this study are highly authoritative， scientific and reliable， which lay a foundation for the standardization of the Guideline.

OBJECTIVE To investigate the effects of formononetin （FMN） on the apoptosis of intestinal epithelial cells in inflammatory bowel disease （IBD） rats and its possible mechanism. METHODS IBD rat model was constructed by using trinitrobenzene sulfonic acid （TNBS） induction. Forty-eight rats with successful modeling were divided into model group （normal saline）， low-dose and high-dose FMN groups （20 and 40 mg/kg FMN）， and high-dose FMN+YAP inhibitor Verteporfin （VTPF） group （40 mg/kg FMN+10 mg/kg VTPF）， with 12 rats in each group. Another 12 rats were set as the normal group （normal saline）. They were given drug/normal saline， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of rats was calculated， and the colon length of rats in each group was measured. The pathological changes in the colon tissue of rats were observed. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in serum were detected， and the apoptosis of intestinal epithelial cells was detected. The expressions of Yes associated protein （YAP）， cleaved cysteine-containing aspartate proteolytic enzyme 3 （cleaved-caspase-3）， B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax） were detected in colon tissue of rats. RESULTS Compared with the normal group， DAI score， the levels of TNF-α and IL- 6， the apoptotic rate of intestinal epithelial cells， and the expressions of cleaved-caspase-3 and Bax protein in the model group were increased greatly （P＜0.05）； the length of the colon was greatly decreased （P＜0.05）， and the serum level of IL-10 and the protein expressions of YAP and Bcl-2 were greatly reduced （P＜0.05）. The cell morphology of colon tissue was abnormal， with disordered arrangement and inflammatory cell infiltration. Compared with IBD group， the above indexes of rats were improved significantly in low-dose and high-dose FMN groups （P＜0.05）， in dose-dependent manner （P＜0.05）. VTPF significantly alleviated the effects of FMN on the above indexes of IBD rats （P＜0.05）. CONCLUSIONS FMN may promote the expression of YAP by inhibiting the Hippo/YAP signaling pathway， thereby inhibiting apoptosis of intestinal epithelial cells in IBD rats.

OBJECTIVE To mine the adverse drug event （ADE） signals of sacituzumab govitecan and provide a reference for its clinical safety application. METHODS The data of sacituzumab govitecan-related ADE reports were collected from the FDA Adverse Event Reporting System （FAERS） database from April 1， 2020 to April 30， 2024. The reporting odds ratio（ROR） method， the United Kingdom Medicines and Healthcare Products Regulatory Agency comprehensive standard method （MHRA） and Bayesian confidence propagation neural network （BCPNN） method were used for data mining. Systematic organ classification （SOC） and preferred term （PT） in the ADE terminology set of version 27.0 of the Medical Dictionary for Regulatory Activities （MedDRA） were used for data classification and statistics. RESULTS A total of 753 ADE reports were obtained for sacituzumab govitecan， including 46 ADE signals， involving 12 SOCs， and 13 new suspicious ADE signals not recorded in the instructions. Top 5 PTs in terms of occurrence frequency were disease progression， death， diarrhea， off label use and inappropriate schedule of product administration. Top 5 PTs in terms of signal strength were febrile bone marrow aplasia， neutropenic colitis， disease progression， pulmonary sepsis， general physical condition abnormal. New ADE not recorded in the drug instructions included neutropenic sepsis， hepatic cytolysis， meningitis， aplasia， etc. CONCLUSIONS When using sacituzumab govitecan in clinical practice， special attention should be paid to ADE with highly reported cases and strong signal intensity， such as febrile neutropenia， febrile bone marrow aplasia， weight fluctuations， colitis. We should also be alert to new suspected ADE such as neutropenic sepsis， hepatic cytolysis， meningitis， and aplasia to ensure patient medication safety.

OBJECTIVE To evaluate the rationality of clinical application of polymyxin B in the inpatients of a third grade class A hospital，so as to provide evidence for the optimization of clinical scheme of the drug. METHODS A retrospective method was conducted on the electronic medical records of inpatients treated with Polymyxin B sulfate for injection from January 2020 to March 2022 to collect the basic information of patients， inpatient departments and time， infection diagnosis， results of pathogenic bacteria test， laboratory test indicators， usage and dosage， and combined medication，etc. Based on the drug instructions， according to relevant guidelines and consensus， the rationality， efficacy and safety of polymyxin B in inpatient were evaluated. RESULTS & CONCLUSIONS A total of 101 inpatients were included， respiratory system infection was the main cause （62.4%）. All patients had received the etiological examination， and the pathogen with the highest detection rate was carbapenem‑resistant Acinetobacter baumannii （40.6%）. One hundred patients were treated by intravenous drip， and 4 patients were treated by combination of aerosol inhalation or intrathecal injection； 99 patients were given the dose of 500 thousand units by continuous intravenous infusion， q12 h. Totally 51.5% of patients were treated for 7-14 days； and 77 patients were treated with other anti-Gram-negative drugs. There were unreasonable phenomena including too short time of medication （29.7%）， no combination of medication （23.8%）， and no indication of medication （17.8%）. The clinical effective rate of 101 patients treated with polymyxin B was 49.5%， and 16 patients （15.8%） had acute kidney injury during the treatment. Clinical pharmacists should actively participate in the clinical treatment of polymyxin B， formulate individualized treatment plans according to the guidelines/consensus and in combination with the patient’s condition and infection status to improve the rationality of clinical medication.

