Renal interstitial fibrosis （RIF） is a common pathological change process from the development of various chronic nephropathies to the end stage， and it is an important histological manifestation of renal function decline. At present， no effective anti-fibrosis drugs have been found in clinical practice. In recent years， with the continuous development of traditional Chinese medicine （TCM） pharmacology， molecular biology， system biology， and network pharmacology， the research on regulating RIF with TCM monomer， single TCM， TCM compound， Chinese patent medicine， and TCM injection is deepening. Among them， Jianpi Yishen recipe， Shendi Bushen capsules， Jianzhong Bushen Xiaozheng decoction， Liuwei Dihuangtang， and Lycium barbarum polysaccharides can regulate transforming growth factor-β/small mother against decapentaplegic （TGF-β₁/Smads）， Wnt/β-catenin， and neurogenic locus notch homolog protein （Notch） signaling pathways. Wulingsan， Zhenwutang， pachymic acid ZA， pachymic acid ZC， and pachymic acid ZD， which mainly induce diuresis， can regulate the Wnt/β-catenin signaling pathway. Hirudin， curcumin， and Fuzheng Huayu recipe， which mainly promote blood circulation， can inhibit inflammation-related pathways such as p-nuclear transcription factor-κB （NF-κB）， Toll-like receptor 4/p-nuclear transcription factor-κB （TLR4/NF-κB）， and Janus kinase 2/signal transducer and activator of transcription 3 （JAK/STAT）， so as to achieve anti-inflammatory and anti-oxidation effects and alleviate the progression of RIF. Shenshuai Xiezhuo decoction， Shenkang injection， and Shenshuai recipe， which are mainly used for invigorating Qi， removing blood stasis， and removing turbidity， can inhibit transdifferentiation of pericytes-myofibroblasts through vascular endothelial growth factor receptor （VEGFR） signaling pathway. At present， there are many studies on the regulation of the RIF signaling pathway by TCM， but there is a lack of a systematic summary. In this study， by combing the signaling pathway of TCM in the treatment of RIF， the effective target of TCM treatment is screened， and its possible mechanism is found， which provides new ideas for clinical treatment and new drug research and development.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective: To investigate the differences and diversity changes in gut microbiota between children and adolescents with constipation and diarrhea, and healthy individuals, and to explore the correlation between changes in stool consistency and gut microbiota, in order to provide a scientific reference for the research on intestinal microecology among children and adolescents. Methods: From October 2021 to March 2022, a total of 42 children and adolescents with constipation and 37 with diarrhea from a tertiary hospital in Hangzhou City, and 43 healthy individuals from 3 primary and secondary schools were included in this study. Fecal samples of children and adolescents were collected and then stool genomic DNA was extracted for 16S rRNA gene high throughput sequencing, and the sequencing results were analyzed. In the analysis of alpha diversity, the Kruskal-Wallis rank sum test was used to compare the differences between the three groups, and the FDR multiple testing correction was used for pairwise comparisons. In the analysis of beta diversity, the Adonis test was used to compare the overall differences between the three groups, and the ANOSIM test was used for pairwise comparisons. In the LEfSe analysis, the LDA scores obtained through LDA analysis (linear regression analysis). Results: Alpha diversity analysis showed that there were statistically significant differences in the Shannon index (4.01, 3.81, 4.19) and Simpson index (0.05, 0.06, 0.04) between the diarrhea group, constipation group, and healthy group ( H=6.05, 6.35, P <0.1). Further pairwise comparison showed that the Shannon index and Simpson index of the healthy group were higher than those of the constipation group ( P <0.1). Beta diversity analysis showed that the impact of grouping factors on inter group differences was statistically significant ( R 2=0.045, P <0.1). Community composition analysis showed that there were 234 species in total among the three groups, and 36 unique species in the healthy group, 36 species in the diarrhea group, and 48 species in the constipation group. Species difference analysis showed significant differences in species composition at the genus level among the three groups ( H=0.000 05, 0.000 16, 0.000 20, 0.000 21, 0.000 53, 0.001 39, P <0.1), including Lachnospiraceae of Firmicutes phylum, Eubacterium hallii, Veillonellaceae, Qscillospiraceae, Butyricicoccaceae and Staphylococcaceae, respectively. KEGG abundance statistics and COG functional analysis showed that there were no significant differences in gene expression abundance of the same function among the three groups ( P >0.1). Conclusions The different stool consistency of children and adolescents is related to changes in gut microbiota composition. Compared to the healthy group, children with constipation or diarrhea have disrupted gut microbiota balance, with a shift in dominant bacteria and a higher abundance of opportunistic pathogens.

