OBJECTIVE To investigate the levels of high-mobility group box 1(HMGB1)protein,soluble fms-like tyrosine kinase 1(sFLT-1)and lactate-to-albumin ratio(LAR)in patients with severe pulmonary infection-associ-ated sepsis undergoing continuous renal replacement therapy(CRRT),and their correlation with 28-day clinical outcomes.METHODS A total of 102 patients with severe pulmonary infection-associated sepsis undergoing CRRT admitted to the People's Hospital of Nanchuan Chongqing from Jul.2021 to Jul.2024 were enrolled.Based on 28-day clinical outcomes,they were divided into a favorable prognosis group(71 cases)and a poor prognosis group(31 cases).The levels of HMGB1,sFLT-1,lactate,albumin and LAR were compared between the two groups.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of HMGB1,sFLT-1 and LAR for 28-day clinical outcomes in patients with severe pulmonary infection-associated sepsis undergoing CRRT.RESULTS Gram-negative bacteria were the predominant pathogens in patients with se-vere pulmonary infection-associated sepsis undergoing CRRT.The poor prognosis group had higher lactate levels(4.01±1.07 mmol/L)and lower albumin levels(27.46±4.15 g/L)than the favorable prognosis group(P＜0.05).The levels of HMGB1(62.66±15.66 ng/ml),sFLT-1(0.71±0.17 ng/ml)and LAR(14.59±3.64％)in the poor prognosis group were significantly higher than those in the favorable prognosis group(P＜0.05).The combined detection of HMGB1,sFLT-1 and LAR yielded an area under the curve(AUC)of 0.949 for predicting poor 28-day mortality in patients with severe pulmonary infection-associated sepsis undergoing CRRT,superior to the single detection of the indexes(P＜0.05),with a sensitivity of 93.55％and specificity of 87.32％.CONCLUSIONS In patients with severe pulmonary infection-associated sepsis undergoing CRRT,gram-negative bacteria are the predominant pathogens.Patients with poor prognosis exhibit abnormally elevated levels of HMGB1,sFLT-1 and LAR,and the combined detection of these three markers demonstrates high predictive value for 28-day mortality.

Objective To observe the synergistic effect of Shengxian Huaxian Prescription and its disassembled prescription on pulmonary fibrosis;To explore whether its mechanism is related to regulating the STAT6/PPAR-y pathway to promote polarization of M2 type macrophages towards M1 type.Methods Ten SD rats were randomly selected from 70 rats as blank group,and the remaining rats were re-established pulmonary fibrosis model by intratracheal infusion of bleomycin.After modeling,the rats were divided into model group,positive group,Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group,with 10 rats in each group.Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group were given 12.60,7.65,3.60 and 2.25 g/kg of corresponding TCM solution,respectively;the positive group was given 0.12 g/kg of pirfenidone suspension;the blank group and the model group were given equal volume of normal saline,once a day,for consecutive 28 days.The lung function of rats was detected,the contents of IL-6 and TGF-β1 in serum were detected by ELISA,the pathological changes in lung tissue were observed by Masson staining,the expression of CD68,iNOS and CD206,Arg-1 in lung tissue were detected by immunofluorescence,the expression of SOCS1,SOCS3,STAT6,p-STAT6 and PPAR-γ in lung tissue were detected by Western blot.Results Compared with the blank group,the PEF,PIF and EF50 in model group rats significantly decreased,and the contents of serum IL-6 and TGF-β1 significantly increased,Masson staining showed a large amount of collagen fiber deposition,Ashcroft score significantly increased,CD206,Arg-1,STAT6,p-STAT6,PPAR-y protein expression significantly increased(P＜0.01),the expressions of SOCS1 and SOCS3 protein significantly decreased(P＜0.01),while the expression of CD68 and iNOS were not significantly changed(P＞0.05).Compared with the model group,the PEF,PIF and EF50 in all administration groups significantly increased,and the contents of serum IL-6 and TGF-β1 significantly decreased,collagen fiber deposition in lung tissue were decreased to varying degree,Ashcroft score significantly decreased,the expression of CD206,Arg-1,STAT6,p-STAT6 and PPAR-γ protein significantly decreased(P＜0.01),the expressions of CD68,iNOS,SOCS1 and SOCS3 protein significantly increased(P＜0.05).The above indicators showed the most significant changes in Shengxian Huaxian Prescription group,followed by Shengxian group(P＜0.01,P＜0.05).Conclusion Both Shengxian Huaxian Prescription and its disassembled prescription have anti pulmonary fibrosis effects,and their mechanism may related to regulating the STAT6/PPAR-y pathway and promoting polarization of M2 type macrophages towards M1 type.Shengxian Huaxian Prescription group has the best effect,while Shengxian group play an important role in the prescription,and the compatibility between each group has a synergistic effect.

