GATA4 Forms a Positive Feedback Loop with CDX2to Transactivate MUC2 in Bile Acids-Induced Gastric Intestinal Metaplasia

Background/Aims@#Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. @*Methods@#The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. @*Results@#GATA4 expression was elevated in bile acid-induced GIM and human specimens.GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. @*Conclusions@#GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Activin and Hepatocyte Growth Factor Promotes Colorectal Cancer Stemness and Metastasis through FOXM1/SOX2/CXCR4Signaling

Background/Aims@#Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear. @*Methods@#In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored. @*Results@#Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133 + subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells.Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis. @*Conclusions@#Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.

Expression and significance of CD4+T cell subtypes and their associated inflammatory factors in NE-FE-COPD patients / 重庆医学

Objective To investigate the expression of CD4+T cell subtypes and related inflammatory factors in patients with neutrophil-predominant frequent acute exacerbation chronic obstructive pulmonary disease(NE-FE-COPD).Methods COPD patients who were treated in the hospital from March 2019 to March 2021 were selected as the research objects.According to different phenotypes,they were divided into the infrequent exacerbator COPD group(IECOPD group,n=11),the eosinophilic dominant frequent acute plus severe COPD group(Eos-FE-COPD group,n=13),and the neutrophil dominant frequent exacerbator COPD group(NE-FE-COPD group,n=15).Patients with normal lung function and smoking history＞10 packs/year were the control group(CTRL group,n=9).Bronchoalveolar lavage fluid(BALF)was collected from each group,and the expression of CD4+T cell subtypes and inflammatory factors were detected by flow cytometry.The correlation between BALF and lung function and the frequency of acute exacerbation was ana-lyzed.CD4+CD28nullT cells and CD4+CD28+T cells were co-cultured with human airway epithelial cells(hAECs)and divided into co-culture group and Control group.The damage of hAECs was observed by immu-nofluorescence staining,and the mRNA and protein expression levels of ZO-1 and occludin were detected by RT-qPCR and Western blot.Results The proportion of CD4+CD28nullT cells and IL-1β level in BALF in the NE-FE-COPD group were higher than those in the CTRL group,the IE-COPD group,and the Eos-FE-COPD group,and the difference was statistically significant(P＜0.05).The proportion of CD4+CD28nullT cells and IL-1βlevel were negatively correlated with lung function(P＜0.05),and positively correlated with acute ex-acerbation frequency(P＜0.05).Compared with the Control group,hAECs tight junctions were damaged in the co-culture group,and mRNA and protein expression levels of ZO-1 and occludin decreased,with statistical significance(P＜0.05).Conclusion CD4+CD28nullT cells and IL-1β may be involved in the occurrence and de-velopment of NE-FE-COPD.

Optical coherence tomography angiography characteristics of exudative and non-exudative treatment-naïve pachychoroid neovasculopathy.

AIM: To describe the optical coherence tomography angiography (OCTA) characteristics of exudative and non-exudative treatment-naïve pachychoroid neovasculopathy (PNV). METHODS: Thirty-five patients with exudative treatment-naïve PNV and 13 with non-exudative treatment-naïve PNV between March 2020 and December 2021 were included. All patients underwent ophthalmologic examination, including fluorescein angiography (FA), indocyanine green angiography (ICGA), spectral-domain OCT, and OCTA. The clinical data of the patients were retrospectively analyzed. RESULTS: The study included 51 eyes from 46 patients, of whom 33 (71.7%) were male. The central macular thickness (CMT) in the exudative PNV group was significantly higher than that in the non-exudative PNV group (383.97±132.16 µm vs 213.13±51.63 µm; P<0.001). The maximum height of flat irregular pigment epithelial detachments (FIPED) was 45.40±11.86 µm in the non-exudative PNV group, significantly lower than the 71.58±20.91 µm (P<0.001) in the exudative PNV group. The area of PNV of the non-exudative PNV group was, significantly larger than that of the exudative PNV group (1.06±0.84 mm2 vs 0.63±0.80 mm2, P=0.016). There was a significant difference in PNV morphology between the two groups (P<0.001). Multivariate logistic regression analysis found that the maximum height of FIPED (OR=1.156, 95%CI: 1.019-1.312; P=0.024) and microvascular branches (OR=69.412, 95%CI: 3.538-1361.844; P=0.005) were independent predictors of PNV activity. CONCLUSION: The OCTA imaging finds that there are significant differences in CMT, maximum height of FIPED, PNV area, and morphology of exudative PNV and non-exudative PNV groups. OCTA can accurately identify the clinical and imaging features of exudative and non-exudative treatment-naïve PNV, and distinguish PNV activity.

