Background: Whether there is a causal relationship between childhood obesity and increased risk of chronic kidney disease (CKD) remains controversial. This study sought to explore how body size in childhood and adulthood independently affects CKD risk in later life using a Mendelian randomization (MR) approach. Methods: Univariate and multivariate MR was used to estimate total and independent effects of body size exposures. Genetic associations with early-life and adult body size were obtained from a genome-wide association study of 453,169 participants in the U.K. Biobank, and genetic associations with CKD were obtained from the CKDGen and FinnGen consortia. Results: A larger genetically predicted early-life body size was associated with an increased risk of CKD (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.14 to 1.41; P= 1.70E-05) and increased blood urea nitrogen (BUN) levels (β=0.010; 95% CI, 0.005 to 0.021; P=0.001). However, the association between the impact of early-life body size on CKD (OR, 1.12; 95% CI, 0.95 to 1.31; P=0.173) and BUN level (β=0.001; 95% CI, –0.010 to 0.012;P= 0.853) did not remain statistically significant after adjustment for adult body size. Larger genetically predicted adult body size was associated with an increased risk of CKD (OR, 1.37; 95% CI, 1.21 to 1.54; P= 4.60E-07), decreased estimated glomerular filtration rate (β=–0.011; 95% CI, –0.017 to –0.006; P=5.79E-05), and increased BUN level (β= 0.010; 95% CI, 0.002 to 0.019; P= 0.018). Conclusion Our research indicates that the significant correlation between early-life body size and CKD risk is likely due to maintaining a large body size into adulthood.

Background: Whether there is a causal relationship between childhood obesity and increased risk of chronic kidney disease (CKD) remains controversial. This study sought to explore how body size in childhood and adulthood independently affects CKD risk in later life using a Mendelian randomization (MR) approach. Methods: Univariate and multivariate MR was used to estimate total and independent effects of body size exposures. Genetic associations with early-life and adult body size were obtained from a genome-wide association study of 453,169 participants in the U.K. Biobank, and genetic associations with CKD were obtained from the CKDGen and FinnGen consortia. Results: A larger genetically predicted early-life body size was associated with an increased risk of CKD (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.14 to 1.41; P= 1.70E-05) and increased blood urea nitrogen (BUN) levels (β=0.010; 95% CI, 0.005 to 0.021; P=0.001). However, the association between the impact of early-life body size on CKD (OR, 1.12; 95% CI, 0.95 to 1.31; P=0.173) and BUN level (β=0.001; 95% CI, –0.010 to 0.012;P= 0.853) did not remain statistically significant after adjustment for adult body size. Larger genetically predicted adult body size was associated with an increased risk of CKD (OR, 1.37; 95% CI, 1.21 to 1.54; P= 4.60E-07), decreased estimated glomerular filtration rate (β=–0.011; 95% CI, –0.017 to –0.006; P=5.79E-05), and increased BUN level (β= 0.010; 95% CI, 0.002 to 0.019; P= 0.018). Conclusion Our research indicates that the significant correlation between early-life body size and CKD risk is likely due to maintaining a large body size into adulthood.

Background: Whether there is a causal relationship between childhood obesity and increased risk of chronic kidney disease (CKD) remains controversial. This study sought to explore how body size in childhood and adulthood independently affects CKD risk in later life using a Mendelian randomization (MR) approach. Methods: Univariate and multivariate MR was used to estimate total and independent effects of body size exposures. Genetic associations with early-life and adult body size were obtained from a genome-wide association study of 453,169 participants in the U.K. Biobank, and genetic associations with CKD were obtained from the CKDGen and FinnGen consortia. Results: A larger genetically predicted early-life body size was associated with an increased risk of CKD (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.14 to 1.41; P= 1.70E-05) and increased blood urea nitrogen (BUN) levels (β=0.010; 95% CI, 0.005 to 0.021; P=0.001). However, the association between the impact of early-life body size on CKD (OR, 1.12; 95% CI, 0.95 to 1.31; P=0.173) and BUN level (β=0.001; 95% CI, –0.010 to 0.012;P= 0.853) did not remain statistically significant after adjustment for adult body size. Larger genetically predicted adult body size was associated with an increased risk of CKD (OR, 1.37; 95% CI, 1.21 to 1.54; P= 4.60E-07), decreased estimated glomerular filtration rate (β=–0.011; 95% CI, –0.017 to –0.006; P=5.79E-05), and increased BUN level (β= 0.010; 95% CI, 0.002 to 0.019; P= 0.018). Conclusion Our research indicates that the significant correlation between early-life body size and CKD risk is likely due to maintaining a large body size into adulthood.