OBJECTIVE To explore the mechanism of Taohong siwu decoction （THD） improving peripheral nerve injury induced by paclitaxel （PTX） in rats. METHODS The effects of THD （1 g/mL drug-containing serum） and PTX （0.1 μmol/L） alone or in combination on the proliferation rate of Schwann cells line RSC96 as well as the expressions of lysosomal-associated membrane protein-2 （LAMP2）， autophagy marker protein yeast Atg 6 homolog （Beclin1）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR） were investigated， and then compared with autophagy promoter rapamycin and autophagy inhibitor 3-methyladenine （3-MA）. The effects of high-dose and low-dose THD on the expressions of myelin basic protein （MBP） and myelin protein zero （MPZ）， S100 calcium-binding protein （S100）， LAMP2， Beclin1， PI3K， Akt and mTOR were tested at the end of the experiment. RESULTS After treatment of THD+PTX， the proliferation rate of RSC96 cells was significantly higher than those treated with PTX alone. After treatment of THD+PTX or THD+ 3-MA， the protein expressions of LAMP2 and Beclin1 in RSC96 cells were significantly higher than those treated with PTX or 3- MA alone， while the protein expressions of PI3K， Akt and mTOR were significantly lower than those treated with PTX or 3-MA alone （P＜0.05）. Compared with model group， the protein expressions of MBP， MPZ， S100， LAMP2 and Beclin1 in sciatic nerve of rats were increased significantly in THD high-dose and low-dose groups， while the protein expressions of PI3K， Akt and mTOR were significantly decreased （P＜0.05）. CONCLUSIONS THD may activate Schwann cell autophagy by inhibiting the PI3K/Akt/ mTOR signaling pathway， thereby improving peripheral nerve injury caused by PTX.

ObjectiveTo analyze the community structure and dynamics of parasitic fleas on the body surface of host animals and nested fleas in different seasons in the natural foci of wild rat plague in Yulong County，Yunnan Province， to explore the relationship between seasonal fluctuation of fleas and the prevalence of plague among animals， so as to provide evidence for plague prevention and control in the natural foci. MethodsNanxi Village， Huangshan Town， the core area of plague epidemic in Yulong County， was selected as the monitoring sample area in December 2019 （winter）， August 2020（summer）， October 2020（autumn） and March 2021（spring）. Host animals were captured by rattrap at night and rat nests were excavated for collecting parasitic fleas on host animals and rat nest fleas in different seasons. Excel 2010 and SPSS 26.0 software were used to analyze the data， and Chi square test was used to compare the rate. Community ecological indicators were used to analyze the community structure and species diversity of the host animals and their parasitic fleas. ResultsA total of 355 vector fleas were captured， belonging to 7 species of 5 genera in 2 families. 441 small animals were captured and 138 rat body fleas were detected with the flea infection rate of 14.51% and the flea index 0.31. 96 effective rat holes were excavated and 217 fleas were detected with the flea infection rate of 35.42% and the flea index 2.26. Among the four seasons， the flea infection rates of rat body and rat nests were higher in summer and winter， showing a significant difference in general （χ²=15.851， P<0.01； χ²=16.398， P<0.01）. The dominant species of flea community were Ctenophthalmus quadratus， Stenischia humilis， Neopsylla specialis and Frontopsylla spadix， with a dominance index of 0.434， 0.254， 0.180 and 0.110， respectively. The diversity and evenness of rat body fleas showed a distribution characteristic of decreasing， increasing and then decreasing again with season changes， and both were the highest in spring， while the ecological dominance showed an opposite trend. The diversity and evenness of rat nest fleas showed a distribution characteristic of increasing first and then decreasing in summer， autumn and winter， with the highest in autumn， while the ecological dominance was diametrically opposite. ConclusionThe fleas community structure is relatively stable in Yulong County， but the number of species in the community is unevenly distributed by seasons， and the status of dominant species is prominent. Local authorities should carry out timely preventive deratization and depulization measures according to the results of daily monitoring， so as to effectively avoid the prevalence and spread of plague among animals in plague foci.