Xiao-Gao-Jiang-Zhuo-containing serum inhibits adipogenesis through SIRT1-IGF-1 crosstalk in 3T3-L1 preadipocytes.

PPARγ, CEBP/α, and SREBP1C are the major transcriptional factors participating in adipogenesis and lipogenesis. SIRT1 and IGF-1 signaling pathways are important pathways involved in body endocrine and metabolism. Our unique Chinese herbal medicine Xiao-Gao-Jiang-Zhuo (XGJZ) has a remarkable clinical effect on obesity. However, the molecular basis remains unknown. XGJZ-containing serum was treated in the incubation of 3T3-L1 preadipocytes to observe its function in the 3T3-L1 cell differentiation. Oil Red O staining was used to monitor the lipid droplets accumulated after 8 days of incubation. RT-qPCR and western blotting were used to investigate the regulatory effects of XGJZ-containing serum on adipogenesis-related factors. The protein levels of main molecules in SIRT1 and IGF-1 signaling pathways were also detected by western blotting. XGJZ-containing serum notably suppressed the lipid accumulation in differentiated adipocytes through SIRT1/IGF-1 pathway. XGJZ-containing serum activated the SIRT1/IGF-1 pathway and reduced the expression levels of PPARγ, CEBP/α, and SREBP1C through this pathway. Additionally, XGJZ-containing serum enhanced the phosphorylation of ATGL and HSL and then induced lipolysis. XGJZ-containing serum has inhibitory effects on adipogenesis in 3T3-L1 preadipocytes through SIRT1/IGF-1 signaling pathway. Our study affirmed the effect of XGJZ-containing serum in the treatment of obesity. It provides a basis for the mechanism of obesity.

Pain Relief and Safety of Microwave Ablation Combined with Percutaneous Vertebroplasty for Vertebral Metastasis: A Pilot Study.

BACKGROUND: We investigate the pain relief and safety of microwave ablation (MWA) combined with percutaneous vertebroplasty (PVP) in the treatment of metastatic vertebral tumors. METHODS: This prospective pilot study enrolled patients with metastatic vertebral tumors treated between January 2018 and October 2019. The participants were randomized to the PVP and MWA + PVP groups. Clinical parameters, pain visual analog scale (VAS), analgesic use scores (AUS), and quality-of-life score (QLS) were compared between groups. RESULTS: Sixty-seven participants were enrolled (PVP: n = 35; MWA + PVP: n = 32). There were no differences in bone cement injection volume, extravasation, and X-ray exposure time between the two groups (p > 0.05), but treatment costs were higher for the MWA + PVP group (26,418 ± 194 vs. 15,606 ± 148 yuan; p < 0.05). There were no significant improvements in VAS from baseline to 24 hours, 72 hours, 7 days, 1 month, and 3 months in the two groups (p > 0.05); at 6 and 12 months after the operation, the improvement from baseline was significant in the two groups (p < 0.05). The VAS was lower at 6 months (2.7 ± 0.7 vs. 3.2 ± 0.7) and 12 months (3.5 ± 0.8 vs. 4.0 ± 0.7) in the MWA + PVP group (both p < 0.01 vs. PVP). The AUS and QLS were improved with PVP at 6 and 12 months (p < 0.05) and with MWA + PVP at 12 months (p < 0.05). The AUS was lower at 6 and 12 months in the MWA + PVP group (p < 0.05 vs. PVP). CONCLUSION: MWA combined with PVP might be a safe and effective palliative treatment for pain from metastatic vertebral tumors.

CHESS endoscopic ruler in objective measurement of diameter of esophageal varices in liver cirrhosis and portal hypertension: a prospective multicenter study / 中华消化杂志