Objective:To investigate the expression of nuclear matrix protein 4 (NMP4) in hepatocellular carcinoma (HCC), and its relationship with clinicopathological features and survival prognosis of patients.Methods:The clinical data of 100 HCC patients who were treated with radical resection of liver cancer in the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Wenzhou Medical University from July 1, 2014 to July 1, 2019 were retrospectively analyzed. There were 63 males and 37 females, aged (58.5±10.4) years old. Immunohistochemical method was used to detect the expression of NMP4 protein in HCC cancer tissue and the corresponding adjacent normal tissue. According to the expression of NMP4 in HCC tissues, 100 patients were divided into two groups: the NMP4-positive expression group ( n=62) and the NMP4-negative expression group ( n=32). Univariate analysis was performed on the relationship between NMP4 expression and clinical pathological features as well as overall survival of HCC patients. Cox multivariate analysis was performed on the factors influencing postoperative prognosis of HCC patients. Results:Immunohistochemistry results showed that NMP4 was primarily expressed in the nucleus, the positive expression rate of NMP4 in HCC tissues was higher than that in adjacent non-cancerous tissues [62.0% (62/100) vs. 8.0%(8/100)], and the difference was statistically significant ( χ2=2.12, P=0.003). Univariate analysis revealed that the overall survival of HCC patients was correlated with the degree of tumor differentiation, tumor length, BCLC stage, number of tumor foci, vascular tumor thrombus and expression of NMP4 (all P<0.05). Cox multivariate analysis revealed that low differentiation, high BCLC stage (stage C), number of tumor foci (≥3), and positive expression of NMP4 were independent risk factors affecting postoperative survival and recurrence-free survival of HCC patients. The median overall survival and median recurrence-free survival of HCC patients in the NMP4-positive expression group were 22.3 months and 11.5 months, respectively. In contrast, that in the NMP4-negative expression group were 40.6 months and 19.4 months, respectively. The cumulative survival rate and recurrence-free survival rate of HCC patients in the NMP4-positive expression group were lower than those in the NMP4-negative expression group, and the differences were statistically significant (both P<0.05). Conclusion:Positive NMP4 expression was closely correlated with malignant biological progression and poor prognosis of HCC patients.

Objective:To investigate the clinical characteristics and drug resistance of Klebsiella pneumoniae infections at different systems, providing laboratory reference for the rational use of antibiotics in clinical practice.Methods:The clinical characteristics and drug resistance of patients with Klebsiella pneumoniae infections in respiratory, urinary, hematologic, and other systems who received treatment in Wuzhou Red Cross Hospital from January 2015 to December 2021 were analyzed.Results:From 2015 to 2021, there were 3 496 cases of Klebsiella pneumoniae infections in the hospital, among which the respiratory system was most affected with 2 250 strains (64.34%). The sex ratio of patients with Klebsiella pneumoniae infections at different systems was statistically significant ( χ2 = 266.77, P < 0.001). The respiratory system and hematological system were more commonly infected by Klebsiella pneumoniae in men, while the urinary system was more commonly infected in women. The sex ratio of patients with Klebsiella pneumoniae infections at other systems were similar. The age distribution of patients with Klebsiella pneumoniae infections at different systems was significantly different ( χ2 = 176.54, P < 0.001). Klebsiella pneumoniae infections of the respiratory, urinary, and hematological systems were the most common in people aged > 60-80 years, while Klebsiella pneumoniae infections in other systems were mainly found in people aged > 18-60 years. There were significant differences in the distribution of departments among different Klebsiella pneumoniae infection systems ( χ2 = 1 415.30, P < 0.001). The ICU had the highest incidence of Klebsiella pneumoniae infections in the respiratory system, while the department of internal medicine had the highest incidence of Klebsiella pneumoniae infections in the urinary and hematological systems, and the department of surgery had the highest incidence of Klebsiella pneumoniae infections in other parts of the body. The resistance rate of Klebsiella pneumoniae to common antibiotics for the hematologic system was lower than that of the other three infection systems. For infections in the respiratory system, urinary system, and other body parts, the resistance rates of Klebsiella pneumoniae to amikacin, meropenem, imipenem, and piperacillin/tazobactam were all below 10%, while the resistance rate to tobramycin was below 20%, and the resistance rate to cephalosporins was around 30%. Conclusion:The proportion of Klebsiella pneumoniae infections in different body parts varies by gender, age, and department. For Klebsiella pneumoniae infections in the hematological system, the resistance rate to commonly used antibiotics is lower than that for infections in the other three systems. In contrast, Klebsiella pneumoniae infections in the respiratory system, urinary system, and other systems have a particularly high resistance rate to third- and fourth-generation cephalosporins but are still sensitive to piperacillin/tazobactam and carbapenem antibiotics.

