ObjectiveTo investigate the protective effects of Zuogui Wan （ZGW） decoction on nephrotic syndrome （NS） through the regulation of gut microbiota. MethodsThirty male Sprague-Dawley （SD） rats were randomly divided into five groups， with 6 rats in each group： The control group， model group， low-dose group， medium-dose group， and high-dose group. The NS rat model was induced by tail vein injection of 6.5 mg·kg^-1 doxorubicin. After successful modeling， the control and model groups were gavaged with normal saline （10 mL·kg^-1） twice daily， while the low- （50 mg·kg^-1）， medium- （100 mg·kg^-1）， and high-dose （200 mg·kg^-1） groups were gavaged with ZGW （10 mL·kg^-1） twice daily. All rats were administered at fixed intervals daily for 8 consecutive weeks. The therapeutic effects of ZGW on NS in rats were observed， and the optimal dose was screened. Renal and intestinal pathological changes in rats were examined. Fecal samples were collected， and 16S rDNA sequencing technology was used to detect the diversity and abundance of gut microbiota in each group. ResultsCompared with the control group， 24-hour urinary protein， serum creatinine， urea nitrogen， and cholesterol levels significantly increased in the model group （P<0.01）， while serum albumin levels decreased （P<0.01）. These changes were ameliorated in the treatment groups （P<0.05， P<0.01）. Renal pathology revealed intact and orderly arranged glomeruli and renal tubules in the control group. In the model group， glomerular atrophy， widened mesangial areas， podocyte swelling， disordered renal tubular arrangement， and numerous casts were observed. Varying degrees of glomerular atrophy and disordered renal tubular arrangement were seen in the treatment groups. Specific protein assays revealed increased serum levels of kidney injury molecule-1（KIM-1） and α1-microglobulin （P<0.01）， and significantly decreased levels of E-cadherin， Podocin， and Nephrin in renal tissues （P<0.01）， along with a significant increase in transforming growth factor-β（TGF-β） （P<0.01） in the model group. In the treatment groups， serum KIM-1 and α1-microglobulin levels decreased， E-cadherin levels significantly increased （P<0.01）， and TGF-β levels significantly decreased （P<0.01）. Podocin and Nephrin levels increased in the high-dose group （P<0.05）. Additionally， intestinal mucosal atrophy， epithelial cell edema， decreased goblet cells， and multiple inflammatory infiltrations were observed in the model group. The sequencing results of gut microbiota demonstrate that ZGW can significantly ameliorate intestinal dysbiosis in rats， restore the abundance of beneficial bacteria， and exert a profound influence on the compositional profile of gut microbiota. ConclusionZGW can alleviate renal injury in rats with nephrotic syndrome by improving gut microbiota and protecting the intestinal barrier.

Echinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin. It is a secondary metabolite of Aspergillus nidulans, and its titer in fermentation is significantly affected by the ECB synthesis pathway and cell morphology. In this study, the key genes related to the transcription activation, hydroxylation, and cell morphology during ECB biosynthesis were investigated to increase the fermentation titer of ECB and to change the cell morphology of Aspergillus nidulans to reduce the viscosity of the fermentation broth. The results indicated that after overexpression of ecdB and ecdK, the ECB titer increased by 25.8% and 23.7%, respectively, compared with that of the wild-type strain, reaching (2 030.5±99.2) mg/L and (1 996.4±151.4) mg/L. However, the deletion of fksA associated with cell wall synthesis resulted in damage to the cell wall, affecting strain growth and product synthesis. The engineered strain overexpressing ecdB was fermented in a 50-L bioreactor, in which the ECB titer reached 2 234.5 mg/L. The findings laid a research foundation for the subsequent metabolic engineering of this strain.
Fermentation ; Aspergillus nidulans/genetics* ; Echinocandins/genetics* ; Bioreactors/microbiology* ; Fungal Proteins/biosynthesis* ; Metabolic Engineering

Metabolic dysfunction-associated fatty liver disease （MAFLD） is a common chronic liver disease in clinical practice， and macrophages are directly involved in the development， progression， and prognosis of MAFLD. Studies have confirmed that glucose metabolic reprogramming in macrophages directly affects immune function， which in turn affects the local inflammatory environment of liver and hepatocyte metabolism. This article reviews the changes in glucose metabolism of macrophages and the corresponding key molecules in the pathogenesis of MAFLD， in order to provide new targets and strategies for the prevention and treatment of MAFLD in the future.

