Objective To investigate the impact of continuous nebulization therapy after lung transplantation on pulmonary function and related complications in lung transplant recipients. Methods A retrospective analysis was conducted on the general data of 71 recipients who underwent allogeneic lung transplantation at the Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2024. Recipients were divided into observation group (those who continued nebulization therapy for more than 3 months after discharge) and control group (those who discontinued nebulization therapy on their own). The main observation indicators were pulmonary function indicators at 6 months after surgery, including forced expiratory volume in the first second as a percentage of predicted value (FEV₁% pred), forced vital capacity as a percentage of predicted value (FVC% pred), ratio of forced expiratory volume in the first second to forced vital capacity as a percentage of predicted value (FEV₁/FVC% pred), forced expiratory flow at 25%, 50% and 75% of forced vital capacity as a percentage of predicted value, and the percentage of predicted value of corrected carbon monoxide diffusion capacity measured by single-breath method, as well as the ratio of corrected carbon monoxide diffusion capacity to alveolar volume as a percentage of predicted value. Additionally, the annual incidence of postoperative pulmonary infections, survival rate and the rate of no severe airway complications were analyzed. Results At 6 months after lung transplantation, the FEV₁% pred and FVC% pred of the observation group were better than those of the control group [FEV₁% pred was 76% (60%, 91%) vs. 67% (62%, 78%), FVC% pred was (75 ± 13)% vs. (69 ± 11)%, both P<0.05]. The observation group had a lower annual incidence of pulmonary infections compared to the control group (P = 0.023), with a risk of 0.485 times that of the control group. There were no statistically significant differences between the two groups in median survival time and the rate of no severe airway complications (both P>0.05). Conclusions Continuous nebulization therapy after lung transplantation may effectively improve pulmonary function, reduce the annual incidence of pulmonary infections, and play a positive role in the long-term maintenance of pulmonary function.

The efficient production of L-glutamate is dependent on the product's rapid efflux, hence researchers have recently concentrated on artificially modifying its transport system and cell membrane wall structure. Considering the unique composition and structure of the cell wall of Corynebacterium glutamicum, we investigated the effects of CmpLs on L-glutamate synthesis and transport in SCgGC7, a constitutive L-glutamate efflux strain. First, the knockout strains of CmpLs were constructed, and it was confirmed that the deletion of CmpL1 and CmpL4 significantly improved the performance of L-glutamate producers. Next, temperature-sensitive L-glutamate fermentation with the CmpL1 and CmpL4 knockout strains were carried out in 5 L bioreactors, where the knockout strains showcased temperature-sensitive characteristics and enhanced capacities for L-glutamate production under high temperatures. Notably, the CmpL1 knockout strain outperformed the control strain in terms of L-glutamate production, showing production and yield increases of 69.2% and 55.3%, respectively. Finally, the intracellular and extracellular metabolites collected at the end of the fermentation process were analyzed. The modification of CmpLs greatly improved the L-glutamate excretion and metabolic flux for both L-glutamate production and transport. Additionally, the CmpL1 knockout strain showed decreased accumulation of downstream metabolites of L-glutamate and intermediate metabolites of tricarboxylic acid (TCA) cycle, which were consistent with its high L-glutamate biosynthesis capacity. In addition to offering an ideal target for improving the stability and performance of the industrial strains for L-glutamate production, the functional complementarity and redundancy of CmpLs provide a novel target and method for improving the transport of other metabolites by modification of the cell membrane and cell wall structures in C. glutamicum.
Corynebacterium glutamicum/genetics* ; Glutamic Acid/biosynthesis* ; Fermentation ; Metabolic Engineering ; Bacterial Proteins/metabolism* ; Bioreactors/microbiology* ; Gene Knockout Techniques