Objective:To analyze the genus, drug resistance/virulence and phylogenetic characteristics of Brucella strains isolated from brucellosis surveillance sentinels in Henan Province from 2013 to 2022, and provide baseline data for the surveillance, early warning and outbreak tracing of brucellosis. Methods:Blood samples were collected from patients with Brucella infection for strain isolation, culture and species identification, drug susceptibility test, whole genome sequencing, splicing and assembly, functional/virulence/resistance gene prediction analysis and phylogenetic tree drawing based on single nucleotide polymorphism (SNP). Results:In 36 brucellosis patients, the majority were men (86.11%, 31/36), young adults aged 18-50 (88.89%, 32/36) and farmers/herdsmen (72.22%, 26/36). A total of 36 strains of Brucella melitensis were isolated, and average 1 305 functional proteins of 21 categories were predicted by strain genome; all the strains carried four main virulence factors (pmm, VirB group, BtpA/BtpB, BvrS/BvrR). The drug sensitivity rate was 100.00% to six types of antibiotics including levofloxacin, rifampicin, doxycycline, streptomycin, tetracycline and gentamicin, they showed different resistances to three antibiotics including compound trimethoprim-sulfamethoxazole, ciprofloxacin and ampicillin. The strains carried four types of resistance genes and two clusters of resistance genes, with four combinations of genotypes, the resistance mechanisms included antibiotic degradation/modification enzymes, resistant nodular cell differentiation (RND) efflux pumps, 16S/23S ribosomal rRNA binding site mutations, etc. The number of SNP differed in the genomes of 36 Brucellamelitensis strains ranged from 0 to 454 and phylogenetic tree was divided into three major branches, with relative branch distances between 0.000 0 and 0.498 6 for each strain. Conclusions:Human Brucellamelitensis strains isolated from surveillance sentinels in Henan from 2013 to 2022 carried multiple virulence and antibiotic resistance genes and had different drug resistance phenotypes. Single nucleotide polymorphism analysis and phylogenetic tree analysis showed significant differences in phylogenetic relationships among different strains.

Objective:To investigate the effect of BOPPPS teaching model combined with virtual simulation technologyin the teaching of Prevention and treatment of Major Infectious Diseases,in order to explore innovative teaching model and provide evidence for improving students'comprehensive ability to deal with major infectious disease events.Methods:Undergraduates from three classes of preventive medicine major in a medical university were selected as the research objects.One class was given the new teaching model,and the other two classes were given the traditional teaching model.The total scores,the theoretical score and the skill score were compared between the two groups.Results:A total of 141 students participated in the survey,49 students in the new teaching model group,and 92 students in the traditional teaching model group.The results showed that compared with the traditional model group,the total score,the theoretical score,the skill score of the new model group was significantly higher(P＜0.01).However,there was no significant difference between male and female students in each group(P＞0.05).Conclusions:Compared with the traditional teaching model,the students in the new teaching model has a good teaching effect,which can improve the students'theoretical knowledge level,cultivate the students'emergency response ability,and improve the students'comprehensive ability of discovery,analysis and solution.Boys and girls have the same acceptance of the two teaching models,and gender does not affect the teaching effect.

