Objective To investigate the gene expression and regulatory mechanisms of mouse embryonic fibroblasts (MEFs) under inflammatory conditions, aiming to elucidate the role of MEFs in inflammatory responses and provide a foundation for discovering anti-inflammatory drugs that act by modulating MEF function. Methods MEFs cultured in vitro were divided into the following groups: lipopolysaccharides (LPS)-treated group, inflammatory conditioned medium (CM)-treated group, and control group, which were treated with LPS, CM, and equal volume solvent, respectively. Transcriptome sequencing was used to analyze the effects of two stimuli on gene expression profile of MEFs. Real time fluorescence quantitative PCR (RT-qPCR) was employed to verify the transcription levels of highly expressed genes of MEFs induced by CM. ELISA was performed to determine the concentrations of cytokines in cell supernatants. Finally, the regulatory effects of CM on the activation of signaling pathways in MEFs were analyzed by immunoblotting. Results Transcriptome analysis showed that both LPS and CM induced the transcription of a large number of genes in MEFs. Compared with LPS, CM potentiated the mRNA transcription of some acute phase proteins, inflammatory cytokines, chemokines, matrix metalloproteinases (MMP), prostaglandin synthetases, and colony-stimulating factors. The transcriptome analysis was verified by RT-qPCR. The results of ELISA showed that CM treatment significantly increased the secretion of interleukin 6 (IL-6), C-C motif chemokine ligand (CCL2), and C-X-C motif chemokine ligand (CXCL1) by MEFs compared with LPS. Mechanism study showed that both LPS and CM induced the phosphorylation of nuclear factor-κB p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), extracellular regulated protein kinases 1/2 (ERK1/2), and TANK-binding kinase (TBK) in MEFs, and CM strongly stimulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in MEFs. Conclusion Both LPS and CM can induce transcription and protein secretion of various inflammation-related genes in MEFs. CM can partly enhance LPS-induced activation of MEFs, and the mechanism may be related to the enhancement effect of CM on the activation STAT3 signaling pathway.
Animals ; Fibroblasts/immunology* ; Mice ; Lipopolysaccharides/pharmacology* ; Inflammation/metabolism* ; Signal Transduction/drug effects* ; Gene Expression Regulation/drug effects* ; Cytokines/genetics* ; Culture Media, Conditioned/pharmacology* ; Cells, Cultured

[Purpose]To analyze the changing trends of the disease burden of liver cancer related to hepatitis B virus(HBV)globally and in China from 1992 to 2021.[Methods]Based on the Global Burden of Disease database in 2021,indicators such as the age-standardized incidence rate and mortality rate of HBV-related liver cancer globally and in China from 1992 to 2021 were collected.The Joinpoint regression model was used to analyze the changing trends of epidemiologi-cal characteristics,and the age-period-cohort model was adopted to analyze the impacts of age,period,and cohort factors on the incidence and mortality risks of HBV-related liver cancer globally and in China.[Results]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer globally generally showed a trend of decreasing.The average annual percentage changes were-0.31％and-0.61％,respectively,and all the down-ward trends were statistically significant(both P＜0.05).During the same period,the average annu-al percentage changes of the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer in China were-0.45％and-0.90％,respectively,and all the downward trends were statistically significant(both P＜0.05).The results of the age-period-cohort model anal-ysis showed that from 1992 to 2021,the annual net drift rates of the incidence of HBV-related liver cancer globally and in China were-0.71％(95％CI:-0.84％～-0.57％)and-0.73％(95％CI:-1.01％～-0.44％),respectively.The annual net drift rates of the mortality were-1.15％(95％CI:-1.28％～-1.02％)and-1.42％(95％CI:-1.69％～-1.14％),respectively,all showing an over-all decline.The age effect showed that the risk of HBV-related liver cancer incidence in both the global and Chinese populations began to increase after 30 years of age,peaking in the 70～74 age group,while the risk of mortality surged after 40 years of age and peaked in the population aged 80 and above.The period effect indicated that the incidence and mortality risks were the highest from 1997 to 2001 and the lowest from 2017 to 2021.The cohort effect revealed that the inci-dence and mortality risks gradually decreased in populations born after 1962,with the 2007-2011 birth cohort having the lowest risks.The results of the Wald x2 test showed that there were statistically significant differences in the changing trends of the age,period,and cohort effects on the incidence and mortality of HBV-related liver cancer globally and in China(all P＜0.05).[Con-clusion]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer showed a downward trend both globally and in China.The disease burden of HBV-related liver cancer in China was higher than the global level.The age-period-cohort model has revealed the historical changes in the incidence and mortality of HBV-related liver cancer.The current and future situation of the disease burden of HBV-related liver cancer is not optimistic.It is recommended to implement precise stratified interventions for populations of different ages,periods,and birth cohorts,and actively transform the prevention,treatment,and management strategies for HBV-related liver cancer.

