OBJECTIVE To identify and analyze adverse drug event （ADE） signals associated with tirzepatide based on the FDA Adverse Event Reporting System （FAERS） database， providing a reference for clinical medication safety. METHODS ADE reports from January 1， 2022， to June 30， 2024， with tirzepatide as the primary suspected drug， were extracted from the FAERS database. Medical Dictionary for Regulatory Activities was used to systematically categorize the selected system organ class （SOC） and preferred term of ADE. Signal mining and analysis were performed using the reporting odds ratio method and the proportional reporting ratio method. RESULTS A total of 39 229 ADE reports related to tirzepatide were obtained， including 3 934 severe ADE reports （10.03%）. The majority of severe ADE reports were related to hospitalization or prolonged hospitalization （3.82%）， involving 131 positive ADE signals. Among the reports with documented patient gender and age， 26 195 were female （66.77%）， 7 869 were male （20.06%）， and the majority of patients were aged 18-64 years （54.26%）. The top three most frequently reported ADE were injection site pain， nausea， and injection site hemorrhage. Strong ADE signals not mentioned in the tirzepatide instruction included injection site coldness， starvation ketoacidosis， injection site hemorrhage， hunger， elevated adrenaline， injection site skin cracking， binge eating， skin laxity， intestinal sepsis， lack of satiety， and dysesthesia. Subgroup analysis for patient’s gender and age showed differences in the proportion of ADE reports across different SOC. Male patients or those aged≥65 years had a higher risk of gastrointestinal system disorders compared to female patients or those aged ＜65 years. CONCLUSIONS In clinical use of tirzepatide， in addition to monitoring ADE listed in the instruction， attention should also be paid to ADE not mentioned in the instruction， such as injection site coldness， starvation ketoacidosis， injection site hemorrhage， elevated adrenaline， and intestinal sepsis， to ensure patient safety.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of tirzepatide for diabetes mellitus type 2 （T2DM） and long-term weight management， and provide evidence-based basis for clinical drug treatment and health insurance policy formulation. METHODS Computer searches were conducted in Embase， PubMed， the Cochrane Library， CNKI and health technology assessment （HTA） official website from their inception to October 1st 2024 to collect HTA report， systematic review/ meta-analysis and pharmacoeconomic study on tirzepatide for the treatment of T2DM or for weight management. After data extraction and quality evaluation， descriptive analysis was performed on the research results. RESULTS Totally 18 papers were included， including 14 systematic reviews/meta-analyses and 4 pharmacoeconomics studies， and no HTA report was retrieved. In terms of efficacy， most results showed that the tirzepatide 10 mg and 15 mg were significantly better than other glucagon-like peptide-1 （GLP-1） receptor agonists in reducing glycosylated hemoglobin， body weight， and waist circumference （P＜0.05）. In terms of safety， compared with other GLP-1 receptor agonists， tirzepatide did not increase the incidence of gastrointestinal-related adverse events （AE）， the incidence of AE of grade ≥3， or the incidence of severe hypoglycemia （P＞0.05）. However， tirzepatide 15 mg may significantly increased the incidence of hypoglycemia and the rate of discontinuation due to adverse reactions （P＜ 0.05）. In terms of cost-effectiveness， based on the background of foreign pharmacoeconomic studies， tirzepatide was more cost- effective compared to semaglutide and liraglutide in the treatment of T2DM or for weight management. CONCLUSIONS Tirzepatide at doses of 10 mg and 15 mg has good efficacy and safety for the treatment of T2DM and for long-term weight management. However， when using the 15 mg dose of tirzepatide， close monitoring is required due to the risk of hypoglycemia and discontinuation due to adverse reactions it may pose. Based on pharmacoeconomic studies conducted abroad results， tirzepatide exhibits economic advantages.

BACKGROUND:With the aging of the population,the number of joint replacement operations is increasing,and correspondingly,the number of joint revision operations is also increasing.Qualitative and quantitative analysis of the current research status,research hotspots,and research frontiers in the field of joint revision is of great significance. OBJECTIVE:To perform visual analysis of the related literature in the field of joint revision in recent 20 years through bibliometrics,explore the research hot spots and dynamic trends in this field in order to provide a reference for further research. METHODS:Computer searches of CNKI,VIP,and WanFang Data from January 1,2003 to December 31,2022 were conducted to include relevant literature on joint revision.Duplicate data were removed using Note Express(3.9.0.9588)software.The scientific knowledge map was drawn by using CiteSpace(6.2.R6),VOS viewer(1.6.20),and Excel(2016)software on the number of papers published,the cooperative network of authors and institutions,the co-occurrence,emergence and clustering of keywords. RESULTS AND CONCLUSION:(1)A total of 1 806 articles were included.In the past 20 years,the overall trend of the annual publication volume in this field tended to be stable.(2)Analysis of the collaborative network showed that the author with the most publications and the highest intermediary centrality was Zhou Yixin;the institution with the most publications was Beijing Jishuitan Hospital,where Zhou Yixin worked,and the institution with the highest intermediary centrality was the General Hospital of the Chinese People's Liberation Army.(3)Keyword analysis showed that the research focus was mainly on hip joint,infection,rehabilitation nursing,bone defect,and prosthesis loosening.(4)The visual analysis of the literature in the field of joint revision clarifies the context for the research in this field,provides research ideas and methods for many scholars,and reveals the research trend and frontier hot spots in this field.

