OBJECTIVE: To observe the effects of acupuncture on podocyte autophagy and long non-coding RNA SOX2 overlapping transcript (LncRNA SOX2OT)/mammalian target of rapamycin C1 (mTORC1)/Unc-51-like kinase 1 (ULK1) pathway in rats with diabetic kidney disease (DKD), and to explore the mechanism by which acupuncture reduces urinary protein. METHODS: A total of 40 SPF-grade male Sprague-Dawley rats were randomly divided into a control group (n=10) and a modeling group (n=30). The DKD model was established by feeding a high-fat, high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) in the modeling group. Twenty rats with successful DKD model were randomly divided into a model group (n=10) and an acupuncture group (n=10). The acupuncture group received "spleen and stomach-regulating" acupuncture at bilateral "Zusanli" (ST36), "Fenglong" (ST40), "Yinlingquan" (SP9), and "Zhongwan" (CV12), 30 min per session, once daily, five times per week, for four weeks. The general condition, fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), serum creatinine (SCr), blood urea nitrogen (BUN), 24-hour urinary protein quantification, and urine albumin-to-creatinine ratio (UACR) were compared before and after the intervention. After intervention, urinary podocyte injury marker SPON2 was measured by ELISA. Podocyte autophagosomes and glomerular basement membrane ultrastructure in renal tissue were observed via transmission electron microscopy. Podocyte apoptosis was assessed by TUNEL staining. The protein expression of microtubule-associated protein 1 light chain 3Ⅱ (LC3-Ⅱ), mTORC1, ULK1, Beclin-1, and p62 in renal tissue was detected by Western blot. LncRNA SOX2OT expression in renal tissue was measured by real-time PCR. RESULTS: After the intervention, compared with the control group, the model group exhibited increased food and water intake, increased urine output, weight loss, and loose stools; compared with the model group, the food and water intake, urine volume, and loose stools were improved in the acupuncture group. Compared with the control group, FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all higher in the model group (P<0.01); compared with the model group, the FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all lower in the acupuncture group (P<0.01). Compared with the control group, the model group showed reduced podocyte autophagosomes and thickened glomerular basement membrane; compared with the model group, the acupuncture group had increased podocyte autophagosomes and less thickened basement membrane. Compared with the control group, the podocyte apoptosis index (AI) was higher in the model group (P<0.01); compared with the model group, the AI was lower in the acupuncture group (P<0.01). Compared with the control group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was lower, and the expression of mTORC1 and p62 proteins was higher in the model group (P<0.01). Compared with the model group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was higher, and the expression of mTORC1 and p62 proteins was lower in the acupuncture group (P<0.01). Compared with the control group, the LncRNA SOX2OT expression was lower in the model group (P<0.01). Compared with the model group, LncRNA SOX2OT expression was higher in the acupuncture group (P<0.01). CONCLUSION The "spleen and stomach-regulating" acupuncture method could improve renal function in DKD rats, reduce blood glucose and urinary protein excretion, alleviate podocyte injury, and enhance podocyte autophagy. The mechanism may be related to modulation of the renal LncRNA SOX2OT/mTORC1/ULK1 pathway.
Animals ; Podocytes/cytology* ; Diabetic Nephropathies/physiopathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Mechanistic Target of Rapamycin Complex 1/genetics* ; Autophagy ; Acupuncture Therapy ; Autophagy-Related Protein-1 Homolog/genetics* ; RNA, Long Noncoding/metabolism* ; Humans ; Signal Transduction

Objective: To discover molecular markers associated with lung adenocarcinoma diagnosis/prognosis and drug resistance through screening of differentially expressed genes based on published chip data in gene expression databases using bioinformatics methods. Methods: Comprehensive analysis was performed in available mRNA microarray datasets including lung adenocarcinoma tissues dataset GSE32863 and lung adenocarcinoma taxane-platin resistance dataset GSE77209 from the gene expression omnibus(GEO) database. Gene ontology enrichment analysis, gene pathway enrichment analysis and protein interaction network analysis were performed based on significantly correlated genes. The expression level of genes was validated in the cancer genome atlas(TCGA) dataset. Survival differences were assessed by the log-rank test in TCGA lung adenocarcinoma dataset. Based on the publications genomics of drug sensitivity in cancer(GDSC) database in CellMiner cross database(CellMiner CDB), Pearson correlation analysis was used to analyze the correlation between differentially expressed genes and the half-maximal inhibitory concentration(IC50) of anticancer drugs. Results : There were a total of 77 genes which had a different expression in resistance lung adenocarcinoma cells and lung adenocarcinoma cancer tissues. The functional enrichment analysis showed that these co-different expression genes were mainly enriched in microtubule, extracellular exosome, cell cycle and signaling by nuclear receptors. Protein-protein interactions(PPI) network screened 6 most connected genes as molecular complex(MCODE). Among the MCODE, overexpressed ubiquitin conjugating enzyme E2 T(UBE2T), kinesin family member 20A(KIF20A), PCNA clamp associated factor(KIAA0101), pituitary tumor-transforming gene 1(PTTG1) and NIMA related kinase 2(NEK2) were associated with poor outcomes. Survival analysis results showed that these five genes were upregulated in lung adenocarcinoma tissues and drug-resistant cells and were significantly associated with poor prognosis in lung adenocarcinoma patients. Drug sensitivity analysis results suggested that high expression of PTTG1 and UBE2T was significantly associated with sensitivity to multiple anticancer drugs, including paclitaxel and docetaxel. RT-PCR validation showed that PTTG1 andUBE2T were highly expressed in docetaxel-resistant cells A549-TXR and H358-TXR. Conclusion PTTG1 andUBE2T holds the potential to be chemoresistance markers in lung adenocarcinoma.