Inguinal hernia is one of the most prevalent general surgical conditions affecting the elderly population.Currently, open or laparoscopic surgical repair represents the only curative approach.Among various surgical techniques, tension-free hernia repair via the preperitoneal space effectively addresses the complications associated with traditional surgical methods, such as excessive tension in the surgical area, postoperative pain and discomfort, and a subsequent decline in patients' quality of life.Nevertheless, a certain recurrence rate persists.This paper aims to highlight the insufficient research on preperitoneal hernia repair procedures within the field of hernia surgery and to conduct a comprehensive analysis of the primary factors contributing to postoperative recurrence.This analysis will be approached from three key perspectives: medical origins, individual patient variability, and the characteristics of the patch used.The goal is to provide a foundation for the theoretical framework and practical strategies aimed at reducing postoperative recurrence rates.

Objective To analyze the application effects of artificial intelligence (AI) software and Mimics software in preoperative three-dimensional (3D) reconstruction for thoracoscopic anatomical pulmonary segmentectomy. Methods A retrospective analysis was conducted on patients who underwent thoracoscopic pulmonary segmentectomy at the Second People's Hospital of Huai'an from October 2019 to March 2024. Patients who underwent AI 3D reconstruction were included in the AI group, those who underwent Mimics 3D reconstruction were included in the Mimics group, and those who did not undergo 3D reconstruction were included in the control group. Perioperative related indicators of each group were compared. Results A total of 168 patients were included, including 73 males and 95 females, aged 25-81 (61.61±10.55) years. There were 79 patients in the AI group, 53 patients in the Mimics group, and 36 patients in the control group. There were no statistical differences in gender, age, smoking history, nodule size, number of lymph node dissection groups, postoperative pathological results, or postoperative complications among the three groups (P>0.05). There were statistical differences in operation time (P<0.001), extubation time (P<0.001), drainage volume (P<0.001), bleeding volume (P<0.001), and postoperative hospital stay (P=0.001) among the three groups. There were no statistical differences in operation time, extubation time, bleeding volume, or postoperative hospital stay between the AI group and the Mimics group (P>0.05). There was no statistical difference in drainage volume between the AI group and the control group (P=0.494), while there were statistical differences in operation time, drainage tube retention time, bleeding volume, and postoperative hospital stay (P<0.05). Conclusion For patients requiring thoracoscopic anatomical pulmonary segmentectomy, preoperative 3D reconstruction and preoperative planning based on 3D images can shorten the operation time, postoperative extubation time and hospital stay, and reduce intraoperative bleeding and postoperative drainage volume compared with reading CT images only. The use of AI software for 3D reconstruction is not inferior to Mimics manual 3D reconstruction in terms of surgical guidance and postoperative recovery, which can reduce the workload of clinicians and is worth promoting.

OBJECTIVE To analyze clinical switching patterns and reasons between bevacizumab biosimilar and originator drugs. METHODS The data were collected from 1 175 cancer patients treated with bevacizumab at Ruijin Hospital， Shanghai Jiao Tong University School of Medicine from January 1， 2018， to December 31， 2023. The patients were divided into originator group （n＝250） and biosimilar group （n＝925）. The switching rate， switching type and reasons of the two groups were compared. RESULTS There were no statistically significant differences in the switching rate， switching types， and the number of switches between the two groups （P＞0.05）. Single， one-way switches were the switching type in both groups. The proportion of patients in the biosimilar group who switched due to adverse events was significantly higher than originator group， while the proportion of patients who switched due to treatment costs was significantly lower than originator group （P＜0.05）. There were no statistically significant differences in the proportions of patients who switched due to efficacy and drug accessibility between the two groups （P＞0.05）. CONCLUSIONS The switching between bevacizumab biosimilar and the originator drugs mainly involves single， one- way switches. Treatment costs and drug accessibility are the main factors for the switches among users of originator drugs， while drug accessibility and adverse events are the main factors for the switches among users of biosimilar.