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

OBJECTIVE To investigate the levels of high-mobility group box 1(HMGB1)protein,soluble fms-like tyrosine kinase 1(sFLT-1)and lactate-to-albumin ratio(LAR)in patients with severe pulmonary infection-associ-ated sepsis undergoing continuous renal replacement therapy(CRRT),and their correlation with 28-day clinical outcomes.METHODS A total of 102 patients with severe pulmonary infection-associated sepsis undergoing CRRT admitted to the People's Hospital of Nanchuan Chongqing from Jul.2021 to Jul.2024 were enrolled.Based on 28-day clinical outcomes,they were divided into a favorable prognosis group(71 cases)and a poor prognosis group(31 cases).The levels of HMGB1,sFLT-1,lactate,albumin and LAR were compared between the two groups.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of HMGB1,sFLT-1 and LAR for 28-day clinical outcomes in patients with severe pulmonary infection-associated sepsis undergoing CRRT.RESULTS Gram-negative bacteria were the predominant pathogens in patients with se-vere pulmonary infection-associated sepsis undergoing CRRT.The poor prognosis group had higher lactate levels(4.01±1.07 mmol/L)and lower albumin levels(27.46±4.15 g/L)than the favorable prognosis group(P＜0.05).The levels of HMGB1(62.66±15.66 ng/ml),sFLT-1(0.71±0.17 ng/ml)and LAR(14.59±3.64％)in the poor prognosis group were significantly higher than those in the favorable prognosis group(P＜0.05).The combined detection of HMGB1,sFLT-1 and LAR yielded an area under the curve(AUC)of 0.949 for predicting poor 28-day mortality in patients with severe pulmonary infection-associated sepsis undergoing CRRT,superior to the single detection of the indexes(P＜0.05),with a sensitivity of 93.55％and specificity of 87.32％.CONCLUSIONS In patients with severe pulmonary infection-associated sepsis undergoing CRRT,gram-negative bacteria are the predominant pathogens.Patients with poor prognosis exhibit abnormally elevated levels of HMGB1,sFLT-1 and LAR,and the combined detection of these three markers demonstrates high predictive value for 28-day mortality.

