Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Background and Aims:Early-onset extensive emphysematous pancreatitis(EP)is a rare but highly lethal subtype of infected pancreatic necrosis(IPN),characterized by abrupt onset and rapid deterioration.This study aimed to investigate its clinical characteristics,microbiological spectrum,treatment approaches,and outcomes to provide evidence for early identification and timely intervention.Methods:A retrospective analysis was performed on 305 IPN patients treated at Xiangya Hospital,Central South University,from January 2010 to October 2023.Eight patients who developed gas accumulation involving≥50%of pancreatic or peripancreatic necrosis within two weeks of onset were defined as early-onset extensive EP.Their clinical data were compared with those of ordinary IPN patients.Results:Early-onset extensive EP accounted for 2.6%of all IPN cases.The early-onset extensive EP group had significantly higher mortality and multiple organ failure rates compared with the ordinary IPN group(75.0%vs.24.6%and 75.0%vs.34.7%,respectively;both P<0.05).A total of 15 microbial isolates were identified from early-onset extensive EP patients,predominantly Klebsiella pneumoniae(62.5%)and Escherichia coli(37.5%).The infection rate of carbapenem-resistant Enterobacteriaceae(CRE)was markedly higher in the EP group than in the ordinary IPN group(75.0%vs.31.1%,P=0.015).Most patients were treated using a step-up approach based on percutaneous catheter drainage,with no significant difference in treatment strategy between the two groups(P=0.625).Conclusion:Early-onset extensive EP represents a rare and fulminant subtype of IPN with extremely poor outcomes.Klebsiella pneumoniae and CRE are the predominant pathogens.Early radiological evaluation and timely intervention are crucial for improving prognosis in these patients.

Objective:To assess the effect of joint exposure to multiple air pollutants on sleep structure in patients with stable chronic obstructive pulmonary disease (COPD), identify key air pollutants, and analyze potential influencing factors.Methods:In this panel study, 92 stable COPD patients were recruited. From March 2021 to September 2023 in Beijing, all participants completed 254 nights of sleep monitoring. The total sleep duration, light sleep duration, deep sleep duration and rapid eye movement sleep duration and their respective proportions in total sleep duration were recorded. The exposure levels of fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), ozone (O 3), sulfur dioxide (SO 2), and carbon monoxide (CO) were estimated based on the infiltration factor method and time-activity logs of participants. To assess the lag effect of air pollutants, moving average concentrations of air pollutants from 0-1 day to 0-3 months were calculated. The linear mixed-effect model and Bayesian kernel machine regression (BKMR) model were used to assess the single and joint effects of air pollutants on sleep structure parameters in COPD patients, respectively. Results:All six types of air pollutants were associated with changes in sleep structure, manifesting as an increase in total sleep duration and light sleep proportion and a reduction in deep sleep proportion. The effects of O 3 were strongest at lag 0-6 days, while other air pollutants were at lag 0-3 months. Joint exposure to multiple air pollutants exerted significant joint effects on sleep structure, and NO 2 was identified as the dominant pollutant. NO 2 had a posterior inclusion probability (PIP) greater than 0.5 for light sleep proportion (PIP=0.691) and deep sleep proportion (PIP=0.957). With an interquartile range (IQR) increase of 8.6 μg/m 3 in NO 2 at lag 0-3 months, the light sleep proportion increased by 10.5% (95% CI: 2.2%-19.4%), and the deep sleep proportion decreased by 19.5% (95% CI:-30.6%- -6.8%). Conclusion:Joint exposure to air pollutants is associated with changes in sleep structure in stable COPD patients, and NO 2 may be a key pollutant.

