OBJECTIVE To explore the distribution of pathogens isolated from the cervical cancer(CC)patients with postoperative urinary catheter-associated urinary tract infection(UTI)and analyze the predictive values of se-rum high mobility group protein B1(HMGB1),Toll-like receptor 4(TLR4)and nuclear factor kappa B(NF-κB).METHODS Totally 116 patients with CC who underwent radical resection in the First Affiliated Hospital of Henan University of Science and Technology from Jan.2021 to Jan.2024 were enrolled in the study and were divided into the infection group with 31 cases and the non-infection group with 85 cases according to the status of complication with UTI after urinary catheterization.The midstream urine specimens were collected by aseptic method,the pathogens were isolated and identified.The serum HMGB1 level was detected by means of enzyme-linked immu-nosorbent assay,the relative expression levels of peripheral blood TLR4 and NF-κB proteins were detected by Western blot.The efficiencies of serum HMGB1,TLR4 and NF-κB in prediction of postoperative urinary catheter-associated UTI in the CC patients were analyzed by means of receiver operating characteristic(ROC)curves.RESULTS Totally 49 strains of pathogens were isolated from 31 CC patients with postoperative urinary catheter-associated UTI,and the patients who had infection of single species were dominant.Gram-negative bacteria were the most common pathogens,accounting for 61.22％.There were significant differences in the age,complication with diabetes mellitus,duration of urinary catheter indwelling,postoperative uroschesis and previous history of UTI between the infection group and the non-infection group(P＜0.05);there were significant differences in the levels of serum HMGB1,TLR4 and NF-κB between the two groups(P＜0.05).The area under the curve(AUC)of the joint detection of serum HMGB1,TLR4 and NF-κB was 0.906 in prediction of the postoperative urinary catheter-associated UTI in the CC patients,with the sensitivity 83.87％;the predictive efficiencies of the joint de-tection of the indexes were better than those of the single detection(P＜0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the CC patients with postoperative urinary catheter-asso-ciated UTI.The joint detection of the serum HMGB1,TLR4 and NF-κB has the highest value in prediction of postoperative urinary catheter-associated UTI in the CC patients.

OBJECTIVE To explore the distribution of pathogens isolated from the cervical cancer(CC)patients with postoperative urinary catheter-associated urinary tract infection(UTI)and analyze the predictive values of se-rum high mobility group protein B1(HMGB1),Toll-like receptor 4(TLR4)and nuclear factor kappa B(NF-κB).METHODS Totally 116 patients with CC who underwent radical resection in the First Affiliated Hospital of Henan University of Science and Technology from Jan.2021 to Jan.2024 were enrolled in the study and were divided into the infection group with 31 cases and the non-infection group with 85 cases according to the status of complication with UTI after urinary catheterization.The midstream urine specimens were collected by aseptic method,the pathogens were isolated and identified.The serum HMGB1 level was detected by means of enzyme-linked immu-nosorbent assay,the relative expression levels of peripheral blood TLR4 and NF-κB proteins were detected by Western blot.The efficiencies of serum HMGB1,TLR4 and NF-κB in prediction of postoperative urinary catheter-associated UTI in the CC patients were analyzed by means of receiver operating characteristic(ROC)curves.RESULTS Totally 49 strains of pathogens were isolated from 31 CC patients with postoperative urinary catheter-associated UTI,and the patients who had infection of single species were dominant.Gram-negative bacteria were the most common pathogens,accounting for 61.22％.There were significant differences in the age,complication with diabetes mellitus,duration of urinary catheter indwelling,postoperative uroschesis and previous history of UTI between the infection group and the non-infection group(P＜0.05);there were significant differences in the levels of serum HMGB1,TLR4 and NF-κB between the two groups(P＜0.05).The area under the curve(AUC)of the joint detection of serum HMGB1,TLR4 and NF-κB was 0.906 in prediction of the postoperative urinary catheter-associated UTI in the CC patients,with the sensitivity 83.87％;the predictive efficiencies of the joint de-tection of the indexes were better than those of the single detection(P＜0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the CC patients with postoperative urinary catheter-asso-ciated UTI.The joint detection of the serum HMGB1,TLR4 and NF-κB has the highest value in prediction of postoperative urinary catheter-associated UTI in the CC patients.

Objective To explore the mechanisms of macrophage pyroptosis regulated by mTORC1 signaling based on transcriptomic sequencing.Methods Western blot,immunofluorescence and ELISA were used to detect the expression of pyroptosis-related proteins in macrophages before and after treatment of mTORC1 specific inhibitor rapamycin.In addition,the differentially expressed genes and proteins associated with mTORC1 signaling were screened by transcriptome analysis.Results mTORC1 inhibition caused macrophage pyroptosis.After rapamycin treatment,transcriptomic sequencing identified a total of 206 differentially expressed genes(DEGs),including 90 upregulated and 116 downregulated ones.The GO function annotation and KEGG enrichment analysis of the DEGs further screen out 4 DEGs(NLRC4,NOTCH4,CARD10,EBF4),which were consistent with the expression trend of transcriptome sequencing.Conclusion This study confirmed that NLRC4,NOTCH4,CARD10 and EBF4 are the key genes for macrophage pyroptosis regulated by mTORC1 signaling,constituting a novel mechanism of macrophage pyroptosis and laying a theoretical foundation for the prevention and treatment of the diseases related to pyroptosis.