Objective:To compare the efficacy and safety of endoscopic sclerotherapy with polycinnamol solution and foam in the treatment of grade II hemorrhagic internal hemorrhoids.Methods:From September 2020 to June 2021, 81 patients with grade II hemorrhagic internal hemorrhoids were collected from the Department of Gastroenterology, the First Affiliated Hospital of University of Science and Technology of China. They were randomly divided into an observation group and a control group. The observation group was injected with polycinnamol solution, and the control group was injected with polycinnamol foam. All of them were treated with endoscopic sclerotherapy. The clinical data of the two groups were compared and analyzed. The operation time, immediate hemostasis rate, incidence of postoperative complications (such as fever, pain, bleeding and Urinary retention), recurrence and rebleeding rate of the two groups were observed, and the efficacy and safety of the two groups in the treatment of grade II hemorrhagic internal hemorrhoids were compared.Results:There was no statistically significant difference in basic data between the two groups of patients (all P>0.05), indicating comparability. The surgical operation time of the observation group patients [(7.40±1.18)min] was shorter than that of the control group [(13.88±0.95)min] ( P<0.05); The injection dose of polycinnamol [(5.79±1.61)ml] in the observation group was higher than that in the control group [(4.38±1.92)ml] ( P<0.05). The immediate postoperative hemostasis rate in the observation group was the same as that in the control group (100%). The incidence of postoperative fever (7.32%), perianal pain (4.88%), bleeding (7.32%), and urinary retention (4.88%) complications in the observation group had no significant difference from that in the control group [postoperative fever (5.00%), anal pain (7.50%), bleeding (7.50%), and urinary retention (2.50%)] (all P>0.05). Two months after surgery, the rebleeding rate in the observation group (4.88%) was not significantly different from that in the control group (7.50%) ( P>0.05), but the rebleeding score in the observation group (1.21±0.63) was lower than that in the control group (2.62±0.71), with a statistically significant difference ( P<0.05). The rebleeding rate (2.44%) and the rebleeding score (2.33±1.51) in the observation group were lower than those in the control group [the rebleeding rate (12.50%) and the rebleeding score (5.54±2.42)] at 12 months after follow-up, and the differences were statistically significant ( P<0.05). Conclusions:Endoscopic sclerotherapy is effective in the treatment of grade II hemorrhagic internal hemorrhoids. There is no significant difference in the immediate and short-term hemostasis rate and the incidence of complications between two different dosage forms of sclerotherapy, namely, polycinnamol solution and foam, but the operation of the solution injection is more time-saving and the long-term recurrence rate is lower, which is worthy of clinical application.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

OBJECTIVE To excavate the risk signals of adverse events （AE） related to dipeptidyl peptidase-4 （DPP-4） inhibitors， and to provide reference for clinical safe use of these drugs. METHODS AE reports of five DPP-4 inhibitors （sitagliptin， saxagliptin， linagliptin， vildagliptin， anagliptin） reported in FAERS database from October 17th， 2006 to December 31st， 2021 were collected. The reporting odds ratio （ROR） method was used for data mining， and the systematic organ classification （SOC） and preferred terms （PT） in the drug ADR terminology set of the Medical Dictionary for Regulatory Activitios （24.0 edition） were used for classification statistics. RESULTS A total of 120 510 AE reports related to DPP-4 inhibitors were retrieved， with 1 707 risk signals， including sitagliptin （80 570 reports， 717 signals）， saxagliptin （10 009 reports， 173 signals）， linagliptin （18 214 reports， 317 signals）， vildagliptin （7 893 reports，375 signals） and anagliptin （3 824 reports，125 signals）. In these reports， women （47.27%） were more than men （44.61%）； the age of the patients mainly ranged from 61 to 75 years old （28.37%）. The United States had the largest number （56.17%）； there were 65 458 serious AE reports （54.32%）， mainly hospitalization or prolonged hospitalization time （36.28%）. Sitagliptin， saxagliptin and anagliptin mainly induced gastrointestinal diseases； sitagliptin mainly caused endocrine system diseases， kidney and urinary system diseases， various examinations； vildagliptin mainly resulted in endocrine system diseases， systemic diseases and various reactions at the administration site， nervous system diseases， etc. Among them， risk signals of sitagliptin and liggliptin mainly manifested as the increase of blood glucose， those of saxagliptin as the congestive heart failure and heart failure， and those of vildagliptin and anagliptin as pemphigoid and vomiting respectively. The results of PT analysis of two or more drugs showed that the increase of blood glucose and pancreatitis had the greatest correlation with sitagliptin； the weight loss had the greatest correlation with saxagliptin； renal failure had the greatest correlation with linagliptin； diabetic ketoacidosis had the greatest correlation with anagliptin. Hypoglycemia， acute kidney injury， increased glycated hemoglobin， pemphigoid and lactic acidosis were the most associated with vildagliptin. CONCLUSIONS When DPP-4 inhibitors were used clinically， the blood glucose level and other blood biochemical indexes of patients should be monitored， and skin condition， the pancreas and kidney function should be paid attention to. If related AE occurred， timely intervention measures should be taken to ensure the medication safety of patients.