Purpose This study aims to explore the effect of peroxisomal membrane protein 4(PXMP4)on the migration and invasion of cervical cancer(CC)cells,as well as the epithelial-mesenchymal transition(EMT)process.Methods Bioinformatics and immunohistochemical analysis were employed to examine the expression of PXMP4 in CC tissues and its correlation with clinical pathological characteristics.Western blot and RT-qPCR were used to detect the expression of PXMP4 in CC cells.CCK-8 assay,scratch healing assay,and Transwell invasion assay were utilized to assess the proliferation,migration,and invasion capabilities of CC cells.Western blot was conducted to measure the expression of N-cadherin,E-cadherin,vimentin,phosphorylated ERK(p-ERK),and total ERK proteins in cervical CC.Results The TCGA database showed that the mRNA expression level of PXMP4 was significantly elevated in non-paired CC tissues(P=0.000 29),while the GEO database showed that the mRNA expression level of PXMP4 was sig-nificantly elevated in paired CC tissues(P=0.02).Immunohistochemical analysis showed that PXMP4 was primarily localized in the cytoplasm and cell membrane,with a positive rate of 70.31％(45/64)in CC tissues,significantly higher than 29.69％(19/64)in adjacent tissues.Clinical pathological analysis found that PXMP4 expression was as-sociated with maximum tumor differentiation(P=0.000 328)and lymph node metastasis(P=0.000 226),but not with age(P=0.637)or tumor diameter(P=0.304).CCK-8 assay,wound healing assay,and Transwell invasion as-say demonstrated that interference with PXMP4 inhibited the proliferation,invasion,and migration of CC cells,while overexpression of PXMP4 promoted these processes.Western blot results indicated that interference with PXMP4 signif-icantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expression(P＜0.05).Conversely,overexpression of PXMP4 led to a significant decrease in E-cadherin and an increase in N-cadherin,vim-entin,and p-ERK expression(P＜0.05).Additionally,stimulation of CC cells with different concentrations of the U0126 inhibitor significantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expres-sion(P＜0.05).Conclusion PXMP4 is highly expressed in CC tissues and is closely related to tumor differentiation and lymph node metastasis.PXMP4 promotes the EMT process of CC cells through the phosphorylated ERK1/2 signa-ling pathway.

OBJECTIVE To observe the clinical efficacy of Shaoqi Yijia Prescription in the treatment of Hashimoto's thyroiditis(HT)with liver depression and spleen deficiency in the non-hypothyroidism stage and its effect on serum inflammatory factors.METHODS A total of 74 patients with Hashimoto's thyroiditis of liver depression and spleen deficiency type in the non-hypothyroid-ism stage who were treated in Putuo District Central Hospital in Shanghai from June to August 2024 were selected and randomly divided into the observation group and the control group with 37 cases in each group(2 cases dropped out in each group).The control group was treated with oral selenium yeast tablets,and the observation group was treated with Shaoqi Yijia Prescription,both for 12 weeks.The traditional Chinese medicine(TCM)syndrome scores,Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD)and fatigue self-assessment scale(FSAS)scores were evaluated before and after treatment;the thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb)and serum inflammatory factors interleukin 4(IL-4),IL-6,IL-10,TNF-α and IFN-γ levels were detected before and after treatment in the two groups of patients.RESULTS After treatment,the total score of TCM syndrome and the scores of epigastric or hypochondrium pain,abdominal distension,poor appetite,depression or irritability,and frequent sighs in the observation group were significantly reduced(P<0.05,P<0.01),and the total score of the observation group was better than that of the control group(P<0.01);after treatment,the serum TPOAb level of the observation group was significantly re-duced(P<0.05),the serum TPOAb level of the control group did not change significantly(P>0.05),and the serum TgAb and TPO-Ab levels of the observation group were better than those of the control group(P<0.05);after treatment,the HAMA and HAMD scores of the observation group were significantly reduced(P<0.01),and the HAMA,HAMD and FSAS scores of the observation group were better than those of the control group(P<0.05);after treatment,the serum IL-4 and IL-10 levels of the observation group were in-creased(P<0.05),and the IL-6,IFN-γ and TNF-α levels were decreased compared with those before treatment(P<0.05).The se-rum IL-4,IL-6 and IL-10 levels of the observation group were significantly different from those of the control group(P<0.05).CONCLUSION Shaoqi Yijia Prescription can alleviate the clinical symptoms of patients with Hashimoto's thyroiditis of liver depres-sion and spleen deficiency type in the non-hypothyroid period,and improve anxiety and depression,which may be related to improving the body's inflammatory response.