Objective To explore the mechanisms of macrophage pyroptosis regulated by mTORC1 signaling based on transcriptomic sequencing.Methods Western blot,immunofluorescence and ELISA were used to detect the expression of pyroptosis-related proteins in macrophages before and after treatment of mTORC1 specific inhibitor rapamycin.In addition,the differentially expressed genes and proteins associated with mTORC1 signaling were screened by transcriptome analysis.Results mTORC1 inhibition caused macrophage pyroptosis.After rapamycin treatment,transcriptomic sequencing identified a total of 206 differentially expressed genes(DEGs),including 90 upregulated and 116 downregulated ones.The GO function annotation and KEGG enrichment analysis of the DEGs further screen out 4 DEGs(NLRC4,NOTCH4,CARD10,EBF4),which were consistent with the expression trend of transcriptome sequencing.Conclusion This study confirmed that NLRC4,NOTCH4,CARD10 and EBF4 are the key genes for macrophage pyroptosis regulated by mTORC1 signaling,constituting a novel mechanism of macrophage pyroptosis and laying a theoretical foundation for the prevention and treatment of the diseases related to pyroptosis.

Bayesian statistics is an approach for learning from evidences as it accumulates, combining prior distribution with current information on a quantity of interest, in which posterior distribution and inferences are being updated each time new data become available using Bayes' Theorem. Though frequentist approach has dominated medical studies, Bayesian approach has been more and more widely recognized by its flexibility and efficiency. Research and development (R&D) on anti-cancer new drugs have been so hot globally in recent years in spite of relatively high failure rate. It is the common demand of pharmaceutical enterprises and researchers to identify the optimal dose, regime and right population in the early-phase R&D stage more accurately and efficiently, especially when the following three major changes have been observed. The R&D on anticancer drugs have transformed from chemical drugs to biological products, from monotherapy to combination therapy, and the study design has also gradually changed from traditional way to innovative and adaptive mode. This also raises a number of subsequent challenges on decision-making of early R&D, such as inability to determine MTD, flexibility to deal with delayed toxicity, delayed response and dose-response changing relationships. It is because of the above emerging changes and challenges that the Bayesian approach is getting more and more attention from the industry. At least, Bayesian approach has more information for decision-making, which could potentially help enterprises achieve higher efficiency, shorter period and lower investment. This study also expounds the application of Bayesian statistics in the early R&D on anticancer new drugs, and compares and analyzes its idea and application scenarios with frequentist statistics, aiming to provide macroscopic and systematic reference for all related stakeholders.
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Humans ; Bayes Theorem ; Lung Neoplasms/drug therapy* ; Research Design ; Antineoplastic Agents/therapeutic use* ; Biological Products ; Pharmaceutical Preparations