Background and Aims:Reconstructing huge abdominal wall defects after abdominal wall tumor resection is a significant challenge for surgeons.Here,we summarize the experience of our team in repairing these defects using an anterolateral thigh chimeric perforator flap combined with artificial materials,within a multidisciplinary collaborative framework,aiming to provide a reference for other practitioners.Methods:The clinicopathologic data of 7 patients who underwent primary reconstruction of large abdominal wall defects after malignant tumor resection,using an anterolateral thigh chimeric perforator flap combined with artificial materials,at Xiangya Hospital,Central South University,between October 2019 and April 2024,were retrospectively analyzed.The clinical outcomes were evaluated.Results:All 7 patients successfully underwent both tumor resection and primary abdominal wall reconstruction without surgery-related mortality.The wound in all patients healed in one stage,with no severe complications such as surgical site infections or flap necrosis.During a follow-up period of 6 to 54 months,2 patients experienced tumor recurrence,one of whom died(exact cause unknown),while the other continued anti-tumor treatment.The remaining 5 patients were alive without recurrence.One patient developed abdominal wall bulging,but no obvious incisional hernia occurred in any of the patients.Conclusion:The use of an anterolateral thigh chimeric perforator flap combined with artificial materials for repairing large abdominal wall defects after abdominal tumor resection can achieve satisfactory therapeutic outcomes.This approach is a feasible and safe method for abdominal wall reconstruction.

Objective:To investigate the clinical efficacy of open anterior myofascial repair surgery on abdominal wall incision hernia.Methods:The retrospective cohort study was conducted. The clinical data of 188 patients who underwent open anterior myofascial repair surgery on abdo-minal wall incision hernia at three medical centers, including Xiangya Hospital of Central South University et al, from December 2016 to December 2024 were collected. There were 85 males and 103 females, aged (62±12)years. Of the 188 patients, 55 cases had large incisional hernia and 133 cases had non-large incisional hernia. Observation indicators: (1) intraoperative conditions; (2) postopera-tive conditions; (3) follow-up. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact test. Comparison of ordinal data between groups was conducted using the nonparametic test. Results:(1) Intra-operative conditions. The operation time of the 55 patients with large incisional hernia was (145±40)minutes, and the volume of intraoperative blood loss was 40.0(22.5,55.0)mL, cases with fascial defect located in the central anterior abdominal wall, the superolateral quadrant, the inferolateral quadrant were 26, 7, 22, the fascial defect area was 140(99,169)cm2, cases used with self-fixating mesh and flat mesh were 29, 26. The above indicators of the 133 patients with non-large incisional hernia were (124±34)minutes, 35.0(30.0,45.0)mL, 47, 26, 60, 25(12,40)cm2, 67, 66, respectively. There were significant differences in operation time and fascial defect area between patients with large incisional hernia and non-large incisional hernia ( t=-3.651, Z=-10.339, P<0.05), and there was no significant difference in the volume of intraoperative blood loss, defect quadrant distribution, and mesh type ( Z=-0.501, χ2=2.692, 0.086, P>0.05). (2) Postoperative conditions. Of the 55 patients with large incisional hernia, 7 cases developed postoperative seroma, including 5 cases combined with concomitant surgical-site infection, and 4 additional cases developed with surgical-site infection. Of the 133 patients with non-large incisional hernia, 15 cases developed postoperative seroma, including 3 cases combined with concomitant surgical-site infection. There was a significant difference in surgical-site infection between patients with large incisional hernia and non-large incisional hernia ( χ2=10.707, P<0.05), and there was no significant difference in postoperative seroma ( χ2=0.079, P>0.05). The duration of postoperative hospital stay was 7(6, 9)days for the 55 patients with large incisional hernia and 5(4, 6)days for the 133 patients with non-large incisional hernia, showing a significant difference between them ( Z=-6.292, P<0.05). (3) Follow-up. All 188 patients were followed up for 43(range, 29-67)months. During the follow-up, 9 patients experienced hernia recurrence, including 7 patients with large incisional hernia and 2 patients with non-large incisional hernia. For the 7 patients of large incisional hernia with hernia recurrence, 4 cases underwent reoperation and 3 cases received conservative treatment. All 2 patients of non-large incisional hernia with hernia recurrence received conservative treatment. There was no significant difference in hernia recurrence between patients with large incisional hernia and non-large incisional hernia ( χ2=8.432, P<0.05). Results of chronic pain score at postoperative 3 month showed that among 55 patients with large incisional hernia, 40 cases had mild pain, 7 cases had moderate pain, and 8 cases had severe pain. Among 133 patients with non-large incisional hernia, the above indicators were 102, 28, and 3, respectively. There was no significant difference in chronic pain score at postoperative 3 month between patients with large incisional hernia and non-large incisional hernia ( Z=-0.968, P>0.05). Conclusions:Open anterior myofascial repair surgery can be used for the treatment of abdominal wall incision hernia. Compared with non-large incisional hernia, patients with large incisional hernia have longer operation time, are more prone to surgical-site infection, have longer postoperative hospital stay, and are more likely to experience hernia recurrence.