Objective:To investigate the clinical characteristics and risk factors for recurrence of perianal abscess in children.Methods:A retrospective study was conducted on the clinical data of 161 children with perianal abscess who were hospitalized in the Children's Hospital affiliated to Zhengzhou University from January 2015 to December 2022.Based on whether or not recurrence occurred after treatment，the patients were divided into the recurrence group(58 cases) and the simple group(103 cases).The clinical manifestations，laboratory examination indexes，and recurrence risk factors of children with perianal abscess were analyzed.Results:The effective rate of treatment for 161 children with perianal abscess was 64.0% (103/161),and 58 cases had recurrent abscess or fistula formation.The main orientations of the lesions were at the 3 o'clock position in 62 cases (38.5%) and at the 9 o'clock position in 67 cases (41.6%) in the lithotomy site.Bacterial culture of drainage fluid from perianal abscesses was positive in 61 (37.9%) children and the pathogens were Klebsiella pneumoniae in 48 cases,Staphylococcus aureus in 7 cases and Escherichia coli in 6 cases.The recurrence group mainly had underlying diseases including 38 cases of Crohn's disease，15 cases of chronic diarrhoea，and 5 cases of immunodeficiency,while the simple group had 3 cases of Crohn's disease，36 cases of chronic diarrhoea，and 2 cases of immunodeficiency，with 62 cases（60.1%）had no underlying diseases.The recurrence group showed significant statistical differences in gender（ χ2= 4.347， P=0.041），age（ χ2= 4.071， P=0.045），abscess size（ χ2= 6.298， P=0.008），abscess with fistula（ χ2= 10.928， P<0.001），combined with underlying diseases（ χ2= 10.673， P<0.001），fever（ χ2= 6.215， P=0.014），growth retardation（ χ2= 8.273， P=0.004），malnutrition（ χ2=4.521， P=0.038），hospitalization cost（ t=5.581， P=0.021），and hospital stay（ t=5.309， P=0.036）compared to the simple group.Additionally，the recurrence group showed significant statistical differences in white blood cells（ t=6.873， P=0.006），C-reactive protein（ t=7.631， P=0.003），fecal calprotectin（ t=10.073， P<0.001），albumin（ t=4.587， P=0.025），interleukin-6（ t=11.648， P<0.001），tumor necrosis factor-α（ t=7.803， P=0.021），lymphocyte count（ t=8.478， P=0.011），CD4 +/CD8 + ratio（ t=10.674， P<0.001），and IgA（ t=6.437， P=0.002）compared to the simple group.Multivariate Logistic regression analysis showed that abscess with fistula，Crohn's disease，low IgA，low CD4 +/CD8 + ratio，and high fecal calprotectin were high risk factors for recurrence of perianal abscess in children. Conclusion:Children with perianal abscesses have a high recurrence rate and are prone to fistula formation.Perianal abscess with fistula，Crohn's disease，low IgA，low CD4 +/CD8 +ratio，and high fecal calprotectin are high risk factors for recurrence in children.

Objective To addresses the challenges arising from the rapid expansion of pharmaceutical clinical trials and the growing demands for quality management,this paper investigates the application of low-code technology in project management.Its goals are to enhance the operational efficiency and execution capabilities of clinical trial institutions,ensure trial quality and safety,and accelerate the translation of pharmaceutical scientific achievements.Methods A brainstorming session was conducted to analyze the technical and functional requirements for managing pharmaceutical clinical trial projects.Utilizing the ＂template design＂ and ＂decision analysis＂ functionalities of low-code technology,the study adopted a modular and visually driven data management approach to develop a system compliant with Good Clinical Practice(GCP)standards.This system integrates key functionalities,including project progress management,funding management,drug inventory management,and quality control.Its effectiveness was evaluated through real-world operation and performance validation.Results The system had demonstrated stable operation with substantial improvements in practical application.Compared with conventional management approaches,it significantly enhanced project management efficiency:the time required for project schedule management was reduced by 80%,the efficiency of financial processing increased by 95%,drug inventory management efficiency improved by 75%,and the time spent on quality control was shortened by 60%.Conclusion The pharmaceutical clinical trial project management system developed using low-code technology offers substantial advantages and promising application potential.It represents a critical practice in applying digital and intelligent tools to advance pharmaceutical productivity in the medical and healthcare sectors.