Objective To evaluate the relationship between macrophage migration inhibitory factor ( MIF) expression and obese-induced abolition of sevoflurane preconditioning-induced cardioprotection in mice. Methods Forty-eight male C57BL∕6J mice, aged 4 weeks, were divided into 2 groups ( n=24 each) using a random number table method: normal diet group ( Lean group ) and high-fat diet group ( Obese group) . Lean group were fed a normal diet ( 10％ kcal) for 12 weeks, while Obese group were fed a high-fat diet ( 60％ kcal) for 12 weeks. The weight of mice was measured. Blood samples were collected from the tail vein for determination of blood glucose concentrations, and plasma concentrations of total cho-lesterol, triglyceride, insulin and leptin. After measurement of the parameters mentioned above, Lean group and Obese group were divided into 3 subgroups ( n=8 each) using a random number table method:sham operation groups (L-Sham group, O-Sham group), myocardial ischemia-reperfusion groups (L-IR group, O-IR group) and sevoflurane preconditioning groups (L-IR+Sev group, O-IR+Sev group). The mice were anesthetized and their hearts were immediately removed and retrogradely perfused in a Langendorff apparatus with an oxygenated K-H solution at 37 ℃. Hearts were continuously perfused with K-H solution for 115 min in L-Sham and O-Sham groups. Hearts were subjected to global ischemia for 25 min, followed by 60-min reperfusion after being retrogradely perfused with K-H solution in L-IR and O-IR groups. In L-IR+Sev and O-IR+Sev groups, hearts were subjected to 3 cycles of 5-min perfusion with sevoflurane-contai-ning K-H solution ( final concentration 0. 6 mmol∕L) and 5-min washout, and then hearts were subjected to global ischemia for 25 min, followed by 60-min reperfusion. Left ventricular developed pressure ( LVDP ) , left ventricular end-diastolic pressure ( LVEDP ) , and the maximum rate of increase or decrease in left ventricular pressure ( ±dp∕dtmax) were recorded at the end of reperfusion. Hearts were obtained at the end of reperfusion for determination of myocardial infarct size and expression of MIF ( by Western blot) . Results Compared with Lean group, the weight, blood glucose, levels of plasma total cholesterol, tri-glyceride, insulin and leptin were significantly increased in Obese group (P<0. 05). Compared with L-Sham group, the LVDP and +dp∕dtmax were significantly decreased, LVEDP and -dp∕dtmax were in-creased, myocardial infarct size was increased, and the expression of myocardial MIF was up-regulated in L-IR and L-IR+Sev groups, and the expression of myocardial MIF was up-regulated in O-Sham group ( P<0. 05) . Compared with L-IR group, LVDP and +dp∕dtmax were significantly increased, LVEDP and-dp∕dtmax were decreased, myocardial infarct size was decreased, and the expression of myocardial MIF was up-regulated in group L-IR+Sev, and the expression of myocardial MIF was significantly up-regulated in group O-IR (P<0. 05). Compared with O-Sham group, LVDP and +dp∕dtmax were significantly de-creased, LVEDP and-dp∕dtmax were increased, and myocardial infarct size was increased, and no signif-icant change was found in the expression of MIF in O-IR and O-IR+Sev groups ( P>0. 05) . Conclusion The mechanism by which obese abolishes sevoflurane preconditioning-induced cardioprotection may be relat-ed to inducing MIF over-expression in mice.

Objective The risk of current pancreaticojejunostomy is carefully considered from the perspective of the morphology of remnant pancreas,and we aimed to discuss the clinical outcomes of selecting different pancreaticojejunostomy techniques based on pancreatic morphology.Methods This was a prospective cohort study.The histopathology of remnant pancreatic tissues was categorized into four types based on preoperative radiological images and intraoperative palpation:Type Ⅰ:pancreas with hard texture in palpation,pancreatic atrophy,dilated pancreatic duct larger than 5 mm and remnant pancreatic surface ＜3 cm;Type Ⅱ:pancreas with hard texture in palpation,pancreatic atrophy and mild dilatation of pancreatic duct with the diameter of 3-5 mm and remnant pancreatic surface ＜3 cm;Type Ⅲ:pancreas with slightly hard texture,no atrophy,and normal or slightly dilated pancreatic duct with the diameter of 3-5 mm and remnant pancreatic surface ≥3 cm;Type Ⅳ:pancreas with soft texture,normal morphology and pancreatic duct.Results From January 2008 to August 2017,116 consecutive patients underwent pancreaticoduodenectomy in our center.Among them,10 patients with type Ⅰ underwent classic pancreatic ductal mucosa to mucosa anastomosis.19 patients with type Ⅱ underwent classic end to end invaginated pancreaticojejunostomy.45 patients with type Ⅲ underwent classic end to end invaginated pancreaticojejunostomy with overlapping U sutures;42 patients with type Ⅵ underwent total invaginated pancreaticojejunostomy.The post-operative pancreatic fistula occurred in 6 patients (5.2％) with one patient died.Postoperative bleeding occurred in 10 patients (8.6％),and gastroparesis occurred in 22 patients (19.0％).Overall complication rate was 33.6％.Conclusions Classification of pancreatic morphology based on preoperative radiological images and intraoperative palpation and the selection of corresponding pancreaticojejunostomy technique is theoretically rational and has the advantage of potentially reducing the risk of remnant pancreatic tissue.

OBJECTIVE: To compare the effect of 7 antipsychotic drugs on the life quality of schizophrenia patients including chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, and aripiprazole. METHODS: A total of 1,227 stable schizophrenic patients within 5 years onset who took 1 of the 7 study medications as maintenance treatment were followed up for 1 year at 10 China sites. Patients were evaluated by the short form-36 health survey (SF-36) at the baseline and at the end of 1 year. RESULTS: The life quality was improved obviously at the end of the follow-up. There was significant difference in body pain, vitality, and mental health (P<0.05) among these antipsychotic drugs. CONCLUSION All 7 antipsychotic drugs can improve the life quality of schizophrenia patients. Atypical antipsychotic drugs, especially olazapine and quetiapine, are superior to typical antipsychotic drugs in improving life quality.
Adolescent ; Adult ; Antipsychotic Agents ; therapeutic use ; Benzodiazepines ; therapeutic use ; Dibenzothiazepines ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Olanzapine ; Quality of Life ; Quetiapine Fumarate ; Schizophrenia ; drug therapy ; Surveys and Questionnaires ; Young Adult