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Effects of paclitaxel on Müller cells in retina / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of antitumor drug paclitaxel(PTX)on the proliferation, apoptosis, cell cycle, cell morphology, and related protein expression of Müller cells, and to evaluate its potential toxicity to the retina.METHODS:Müller cells were cultured in vitro and divided into two groups: control group(normal medium)and PTX group. Retinal Müller cells were treated with different concentrations of PTX(0.005, 0.05, 0.5 and 5mg/L)for varying durations(12, 24, 36, 48 and 72h). The CCK8 method was used to assess the effects of different concentrations of PTX and treatment duration on the proliferation Müller cells. Flow cytometry was employed to investigate the impact of different concentrations of PTX on Müller cells apoptosis and cell cycle arrest. Immunofluorescence was used to observe morphological changes in Müller cells. The effects of PTX on the expression of apoptosis-related proteins and aquaporins were analyzed by Western blot and qRT-PCR.RESULTS: PTX exhibits the ability to inhibit the proliferation of Müller cells when cultured in vitro. The efficacy of this inhibition was found to be dependent on both the concentration of the drug and the duration of the stimulation. Higher concentrations of the drug and longer stimulation times resulted in a weaker ability of the cells to proliferate. Additionally, PTX also induces apoptosis in Müller cells, with increased drug concentrations and longer stimulation times leading to higher apoptosis rates. Flow cytometry analysis demonstrates that PTX arrests Müller cells in the G2-M phase of the cell cycle. Moreover, there is a distinct change in cell morphology, with a shift from the typical appearance characterized by clear and slender fibrous structures to a rounder morphology, accompanied by a significant decrease in cell numbers. Further, our findings reveal that there is a transient increase in the expression of cytoinflammatory factors following drug treatment compared to the control group. However, discontinuation of drug stimulation can alleviate this heightened expression. In treated cells, the expression of the CA XIV protein is upregulated compared to the control group, while the expression of vascular endothelial growth factor(VEGF)is downregulated(P&#x0026;#x003C;0.05). Additionally, the levels of inflammatory factors in the PTX group are significantly higher than those in the control group(P&#x0026;#x003C;0.05), suggesting that PTX has the potential to disrupt the retinal barrier function.CONCLUSION: PTX affects the proliferation and apoptosis of Müller cells, with the effects dependent on stimulation duration and drug concentration. In addition, PTX blocks the Müller cell cycle at the G2-M phase and alters cell morphology, leading to a transient upregulation of inflammatory factors and affecting the integrity of the retinal barrier. These findings indicate the potential toxicity of the antitumor drug PTX to the retina.

Prognostic evaluating value of serum tenascin-X level in patients with acute ST-segment elevation myocardial infarction / 中国医师进修杂志

Objective:To explore the prognostic evaluating value of serum tenascin-X in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods:The clinical data of 121 patients with STEMI in the Affiliated Sinopharm Dongfeng General Hospital, Hubei University of Medicine from August 2017 to August 2018 were retrospectively analyzed. The clinical data were collected, the serum tenascin-X level was measured by enzyme-linked immunosorbent assay. The patients were followed up for 3 years, the major adverse cardiovascular events (MACE) were identified as endpoint events. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum tenascin-X for MACE in patients with STEMI. The Kaplan-Meier survival curve was drawn, the rates of non-MACE survival in patients with different serum tenascin-X levels were analyzed by log-rank method. Multivariate Cox regression was used to analyze the independent risk factors of MACE in patients with STEMI.Results:Until the end of follow-up, among 121 patients with STEMI, 42 cases (34.7%) developed MACE (MACE group), and 79 cases had not MACE (non-MACE group). The left ventricular ejection fraction (LVEF) in the MACE group was significantly lower than that in the non-MACE group: (47.14 ± 6.70)% vs. (52.67 ± 4.41)%, the C-reactive protein (CRP), B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and tenascin-X were significantly higher than those in non-MACE group: (27.92 ± 8.06) mg/L vs. (8.77 ± 3.49) mg/L, (918.31 ± 315.47) μg/L vs. (220.47 ± 108.37) μg/L, (214.73 ± 80.46) μg/L vs. (81.35 ± 28.96) μg/L and (110.67 ± 42.55) μg/L vs. (65.21 ± 28.06) μg/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the area under the curve of serum tenascin-X to predict the MACE in patients with STEMI was 0.806 (95% CI 0.724 to 0.872), and the optimal cut-off was 93.25 μg/L, the sensitivity was 69.0%, the specificity was 86.1%. Kaplan-Meier survival curve analysis result showed that the rate of non-MACE in 80 patients with low serum tenascin-X level (<93.25 μg/L) was significantly higher than that in 41 patients with high serum tenascin-X level (≥93.25 μg/L): 83.8% vs. 29.3%, and there was statistical difference ( χ2 = 42.47, P<0.01). Multivariate Cox regression analysis result showed that the CRP, BNP and tenascin-X were the independent risk factors of MACE in patients with STEMI ( HR = 1.092, 1.001 and 1.018; 95% CI 1.051 to 1.135, 1.000 to 1.002 and 1.008 to 1.027; P<0.01 or <0.05). Conclusions:The significant increase in serum tendon protein X levels in patients with STEMI has predictive value for the MACE, and it is an independent predictor of MACE within 3 years.