Objective:To evaluate the anesthetic effect of remazolam when combined with sufentanil in elderly patients with liver cirrhosis and esophageal and gastric varices undergoing endoscopic sclerotherapy.Methods:A total of 150 cirrhotic patients with liver cirrhosis and esophageal and gastric varices, regardless of gender, aged 65-80 yr, with body mass index of 18-24 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ, who underwent endoscopic sclerotherapy under non-intubated general anesthesia from March 2022 to September 2023 in our hospital, were selected and divided into 2 groups ( n=75 each) by a random number table method: sufentanil plus propofol group (PS group) and sufentanil plus remazolam group (RS group). Anesthesia was induced with intravenous propofol 1-2 mg/kg and sufentanil 0.1 μg/kg and maintained by intravenous infusion of propofol 4-10 mg·kg -1·h -1 in PS group. Anesthesia was induced with intravenous remimazolam 0.1-0.2 mg/kg and sufentanil 0.1 μg/kg and was maintained with intravenous infusion of remimazolam 0.5-2.0 mg·kg -1·h -1 in RS group. BIS values were maintained between 40 and 60 during operation in both groups. Endoscopy was placed when the patients lost consciousness (modified observer′s assessment of alertness/sedation score ≤1). Sclerosing agent laurosinol injection was injected into esophageal submucosal varices in both groups. The time to loss of consciousness and recovery of consciousness, intraoperative body movement and cardiovascular events, and postoperative hypoxemia and nausea and vomiting were recorded. The operator-patient satisfaction was assessed by the visual analogue scale. Results:Compared with PS group, no significant changes were found in the incidence of intraoperative bradycardia, time to loss of consciousness and time to recovery of consciousness( P>0.05), the incidence of intraoperative hypotension was significantly decreased, the incidence of postoperative hypoxemia and nausea and vomiting was decreased, and the satisfaction scores for operators and patients were increased in RS group ( P<0.05). No obvious body movement was found in the two groups. Conclusions:Sufentanil combined with remifentanil provides better anesthetic effect than sufentanil combined with propofol in elderly patients with esophageal and gastric varices undergoing endoscopic sclerotherapy.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

ObjectiveTo adapt the Stanford Expectations of Treatment Scale（SETS） into Chinese（C-SETS） and test the feasibility， validity and reliability of its application in patients with diarrhea-predominant irritable bowel syndrome（IBS-D） with liver-constraint and spleen-deficiency syndrome treated with traditional Chinese medicine（TCM）. MethodsWe obtained authorisation from the developer of the SETS， and followed the principle of "two-way translation" to translate the SETS by literal translation and back translation to form the C-SETS. Ninety-six IBS-D patients with liver-constraint and spleen-deficiency syndrome were enrolled as respondents and filled out C-SETS before receiving treatment； the feasibility was assessed by the recall rate， completion rate and the duration of filling out the scale； the reliability was assessed by Cronbach's α； the structural validity was assessed by exploratory and confirmatory factor analysis， and the content validity was assessed by correlation analysis. ResultsThe C-SETS consists of 10 items， with the 1st， 3rd， and 5th rating items constituting the Positive Expectations subscale， and the 2nd， 4th， and 6th rating items constituting the Negative Expectations subscale， each of which is rated on a 7-point Likert Scale. The recall of C-SETS was 100%（96/96）， the completion rate was 89.58%（86/96）； Cronbach's α for the Positive and Negative Treatment Expectations subscales were 0.845 and 0.854， respectively； exploratory factor analysis showed that the coefficient of commonality for all six entries was larger than 0.4， and that the six entries could be used by both factors to explain 77.092% of the total variance； validation factor analysis showed that the goodness-of-fit index， comparative fit index， root mean square of approximation error， canonical fit coefficient， and chi-square degrees of freedom ratio took the values of 0.943， 1.003， 0， 0.943， and 0.626， respectively； and the results of Spearman's analysis suggested that the C-SETS had good content validity. ConclusionThe C-SETS has well feasibility， reliability， and validity， which initially proves that it can be used as a tool to assess the treatment expectation of patients with IBS-D with liver-constraint and spleen-deficiency syndrome before receiving TCM treatment.