The widespread implementation of low-dose computed tomography screening has led to a substantial rise in the detection of pulmonary nodules,with multiple pulmonary nodules(MPNs)now representing a common clinical presentation.Conventional diagnostic and therapeutic paradigms,characterized by sequential,multi-site processes,are often limited by inefficiency,safety concerns,and suboptimal patient outcomes.In contemporary thoracic surgery,a transformative"one-stop"precision management strategy has emerged within hybrid operating theaters.This integrated approach synergizes intraoperative imaging,advanced navigation,and surgical intervention to address these limitations.Cone-beam CT plays a pivotal role in this model by leveraging its maneuverability,low radiation,and high spatial resolution to greatly facilitate the development of precise diagnosis and treatment for MPNs.

Objective To investigate the expression of PROM2,RALY and Rab15 in non-small cell lung cancer(NSCLC)and the predictive value for the development of bone metastasis in NSCLC.Methods One hundred and thirty four patients diagnosed with NSCLC in our hospital from Mar 2016 to Feb 2022 were retrospectively analyzed.Patients were divided into bone metastasis(BM)and non-bone metastasis(NBM)groups based on the occurrence of bone metastasis during follow-up.Immunohistochemistry was used to detect the expression of PROM2,RALY,and Rab15 in cancer tissues.The relationship between the expression of these markers and bone metastasis was analyzed,and Cox regression was used to identify risk factors for bone metastasis in NSCLC patients.Results During the follow-up period,43 patients with NSCLC developed bone metastases.Patients with bone metastases had higher age,BMI,percentage of adenocarcinoma,and positive expression of PROM2,RALY and Rab15 than those without bone metastases(P＜0.05).Multifactorial Cox analysis showed that age,type of pathology,ECOG,and the positive PROM2 expression were significant risk factors for bone metastases in NSCLC patients(P＜0.05).Among patients with bone metastases,those with positive PROM2 expression had a shorter median bone metastasis-free survival time compared to PROM2-negative patients(P＜0.05).Conclusion PROM2 positive expression is an independent risk factor for bone metastasis in NSCLC patients,and is closely related to their prognosis.

The widespread implementation of low-dose computed tomography screening has led to a substantial rise in the detection of pulmonary nodules,with multiple pulmonary nodules(MPNs)now representing a common clinical presentation.Conventional diagnostic and therapeutic paradigms,characterized by sequential,multi-site processes,are often limited by inefficiency,safety concerns,and suboptimal patient outcomes.In contemporary thoracic surgery,a transformative"one-stop"precision management strategy has emerged within hybrid operating theaters.This integrated approach synergizes intraoperative imaging,advanced navigation,and surgical intervention to address these limitations.Cone-beam CT plays a pivotal role in this model by leveraging its maneuverability,low radiation,and high spatial resolution to greatly facilitate the development of precise diagnosis and treatment for MPNs.

Objective To investigate the expression of PROM2,RALY and Rab15 in non-small cell lung cancer(NSCLC)and the predictive value for the development of bone metastasis in NSCLC.Methods One hundred and thirty four patients diagnosed with NSCLC in our hospital from Mar 2016 to Feb 2022 were retrospectively analyzed.Patients were divided into bone metastasis(BM)and non-bone metastasis(NBM)groups based on the occurrence of bone metastasis during follow-up.Immunohistochemistry was used to detect the expression of PROM2,RALY,and Rab15 in cancer tissues.The relationship between the expression of these markers and bone metastasis was analyzed,and Cox regression was used to identify risk factors for bone metastasis in NSCLC patients.Results During the follow-up period,43 patients with NSCLC developed bone metastases.Patients with bone metastases had higher age,BMI,percentage of adenocarcinoma,and positive expression of PROM2,RALY and Rab15 than those without bone metastases(P＜0.05).Multifactorial Cox analysis showed that age,type of pathology,ECOG,and the positive PROM2 expression were significant risk factors for bone metastases in NSCLC patients(P＜0.05).Among patients with bone metastases,those with positive PROM2 expression had a shorter median bone metastasis-free survival time compared to PROM2-negative patients(P＜0.05).Conclusion PROM2 positive expression is an independent risk factor for bone metastasis in NSCLC patients,and is closely related to their prognosis.