Objective:To predict pre-treatment clinical parameters that are associated with poor response and prognosis to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC) and to use second-line treatment drugs in the early stages to delay the progression of the disease so that patients can benefit from early-stage treatment.Methods:Patients diagnosed with PBC at the Second Affiliated Hospital of Kunming Medical University from 2013 to 2022 were collected. Two hundred fifty-seven cases were screened in accordance with the inclusion and exclusion criteria. The response and prognosis conditions one year after treatment were followed up in outpatient and inpatient departments, as well as through telephone calls. Statistical analyses were performed using t-tests, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis according to different data. Results:A total of 257 PBC cases were included, with 223 females (86.80%) and 34 males (13.20%). Univariate and multivariate binary logistic regression analyses showed that baseline high albumin levels [odds ratio ( OR): 0.882, 95% confidence interval ( CI): 0.805～0.967, P=0.008] were a protective factor for PBC patients' response to UDCA treatment after adjusting for different confounding factors, while baseline high alkaline phosphatase ( OR: 1.012, 95% CI: 1.008～1.016, P<0.001) and baseline high neutrophil/lymphocyte ratio (NLR) level ( OR: 1.462, 95% CI:1.079～1.981, P=0.014) were risk factors for a poor response to UDCA. Trend analysis showed that the baseline NLR quantile was positively correlated with the risk of poor response to UDCA ( OR: 5.512, 95% CI: 1.040～29.216, P=0.045) in patients with PBC. Cox proportional hazards regression analysis identified that age [hazard ratio ( HR): 1.050, 95% CI: 1.019～1.082] and NLR value ( HR:1.089, 95% CI:1.021～1.161) were independent influencing risk factors for all-cause mortality in PBC patients ( P<0.05). Conclusion:Baseline high albumin levels are protective factors against a poor biochemical response to UDCA, while baseline high alkaline phosphatase levels and high NLR are risk factors for a poor biochemical response to UDCA in patients with PBC. Additionally, baseline high NLR values are positively correlated with poor biochemical response to UDCA treatment.

[Purpose]To analyze the changing trends of the disease burden of liver cancer related to hepatitis B virus(HBV)globally and in China from 1992 to 2021.[Methods]Based on the Global Burden of Disease database in 2021,indicators such as the age-standardized incidence rate and mortality rate of HBV-related liver cancer globally and in China from 1992 to 2021 were collected.The Joinpoint regression model was used to analyze the changing trends of epidemiologi-cal characteristics,and the age-period-cohort model was adopted to analyze the impacts of age,period,and cohort factors on the incidence and mortality risks of HBV-related liver cancer globally and in China.[Results]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer globally generally showed a trend of decreasing.The average annual percentage changes were-0.31％and-0.61％,respectively,and all the down-ward trends were statistically significant(both P＜0.05).During the same period,the average annu-al percentage changes of the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer in China were-0.45％and-0.90％,respectively,and all the downward trends were statistically significant(both P＜0.05).The results of the age-period-cohort model anal-ysis showed that from 1992 to 2021,the annual net drift rates of the incidence of HBV-related liver cancer globally and in China were-0.71％(95％CI:-0.84％～-0.57％)and-0.73％(95％CI:-1.01％～-0.44％),respectively.The annual net drift rates of the mortality were-1.15％(95％CI:-1.28％～-1.02％)and-1.42％(95％CI:-1.69％～-1.14％),respectively,all showing an over-all decline.The age effect showed that the risk of HBV-related liver cancer incidence in both the global and Chinese populations began to increase after 30 years of age,peaking in the 70～74 age group,while the risk of mortality surged after 40 years of age and peaked in the population aged 80 and above.The period effect indicated that the incidence and mortality risks were the highest from 1997 to 2001 and the lowest from 2017 to 2021.The cohort effect revealed that the inci-dence and mortality risks gradually decreased in populations born after 1962,with the 2007-2011 birth cohort having the lowest risks.The results of the Wald x2 test showed that there were statistically significant differences in the changing trends of the age,period,and cohort effects on the incidence and mortality of HBV-related liver cancer globally and in China(all P＜0.05).[Con-clusion]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer showed a downward trend both globally and in China.The disease burden of HBV-related liver cancer in China was higher than the global level.The age-period-cohort model has revealed the historical changes in the incidence and mortality of HBV-related liver cancer.The current and future situation of the disease burden of HBV-related liver cancer is not optimistic.It is recommended to implement precise stratified interventions for populations of different ages,periods,and birth cohorts,and actively transform the prevention,treatment,and management strategies for HBV-related liver cancer.