Objective To observe the effects of Yifei Jianpi Prescription on airway mucus hypersecretion and protein expressions of EGFR/PKC/NF-κB pathway in lipopolysaccharide(LPS)-induced acute lung injury(ALI)model rats;To explore its mechanism in the treatment of ALI.Methods Ten of 60 SPF SD rats were randomly selected as blank group,and the other rats were intratracheal instilled with LPS to establish ALI model.The model rats were randomly divided into model group,dexamethasone group and Yifei Jianpi Prescription high-,medium-and low-dosage groups,with 8 rats in each group.Each treatment group was given corresponding drug solution by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 14 days.The pulmonary functions of rats were measured[peak expiratory flow(PEF),tidal volume(TV),expiratory volume(EV),50%expiratory flow rate(EF50)],HE staining was used to observe the morphology of lung tissue,AB-PAS staining was used to evaluate the proliferation and mucus secretion of goblet cells,the expressions of epidermal growth factor receptor(EGFR),protein kinase C(PKC),nuclear factor-κB(NF-κB)p65 and MUC5AC in lung tissue were detected by immunofluorescence staining,the mRNA expressions of EGFR and MUC5AC in lung tissue were detected by fluorescent quantitative PCR,and the content of MUC5AC in lung tissue was detected by ELISA.Results Compared with the blank group,PEF,TV,EV and EF50 of the model group rats significantly decreased(P<0.01);the bronchial wall was significantly thickened,the lumen narrowed,pulmonary interstitial edema and hyperemia,the thickness of alveolar wall increased,accompanied by a large number of inflammatory cells infiltration,and the lung tissue injury score increased significantly(P<0.01);goblet cells proliferated significantly,mucus secretion increased significantly(P<0.01);the protein expressions of EGFR,PKC,NF-κB p65,MUC5AC and mRNA expressions of EGFR and MUC5AC in lung tissue increased significantly(P<0.01),and the content of MUC5AC in lung tissue increased significantly(P<0.01).Compared with the model group,PEF,TV,EV and EF50 in dexamethasone group and Yifei Jianpi Prescription each dosage groups increased in varying degrees;the pathological injury of lung tissue was alleviated to varying degrees,the score of lung tissue injury was reduced;the proliferation of goblet cells was reduced,and the secretion of mucus was reduced,the expressions of EGFR,PKC,NF-κB p65,MUC5AC protein and EGFR,MUC5AC mRNA in lung tissue decreased,and the content of MUC5AC in lung tissue decreased.There was statistical significance in dexamethasone group and Yifei Jianpi Prescription high-and medium-dosage groups(P<0.01).Conclusion Yifei Jianpi Prescription can inhibit the hypersecretion of airway mucus and the high expression of EGFR/PKC/NF-κB pathway protein in rats with ALI induced by LPS.

Objective:To understand the contract renewal willingness and its influencing factors among rural order-oriented medical students in Shaanxi Province. M ethods This study employed an explanatory sequential mixed methods design to examine contract renewal patterns among rural order-oriented medical graduates. From February to July 2024, a questionnaire survey was conducted among rural order-oriented medical students who graduated from 2015 to 2023 in Shaanxi Province. The participants were first stratified into three strata based on their year of graduation and stage of service, and one-third of each stratum was randomly selected as the research subjects. Univariate and multivariate analysis methods were used to explore the influencing factors of their willingness to renew their service in rural areas. Secondly, qualitative research methods were employed to conduct thematic interviews with 36 targeted medical students on the influencing factors of their willingness to renew their service. Results:A total of 513 valid questionnaires were collected during the quantitative research phase, including 224 males and 289 females. Of these, 14 were from the 2015-2017 cohort, 247 from the 2018-2020 cohort, and 252 from the 2021-2023 cohort. The results showed that only 30.4%(156/513) of the orientation medical students were willing to practice in primary care after the period of service. Univariate analysis showed that there were six factors related to the willingness to renew the contract, the consistency of the source and implementation of the contract, the completion of the standardized training of residents, the satisfaction with primary work, professional identity, the ability of primary diagnosis and treatment, and the training system and the suitability of primary work. Multivariate analysis showed that the willingness to renew the contract was significantly higher in the students who had the same place of origin and the place of performance( OR=1.7, 95% CI: 1.1-2.6, P=0.022). The willingness to renew the contract was significantly higher among students who participated in the standardized residency training than those who completed the training( OR=2.0, 95% CI: 1.3-3.0, P=0.003), and students with a better fit between the training system and working in primary care were more likely to renew their contract( OR=4.1, 95% CI: 2.8-6.0, P<0.001). Four themes were extracted from the interview: subjective factors, objective environment, policy factors and other factors. Conclusions:The study shows that improving the consistency of the source of students and the implementation of the contract, strengthening the standardized training of residents, and optimizing the adaptation of the training system to the primary work are the key measures to improve the willingness of directional medical students to renew their contract at the primary level.