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Adult ; Humans ; Cardiovascular Diseases/prevention & control* ; East Asian People ; Prospective Studies ; Risk Factors ; Smoking

Objective:To investigate the clinical features, diagnostic methods and treatments of left ventricular apical fibroma.Methods:The clinical manifestations, ECG, imaging features and treatment plans of 2 patients with giant fibroma of left ventricular apex diagnosed in September 2020 and May 2022 were analyzed retrospectively, and the related literature was reviewed.Results:Both patients had slight chest distress and discomfort after activities. The ECG showed T-wave inversion of different degrees, which were misdiagnosed as “myocarditis” and “coronary heart disease” respectively. The cardiac magnetic resonance imaging and echocardiography showed left ventricular apical mass. Coronary artery stenosis was not found in coronary angiography. One patient required conservative treatment, and there was no significant change in clinical symptoms and tumor size in the follow-up for half a year; Another patient underwent cardiac mass removal, and the pathological examination after operation confirmed that it was cardiac fibroma, and there was no recurrence in the follow-up 2 years.Conclusion:Fibroma of left ventricular apex is a rare cardiac tumor, which is easy to be missed and misdiagnosed, and is one of the rare causes of T-wave inversion. Cardiac magnetic resonance imaging, CT and echocardiography are commonly used imaging methods to diagnose cardiac fibroma, and surgical resection is an effective treatment.

With the advance of the economy and population aging, the acceleration of urbanization and the change of people's lifestyles, the prevalence of chronic diseases has become very serious. However, the etiologies and pathogeneses of the diseases are not yet clear, and the evidence of effective prevention and treatment strategies is lacking. Cohort study is an important method for exploring etiology and pathogenesis. Therefore, based on the support of the Ministry of Science and Technology for precision medicine in 2016, we launched a prospective cohort study of common chronic and non-communicable diseases in three provinces (Hubei, Hunan and Henan) in central China. Three independent and integratable sub-cohorts consisting of 115 424 participants at baseline survey and 107 252 participants in follow up were established, including dynamic measurements in 39 000 subjects in Dongfeng-Tongji prospective cohort. Each participant was asked to complete a questionnaire survey, an anthropometric measurement, a laboratory measurement, and blood and urine samples were collected from them. The cohort study contributes greatly to elucidating the etiologies and pathogeneses of common chronic and non-communicable disease in Chinese population and the development of precision medicine in China. This paper briefly introduces the design concept, basic information, major achievements and progress, and challenges of the prospective cohort study of common chronic and non-communicable diseases in central China.

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8⁺ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.

