Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Objective To explore the efficacy and safety of remimazolam combined with propofol for gastroscopy in school-age children.Methods A total of 106 children who underwent painless gastroscopy from january to february 2024 were selected,56 males and 50 females,aged 7-12 years,ASA physical status Ⅰ or Ⅱ.Children were randomly divided into two groups:propofol group(group P)and remimazolam combined with propofol group(group RP),53 children in each group.After intravenous injec-tion of alfentanil 8 μg/kg,group P was intravenously injected with propofol 2.5 mg/kg,and group RP was intravenously injected with remimazolam 0.183 mg/kg and propofol 1 mg/kg in turn.Gastroscopy was per-formed when the eyelash reflex disappeared and the modified observer's assessment alertness/sedation scale(MOAA/S)score≤1.The onset time of anesthesia,examination time,and recovery time were recorded.The number of add propofol and successful sedation cases were recorded.Adverse reactions such as respira-tory depression,hypotension,bradycardia,injection pain,hiccups,nausea and vomiting were recorded.Results Compared with group P,the onset time of anesthesia in group RP was significantly prolonged,and the recovery time was significantly shortened(P＜0.05).Compared with group P,the incidence of add propofol,hypotension,respiratory depression and injection pain in group RP were significantly decreased(P＜0.05).Conclusion Remazolam combined with propofol for gastroscopy in children can not only en-sure the sedative effect,but also reduce the incidence of adverse reactions,stabilize hemodynamic changes and shorten the recovery time.

Objective:To determine the median effective dose (ED 50) and 95% effective dose (ED 95) of remimazolam for gastroscopy when combined with propofol in pediatric patients of different ages. Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ pediatric patients, aged 3-12 yr, who underwent painless gastroscopy in Hainan Women and Children′s Medical Center from January to February 2024, were divided into the following groups: preschool group (3-6 yr) and school-age group (7-12 yr). Penehyclidine 0.01 mg/kg, afentanil 8 μg/kg and corresponding doses of remimazolam and propofol 1 mg/kg were intravenously injected, and gastroscopy was performed when the Modified Observer′s Assessment of Alertness/Sedation Scale score)≤1. Up-and-down sequential allocation was used. A positive response was defined as bucking, nausea, vomiting, body movement, and frowning occurred when the gastroscope entered the pharynx. The initial dose of remimazolam was 0.2 mg/kg, and the dose of remimazolam was increased/decreased by 0.02 mg/kg each time in the next patient. Probit regression method was applied to calculate the ED 50, ED 95 and 95% confidence interval ( CI) of remimazolam inhibiting responses to gastroscope placement when combined with propofol. The anesthesia-related adverse events were recorded. Results:A total of 27 pediatric patients completed the trial in preschool group and 26 cases in school-age group. The ED 50 of remimazolam was 0.266 mg/kg (95% CI 0.249-0.285 mg/kg) and the ED 95 was 0.302 mg/kg (95% CI 0.283-0.409 mg/kg) in preschool group. The ED 50 of remimazolam was 0.16 mg/kg (95% CI 0.147-0.170 mg/kg) and ED 95 was 0.183 mg/kg (95% CI 0.172-0.234 mg/kg) in school-age group. The ED 50 and ED 95 were significantly decreased in school-age group as compared with preschool group ( P<0.05). During anesthesia, 3 patients suffered hypotension (11%) in preschool group, and 3 patients suffered hypotension (12%), 2 patients suffered respiratory depression (8%), 2 patients suffered hiccup (8%), 1 patient suffered injection pain (4%) and 1 patient suffered muscle rigidity (4%) in school-age group. There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:When combined with propofol, the ED 50 of remimazolam for gastroscopy in preschool and school-age pediatric patients is 0.266 mg/kg and 0.160 mg/kg, respectively, and the ED 95 is 0.302 mg/kg and 0.183 mg/kg, respectively, indicating a stronger anesthetic potency in school-age children. The probability of adverse reactions is low when the two are combined.