Key issues of lung protective ventilation strategies and diaphragm protection / 解放军医学杂志

With the continuous development and progress of medicine,the total number of general anesthetic surgery is increasing,and postoperative complications are also on the rise,especially postoperative pulmonary complications(PPCs)caused by perioperative lung injury.PPCs are the main cause of prolonged hospitalization,increased morbidity and mortality,poor prognosis,and increased medical burden in patients undergoing general anesthesia.With the enhancement of awareness of mechanical ventilation and the implementation of the enhanced recovery after surgery(ERAS)concept,lung-protective ventilation strategies(LPVS)are receiving more and more attention.However,the debate continues on how to apply the LPVS effectively.The recent introduction of diaphragm-protective ventilation as a novel concept has led to the realization that the application of protective ventilation strategies should limit the adverse effects of mechanical ventilation on diaphragm function within the context of lung protective ventilation.How to apply protective ventilation strategies effectively to prevent the development of ventilator-induced lung injury(VILI)and ventilator-induced diaphragm dysfunction(VIDD),reduce the incidence of PPCs,improve patient prognosis,and reduce the medical burden is an important challenge in the management of mechanically ventilated patients.In this paper,we will focus on ventilation strategies of lung and diaphragm combined with the latest progress of LPVS,to elaborate the research on the application of individualized ventilation strategies and the mechanisms of VILI and VIDD occurrence.Finally,prospecting the future research direction of protective ventilation strategies.

Analysis of risk factors for recurrence of differentiated thyroid carcinoma after surgical resection combined with iodine-131 and TSH suppression therapy / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the risk factors of recurrence after surgical resection of differentiated thyroid carcinoma combined with iodine-131 and TSH（Thyroid stimulating hormone） inhibition therapy. Methods:From January 2015 to April 2020, the clinical data of patients with structural recurrence and without recurrence were retrospectively collected after surgical treatment combined with iodine-131 and TSH inhibition therapy in the First Medical Center of PLA General Hospital. The general conditions of the two groups of patients were analyzed and the measurement data in line with the normal distribution was used for comparison between groups. For measurement data with non-normal distribution, the rank sum test was used for inter-group comparison. The Chi-square test was used for comparison between the counting data groups. Univariate and multivariate regression analyses were used to determine the risk factors associated with relapse. Results:The median follow-up period was 43 months（range 18-81 months） and 100 patients（10.5%） relapsed among the 955 patients. Univariate analysis showed that tumor size, tumor multiple, the number of lymph node metastases>5 in the central region of the neck, and the number of lymph node metastases>5 in the lateral region were significantly correlated with post-treatment recurrence（P<0.001, P=0.018, P<0.001, P<0.001）. Multivariate analysis showed that tumor size（adjusted odds ratio OR: 1.496, 95%CI: 1.226-1.826, P<0.001）, tumor frequency（adjusted odds ratio OR: 1.927, 95%CI: 1.003-3.701, P=0.049）, the number of lymph node metastases in the central neck region>5（adjusted odds ratio OR: 2.630, 95%CI: 1.509-4.584, P=0.001） and the number of lymph node metastases in the lateral neck region>5（adjusted odds ratio OR: 3.074, 95%CI: 1.649-5.730, P=0.001） was associated with tumor recurrence. Conclusion:The study showed that tumor size, tumor multiple, the number of lymph node metastases in the central region of the neck>5 and the number of lymph node metastases in the side of the neck >5 are independent risk factors for recurrence of differentiated thyroid cancer after surgical resection combined with iodine-131 and TSH inhibition therapy.

Huangdi Anxiao Capsules-containing serum protects cell model from cognitive dysfunction in diabetes via inhibiting NLRP3-mediated pyroptosis / 中国中药杂志

This study aims to investigate the effects and the molecular mechanism of Huangdi Anxiao Capsules(HDAX)-containing serum in protecting the rat adrenal pheochromocytoma(PC12) cells from diabetes-associated cognitive dysfunction induced by high glucose and whether the mechanism is related to the regulation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis. The PC12 cell model of diabetes-associated cognitive dysfunction induced by high glucose was established and mcc950 was used to inhibit NLRP3. PC12 cells were randomized into control, model, HDAX-containing serum, mcc950, and HDAX-containing serum+mcc950 groups. Methyl thiazolyl tetrazolium(MTT) assay was employed to determine the viability, and Hoechst 33258/PI staining to detect pyroptosis of PC12 cells. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1 beta(IL-1β) and IL-18. Western blot was employed to determine the protein levels of postsynaptic density protein 95(PSD-95), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), GSDMD-N, and cleaved cysteinyl aspartate specific proteinase-1(caspase-1), and RT-PCR to determine the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1. The immunofluorescence assay was adopted to measure the levels and distribution of NLRP3 and GSDMD-N in PC12 cells. Compared with the control group, the model group showed decreased cell proliferation, increased PI positive rate, down-regulated protein level of PSD-95, up-regulated protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1, up-regulated mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and elevated levels of IL-1β and IL-18. Compared with the model group, HDAX-containing serum, mcc950, and the combination of them improved cell survival rate and morphology, decreased the PI positive rate, down-regulated the protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1 and the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and promoted the secretion of IL-1β and IL-18. The findings demonstrated that HDAX-containing serum can inhibit the pyroptosis-mediated by NLRP3 and protect PC12 cells from the cognitive dysfunction induced by high glucose.