Objective To addresses the challenges arising from the rapid expansion of pharmaceutical clinical trials and the growing demands for quality management,this paper investigates the application of low-code technology in project management.Its goals are to enhance the operational efficiency and execution capabilities of clinical trial institutions,ensure trial quality and safety,and accelerate the translation of pharmaceutical scientific achievements.Methods A brainstorming session was conducted to analyze the technical and functional requirements for managing pharmaceutical clinical trial projects.Utilizing the ＂template design＂ and ＂decision analysis＂ functionalities of low-code technology,the study adopted a modular and visually driven data management approach to develop a system compliant with Good Clinical Practice(GCP)standards.This system integrates key functionalities,including project progress management,funding management,drug inventory management,and quality control.Its effectiveness was evaluated through real-world operation and performance validation.Results The system had demonstrated stable operation with substantial improvements in practical application.Compared with conventional management approaches,it significantly enhanced project management efficiency:the time required for project schedule management was reduced by 80%,the efficiency of financial processing increased by 95%,drug inventory management efficiency improved by 75%,and the time spent on quality control was shortened by 60%.Conclusion The pharmaceutical clinical trial project management system developed using low-code technology offers substantial advantages and promising application potential.It represents a critical practice in applying digital and intelligent tools to advance pharmaceutical productivity in the medical and healthcare sectors.

OBJECTIVE To develop a nomogram model for prediction of the risk of sepsis in the patients with acute liver failure(ALF)and validate its clinical value.METHODS Totally 228 patients with ALF who were treated in the Fifth Medical Center of Chinese PLA General Hospital from Jan.2009 to Mar.2023 were recruited as the re-search subjects and were grouped according to the occurrence of sepsis,the clinical characteristics and results of laboratory tests were collected from the patients.The subjects were brought into multivariate logistic regression a-nalysis after the primary screening with univariate regression analysis,the independent predictive factors were screened out,and the nomogram model was established.The accuracy,calibration accuracy and clinical practica-bility of the model were assessed by means of receiver operating characteristic(ROC)curves,calibration curves and decision curve analysis(DCA).RESULTS Among the 228 patients with ALF,159(69.74％)were diagnosed with sepsis.Totally 6 independent predictive factors were screened out by the multivariate analysis,including age[odd ratio(OR)=1.098,95％CI:1.030 to 1.220],aspartate transaminase(OR=0.998,95％CI:0.996 to 0.999),white blood cells counts(OR=1.037,95％CI:1.020 to 1.064),hemoglobulin(OR=0.981,95％CI:0.962 to 0.998),lactic acid(OR=1.187,95％CI:1.022 to 1.426)and mechanical ventilation(OR=3.463,95％CI:2.340 to 5.125).The area under the curve(AUC)of the nomogram model was 0.864(95％CI:0.807 to 0.921)in the training set,0.817(95％CI:0.717 to 0.918)in the validation set,remarkably better than that of sequential organ failure assessment(SOFA)scores[0.710(95％CI:0.625 to 0.795)and 0.647(95％CI:0.515 to 0.779)].Hosmer-Lemeshow test(P=0.512)and the calibrated curves showed that the predication probability of the model was highly consistent with the actual risk,and DC A indicated that the net clinical benefit was brought more from the model than from SOFA score.CONCLUSION The age,hemoglobulin,aspartate transaminase,white blood cells counts,lactic acid and mechanical ventilation are the independent predictive factors for the sepsis in the ALF patients.The nomogram model established based on the factors has high predictive efficiency and clini-cal application value.