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To investigate the application value of self-pulling and latter transection (SPLT) technique in double anti-reflux double-tract reconstruction of totally laparoscopic proximal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 103 patients with Siewert type Ⅱ adenocarcinoma of esophagogastric junction in clinical stage Ⅰ-Ⅱ who were admitted to Shanxi Cancer Hospital from January 2018 to January 2020 were collected. There were 65 males and 38 females, aged from 45 to 79 years, with a median age of 59 years. Of 103 patients, 49 cases undergoing totally laparoscopic proximal gastrectomy with double-tract reconstruction of SPLT were assigned into the SPLT group, 54 cases undergoing totally laparoscopic proximal gastrectomy with conventional double-tract reconstruction were assigned into the traditional group. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone inter-view to detect postoperative reflux esophagitis of patients up to December 2021. Measurement data with normal distribution were represented as Mean± SD, and the t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and the Wilcoxon test was used for comparison between groups. Count data were described as absolute numbers or percentages, and comparison between groups was performed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Intraoperative situations: the operation time, digestive tract reconstruction time, volume of intraoperative blood loss, the number of inferior mediastinal lymph nodes dissected, cases with auxiliary incisions for the SPLT group were (261±48)minutes, (26±4)minutes, (114±42)mL, 8.0(6.5,9.5), 1, respectively. The above indicators were (244±42)minutes, (30±6)minutes, (118±46)mL, 5.5(4.0,8.0), 9 for the traditional group, respectively. There were significant differences in the digestive tract reconstruction time, the number of inferior mediastinal lymph nodes dissected and cases with auxiliary incisions between the two groups ( t=-3.34, Z=-4.05, χ2=4.72, P<0.05). There was no significant difference in the operation time or volume of intraoperative blood loss between the two groups ( t=1.87, -0.47, P>0.05). (2) Postoperative situations: duration of postopera-tive hospital stay and cases with postoperative complications were (11.5±2.7)days and 4 for the SPLT group, versus (12.5±4.3)days and 9 for the traditional group, showing no significant difference between the two groups ( t=-1.47, χ2=1.68, P>0.05). There were 13 of 103 patients with postopera-tive complications, including 5 cases of left pleural effusion, 4 cases of anastomotic leakage, 2 cases of mild pneumonia, 1 case of incision infection, 1 case of chylous leakage. Four patients had anasto-motic leakage at the esophagojejunostomy, the abdominal esophagus of whom was invaded by more than 1 cm. During the operation, mediastinal drainage tubes were placed through the abdominal wall. The 4 patients were cured after enteral and parenteral nutrition support and adequate drainage, and the remaining patients with complications were cured after symptomatic treatment. (3) Follow-up: of 49 patients in the SPLT group, 43 cases were followed up for (18±4)months. During the follow-up, 1 case showed reflux esophagitis by gastroscopy, with the incidence of 2.33%(1/43). Of 54 patients in the traditional group, 53 cases were followed up for (17±4)months. During the follow-up, 4 cases showed reflux esophagitis by gastroscopy, with the incidence of 7.55%(4/53). There was no significant difference in the incidence of reflux esophagitis between the two groups ( χ2=0.47, P>0.05). Conclusions:SPLT technology is feasible for double anti-reflux double-tract reconstruction of proximal gastrectomy. Compared with traditional double-tract reconstruction of totally laparos-copic proximal gastrectomy, SPLT technology can reduce the auxiliary incisions, increase the number of lower mediastinal lymph nodes dissected, and shorten the digestive tract reconstruction time.

There are still many controversies in the surgical treatment of esophagogastric junction tumors in terms of surgical approach, cleaning range, and resection scope. The reason is the confusion about the scope of the esophagogastric junction. The previous domestic and foreign anatomy descriptions of this part are not enough to solve the current problems. Based on a large number of basic anatomy and clinical operations, this article proposes that the esophagogastric junction may be wrapped by a complete and separate esophagogastric junction membrane with independent anatomy other than infracardiac bursa. The structure of the transitional tissue, mainly from the distribution of submucosal veins, explained the relationship and significance of tissue transitional changes and clinical operations, and made a reasonable analysis of the current controversy based on the anatomical characteristics, which is worthy of further investigation.