Objective:To investigate the expression characteristics of mucin 5B (MUC5B) protein and programmed cell death factor 4 (PDCD4) protein in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram model for prognosis prediction.Methods:Clinical data of 100 patients who underwent radical surgical resection and were diagnosed as ICC by postoperative pathology from September 2009 to September 2020 in the Third Affiliated Hospital of Wenzhou Medical University were retrospectively selected, including 46 males and 54 females, aged (56.9±12.2) years old. Immunohistochemistry was used to detect the expression of MUC5B and PDCD4 protein in 100 cases of ICC and corresponding adjacent tissues respectively, and the relationship between them and clinicopathological factors of ICC patients was analyzed. Univariate and multivariate Cox regression analysis were performed to analyze the influencing factors on postoperative prognosis of ICC patients. The nomogram model was constructed using rms package and performed internal verification.Results:The positive expression rate of MUC5B protein in ICC was 76.0% (76/100), which was higher than that in para-cancer tissues 27.0%(27/100), and the difference was statistically significant ( χ2=11.33, P=0.015). While the positive expression rate of PDCD4 protein in ICC was 21.0%(21/100), which was lower than that in normal tissues 73.0% (73/100), and the difference was statistically significant ( χ2=15.57, P=0.007). Multivariate Cox regression analysis showed that ICC patients with carbohydrate antigen 19-9>37 kU/L, tumor length>5 cm, tumor TNM stage Ⅱ/Ⅲ, tumor medium/low differentiation, MUC5B positive expression, and PDCD4 negative expression had a high risk of short survival after resection (all P<0.05). The nomogram model was constructed based on the above indicators, and the C-index was 0.801. The postoperative survival calibration curve showed that the high predictive survival fit of the nomogram model, and the area under the receiver operating characteristic curve was 0.862. Conclusions:Positive expression of MUC5B protein and negative expression of PDCD4 protein in ICC tissue suggest poor prognosis of ICC patients. The nomogram model constructed on the basis of MUC5B and PDCD4 protein is well distinguished and has ideal predictive efficacy.

Objective:To investigate the efficacy and safety of irreversible electroporation in focal ablation of localized prostate cancer.Methods:Clinical data of 128 patients with localized prostate cancer treated with irreversible electroporation from August 2019 to September 2023 at Renji Hospital of Shanghai Jiaotong University School of Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Dongfang Hospital of Tongji University, were retrospectively analyzed. The median age was 68 (62, 75) years. The median PSA was 8.64 (5.83, 12.57) ng/ml. Gleason score was 6 in 57 cases, 7 in 39 cases, and greater than 7 in 19 cases. There were 4 cases of T 1c, 69 cases of T 2a, 27 cases of T 2b, and 28 cases of T 2c. No lymph node or distant metastasis was seen in preoperative examination. All patients had no preoperative urinary retention or urinary incontinence. Irreversible electroporation treatment was administered under general anesthesia with patients in the lithotomy position. A transrectal ultrasound probe was used to measure prostate lesion size, determining the type and number of electrode needles. Electrode needles were strategically positioned around the targeted lesion. The distance between each pair of needles used for ablation ranged from 0.5 to 2.0 cm. The system automatically generated treatment parameters, including voltage, current, and the number of pulses, with each pulse cycle lasting approximately 5 minutes. After treatment, the needles were removed, gauze was applied for 1 minute. The urethra was then irrigated with a painless iodine solution diluted 1∶1 with 0.9% saline, followed by the insertion of a urinary catheter. Treatment efficacy and adverse reactions were documented. Biochemical recurrence was defined as a PSA increase of over 2 ng/ml from the post-treatment nadir; imaging recurrence was identified by abnormal lesions on MRI or contrast-enhanced ultrasound. Results:All 128 surgeries were successfully completed. At 6 months postoperatively, 116 cases were followed. Tne median PSA was 1.58 (0.56, .95) ng/ml, which was 82.22% (65.37%, 93.33%) lower than preoperative level( P<0.01). Five patients (4.31%) had biochemical recurrence, and MRI or contrast-enhanced ultrasound examinations were negative, 1 patient underwent radical prostatectomy with pathology of prostate cancer, and the remaining 4 were continued to be followed up. Ninety-eight patients underwent MRI or contrast-enhanced ultrasound review, including 6 patients (6.12%) detected imaging recurrence, of which 2 patients underwent radical prostatectomy with pathology of prostate cancer, and the remaining 4 underwent endocrine therapy. The postoperative continence rate was 98.28%, and 8 patients (6.89%) had complications of class II. Conclusions:Irreversible electroporation for focal treatment of localized prostate cancer has shown favorable results in terms of tumor control, safety and urinary continence.