Purpose This study aims to explore the effect of peroxisomal membrane protein 4(PXMP4)on the migration and invasion of cervical cancer(CC)cells,as well as the epithelial-mesenchymal transition(EMT)process.Methods Bioinformatics and immunohistochemical analysis were employed to examine the expression of PXMP4 in CC tissues and its correlation with clinical pathological characteristics.Western blot and RT-qPCR were used to detect the expression of PXMP4 in CC cells.CCK-8 assay,scratch healing assay,and Transwell invasion assay were utilized to assess the proliferation,migration,and invasion capabilities of CC cells.Western blot was conducted to measure the expression of N-cadherin,E-cadherin,vimentin,phosphorylated ERK(p-ERK),and total ERK proteins in cervical CC.Results The TCGA database showed that the mRNA expression level of PXMP4 was significantly elevated in non-paired CC tissues(P=0.000 29),while the GEO database showed that the mRNA expression level of PXMP4 was sig-nificantly elevated in paired CC tissues(P=0.02).Immunohistochemical analysis showed that PXMP4 was primarily localized in the cytoplasm and cell membrane,with a positive rate of 70.31％(45/64)in CC tissues,significantly higher than 29.69％(19/64)in adjacent tissues.Clinical pathological analysis found that PXMP4 expression was as-sociated with maximum tumor differentiation(P=0.000 328)and lymph node metastasis(P=0.000 226),but not with age(P=0.637)or tumor diameter(P=0.304).CCK-8 assay,wound healing assay,and Transwell invasion as-say demonstrated that interference with PXMP4 inhibited the proliferation,invasion,and migration of CC cells,while overexpression of PXMP4 promoted these processes.Western blot results indicated that interference with PXMP4 signif-icantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expression(P＜0.05).Conversely,overexpression of PXMP4 led to a significant decrease in E-cadherin and an increase in N-cadherin,vim-entin,and p-ERK expression(P＜0.05).Additionally,stimulation of CC cells with different concentrations of the U0126 inhibitor significantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expres-sion(P＜0.05).Conclusion PXMP4 is highly expressed in CC tissues and is closely related to tumor differentiation and lymph node metastasis.PXMP4 promotes the EMT process of CC cells through the phosphorylated ERK1/2 signa-ling pathway.

OBJECTIVE To observe the clinical efficacy of Shaoqi Yijia Prescription in the treatment of Hashimoto's thyroiditis(HT)with liver depression and spleen deficiency in the non-hypothyroidism stage and its effect on serum inflammatory factors.METHODS A total of 74 patients with Hashimoto's thyroiditis of liver depression and spleen deficiency type in the non-hypothyroid-ism stage who were treated in Putuo District Central Hospital in Shanghai from June to August 2024 were selected and randomly divided into the observation group and the control group with 37 cases in each group(2 cases dropped out in each group).The control group was treated with oral selenium yeast tablets,and the observation group was treated with Shaoqi Yijia Prescription,both for 12 weeks.The traditional Chinese medicine(TCM)syndrome scores,Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD)and fatigue self-assessment scale(FSAS)scores were evaluated before and after treatment;the thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb)and serum inflammatory factors interleukin 4(IL-4),IL-6,IL-10,TNF-α and IFN-γ levels were detected before and after treatment in the two groups of patients.RESULTS After treatment,the total score of TCM syndrome and the scores of epigastric or hypochondrium pain,abdominal distension,poor appetite,depression or irritability,and frequent sighs in the observation group were significantly reduced(P<0.05,P<0.01),and the total score of the observation group was better than that of the control group(P<0.01);after treatment,the serum TPOAb level of the observation group was significantly re-duced(P<0.05),the serum TPOAb level of the control group did not change significantly(P>0.05),and the serum TgAb and TPO-Ab levels of the observation group were better than those of the control group(P<0.05);after treatment,the HAMA and HAMD scores of the observation group were significantly reduced(P<0.01),and the HAMA,HAMD and FSAS scores of the observation group were better than those of the control group(P<0.05);after treatment,the serum IL-4 and IL-10 levels of the observation group were in-creased(P<0.05),and the IL-6,IFN-γ and TNF-α levels were decreased compared with those before treatment(P<0.05).The se-rum IL-4,IL-6 and IL-10 levels of the observation group were significantly different from those of the control group(P<0.05).CONCLUSION Shaoqi Yijia Prescription can alleviate the clinical symptoms of patients with Hashimoto's thyroiditis of liver depres-sion and spleen deficiency type in the non-hypothyroid period,and improve anxiety and depression,which may be related to improving the body's inflammatory response.