Objective To observe the effects of Yifei Jianpi Prescription on airway mucus hypersecretion and protein expressions of EGFR/PKC/NF-κB pathway in lipopolysaccharide(LPS)-induced acute lung injury(ALI)model rats;To explore its mechanism in the treatment of ALI.Methods Ten of 60 SPF SD rats were randomly selected as blank group,and the other rats were intratracheal instilled with LPS to establish ALI model.The model rats were randomly divided into model group,dexamethasone group and Yifei Jianpi Prescription high-,medium-and low-dosage groups,with 8 rats in each group.Each treatment group was given corresponding drug solution by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 14 days.The pulmonary functions of rats were measured[peak expiratory flow(PEF),tidal volume(TV),expiratory volume(EV),50%expiratory flow rate(EF50)],HE staining was used to observe the morphology of lung tissue,AB-PAS staining was used to evaluate the proliferation and mucus secretion of goblet cells,the expressions of epidermal growth factor receptor(EGFR),protein kinase C(PKC),nuclear factor-κB(NF-κB)p65 and MUC5AC in lung tissue were detected by immunofluorescence staining,the mRNA expressions of EGFR and MUC5AC in lung tissue were detected by fluorescent quantitative PCR,and the content of MUC5AC in lung tissue was detected by ELISA.Results Compared with the blank group,PEF,TV,EV and EF50 of the model group rats significantly decreased(P<0.01);the bronchial wall was significantly thickened,the lumen narrowed,pulmonary interstitial edema and hyperemia,the thickness of alveolar wall increased,accompanied by a large number of inflammatory cells infiltration,and the lung tissue injury score increased significantly(P<0.01);goblet cells proliferated significantly,mucus secretion increased significantly(P<0.01);the protein expressions of EGFR,PKC,NF-κB p65,MUC5AC and mRNA expressions of EGFR and MUC5AC in lung tissue increased significantly(P<0.01),and the content of MUC5AC in lung tissue increased significantly(P<0.01).Compared with the model group,PEF,TV,EV and EF50 in dexamethasone group and Yifei Jianpi Prescription each dosage groups increased in varying degrees;the pathological injury of lung tissue was alleviated to varying degrees,the score of lung tissue injury was reduced;the proliferation of goblet cells was reduced,and the secretion of mucus was reduced,the expressions of EGFR,PKC,NF-κB p65,MUC5AC protein and EGFR,MUC5AC mRNA in lung tissue decreased,and the content of MUC5AC in lung tissue decreased.There was statistical significance in dexamethasone group and Yifei Jianpi Prescription high-and medium-dosage groups(P<0.01).Conclusion Yifei Jianpi Prescription can inhibit the hypersecretion of airway mucus and the high expression of EGFR/PKC/NF-κB pathway protein in rats with ALI induced by LPS.