Effects of catgut embedding and PGLA embedding at "Zusanli" (ST 36) on skin mast cells, substance P and histamine in healthy rats / 中国针灸

OBJECTIVE@#To observe the effects of catgut embedding and polyglycolic acid/poly-lactic acid (PGLA) embedding at "Zusanli" (ST 36) on the activation of local skin mast cells (MC), and expression of substance P (SP) and histamine (HA), and to explore the mechanism of the temporal stimulation effect of acupoint catgut embedding and provide a foundation for further research on the initiation mechanism of acupoint catgut embedding.@*METHODS@#One hundred and sixty male SPF-grade SD rats were randomly divided into a blank group (10 rats), a sham-embedding group (50 rats), a catgut group (50 rats), and a PGLA group (50 rats). Each intervention group was further randomly divided into five subgroups according to the time points after intervention: 8 hours, 3 days, 7 days, 14 days, and 21 days, with 10 rats in each subgroup. One-time sham-embedding, catgut embedding and PGLA embedding was given at left "Zusanli" (ST 36) in each intervention group, respectively. The skin and subcutaneous connective tissue of the left "Zusanli" (ST 36) were collected at the corresponding time points after intervention, except for the blank group (only one day before intervention). Toluidine blue staining was used to detect MC count and degranulation, and immunohistochemical staining was used to detect the expression of SP and HA positive cells.@*RESULTS@#There was no significant difference in MC count between the subgroups of each intervention group and the blank group (P>0.05). There was no significant difference in MC count between the subgroups of the catgut group and the PGLA group (P>0.05). The MC count in the 8-hour subgroup of PGLA group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the MC count in the 21-day subgroup of PGLA group was lower than that in the 21-day subgroup of catgut group (P<0.05). Compared with the blank group, the degranulation rates of MC were increased in the 8-hour and 3-day subgroups of sham-embedding group, 8-hour, 3-day, and 7-day subgroups of catgut group, and 8-hour, 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.01, P<0.05, P<0.001). There was no significant difference in the degranulation rate of MC between the subgroups of the catgut group and the PGLA group (P>0.05), and no significant difference in the degranulation rate of MC between the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of SP positive cells was increased in the 8-hour subgroup of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.001, P<0.05). The expression of SP positive cells in the 7-day subgroup of catgut group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.001). The expression of SP positive cells in the 7-day subgroup of PGLA group was higher than that in the 3-day subgroup of PGLA group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.01). There was no significant difference in the expression of SP positive cells between the subgroups of the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of HA positive cells was increased in the 8-hour, 3-day subgroups of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 8-hour, 3-day, 7-day, 14-day, and 21-day subgroups of PGLA group (P<0.001, P<0.01, P<0.05). The expression of HA positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.05), while the expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 8-hour subgroup of PGLA group (P<0.05), and the expression of HA positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.05). The expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 3-day subgroup of catgut group (P<0.05).@*CONCLUSION@#Catgut and PGLA embedding at "Zusanli" (ST 36) in healthy rats could induce changes in local skin MC, SP, and HA, which may be one of the mechanisms of the temporal stimulation effect after acupoint embedding. There are certain differences between different suture materials. A moderate inflammatory response in the acupoint area, mediated by MC and involving SP and HA, may be one of the initiating factors for the effect of acupoint catgut embedding.