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.

Objectives:To investigate the association between social determinants of health(SDOH)and incident stroke and analyze the main risk factors for stroke among resident with different SDOH levels. Methods:From 2012 to 2015,30 036 residents(≥35 years old)from 30 districts in 14 provincial-level administrative divisions in China were enrolled this study based on stratified multi-stage-random-sampling method.The prevalence of cardiovascular diseases and related risk factors were investigated,and stroke events were followed up in 2018 to 2019.Principal component analysis was performed to establish SDOH scores based on 9 indicators related to socioeconomic and healthcare resources,participants were divided into low SDOH group(n=8 343)when it was≥-2.01 to<-1.14,middle SDOH group(n=7 257)when it was≥-1.14 to<0.10,and high SDOH group(n=8 457)when it was≥0.10 to≤5.79.Multivariate Cox regression was applied to estimate the association of SDOH levels with incident stroke.The random survival forest method was used to analyze the major risk factors in different SDOH levels. Results:A total of 24 057 participants were finally included,669(2.8%)participants developed stroke during a mean of(4.7±0.8)years follow-up.The incidence densities of stroke in the low,medium,and high SDOH groups were 468.39,628.85,and 700.39/100 000 person-years,respectively(Pdifference<0.05,Ptrend=0.01).Compared with individuals with low SDOH level group,fully HR for incident stroke among those with medium and high were 1.91(95%CI:1.54-2.36)and 1.59(95%CI:1.30-1.95),respectively(Ptrend<0.001).Advanced age is the primary risk factor for stroke in the population,especially in districts with high SDOH level.In districts with medium SDOH level,diabetes is an important risk factor for stroke.High blood pressure and alcohol consumption are important modifiable risk factors in low SDOH level districts. Conclusions:Present study shows that higher levels of SDOH are associated with increased risk of stroke.The main risk factors for stroke differ among participants with different SDOH level districts.Targeted interventions should be implemented to improve the prevention and treatment of stroke in populations with different levels of SDOH.

Objective To investigated the correlation between the effects of the compatibility of fried Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma Praeparata cum Melle on chemical composition and anti-inflammatory effects.Methods An HPLC-DAD method was employed for the simultaneous determination of various components of fried Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,including paeoniflorin,albiflorin,benzoylpaeoniflorin,oxypaeoniflorin,glycyrrhizic acid and glycyrrhizin.An adjuvant-induced arthritis rat model was established.Administration groups were given fried Paeoniae Radix Alba,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,and fried Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma Praeparata cum Melle liquid by gavage for 2 weeks,respectively.Enzyme-linked immunosorbent assay was conducted to detect the levels of inflammatory factors IL-1β,TNF-α and PGE2 in serum of each group.Factorial design,bivariate correlation analysis,and multiple linear regression were employed to explore the effect of compatibility on chemical composition and its correlation with anti-inflammatory efficacy.Results The established HPLC-DAD analysis method revealed a significant increase in the content of oxypaeoniflorin,albiflorin and benzoylpaeoniflorin following the compatibility of fried Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma Praeparata cum Melle(P<0.05).Compared with the model group,the contents of IL-1β,TNF-α and PGE2 in serum of each administration group decreased(P<0.01),and the contents of IL-1β,TNF-α and PGE2 in serum of compatibility group were lower than fried Paeoniae Radix Alba group and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle group(P<0.05,P<0.01).The results from the factorial design indicated the presence of an interaction effect between fried Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.Bivariate correlation analysis results showed negative correlations between oxypaeoniflorin,albiflorin,paeoniflorin,glycyrrhizin,benzoylpaeoniflorin and glycyrrhizic acid with the contents of IL-1β,TNF-α and PGE2,respectively.Multiple linear regression results revealed that glycyrrhizin and glycyrrhizic acid were negatively correlated with the contents of IL-1β,TNF-α and PGE2.Conclusion The established method for analyzing multiple constituents in the compatibility of fried Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma Praeparata cum Melle is straightforward,rapid,highly specific,accurate,and reliable,suitable for quality evaluation and control.The compatibility of fried Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma Praeparata cum Melle can inhibit the expressions of IIL-1β,TNF-α and PGE2,and the content of chemical composition is correlated with anti-inflammatory effects.