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.

Objective:To analyze and evaluate the equity of children's health in countries along the"the Belt and Road",promote further attention to children's health in countries along the route,and promote cooperation and exchanges on children's health between China and countries along the"the Belt and Road".Methods:Using concentration index and concentration curve to measure overall equity,and using the Thiel index for intraregional and interregional euqity measurement.Results:The under-five mortality concentration index is 0.349 7,the concentration curve is below the absolute fair line.The Thiel index shows that inequality in low-income countries,lower-middle-income countries,upper-middle-income countries and high-income countries is the leading cause of child health inequities in the"the Belt and Road"countries.Conclusion:There is inequity in the health of children in countries along"the Belt and Road Initiative",countries along the"the Belt and Road"should take comprehensive measures to reduce the under-five mortality rate,at the same time strengthen international cooperation to further promote equity in children's health in"Belt and Road"countries.

Objective:To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ 2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M( Q1, Q3) and the Mann–Whitney U test was used for inter group comparison. Results:The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x 3-4.4757x 2+164.97x-264.4 ( P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor ( P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups ( P=0.238). Conclusion:Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

ObjectiveTo explore the association between short-term exposure to atmospheric fine particulate matter （PM_2.5） and ozone （O₃） and systemic inflammatory indicators in patients with pneumonia， and to identify the susceptible populations. MethodsFrom September 2018 to April 2020， data of 1 480 patients admitted for pneumonia was collected from a tertiary hospital in Taiyuan City. Generalized additive models （GAMs） were used to explore the associations between PM_2.5 and O₃ exposure and inflammatory indicators of patients with pneumonia； and to explore the susceptibility factors and susceptible populations to PM_2.5 and O₃ exposures through stratified analyses. ResultsThe short-term exposure to PM_2.5 was associated with changes in peripheral blood C-reation protein （CRP）， erythrocyte sedimentation （ESR）， easinophil （EOS）， neutrophil （NEU） and neutrophil-lymphocyte ratio （NLR） in patients with pneumonia， and there were different degrees of hysteresis effects， with the effect values reaching a maximum at lag03， lag03， lag0， lag03， lag03， respectively， which were 4.13% （95%CI： 0.43%‒7.84%）， 3.10% （95%CI： 0.24%‒5.97%）， 5.27% （95%CI： 3.12%‒7.42%）， 1.85% （95%CI： 0.36%‒3.34%）， and 2.53% （95%CI： 0.53%‒4.74%） for every 10 μg·m^-3 of PM_2.5. The changes in O₃ concentration were associated with the elevation of peripheral blood PCT and ESR in patients with pneumonia， and their effect values all reached the maximum at lag01 d， every 1 μg·m^-3 of O₃ elevation increased by 0.38% （95%CI： 0.04%‒0.73%） and 0.47% （95%CI： 0.19%‒0.76%）， respectively. Stratified analyses showed that the associations of PM_2.5 with peripheral blood CRP， ESR， NEU， and NLR in pneumonia patients were more significant in males， the elderly， and those with onset in the cold season； the associations of O₃ with peripheral blood PCT and ESR in pneumonia patients were more significant in the elderly and those with onset in the warm season， and the peripheral blood CRP and PCT in female patients with pneumonia were more susceptible to the changes of O₃. ConclusionShort-term exposure to atmospheric PM_2.5 and O₃ are positively associated with changes in inflammatory indicators in patients with pneumonia， and the effects of PM_2.5 on patients with pneumonia are more extensive than those of O₃， with a longer lag effect. In addition， elderly patients with pneumonia are more sensitive to air pollution， male patients with pneumonia are more sensitive to PM_2.5， and female patients with pneumonia are more sensitive to O₃. Cold and warm seasons can exacerbate the effects of PM_2.5 and O₃ on inflammatory indicators in patients with pneumonia， respectively， and the patients must be protected well.