Correlation between right atrial volume and function and liver function grading in patients with hepatitis B cirrhosis by four-dimensional ultrasound automatic quantitation analysis / 中华超声影像学杂志

Objective:To evaluate right atrial (RA) volume and function in patients with hepatitis B cirrhosis by four-dimensional automatic quantitation analysis technique, and to explore its correlation with liver function grading.Methods:Ninety patients with hepatitis B cirrhosis who were clinically confirmed in Henan Provincial People′s Hospital from December 2020 to July 2021 were randomly enrolled as the research subjects. According to Child-Pugh liver function score criteria, the patients were divided into three groups: Child-Pugh A group ( n=31), Child-Pugh B group ( n=31), Child-Pugh C group ( n=28). Another 30 healthy volunteers with gender and age matched at the same period were selected as the control group. The RA maximum volume (RAVmax), RA minimum volume (RAVmin), RA presystolic volume (RAVpreA), RA maximum volume index (RAVImax), RA emptying volume (RAEV), RA ejection fraction (RAEF), RA reservoir longitudinal and circumferential strains (RASr, RASr-c), RA conduit longitudinal and circumferential strains (RAScd, RAScd-c), RA contraction longitudinal and circumferential strains (RASct, RASct-c) were obtained by four-dimensional automatic quantitation analysis technique. Spearman correlation analysis was used to explore the correlation between the volume and strain parameters of right atrium and liver function grading, and the independent correlation factors of RASr-c were analyzed by univariate and multivariate linear regression analyses. Results:Compared with the control group, Child-Pugh A and Child-Pugh B groups, RAVmax, RAVmin, RAVpreA, RAVImax, and RAEV were all increased in Child-Pugh C group (all P<0.05). Compared with control group, the absolute values of RASr, RASct, RASr-c and RASct-c were increased, and the absolute values of RAScd and RAScd-c were decreased in Child-Pugh A group (all P<0.05). Compared with control group, Child-Pugh A and Child-Pugh B groups, the absolute values of RASr, RAScd, RASct, RASr-c, RAScd-c and RASct-c were decreased in the Child-Pugh C group (all P<0.05). Correlation analysis showed that the volume and strain parameters of the right atrium were correlated with liver function grading. RASr-c was independently correlated with E/e, ALB and BNP(β=-0.543, 0.521, and -0.562 respectively, all P<0.05). Conclusions:During the compensatory stage in patients with hepatitis B cirrhosis, the RA functions of reservoir and contractile were increased, but the function of conduit was decreased. With the aggravation of liver cirrhosis, the RA functions of reservoir, conduit and contractile were all decreased. The four-dimensional volume and strain parameters of the right atrium were correlated with Child-Pugh liver function grading, and RASr-c was independently correlated with E/e, ALB and BNP.

Evaluation of left atrial function and predictive value of risk stratification in patients with hypertensive disorder of pregnancy by four-dimensional automatic left atrial quantitative analysis / 中华超声影像学杂志

Objective:To investigate the change of left atrial volume and function in patients with hypertensive disorders of pregnancy (HDPs) by four-dimensional automatic left atrial quantitative analysis (4D LAQ) and analyze the predictive value of risk stratification.Methods:A total of 60 patients diagnosed with hypertensive disorder of pregnancy in Henan Provincial People′s Hospital from March to December 2021 were randomly enrolled, which were divided into gestational hypertension group (low risk group, n=30) and preeclampsia group (medium and high risk group, n=30) according to the disease development and risk stratification method reported in the literature; another 30 healthy pregnant women matched for age, gestational weeks and body mass index were selected as the control group. Left atrial anteroposterior diameter (LAd), interventricular septum thickness (IVSd), left ventricular end diastolic diameter (LVd), left ventricular ejection fraction (LVEF), left ventricular myocardial mass index (LVMI), peak early diastolic (E) and late diastolic (A) velocities of mitral inflow, and e′ values on the septal and lateral mitral annulus sides were routinely measured to calculate E/A and E/e′ values. Left atrial volume and strain parameters were obtained using 4D LAQ technique, including left atrial minimum volume (LAVmin), left atrial maximum volume (LAVmax), left atrial presystolic volume (LAVpreA), left atrial maximum volume index (LAVImax), left atrial inflation index (LAEI), left atrial stroke volume (LAEV), left atrial fraction (LAEF), longitudinal strain of left atrial reserve, conduit and systolic period (LASr, LAScd, LASct), circumferential strain of left atrial reserve, conduit and systolic period(LASr-c, LAScd-c, LASct-c). The differences among the three groups were compared. Multiple Logistics regression analysis was used to obtain the relevant indicators of risk stratification of HDPs and ROC curves were used for assessment. Results:Compared with the control group, E/e′, LAVmin, LAVpreA, LAScd, and LAScd-c increased, and LAEI, LAEF, LApEF, LASr, and LASr-c decreased in the gestational hypertension group (all P<0.05). Compared with the control group and gestational hypertension group, LAd, IVSd, LVd, LVMI, E/e′ LAVmin, LAVmax, LAVpreA, LAVImax, LAEV, LAScd, and LAScd-c increased, and LVEF, LAEF, LAEI, LApEF, LASr, and LASr-c decreased in the preeclamptic group, and the differences were statistically significant (all P<0.05). The results of multiple Logistics regression showed that LAVmax, LAScd-c and LASr were the indicators relevant to risk stratification of HDPs(β=0.344, 0.216 and -0.249, respectively, all P<0.05). ROC analysis showed when the cut-off value of left atrial strain parameter LASr was 30.5%, the AUC, sensitivity, and specificity were 0.725, 0.58, 0.90, respectively; when the cut-off value of LAVmax was 44.5 ml, the AUC, sensitivity, and specificity were 0.662, 0.80, and 0.56, respectively; and when the cut-off value of LAScd-c was -17.5%, the AUC, sensitivity, and specificity were 0.706, 0.56, and 0.78, respectively. Conclusions:Left atrial remodeling occured in pregnant women with hypertensive disorders, their reserve and conduit function were impaired, and aggravated with the progress of the disease. The four-dimensional parameters LASr, LAVmax, and LAScd-c were relevant indicators for risk stratification of HDPs. In predicting the severity of HDPs, LASr has high diagnostic value and good specificity; LAVmax and LAScd-c can be considered as supplementary parameters to predict the risk stratification of HDPs.