Objective:To investigate the efficacy of primary closure versus T-tube drainage in patients with common bile duct stones after laparoscopic common bile duct exploration and stone extraction. Methods:Fifty-two patients with common bile duct stones who received treatment at The Second Affiliated Hospital of Guizhou Medical University between February 2021 and February 2023 were included in this study. All patients underwent laparoscopic common bile duct exploration and stone extraction and then were divided into two groups ( n = 26 per group) using a randomized controlled trial design with allocation based on a random number table. The control group received T-tube drainage postoperatively, whereas the observation group underwent primary suture treatment. Both groups were observed for 3 days postoperatively to compare various postoperative clinical indicators, including serum levels of cortisol, adrenaline, C-reactive protein, interleukin-6, direct bilirubin, total bile acid, alkaline phosphatase, and gamma-glutamyl transferase, and the occurrence of postoperative complications. Results:The operative time in the observation group was significantly shorter than that in the control group [(105.30 ± 5.89) minutes vs. (121.36 ± 5.86) minutes, t = 9.86, P < 0.001]. The intraoperative blood loss in the observation group was significantly less than that in the control group [(40.31 ± 4.53) mL vs. (45.20 ± 4.76) mL, t = 3.80, P < 0.001]. The length of hospital stay in the observation group was significantly shorter than that in the control group [(12.01 ± 2.86) days vs. (14.32 ± 2.73) days, t = 2.98, P = 0.005]. The gastrointestinal function recovery time in the observation group was shorter than that in the control group [(31.42 ± 2.59) days vs. (37.62 ± 2.63) days, t = 8.57, P < 0.001]. The bile drainage volume in the observation group was less than that in the control group [(168.69 ± 15.41) mL vs. (275.62 ± 15.32) mL, t = 25.09, P < 0.001]. The serum level of cortisol in the observation group was significantly higher than that in the control group [(469.63 ± 20.62) mmol/L vs. (359.65 ± 19.87) mmol/L, t = 19.58, P < 0.001]. The serum level of adrenaline in the observation group was significantly higher than that in the control group [(274.62 ± 20.21) ng/L vs. (198.64 ± 20.16) ng/L, t = 13.57, P < 0.001]. The serum level of C-reactive protein in the observation group was significantly higher than that in the control group [(3.42 ± 0.37) mg/L vs. (2.74 ± 0.25) mg/L, t = 7.77, P < 0.001]. The serum level of interleukin-6 in the observation group was significantly higher than that in the control group [(112.36 ± 8.94) μg/L vs. (87.62 ± 8.63) μg/L, t = 10.15, P < 0.001]. The serum level of direct bilirubin in the observation group was significantly lower than that in the control group [(24.52 ± 4.62) μmol/L vs. (35.62 ± 4.87) μmol/L, t = 8.43, P < 0.001]. The serum level of total bile acid in the observation group was significantly lower than that in the control group [(10.62 ± 4.21) U/L vs. (17.64 ± 4.16) U/L, t = 6.05, P < 0.001]. The serum level of alkaline phosphatase in the observation group was significantly lower than that in the control group [(100.21 ± 10.24) mg/L vs. (112.74 ± 11.25) mg/L, t = 4.20, P < 0.001]. The serum level of gamma-glutamyl transferase in the observation group was significantly lower than that in the control group [(122.36 ± 8.94) μg/L vs. (142.62 ± 5.63) μg/L, t = 9.78, P < 0.001]. The incidence of complications in the observation group was significantly lower than that in the control group [7.69% (2/26) vs. 30.77% (8/26), χ2 = 4.46, P = 0.035]. Conclusion:Compared with T-tube drainage, primary closure following laparoscopic common bile duct exploration and stone extraction can reduce patient stress responses, improve liver function, shorten postoperative recovery time, and result in a lower incidence of complications.