Objective To construct an in vitro"metabolic memory"cell model of HT-22 mouse hippocampal neurons induced by high glucose,and to investigate the effect of"metabolic memory"on apoptosis and histone acetylation in HT-22 cells.Methods HT-22 cells were cultured in high glucose medium(glucose concentration was 55 mmol/L)and conventional glucose medium(glucose concentration was 25 mmol/L),and cells were divided into the control group(NG 4,6 and 8 groups,25 mmol/L glucose was cultured for 4,6 and 8 days,respectively),the high glucose group(HG 4,6 and 8 groups,respectively)and the metabolic memory group(HG2NG2,HG2NG4,HG2NG6,HG4NG2 and HG4NG4 groups,high glucose culture for 2 days to 25 mmol/L glucose culture for 2,4 or 6 days,high glucose culture for 4 days to 25 mmol/L glucose culture for 2 or 4 days).Cell viability was detected by CCK-8 method.The release of lactate dehydrogenase(LDH)in cell culture supernatant was detected,and the optimal time to establish a"metabolic memory"model was selected.Subsequently,cells were divided into the NG4 group,the NG8 group,the HG4 group,the HG4NG4 group and the HG8 group,and the cell morphology of each group was observed by optical microscope.The apoptosis rate was detected by flow cytometry.The activities of deacetylase(HDAC)and histone acetyltransferase(HAT)were detected by enzyme-linked immunosorbent assay(ELISA).Western blot assay was used to detect expression levels of histone deacetylase 4(HDAC4),B lymphocyte tumor 2(Bcl-2),Bcl-2 related X protein(Bax)and Caspase-3 protein.Results The HG4NG4 group was the ideal cell model with high glucose metabolic memory.Cells of the NG4 group and the NG8 group were interwoven into a dense network,growing well,with spindle shaped cells and distinct synaptic structures.However,in the HG4 group and the HG8 group,the cell body became round,synaptic structure disappeared and growth was inhibited.In the HG4NG4 group,the number of cells increased but their morphology was damaged.Results of flow cytometry showed that compared with the NG8 group,the apoptosis rates were significantly increased in the HG8 group and the HG4NG4 group(P＜0.05).ELISA results showed that compared with the NG8 group,the expression levels of HDAC4,Bax,and Caspase-3 proteins increased in the HG8 group and the HG4NG4 group,while the expression level of Bcl-2 protein significantly decreased(P＜0.05).Compared with the HG8 group,there were no significant differences in protein expression levels of HAT and HDAC in the HG4NG4 group.Western blot reslts showed that compared with the NG8 group,the levels of HDAC4,Bax and Caspase-3 protein increased in the HG8 group and the HG4NG4 group(P＜0.05).Compared with the HG8 group,there were no significant differences in protein expression levels in the HG4NG4 group.Conclusion HT-22 mouse hippocampal neurons cultured with 55mmol/L high glucose for 4 days,and then cultured with 25 mmol/L glucose for 4 days are the ideal"metabolic memory"cell model.The mechanism may be related to the increased activity of HDAC,HAT and HDAC4 expression in the hyperglycemic model.

Background Non-suicidal self-injury(NSSI)behavior has become a major public health concern and can have significant implications for the physical and mental health of adolescents.Peer victimization is a risk factor for adolesents to have NSSI behavior,so exploring the relationship and underlying mechanism between peer victimization and NSSI functions will provide a promising strategy for the prevention and intervention of NSSI behavior.Objective To investigate the relationship between peer victimization and NSSI functions in adolescents with unipolar and bipolar depression,so as to provide references for the intervention of NSSI behavior in adolescent patients with unipolar and bipolar depression.Methods Using multi-stage stratified sampling,940 adolescents with unipolar and bipolar depression who met the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)criteria for bipolar depressive episodes or depressive disorders were selected from 14 psychiatric hospitals in China.All participations were assessed using Chinese version of the Functional Assessment of Self-Mutilation(C-FASM),Multidimensional Peer-Victimization Scale(MPVS),UCLA Loneliness Scale(UCLA-LS)and Patient Health Questionnaire-9 item(PHQ-9).Pearson correlation coefficient was to assess the correlation among above scales,and the model fit and path coefficients for mediation were analyzed with model 4 in Process 4.0 for SPSS.Results A total of 698(74.26%)adolescents with unipolar and bipolar depression completed the questionnaire survey.NSSI behavior was detected in 374 patients(53.58%).Among adolescents with unipolar and bipolar depression and NSSI behavior,MPVS total score was positively correlated with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.104,0.130,0.266,P<0.05 or 0.01),UCLA-LS score also yielded a positive correlation with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.321,0.112,0.246,P<0.05 or 0.01),and UCLA-LS score was positively correlated with MPVS total score(r=0.241,P<0.01).Loneliness demonstrated a complete mediating role in the relationship between peer victimization and emotion regulation function,with an indirect effect value of 0.033(95%CI:0.019～0.050)and an effect size of 73.33%.A partial mediating effect of loneliness was also observed for the relationship between peer victimization and social avoidance function,with an indirect effect value of 0.016(95%CI:0.007～0.025)and an effect size of 17.98%.Conclusion Loneliness may act as a mediator in the relationship between the peer victimization and the NISS emotion regulation and social avoidance functions in adolescents with unipolar and bipolar depression and NSSI behaviors.