Naringenin regulates gut microbiota and SIRT1/ PGC-1ɑ signaling pathway in rats with letrozole-induced polycystic ovary syndrome.

PURPOSE: To evaluate the effect of naringenin on improving PCOS and explore the mechanism. METHODS: Firstly, we carried out differential gene expression analysis from transcriptome sequencing data of human oocyte to screen the KEGG pathway, then the PCOS-like rat model was induced by letrozole. They were randomly divided into four groups: Normal group (N), PCOS group (P), Diane-35 group (D), and Naringenin group (Nar). The changes of estrus cycle, body weight, ovarian function, serum hormone levels, glucose metabolism, along with the expression of SIRT1, PGC-1ɑ, claudin-1 and occludin of the ovary and colon were investigated. Furthermore, the composition of the gut microbiome of fecal was tested. RESULTS: By searching the KEGG pathway in target genes, we found that at least 15 KEGG pathways are significantly enriched in the ovarian function, such as AMPK signaling pathway, insulin secretion, and ovarian steroidogenesis. Interestingly, naringenin supplementation significantly reduced body weight, ameliorated hormone levels, improved insulin resistance, and mitigated pathological changes in ovarian tissue, up-regulated the expression of PGC-1ɑ, SIRT1, occludin and claudin-1 in colon. In addition, we also found that the abundance of Prevotella and Gemella was down-regulated, while the abundance of Butyricimonas, Lachnospira, Parabacteroides, Butyricicoccus, Streptococcus, Coprococcus was up-regulated. CONCLUSION: Our data suggest that naringenin exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota and SIRT1/PGC-1ɑ signaling pathway. Our research may provide a new perspective for the treatment of PCOS and related diseases.

Quinoa Reduces High-Fat Diet-Induced Obesity in Mice via Potential Microbiota-Gut-Brain-Liver Interaction Mechanisms.

The gut microbiota is important in the occurrence and development of obesity. It can not only via its metabolites, but also through microbiota-gut-brain-liver interactions, directly or indirectly, influence obesity. Quinoa, known as one kind of pseudocereals and weight loss food supplements, has been high-profile for its high nutritional value and broad applications. In this context, we produced high-fat diet-induced (HFD) obese mouse models and assessed the efficacy of quinoa with saponin and quinoa without saponin on obesity. We explored the potential therapeutic mechanisms of quinoa using methods such as 16S rRNA, Western blotting, Immunohistochemical (IHC). Our results indicated that quinoa can improve the obese symptoms significantly on HFD mice, as well as aberrant glucose and lipid metabolism. Further analyses suggest that quinoa can regulate microbiota in the colon and have predominantly regulation on Bacteroidetes, Actinobacteria and Desulfovibrio, meanwhile can decrease the F/B ratio and the abundance of Blautia. Contemporaneously, quinoa can upregulate the expression of TGR5 in the colon and brain, as well as GLP-1 in the colon, liver and brain. while downregulate the expression of TLR4 in the colon and liver, as well as markers of ER stress and oxidative stress in livers and serums. Beyond this, tight junctional proteins in colons and brains are also increased in response to quinoa. Therefore, quinoa can effectively reduce obesity and may possibly exert through microbiota-gut-brain-liver interaction mechanisms. IMPORTANCE Gut microbiota has been investigated extensively, as a driver of obesity as well as a therapeutic target. Studies of its mechanisms are predominantly microbiota-gut-brain axis or microbiota-gut-liver axis. Recent studies have shown that there is an important correlation between the gut-brain-liver axis and the energy balance of the body. Our research focus on microbiota-gut-brain-liver axis, as well as influences of quinoa in intestinal microbiota. We extend this study to the interaction between microbiota and brains, and the result shows obvious differences in the composition of the microbiome between the HFD group and others. These observations infer that besides the neurotransmitter and related receptors, microbiota itself may be a mediator for regulating bidirectional communication, along the gut-brain-liver axis. Taken together, these results also provide strong evidence for widening the domain of applicability of quinoa.