Inguinal hernia is one of the most prevalent general surgical conditions affecting the elderly population.Currently, open or laparoscopic surgical repair represents the only curative approach.Among various surgical techniques, tension-free hernia repair via the preperitoneal space effectively addresses the complications associated with traditional surgical methods, such as excessive tension in the surgical area, postoperative pain and discomfort, and a subsequent decline in patients' quality of life.Nevertheless, a certain recurrence rate persists.This paper aims to highlight the insufficient research on preperitoneal hernia repair procedures within the field of hernia surgery and to conduct a comprehensive analysis of the primary factors contributing to postoperative recurrence.This analysis will be approached from three key perspectives: medical origins, individual patient variability, and the characteristics of the patch used.The goal is to provide a foundation for the theoretical framework and practical strategies aimed at reducing postoperative recurrence rates.

Objective:To predict pre-treatment clinical parameters that are associated with poor response and prognosis to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC) and to use second-line treatment drugs in the early stages to delay the progression of the disease so that patients can benefit from early-stage treatment.Methods:Patients diagnosed with PBC at the Second Affiliated Hospital of Kunming Medical University from 2013 to 2022 were collected. Two hundred fifty-seven cases were screened in accordance with the inclusion and exclusion criteria. The response and prognosis conditions one year after treatment were followed up in outpatient and inpatient departments, as well as through telephone calls. Statistical analyses were performed using t-tests, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis according to different data. Results:A total of 257 PBC cases were included, with 223 females (86.80%) and 34 males (13.20%). Univariate and multivariate binary logistic regression analyses showed that baseline high albumin levels [odds ratio ( OR): 0.882, 95% confidence interval ( CI): 0.805～0.967, P=0.008] were a protective factor for PBC patients' response to UDCA treatment after adjusting for different confounding factors, while baseline high alkaline phosphatase ( OR: 1.012, 95% CI: 1.008～1.016, P<0.001) and baseline high neutrophil/lymphocyte ratio (NLR) level ( OR: 1.462, 95% CI:1.079～1.981, P=0.014) were risk factors for a poor response to UDCA. Trend analysis showed that the baseline NLR quantile was positively correlated with the risk of poor response to UDCA ( OR: 5.512, 95% CI: 1.040～29.216, P=0.045) in patients with PBC. Cox proportional hazards regression analysis identified that age [hazard ratio ( HR): 1.050, 95% CI: 1.019～1.082] and NLR value ( HR:1.089, 95% CI:1.021～1.161) were independent influencing risk factors for all-cause mortality in PBC patients ( P<0.05). Conclusion:Baseline high albumin levels are protective factors against a poor biochemical response to UDCA, while baseline high alkaline phosphatase levels and high NLR are risk factors for a poor biochemical response to UDCA in patients with PBC. Additionally, baseline high NLR values are positively correlated with poor biochemical response to UDCA treatment.

Objective To construct a pelvic floor muscle training program for patients undergoing radical prostatectomy,and to provide a reference for clinical practice.Methods The evidence related to pelvic floor muscle training in patients undergoing radical prostatectomy was systematically searched and the quality was evaluated.The draft of pelvic floor muscle training program for patients undergoing radical prostatectomy was constructed based on the KAP theory and it was demonstrated and revised by expert meetings.From February to March 2023,Delphi method was used to determine the final scheme.37 patients were selected as the control group and 38 patients as the experimental group to implement the scheme and evaluate the application effect.Results 2 rounds of Delphi consultations were conducted among 17 experts,and the recovery rate of the questionnaire was 100％.The expert authority coefficient was 0.89.The Kendall harmony coefficients of the importance and feasibility of the second round of consultation were 0.270 and 0.209(P＜0.001).The coefficient of variation of importance and feasibility of items were 0～0.18 and 0～0.20.The final program included 3 first-level items,8 second-level items and 29 third-level items.1 month after surgery,there was no significant difference in urinary incontinence score(P=0.242)and there was significant difference in pelvic floor muscle training compliance(P=0.011)between 2 groups.Conclusion The program was applied preliminary in clinical practice and it was confirmed with scientific and practical meaning,so it can provide a reference for clinical nursing.