Objective:To evaluate the effect of ultrasound-guided adductor canal block with bupivacaine liposome on analgesia in elderly patients undergoing total knee arthroplasty.Methods:This was a prospective study. Sixty American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, regardless of gender, aged 65-83 yr, weighing 50-80 kg, scheduled for elective unilateral total knee arthroplasty under subarachnoid anesthesia from April 2023 to January 2024 in Zhengzhou Orthopaedic Hospital, were divided into 2 groups ( n=30 each) using a random number table method: bupivacaine liposome group (LB group) and ropivacaine group (R group). Ultrasound-guided adductor canal block was performed at 30 min before subarachnoid anesthesia, bupivacaine liposome diluent 20 ml (133 mg) was injected in LB group, and 0.5% ropivacaine 20 ml was injected in R group. Patient-controlled intravenous analgesia was performed after operation, and tramadol was used for rescue analgesia when the visual analogue scale (VAS) score ≥3. VAS scores at rest and during activity were recorded at 8, 12, 24, 48 and 72 h after surgery. The time to the first pressing analgesia pump and rescue analgesia were recorded within 72 h after surgery. The quadriceps muscle strength was measured at 1 day before surgery and 12, 24, 48 and 72 h after surgery. The knee joint range of motion was assessed at 1 day before surgery and 24, 48 and 72 h after surgery. Patient′s satisfaction with analgesia was recorded at 72 h after surgery. The adverse reactions within 72 h after surgery were also recorded. Results:Compared with R group, VAS scores at rest and during activity were significantly decreased at 12, 24, 48 and 72 h after surgery, the time to the first pressing analgesia pump was prolonged, the rate of rescue analgesia after surgery was decreased, the score for the patient′s satisfaction with analgesia was increased, the knee joint range of motion was increased ( P<0.05), and no significant change was found in the quadriceps muscle strength and incidence of adverse reactions in LB group ( P>0.05). Conclusions:Ultrasound-guided adductor canal block with bupivacaine liposome provides better analgesia than ropivacaine in elderly patients undergoing total knee arthroplasty.

Objective To explore the effect and mechanism of penehyclidine hydrochloride (PHCD) on vascular endothelial injury in septic rats. Methods Fifty male SD rats were randomly divided into control group, lipopolysaccharide (LPS) induced sepsis group (model group), low dose PHCD (0.3 mg/kg) group, medium dose PHCD (1.0 mg/kg) group and high dose PHCD (3.0 mg/kg) groups, ten mice for each group. Normal saline was injected into the tail vein of the control group, and 10 mg/kg lipopolysaccharide (LPS) was injected into the tail vein of the rats in other groups to prepare the sepsis rat models. After the models were successfully established, low, medium and high doses (0.3, 1.0, 3.0 mg/kg) of PHCD solution were injected into the tail vein of the rats of corresponding groups. Wet/dry mass ratio (W/D) of lung tissue of rats in each group was measured, and ELISA was used to assay interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 content and rat plasma angiopoietin 2 (Ang2) content in bronchoalveolar lavage fluid (BALF). HE staining was used to observe the pathological changes of lung tissues. Immunohistochemical staining was used to observe the expression of Ang2 in the right lung tissues. Western blot analysis was performed to detect Ang2 and vascular endothelial cadherin (VE-cadherin) protein in lung tissues. Results Compared with the control group, the W/D ratio of the lung tissues of rats in the model group and the contents of IL-1β, IL-6 and TNF-α in BALF were significantly increased; the lung tissues showed obvious pathological damage, with up-regulation of Ang2 expression and down-regulation of VE-Cadherin expression. Compared with the model group, the W/D ratio of the lung tissues of rats in three PHCD treatment groups and the contents of IL-1β, IL-6 and TNF-α in BALF were significantly reduced; the pathological damage of lung tissue was significantly reduced, with down-regulation of Ang2 expression and up-regulation of VE-cadherin expression. Conclusion PHCD can reduce LPS-induced lung inflammation in rats with sepsis by regulating the Ang2/VE-Cadherin pathway, thereby improving vascular endothelial injury.
Rats ; Mice ; Animals ; Male ; Lipopolysaccharides/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Angiopoietin-2/pharmacology* ; Interleukin-6/metabolism* ; Rats, Sprague-Dawley ; Lung ; Acute Lung Injury/metabolism* ; Sepsis/metabolism*