Objective:To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ 2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M( Q1, Q3) and the Mann–Whitney U test was used for inter group comparison. Results:The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x 3-4.4757x 2+164.97x-264.4 ( P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor ( P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups ( P=0.238). Conclusion:Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

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

Objective:To investigate the characteristics of nasal flora and the pathogenic role of differential microbiome in patients with allergic rhinitis (AR) and non-allergic rhinitis (nAR).Methods:Thirty-five patients with AR who attended the rhinology outpatient clinic of the Second Hospital of Harbin Medical University from February to July 2022 were selected. A total of 35 nAR patients were selected as the test group, and 20 cases of healthy people with physical examination at the same period were selected as the control group, including 39 males and 51 females, aged 8 to 55 years. 16SrDNA High-throughput sequencing was used to analyze the relative abundance from nasal flora in the three groups of subjects. Alpha diversity index analysis was conducted with R software, and differences between groups were analyzed with LEfSe, Metastats, and t tests. At the same time, the role of microbiome and its relationship with environmental factors were analyzed with R software. Results:There was a significant difference in the bacterial composition of the samples from the three groups, with the relative abundance of Staphylococcus aureus ( P=0.032) and Corynebacterium proinquum ( P=0.032) within the AR group being significantly higher than that of the nAR group, and that of Lactobacillus murinus, Lactobacillus kunkeei, and Alcaligenes faecalis ( P value was 0.016, 0.005, and 0.001, respectively) being significantly lower than that of the nAR group. The relative abundance of Ackermannia muciniphila within the nAR group was higher than that of the control group ( P=0.009). Correlation analysis of environmental factors showed a negative correlation between Lactobacillus kunkeei and IgE ( P=0.044), and a positive correlation between Lactobacillus murinus and age ( P=0.019). AR and nAR random forest prediction models were constructed for the five genera, respectively, and the area under the curve (AUC) of the models of Streptococcus-SP-FF10, Pseudoalteromonas luteoviolacea, Pseudomonas parafulva, Acinetobacter ursingii, and Azotobacter chroococcum in the AR group was 100% (95%CI: 100% to 100%). The AUC for the Pseudomonas parafulva, Azotobacter chroococcum, Closoridium baratii, Turicibacter-SP-H121, and Streptococcus lutetiensis models in the nAR group was 98.4% (95%CI: 94.9% to 100%). Conclusions:The distribution of nasal flora in AR patients, nAR patients and healthy subjects is significantly different, and the changes of bacterial flora abundance are significantly related to the occurrence of AR and nAR. Combined detection of microbiota has the potential to diagnose AR and nAR patients.

Objective:To investigate the safety and clinical efficacy of primary anterior lesion removal and bone graft fusion combined with secondary posterior fixation in the treatment of cervical suppurative spondylitis.Methods:Retrospective analysis was performed on the data of twenty cervical suppurative spondylitis patients treated with primary anterior lesion removal and bone graft fusion combinedwith secondary posterior fixation in our hospital from May 2016 to December 2020, including 14 males and 6 females. Aging from 40 to 87 years, with an average of 60.2±12.6 years. The laboratory tests of preoperative blood culture, such as white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and hypersensitive C-reactive protein (CRP) were performed.The selection and duration of antibiotic usewere guided according to bacterial culture and laboratory test results. visual analogue scale (VAS) score, Japanese Orthopeadic Association (JOA) score and Frankle classification of neurological function were evaluated before surgery, 3 months after surgery, and 12 months after surgery, so were the Cobb angle and segmental angle of cervical lordosis. Single factor repeated measure ANOVA was used for statistical analysis of data.Results:Surgeries were performed successfully for all the 20 patients. 9 cases of Staphylococcus aureus, 4 cases of Streptococcus and 2 case of Escherichia coli were detected by pathogen examination. The remaining 5 cases were negative in bacterial culture. All 20 patients were followed up for 18.3±6.7 months. WBC, ESR and CRP at 3 and 12 months after surgery were significantly lower than those before surgery ( F value: 17.90, 30.65, 18.64, P<0.001). The VAS at 3 months after surgery 1.35±0.49 and 12 months after surgery 1.15±0.48 were significantly lower than that before surgery 4.95±1.10 ( F=176.12, P<0.001). The JOA score at 3 months after surgery 15.40±1.93 and 12 months after surgery 16.06±1.36 were significantly better than that before surgery 11.45±2.78 ( F=65.33, P<0.001). The Cobb Angle of C 2-C 7 cervical lordosis after surgery 14.45°±4.36° and 12 months after surgery (13.70°±3.15°) were significantly larger than that before surgery (8.25°±4.36°) ( F=72.54, P<0.001). Cobb angle of the lesion segment after surgery (3.60°±1.90°) and 12 months after surgery (2.90°±1.44°) were significantly better than that before surgery (-3.55°±5.74°) (negative value indicated kyphosis) ( F=42.49, P<0.001). Bone fusion was observed in all graft areas at 12 months of follow-up. Conclusion:The treatment of cervical suppurative spondylitis with primary anterior lesion removal and bone graft fusion combined with secondary posterior fixation can effectively obtain intraspinal decompression, improve pain and nerve function, as well as restore cervical stability and correct kyphosis, with satisfactory clinical efficacy.