Objective:To investigate the influencing factors for postoperative venous thromboembolism (VTE) of inguinal hernia.Methods:The retrospective case-control study was conducted. The clinical data of 350 patients undergoing surgical treatment of inguinal hernia who were admitted to Affiliated Hospital of Zunyi Medical University from January to December 2017 were collected. There were 287 males and 63 females, aged from 15 to 89 years, with a median age of 57 years. Observation indicators: (1) surgical and postoperative situations; (2) follow-up; (3) analysis of influencing factors for postoperative VTE of inguinal hernia. Follow-up using outpatient examination and telephone interview was performed to detect recurrence and complications of inguinal hernia after patients being discharged from hospital. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the nonparametric rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Multivariate analysis was conducted using the binary Logistic regression model. Results:(1) Surgical and postoperative situations: of the 350 patients, 173 underwent open inguinal hernia surgery including 66 cases with plain patch repair, 54 cases with Lichtenstein repair, 30 cases with mesh plug plain patch repair, 23 cases with Bassini repair, and 177 underwent laparoscopic inguinal hernia surgery including 134 cases with laparoscopic transabdominal preperitoneal prothetic repair, 43 cases with laparoscopic totally extraperitoneal prothetic repair. There were 335 of the 350 patients negative for postoperative VTE while 15 patients positive for postoperative VTE. Of the 15 patients who were diagnosed with postoperative VTE, 13 cases underwent open surgery while 2 cases underwent laparoscopic surgery including 1 died; 12 cases were diagnosed with deep vein thrombosis and 3 cases were diagnosed with pulmonary thromboembolism including 1 died. (2) Follow-up: 349 of the 350 patients were followed up for one year after operation. Of the 349 patients, 2 had recurrence of inguinal hernia and 18 had seroma in the operation area within one year. None of the 349 patients had postoperative patch-related infection or incision infection in the operation area. Of the 14 patients who were diagnosed with postoperative VTE, recurrence of inguinal hernia was not observed within one year. (3) Analysis of influencing factors for VTE of inguinal hernia. Results of univariate showed that age, body mass index (BMI), hypertension, type of operation, the compression time of operative area, time to first out-of-bed activities, duration of hospital stay, postoperative Caprini score were influencing factors for postoperative VTE of inguinal hernia ( χ2=13.217, 9.183, 4.388, 8.694, Z=-4.690, -5.265, -4.281, -4.883, P<0.05), and age, cases with chronic bronchitis, the stable stage of chronic obstructive pulmonary disease (COPD) were influencing factors for postoperative VTE of inguinal hernia ( P<0.05). Results of multivariate analysis showed that age≥65 years, BMI≥25.0 kg/m 2, chronic bronchitis, the stable stage of COPD, open surgery, the compression time of operative area≥42 hours, time to first out-of-bed activities≥60 hours, postoperative Caprini score>5 were independent risk factors for postoperative VTE of inguinal hernia ( odds ratio=1.085, 1.320, 0.256, 0.013, 7.874, 1.112, 1.027, 6.909, 95% confidence interval: 1.031-1.141, 1.024-1.702, 0.071-0.929, 0.016-0.800, 1.489-41.630, 1.061-1.165, 1.008-1.047, 3.045-15.678, P<0.05). Conclusions:Age≥65 years, BMI≥25.0 kg/m 2, cases with chronic bronchitis preoperatively, the stable stage of COPD, open surgery, the compression time of operative area≥42 hours, time to first out-of-bed activities≥60 hours, postoperative Caprini score>5 are independent risk factors for postoperative VTE of inguinal hernia.

Objective To report the clinical features,microsurgical techniques and outcomes of 5 patients admitted in our hospital,who had solid hemangioblastoma in medulla oblongata in the last 5 years.Methods 5 consecutive cases of solid hemangioblastoma in medulla oblongata operated from March,2011 to May,2016 were reviewed and fl lowed up.Results All patients suffered headache,dizziness and cerico-occipital pain from the beginning plus one was found because of obstructive hydrocephalus.The mean duration before operation was 6.7 months.The mean maximum diameter of tumor was (33.7±3.4)mm.The suboccipital posterior midline approach was performed and gross total resection was achieved in all 5 cases.After operation,endotracheal tube was removed in all 5 patients,but 3 received tracheotomy,and all patients can take food freely now through rehabilitation exercise.Followed up until September 2016,all patients lived a normal life.Conclusion The operation of solid hemangioblastoma in medulla oblongata is full of huge risk,but microsurgical resection is the only cure means for the tumor.

[Abstract ] Objective To investigate effect of phloretin on apoptotic of hepatoma carcinoma cells SMMC-7721, and explore its mechanisms.Methods Logarithmic phase of hepatoma carcinoma cells SMMC-7721 were cultured separately with 30, 60, 120 mg/L phloretin, morphological alterations of apoptotic were observed by phase contrast microscopy and AO/EB double fluorescence staining method was used to observe were low, medium and high concentration trentment group, respectively.the cells treated by phloretin.Apoptotic rates, cell cycle progression, mitochondrial trans-membrane potential and intracellular calcium homeostasis were detected by flow cytometry.Results Cells appeared typical apoptosis morphological alterations.Phloretin induced SMMC-7721 cell line apoptosis in a dosage and duration dependent manner.Cell cycle was arrested at G1 phase, mitochondrial trans-membrane potential decreased, intracellular free Ca2 +increased.Conclusion Phloretin induce apoptosis of SMMC-7721 by affecting cell cycle progression, reducing mitochondrial trans-membrane potential and changing intracellular calcium homeostasis.

Objective To investigate proliferative and apoptotic effects of phloretin on hepatoma carcinoma cells, hepatoma carcinoma cells HepG-2 was used as research materials.Methods This research observed morphological alterations using phase contrast microscopy and electron microscopy, cell proliferation were detected by MTT assay, and using flow cytometry detected apoptotic rates, cell cycle progression, mitochondrial trans-membrane potential and intracellular calcium homeostasis.ResuIts Apoptotic cells appeared morphological alterations.Phloretin exerted a inhibitory the proliferation of HepG-2 cell line, and induced its apoptosis in a dosage and duration dependent manner.Cell cycle was arrested at G1 phase, mitochondrial trans-membrane potential dropped, intracellular free Ca2 + increased.ConcIusion Phloretin can induce apoptosis of HepG-2 via arresting cell cycle progression, reducing mitochondrial trans-membrane potential and disturbing intracellular calcium homeostasis.