Objective:To understand the contract renewal willingness and its influencing factors among rural order-oriented medical students in Shaanxi Province. M ethods This study employed an explanatory sequential mixed methods design to examine contract renewal patterns among rural order-oriented medical graduates. From February to July 2024, a questionnaire survey was conducted among rural order-oriented medical students who graduated from 2015 to 2023 in Shaanxi Province. The participants were first stratified into three strata based on their year of graduation and stage of service, and one-third of each stratum was randomly selected as the research subjects. Univariate and multivariate analysis methods were used to explore the influencing factors of their willingness to renew their service in rural areas. Secondly, qualitative research methods were employed to conduct thematic interviews with 36 targeted medical students on the influencing factors of their willingness to renew their service. Results:A total of 513 valid questionnaires were collected during the quantitative research phase, including 224 males and 289 females. Of these, 14 were from the 2015-2017 cohort, 247 from the 2018-2020 cohort, and 252 from the 2021-2023 cohort. The results showed that only 30.4%(156/513) of the orientation medical students were willing to practice in primary care after the period of service. Univariate analysis showed that there were six factors related to the willingness to renew the contract, the consistency of the source and implementation of the contract, the completion of the standardized training of residents, the satisfaction with primary work, professional identity, the ability of primary diagnosis and treatment, and the training system and the suitability of primary work. Multivariate analysis showed that the willingness to renew the contract was significantly higher in the students who had the same place of origin and the place of performance( OR=1.7, 95% CI: 1.1-2.6, P=0.022). The willingness to renew the contract was significantly higher among students who participated in the standardized residency training than those who completed the training( OR=2.0, 95% CI: 1.3-3.0, P=0.003), and students with a better fit between the training system and working in primary care were more likely to renew their contract( OR=4.1, 95% CI: 2.8-6.0, P<0.001). Four themes were extracted from the interview: subjective factors, objective environment, policy factors and other factors. Conclusions:The study shows that improving the consistency of the source of students and the implementation of the contract, strengthening the standardized training of residents, and optimizing the adaptation of the training system to the primary work are the key measures to improve the willingness of directional medical students to renew their contract at the primary level.

Objective To observe the synergistic effect of Shengxian Huaxian Prescription and its disassembled prescription on pulmonary fibrosis;To explore whether its mechanism is related to regulating the STAT6/PPAR-y pathway to promote polarization of M2 type macrophages towards M1 type.Methods Ten SD rats were randomly selected from 70 rats as blank group,and the remaining rats were re-established pulmonary fibrosis model by intratracheal infusion of bleomycin.After modeling,the rats were divided into model group,positive group,Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group,with 10 rats in each group.Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group were given 12.60,7.65,3.60 and 2.25 g/kg of corresponding TCM solution,respectively;the positive group was given 0.12 g/kg of pirfenidone suspension;the blank group and the model group were given equal volume of normal saline,once a day,for consecutive 28 days.The lung function of rats was detected,the contents of IL-6 and TGF-β1 in serum were detected by ELISA,the pathological changes in lung tissue were observed by Masson staining,the expression of CD68,iNOS and CD206,Arg-1 in lung tissue were detected by immunofluorescence,the expression of SOCS1,SOCS3,STAT6,p-STAT6 and PPAR-γ in lung tissue were detected by Western blot.Results Compared with the blank group,the PEF,PIF and EF50 in model group rats significantly decreased,and the contents of serum IL-6 and TGF-β1 significantly increased,Masson staining showed a large amount of collagen fiber deposition,Ashcroft score significantly increased,CD206,Arg-1,STAT6,p-STAT6,PPAR-y protein expression significantly increased(P＜0.01),the expressions of SOCS1 and SOCS3 protein significantly decreased(P＜0.01),while the expression of CD68 and iNOS were not significantly changed(P＞0.05).Compared with the model group,the PEF,PIF and EF50 in all administration groups significantly increased,and the contents of serum IL-6 and TGF-β1 significantly decreased,collagen fiber deposition in lung tissue were decreased to varying degree,Ashcroft score significantly decreased,the expression of CD206,Arg-1,STAT6,p-STAT6 and PPAR-γ protein significantly decreased(P＜0.01),the expressions of CD68,iNOS,SOCS1 and SOCS3 protein significantly increased(P＜0.05).The above indicators showed the most significant changes in Shengxian Huaxian Prescription group,followed by Shengxian group(P＜0.01,P＜0.05).Conclusion Both Shengxian Huaxian Prescription and its disassembled prescription have anti pulmonary fibrosis effects,and their mechanism may related to regulating the STAT6/PPAR-y pathway and promoting polarization of M2 type macrophages towards M1 type.Shengxian Huaxian Prescription group has the best effect,while Shengxian group play an important role in the prescription,and the compatibility between each group has a synergistic effect.

Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.