Since the concept of patient versions of guidelines （PVGs） was introduced into China， several PVGs have been published in China， but we found that there is a big difference between the concept of PVG at home and abroad， and the reason for this difference has not been reasonably explained， which has led to ambiguity and even misapplication of the PVG concept by guideline developers. By analyzing the background and purpose of PVGs， and the understanding of the PVG concept by domestic scholars， we proposed the term patient guidelines （PGs）. This refers to guidelines developed under the principles of evidence-based medicine， centered on health issues that concern patients， and based on the best available evidence， intended for patient use. Except for the general attribute of providing information or education， which is typical of common health education materials， PGs also provide recommendations and assist in decision-making， so PGs include both the patient versions of guidelines （PVG） as defined by the Guidelines International Network （GIN） and "patient-directed guidelines"， i.e. clinical practice guidelines resulting from the adaptation or reformulation of recommendations through clinical practice guidelines.

ObjectiveTo analyze the HIV infection characteristics and influencing factors among the spouses of HIV/AIDS patients in Shanghai. MethodsA cross-sectional survey was conducted to collect demographic， behavioral， epidemiological and spousal HIV detection information of newly reported and married patients with HIV/AIDS in Shanghai from January 2018 to July 2022 in the comprehensive HIV prevention and control information system of Chinese Center for Disease Prevention and Control. Descriptive analysis was used to analyze the HIV positivity rate of the spouses of HIV patients and the influencing factors were analyzed by univariate and multivariate logistic regression models. ResultsA total of 1 233 subjects were investigated， and the first HIV-testing positivity rate of the spouses of HIV/AIDS patients was 29.3% （361/1 233）. There were statistically significant differences in the HIV-testing positivity rate among spouses of HIV/AIDS patients by different age， gender， education level， occupation， transmission route， quantity of non-marital sexual activities， quantity of homo-sexual activities， and baseline CD4 cell count level （P<0.05）. Spouses of the HIV/AIDS patients aged ≥65 years old， female， heterosexual transmission， less non-marital sex， and no history of homosexual sex had relatively high HIV positive rate. The HIV-positive detection rate of spouses in the ≥65 age group was 1.81 times higher than that in the <45 age group. The HIV-positive detection rate of spouses in the female group was 3.66 times higher than that in the male group， and the HIV-positive detection rate of spouses in the homosexual transmission group was 0.25 times higher than that of the heterosexual transmission group. ConclusionRisk awareness of HIV infection among married people with spouses should be improved. The key populations with the characteristics such as females as the first HIV-positive reporter， and heterosexual transmission should be paid special attention.Their spouses should be mobilized to conduct HIV-testing as early as possible

Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.
Humans ; Receptors, Chimeric Antigen/therapeutic use* ; Immunotherapy, Adoptive ; Hematologic Neoplasms/therapy* ; Treatment Outcome

Objective:To investigate the correlation of lung ultrasound score and poor prognosis in internal shock patients in intensive care unit (ICU).Methods:The clinical data of 200 shock patients admitted to the ICU of Wuzhou Red Cross Hospital from July 2019 to June 2021 were selected for study. According to the prognosis of patients, they were divided into survival group and death group. The clinical data of shock patients in ICU with different prognosis were analyzed by single factor analysis, multiple factor regression analysis and predictive value analysis.Results:All patients were followed up. The end point of the study was death or transfer from ICU. The follow-up period was 28 days, with a median of 16 days. The 28-day survival rate (OS) of all patients was 62.5%(125/200). The Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, prothrombin time (PT), Fbg, D-dimer(D-D), lactic acid, oxygenation index and lung ultrasound score of the patients in the survival group and the death group were significantly different (all P<0.05), while other indexes were not significantly different (all P>0.05). The results of COX multivariate analysis showed that APACHE Ⅱ score, lactate, and lung ultrasound score were independent prognostic factors of shock patients in ICU (all P<0.05). The survival curves of patients with different lung ultrasound scores were significantly different ( P<0.05). The higher the lung ultrasound score, the lower the 28-day survival rate ( P<0.05). The receiver operating characteristic(ROC) curve analysis showed that the area under curve (AUC), sensitivity and specificity of predicting the prognosis of patients with lung ultrasound score were 0.753, 76.0% and 71.2%, respectively; The AUC , sensitivity and specificity of APACHE Ⅱ score were 0.774, 77.3% and 79.2% respectively; The AUC, sensitivity and specificity of lactic acid were 0.783, 81.3% and 68.8% respectively, with no significant difference (all P>0.05). Conclusions:The lung ultrasound score , lactic acid and APACHE Ⅱ scores are independent risk factors affecting the prognosis of ICU shock patients, and have considerable predictive value.