Objective:To evaluate the necessity, safety and efficacy of endovascular treatment for cerebral infarction caused by middle cerebral artery (MCA) stenosis with hypoperfusion in the blood supply area of the lenticulostriate artery.Methods:The clinical and surgical data of patients with MCA atherosclerotic disease who underwent endovascular treatment in the First Affiliated Hospital of Zhengzhou University from January 2014 to October 2021 were retrospectively analyzed. A total of 6 patients with cerebral infarction caused by MCA stenosis with hypoperfusion in the blood supply area of the lenticulostriate artery were selected. The preoperative and postoperative clinical imaging characteristics, perioperative complications and follow-up of these 6 patients were summarized and evaluated.Results:After the endovascular treatment, the imaging of the lenticulostriate artery in all the 6 patients was clearer than that before the operation, and the number of main trunks of the lenticulostriate artery shown by imaging in 2 patients was more than that before operation. The computer tomography perfusion of 6 patients after the endovascular treatment showed that perfusion in the supply area of the lenticulostriate artery was significantly improved compared with pre-operation. No stroke, transient ischemic attack (TIA) and death occurred during the perioperative period. The time of clinical follow-up was 360 (322, 495) days, and there were no stroke, TIA or death occurring in the corresponding artery. All the 6 patients underwent imaging follow-up, of which 3 patients underwent digital subtraction angiography and 3 underwent CT angiography. The lumen of the target vessels showed patency in all patients.Conclusions:With rigorous imaging evaluation, endovascular treatment may be safe and effective for cerebral infarction caused by MCA stenosis with hypoperfusion in the blood supply area of the lenticulostriate artery.

Objective To investigate the clinical curative effect of Modified Gualou Xiebai Banxia Decoction in the treatment of stable angina pectoris(SAP)with internal resistance of phlegm and turbidity and its effect on gut microbiota.Methods The clinical data of 72 cases of SAP patients with phlegm turbidity and internal resistance type in our hospital were selected for prospective study,sorted according to the order of admission,and divided into control group and observer by random number table method,with 36 cases in each group.The control group was given standardized western medicine treatment,and the observation group was given the addition of Modified Gualou Xiebai Banxia Decoction on the basis of the control group.The clinical efficacy and gut microbiota composition of the two groups of patients were compared.Results After treatment,the clinical efficacy of the observation group was better than that of the control group(P<0.05);there was no significant difference in the ECG efficacy between the two groups(P>0.05).Based on 16S rDNA technology,at the phylum and genus levels,there was no difference in the abundance of Bacteroidota,Bacteroides and Faecalibacterium(P>0.05).After treatment,the abundance of Bacteroidota in the observation group increased more significantly than that in the control group(P<0.05).Conclusion Modified Gualou Xiebai Banxia Decoction can effectively improve the clinical efficacy of SAP patients with phlegm-turbid internal resistance by regulating gut microbiota,which provides new inspiration for the further development of Gualou Xiebai Banxia Decoction.

Objective To explore and validate the mechanism of Prepared Radix Polygoni Multiflori in the treatment of NAFLD based on network pharmacology and animal non-alcoholic fatty liver disease(NAFLD)model experiments.Methods Consult the literature to compare the differences between Radix Polygoni Multiflori and Prepared Radix Polygoni Multiflori(PRPM).Herb database and SwissADME database were used to screen the active ingredients of Prepared Radix Polygoni Multiflori,SwissTargetPrediction database was used to predict its targets,OMIM,DISGENET and GEENCARDS databases were used to screen the NAFLD-related targets,conduct GO functional enrichment analysis and KEGG pathway enrichment analysis.The active ingredient-target-KEGG signaling pathway-NAFLD network was mapped later.The mice with NAFLD were treated with Prepared Radix Polygoni Multiflori by gavage for 8 weeks;serum triglyceride level and alanine aminotransferase(ALT)activity were measured;the liver lesions were observed by HE staining;the potential mechanism of action of Radix Polygoni Multiflori in the treatment of NAFLD was verified by Western blot.Results The differences between Radix Polygoni Multiflori and PRPM were consulted.Six pharmacological components and 32 potential action targets of Radix Polygoni Multiflori for the treatment of NAFLD were screened by network pharmacology,GO and KEGG pathways were enriched to lipid and atherosclerosis-related pathways,AMPK signaling pathway,etc.;HE staining verified that Prepared Radix Polygoni Multiflori has the function of improving NAFLD and is associated with the alteration of FASN,ACC,SCD protein of AMPK signaling pathway.Conclusion Radix Polygoni Multiflori has the potential to improve NAFLD by regulating FASN,ACC and SCD.