Objective:To screen and analyze ferroptosis-related genes (FRG) impacting the prognosis of colorectal adenocarcinoma patients based on bioinformatics.Methods:RNA sequencing data including the clinical information of 545 colorectal adenocarcinoma patients and 602 data sets were downloaded from the Cancer Genome Atlas (TCGA) database. FRG gene sets were downloaded from FerrDb database. FRG expression dataset could be obtained after taking the intersection between FRG gene sets and TCGA database gene sets. Differentially expressed FRG and prognosis-related genes between colorectal adenocarcinoma tissues and the adjacent tissues were screened by using R software, and finally FRG influencing the prognosis of colorectal adenocarcinoma were obtained. According to protein-protein interaction networks, the interaction and the expression association of proteins were analyzed. LASSO regression analysis was used to build a risk model for patients' 5-year overall survival rate. The risk value was calculated for 509 colorectal adenocarcinoma samples in the TCGA database, and then the median risk value was taken as the cut-off value. All patients were divided into the high-risk group (≥ median risk value) and the low-risk group (< median risk value), and the survival curves of the two groups were drawn. The receiver operating characteristic (ROC) curve was drawn for predicting the 5-year overall survival rate of colorectal adenocarcinoma patients in a time-dependent way in TCGA database according to the risk value of FRG prognosis model. Cox proportional risk model was used to make univariate and multivariate survival analysis in order to screen factors affecting the prognosis. The pathway enrichment analysis of prognosis-related FRG of colorectal adenocarcinoma was performed based on gene ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database.Results:The clinical information of 545 patients and 602 datasets were extracted from the database. A total of differential expressed 199 FRG in colorectal adenocarcinoma and 28 prognosis-related FRG were identified. After taking the intersection, 21 FRG affecting the prognosis of colorectal adenocarcinoma patients were identified. DUOX2, NOX4, NOX1, DDIT3, JDP2, ATP6V1G2, ULK1, ATG3 were probably associated with WIPI1; expressions of NOX4, NOX5, PLIN4 were positively correlated with ATP6V1G2, while the expression of ULK1 was negatively correlated with MAPK1, MYB, FANCD2, ATG3 and ATP5MC3. LASSO regression analysis showed that 15 FRG were finally screened out (ATP5MC3, NOX4, NOX5, ALOX12B, ATG3, WIPI1, MAPK1, MYB, AKR1C1, DDIT3, JDP2, ATP6V1G2, DRD4, SLC2A3, PLIN4), and the risk model was constructed by calculating the risk value, and the risk value = NOX4×0.139-ATP5M3×0.108+NOX5×1.486+ALOX12B×0.475-ATG3×0.030-WIPI1×0.170-MAPK1×0.271-MYB×0.063+AKR1C1×0.021+DDIT3×0.186+JDP2×0.292+ATP6V1G2×0.777+DRD4×0.294+SLC2A3×0.059+PLIN4×0.113. The overall survival of patients in the high-risk group was worse than that in the low-risk group ( P < 0.001). The 5-year overall survival rate was 48.2% in the high-risk group and 76.8% in the low-risk group. Multivariate survival showed that the age and risk value were independent affecting factors of the prognosis. ROC curves revealed that the risk model constructed by using prognosis-related FRG could well predict the 5-year overall survival rate of patients (the area under the curve was 0.728). The differential expressed genes of both groups may be associated with genetic pathways such as extracellular matrix composition, extracellular structure composition and focal adhesion. Conclusions:The prognostic risk model constructed by the screened FRG can better evaluate the prognosis of colorectal adenocarcinoma patients. These FRG are expected to become new candidate biomarkers related to the prognosis of colorectal adenocarcinoma.