Damage of retinal pigment epithelial cells function by paclitaxel and its potential mechanism / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the potential toxic effects of paclitaxel(PTX)on the proliferation, apoptosis, cell cycle, morphology, and blood-retinal barrier(BRB)of human retinal pigment epithelial cells(ARPE-19). <p>METHODS: ARPE-19 cells were cultured <i>in vitro</i> and divided into two groups: Control group(Control)and drug plus group(PTX). ARPE-19 cells were treated with different concentrations of PTX(0.005, 0.05, 0.5, 5mg/L)for a certain period of time(12, 24, 36, 48, 72h), and CCK8 assay and flow cytometry were used to detect the effects of drug on proliferation and apoptosis of ARPE-19 cells at different concentrations and time points. The same time, the cell cycle was detected by flow cytometry. Morphological changes of cells were observed by immunofluorescence. Expressions of apoptosis-related proteins and barrier function-related proteins were detected by Western blot. The effect of the drug on the cell barrier was measured by measuring the transepithelial resistance of the cells. <p>RESULTS: PTX reduced the proliferation ability of ARPE-19 cells. After 36h of treatment with low concentration of 0.005mg/L paclitaxel, cell proliferation began to be affected. At the same time, PTX accelerated cell apoptosis was dependent on drug concentration and time. Flow cytometry showed that the cells were arrested in the G2-M phase. In addition, PTX causes significant morphological changes in cells, with normal cells fusiform or irregular. In the PTX group, the number of cells decreased and the cell shape tended to be round. PTX affected retinal barrier function, and the transepithelial resistance of cells was significantly decreased after treatment, and the expression of tight junction proteins ZO-1 and Occludin were significantly decreased compared with the control group(<i>P</i><0.05). The expression levels of Cleaved-caspase-3 and Bax were significantly increased compared with the control group, while the expression levels of Bcl-2 were significantly decreased(<i>P</i><0.05)and was dependent on drug concentration and time. <p>CONCLUSION: PTX can affect the proliferation and apoptosis of ARPE-19 cells, and it depends on time and concentration. In addition, PTX affected the cell cycle and morphology of ARPE-19 cell. At the same time PTX can destroy the barrier function of the retina,suggesting that anti-tumor drugs have a potential toxic effect on the retina.

Lifestyle for young and middle-aged stroke patients: 268 cases investigation / 中国康复理论与实践

@#Objective To investigate the lifestyles for young and middle-aged stroke patients (aged 18 to 59). Methods From October, 2020 to March, 2021, 268 young adult stroke inpatients in Beijing Bo'ai Hospital and 363 healthy controls for healthy examination were collected the basic information (gender, age, marital status and educational level). The lifestyles were investigated with questionnaire based on Activity-Interest-Opinion (AIO) scale and Health Education and Health Advocacy in China, including 26 items in five dimensions of smoking, drinking, sleep, diet and exercise (before the onset for patients). The lifestyles were compared between the two groups, and analyzed with Logistic regression. Results Frequent smoking (OR = 1.383, P = 0.048), frequent passive smoking (OR = 1.511, P < 0.001), less sleeping time (OR = 0.582, P = 0.018), staying up later (OR = 0.400, P < 0.001), irregular meal time (OR = 0.454, P < 0.001), less weekly breakfast (OR = 0.752, P = 0.012), more oil intake (OR = 0.623, P < 0.001), more barbecue and fried food intake (OR = 0.440, P < 0.001), frequent takeaway or catering (OR = 0.716, P < 0.001), more alcohol consumption (OR = 1.502, P < 0.001) and less aerobic exercise (OR = 1.540, P < 0.001) were the risk factors for stroke in young and middle-aged persons. Conclusion Adverse lifestyle affects the occurrence of stroke in young and middle-aged people.