Background and Aims:Reconstructing huge abdominal wall defects after abdominal wall tumor resection is a significant challenge for surgeons.Here,we summarize the experience of our team in repairing these defects using an anterolateral thigh chimeric perforator flap combined with artificial materials,within a multidisciplinary collaborative framework,aiming to provide a reference for other practitioners.Methods:The clinicopathologic data of 7 patients who underwent primary reconstruction of large abdominal wall defects after malignant tumor resection,using an anterolateral thigh chimeric perforator flap combined with artificial materials,at Xiangya Hospital,Central South University,between October 2019 and April 2024,were retrospectively analyzed.The clinical outcomes were evaluated.Results:All 7 patients successfully underwent both tumor resection and primary abdominal wall reconstruction without surgery-related mortality.The wound in all patients healed in one stage,with no severe complications such as surgical site infections or flap necrosis.During a follow-up period of 6 to 54 months,2 patients experienced tumor recurrence,one of whom died(exact cause unknown),while the other continued anti-tumor treatment.The remaining 5 patients were alive without recurrence.One patient developed abdominal wall bulging,but no obvious incisional hernia occurred in any of the patients.Conclusion:The use of an anterolateral thigh chimeric perforator flap combined with artificial materials for repairing large abdominal wall defects after abdominal tumor resection can achieve satisfactory therapeutic outcomes.This approach is a feasible and safe method for abdominal wall reconstruction.

Background and Aims:Early-onset extensive emphysematous pancreatitis(EP)is a rare but highly lethal subtype of infected pancreatic necrosis(IPN),characterized by abrupt onset and rapid deterioration.This study aimed to investigate its clinical characteristics,microbiological spectrum,treatment approaches,and outcomes to provide evidence for early identification and timely intervention.Methods:A retrospective analysis was performed on 305 IPN patients treated at Xiangya Hospital,Central South University,from January 2010 to October 2023.Eight patients who developed gas accumulation involving≥50%of pancreatic or peripancreatic necrosis within two weeks of onset were defined as early-onset extensive EP.Their clinical data were compared with those of ordinary IPN patients.Results:Early-onset extensive EP accounted for 2.6%of all IPN cases.The early-onset extensive EP group had significantly higher mortality and multiple organ failure rates compared with the ordinary IPN group(75.0%vs.24.6%and 75.0%vs.34.7%,respectively;both P<0.05).A total of 15 microbial isolates were identified from early-onset extensive EP patients,predominantly Klebsiella pneumoniae(62.5%)and Escherichia coli(37.5%).The infection rate of carbapenem-resistant Enterobacteriaceae(CRE)was markedly higher in the EP group than in the ordinary IPN group(75.0%vs.31.1%,P=0.015).Most patients were treated using a step-up approach based on percutaneous catheter drainage,with no significant difference in treatment strategy between the two groups(P=0.625).Conclusion:Early-onset extensive EP represents a rare and fulminant subtype of IPN with extremely poor outcomes.Klebsiella pneumoniae and CRE are the predominant pathogens.Early radiological evaluation and timely intervention are crucial for improving prognosis in these patients.

