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 generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety.

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 observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.
Animals ; Mice ; Colitis/chemically induced* ; Immunity, Innate ; Intestine, Small ; Lymphocytes ; Mice, Inbred C57BL

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.

In order to evaluate the safety and effectiveness of endoscopic hemorrhoids treatment, a retrospective analysis was conducted on data of 166 patients with grade I to Ⅲ hemorrhoids who underwent endoscopic treatment in the First Affiliated Hospital of University of Science and Technology of China from January 2018 to June 2020 with complete follow-up data. There were 35 cases in the simple sclerotherapy group, 104 cases in the simple ligation group, and 27 cases in the ligation combined sclerotherapy group. The results showed that, no serious complications occurred in the 3 groups after surgery. In the simple ligation group and the ligation combined with sclerotherapy group, the incidence of postoperative anal pain [35.6% (37/104) and 33.3% (9/27), respectively,] and anal pendant distension [70.2% (73/104) and 70.4% (19/27), respectively] were higher, but symptoms could be tolerated or relieved after simple treatment. The satisfaction of patients in the 3 groups was all more than 90% before discharge, and the degree of operation acceptance was more than 95%. The effective rate of the 3 groups was above 90.0% at 3 months after surgery, At 12 months after surgery, the effective rate of the simple sclerotherapy group was the lowest [74.3% (26/35)], and the effective rate of the other two groups was still above 85.0%. In conclusion, minimally invasive treatment for internal hemorrhoids under endoscopy is safe and effective with effective improvement of symptoms, high postoperative satisfaction of patients and high degree of acceptance.

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 mine the risk signals of linaclotide， so as to provide evidence for clinically safe drug use. METHODS OpenVigil 2.1 data platform was used to obtain the adverse drug event （ADE） report data of linaclotide from August 30， 2012 to December 31， 2021 in the database of FDA adverse event reporting system （FAERS）. The reporting odds ratio （ROR） and proportional report ratio （PRR） of the proportional imbalance method were used to mine the data of ADE reports. The mined risk signals were statistically classified and described by the preferred system organ class （SOC） and preferred term （PT） stated in the Medical Dictionary for Regulatory Activities （23.1 edition）. RESULTS There were 17 590 ADE reports related to linaclotide， including 5 494 reports of severe ADE， accounting for about 31.23%. A total of 120 risk signals were detected. According to the frequency of occurrence， top 10 risk signals （measured by PT） were diarrhea， ineffective drugs， off-label drug use， abdominal distension， abdominal pain， improper administration time， epigastric pain， flatulence， product storage error and intentional misuse of products. According to the signal intensity， the increase of dihydrotestosterone （ROR was 271.258， PRR was 271.131） ranked the first， and two signals such as the increase of dihydrotestosterone and the compression of intervertebral disc were not mentioned in the drug instructions. The SOC of risk signals obtained by two sorting methods mainly included various examinations， gastrointestinal diseases， systemic diseases and various reactions at the administration site. CONCLUSIONS In clinical application of linaclotide， in addition to the adverse drug reactions mentioned in the drug instructions， close attention should be paid to safety risks such as increase of dihydrotestosterone and the compression of intervertebral disc， which are not mentioned in the instructions， so as to guarantee the safety of drug use.

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.