Objective:To assess the effect of joint exposure to multiple air pollutants on sleep structure in patients with stable chronic obstructive pulmonary disease (COPD), identify key air pollutants, and analyze potential influencing factors.Methods:In this panel study, 92 stable COPD patients were recruited. From March 2021 to September 2023 in Beijing, all participants completed 254 nights of sleep monitoring. The total sleep duration, light sleep duration, deep sleep duration and rapid eye movement sleep duration and their respective proportions in total sleep duration were recorded. The exposure levels of fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), ozone (O 3), sulfur dioxide (SO 2), and carbon monoxide (CO) were estimated based on the infiltration factor method and time-activity logs of participants. To assess the lag effect of air pollutants, moving average concentrations of air pollutants from 0-1 day to 0-3 months were calculated. The linear mixed-effect model and Bayesian kernel machine regression (BKMR) model were used to assess the single and joint effects of air pollutants on sleep structure parameters in COPD patients, respectively. Results:All six types of air pollutants were associated with changes in sleep structure, manifesting as an increase in total sleep duration and light sleep proportion and a reduction in deep sleep proportion. The effects of O 3 were strongest at lag 0-6 days, while other air pollutants were at lag 0-3 months. Joint exposure to multiple air pollutants exerted significant joint effects on sleep structure, and NO 2 was identified as the dominant pollutant. NO 2 had a posterior inclusion probability (PIP) greater than 0.5 for light sleep proportion (PIP=0.691) and deep sleep proportion (PIP=0.957). With an interquartile range (IQR) increase of 8.6 μg/m 3 in NO 2 at lag 0-3 months, the light sleep proportion increased by 10.5% (95% CI: 2.2%-19.4%), and the deep sleep proportion decreased by 19.5% (95% CI:-30.6%- -6.8%). Conclusion:Joint exposure to air pollutants is associated with changes in sleep structure in stable COPD patients, and NO 2 may be a key pollutant.

Objective:To investigate the clinical efficacy of open anterior myofascial repair surgery on abdominal wall incision hernia.Methods:The retrospective cohort study was conducted. The clinical data of 188 patients who underwent open anterior myofascial repair surgery on abdo-minal wall incision hernia at three medical centers, including Xiangya Hospital of Central South University et al, from December 2016 to December 2024 were collected. There were 85 males and 103 females, aged (62±12)years. Of the 188 patients, 55 cases had large incisional hernia and 133 cases had non-large incisional hernia. Observation indicators: (1) intraoperative conditions; (2) postopera-tive conditions; (3) follow-up. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact test. Comparison of ordinal data between groups was conducted using the nonparametic test. Results:(1) Intra-operative conditions. The operation time of the 55 patients with large incisional hernia was (145±40)minutes, and the volume of intraoperative blood loss was 40.0(22.5,55.0)mL, cases with fascial defect located in the central anterior abdominal wall, the superolateral quadrant, the inferolateral quadrant were 26, 7, 22, the fascial defect area was 140(99,169)cm2, cases used with self-fixating mesh and flat mesh were 29, 26. The above indicators of the 133 patients with non-large incisional hernia were (124±34)minutes, 35.0(30.0,45.0)mL, 47, 26, 60, 25(12,40)cm2, 67, 66, respectively. There were significant differences in operation time and fascial defect area between patients with large incisional hernia and non-large incisional hernia ( t=-3.651, Z=-10.339, P<0.05), and there was no significant difference in the volume of intraoperative blood loss, defect quadrant distribution, and mesh type ( Z=-0.501, χ2=2.692, 0.086, P>0.05). (2) Postoperative conditions. Of the 55 patients with large incisional hernia, 7 cases developed postoperative seroma, including 5 cases combined with concomitant surgical-site infection, and 4 additional cases developed with surgical-site infection. Of the 133 patients with non-large incisional hernia, 15 cases developed postoperative seroma, including 3 cases combined with concomitant surgical-site infection. There was a significant difference in surgical-site infection between patients with large incisional hernia and non-large incisional hernia ( χ2=10.707, P<0.05), and there was no significant difference in postoperative seroma ( χ2=0.079, P>0.05). The duration of postoperative hospital stay was 7(6, 9)days for the 55 patients with large incisional hernia and 5(4, 6)days for the 133 patients with non-large incisional hernia, showing a significant difference between them ( Z=-6.292, P<0.05). (3) Follow-up. All 188 patients were followed up for 43(range, 29-67)months. During the follow-up, 9 patients experienced hernia recurrence, including 7 patients with large incisional hernia and 2 patients with non-large incisional hernia. For the 7 patients of large incisional hernia with hernia recurrence, 4 cases underwent reoperation and 3 cases received conservative treatment. All 2 patients of non-large incisional hernia with hernia recurrence received conservative treatment. There was no significant difference in hernia recurrence between patients with large incisional hernia and non-large incisional hernia ( χ2=8.432, P<0.05). Results of chronic pain score at postoperative 3 month showed that among 55 patients with large incisional hernia, 40 cases had mild pain, 7 cases had moderate pain, and 8 cases had severe pain. Among 133 patients with non-large incisional hernia, the above indicators were 102, 28, and 3, respectively. There was no significant difference in chronic pain score at postoperative 3 month between patients with large incisional hernia and non-large incisional hernia ( Z=-0.968, P>0.05). Conclusions:Open anterior myofascial repair surgery can be used for the treatment of abdominal wall incision hernia. Compared with non-large incisional hernia, patients with large incisional hernia have longer operation time, are more prone to surgical-site infection, have longer postoperative hospital stay, and are more likely to experience hernia recurrence.

Objective:To investigate the application value of metagenomic next-genera-tion sequencing (mNGS) in pathogenic diagnosis of suspected infected severe acute pancreatitis (SAP).Methods:The prospective study was conducted. The clinical data of 25 patients with suspected infected SAP who were admitted to the Xiangya Hospital of Central South University from May to September 2023 were collected. Upper limb venous blood samples of all the patients were collected for both of mNGS and routine pathogen microbial culture. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture; (3) results of peripheral blood pathogen microbial testing and peri-pancreatic effusion microbial culture; (4) testing time and cost. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 25 patients were selected for eligibility. There were 18 males and 7 females, aged 48(40,59)years. The duration of hospital stay of 25 patients was 30(20,50)days. The etiologies of 25 patients included 14 cases of hyperlipidemic pancreatitis, 8 cases of biliary pancreatitis, 1 case of alcohol-induced acute pancreatitis, and 2 cases of pancreatitis caused by other causes. Of the 25 patients, there were 17 cases with infected pancreatic necrosis (IPN) including 7 cases of death, and 8 cases with sterile pancreatic necrosis including no death. (2) Comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture. The positive rates of mNGS and routine pathogen microbial culture in diagnosis of suspected infected SAP were 72.0%(18/25) and 32.0%(8/25), respectively, showing a significant difference between them ( χ2=8.01, P<0.05). The sensitivity and negative predic-tive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 94.1%(16/17), 35.3%(6/17) and 85.7%(6/7), 35.3%(6/17), showing significant differences between them ( χ2=12.88, 5.04, P<0.05). The specificity and positive predictive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 75.0%(6/8), 75.0%(6/8) and 88.9%(16/18), 75.0%(6/8), showing no significant difference between them ( χ2=0, 0.82, P>0.05). (3) Results of peripheral blood pathogen microbial testing and peripancreatic effusion microbial culture. Of the 17 patients with IPN, 36 strains of pathogenic bacteria were detected by mNGS, and 6 strains were detected by routine pathogen microbial culture. There were 16 of 17 patients with IPN showing positive mNGS pathogenic testing, of which 13 cases were consistent with the pathogenic testing results of peri-pancreatic effusion microbial culture, showing a consistency rate of 76.5%(13/17). There were 6 pati-ents with IPN showing positive routine pathogen microbial culture, with a consistency rate of 35.3%(6/17) to peripancreatic effusion microbial culture. (4) Testing time and cost. Testing time of mNGS and routine pathogen microbial culture were (43±17)hours and (111±36)hours, showing a signifi-cant difference between them ( t=9.31, P<0.05). Testing cost of mNGS was (2 267±0)yuan/case, accoun-ting for 1.7% of the hospitalization expenses of (133 759±120 744)yuan/case. Testing cost of routine pathogen microbial culture was (240±0)yuan/case, accounting of 0.2% of the hospitalization expenses. Conclusion:mNGS has important value for early pathogenic diagnosis of suspected infected SAP, and has a high timeliness.