Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD⁺/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice ; Animals ; Butyric Acid/metabolism* ; Ketone Bodies/metabolism* ; Liver/metabolism* ; Hydroxybutyrates/metabolism* ; Down-Regulation ; Sirtuins/metabolism* ; Hydroxymethylglutaryl-CoA Synthase/metabolism*

Objective     To investigate the surgical procedure selection, operation technique and safety of anatomic sublobar resection for pulmonary nodules. Methods     The clinical data of 242 patients with clinical stage ⅠA lung cancer who underwent anatomic sublobar resection in our hospital between 2017 and 2020 were retrospectively analyzed. There were 81 males and 161 females with a median age of 57.0 (50.0, 65.0) years. They were divided into 4 groups according to the surgical methods, including a segmentectomy group (n=148), a combined segmentectomy group (n=31), an enlarged segmentectomy group (n=43) and an anatomic wedge resection group (n=20). The preoperative CT data, operation related indexes and early postoperative outcomes of each group were summarized. Results     The median medical history of the patients was 4.0 months. The median maximum diameter of nodule on CT image was 1.1 cm, and the consolidation/tumor ratio (CTR) was ≤0.25 in 81.0% of the patients. A total of 240 patients were primary lung adenocarcinoma. The median operation time was 130.0 min, the median blood loss was 50.0 mL, the median chest drainage time was 3.0 d, and the hospitalization cost was (53.0±12.0) thousand yuan. The operation time of combined segmentectomy was longer than that of the segmentectomy group (P=0.001). The operation time (P=0.000), intraoperative blood loss (P=0.000), lymph nodes dissected (P=0.007) and cost of hospitalization (P=0.000) in the anatomic wedge resection group were shorter or less than those in the other three groups. There was no significant difference in the drainage time, total drainage volume, air leakage or postoperative hospital stay among the four groups (P>0.05). Conclusion     The combined application of segmentectomy and wedge resection technique provides a more flexible surgical option for the surgical treatment of early lung cancer with ground glass opacity as the main component.

Nonalcoholic fatty liver disease (NAFLD) is a clinical syndrome characterized by hepatic steatosis and fat deposition in hepatocytes in the absence of significant alcohol use. A growing number of studies have shown significant dysregulation of intestinal microbiota in patients with chronic liver disease and cirrhosis. Small intestinal bacterial overgrowth (SIBO) is a clinical syndrome induced by excessive bacteria in small intestine. This article reviewed the correlation between SIBO and NAFLD, as well as the effect of probiotics on treatment of NAFLD.

Objective: To evaluate the incidence of postoperative venous thromboembolism (VTE) after thoracic surgery and its characteristic. Methods: This was a single-center, prospective cohort study. Patients undergoing major thoracic surgeries between July 2016 and March 2017 at Department of Thoracic Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University were enrolled in this study. Besides the routine examination, all patients were screened for deep venous thrombosis (DVT) by using noninvasive duplex lower-extremity ultrasonography after surgery. CT pulmonary angiography (CTPA) was carried out if patients had one of the following conditions including typical symptoms of PE, high Caprini score (>9 points) or new diagnosed postoperative DVT. Caprini risk assessment model was used to detect high risk patients. No patients received any prophylaxis of VTE before surgery. Further data was analyzed for identifying the incidence of postoperative VTE. The t-test, χ² test or Wilcoxon rank-sum test was used to analyze the quantitative data and classification data, respectively. Results: Totally 345 patients who undergoing major thoracic surgery were enrolled in this study including 145 benign diseases and 200 malignant diseases.There were 207 male and 138 female, aging from 15 to 85 years. Surgery procedures included 285 lung surgeries, 27 esophagectomies, 22 mediastinal surgeries and 11 other procedures. The overall incidence of VTE was 13.9% (48 of 345) after major thoracic surgery including 39 patients with newly diagnosed DVT (81.2%), 1 patient with PE (2.1%) and 8 patients with DVT+ PE (16.7%). The median time of VTE detected was 4.5 days postoperative. There were 89.6% (43/48) VTE cases diagnosed in 1 week. The incidence of VTE was 9.0% in patients with benign diseases, while 17.5% in malignant diseases (χ²=5.112, P<0.05). The incidence of VTE in patients with pulmonary diseases was 12.6%, among that, in patients with lung cancer and benign lung diseases was 16.4% and 7.5 % (χ²=4.946, P<0.05), respectively. Regarding to Caprini risk assessment model, the incidence of VTE in low risk patients, moderate risk patients (Caprini score 5 to 8 points)and high risk patients(≥9 points)were 0(0/77), 15.2%(33/217) and 29.4%(15/51), respectively(Z=-12.166, P<0.05). In patients with lung cancer, 98.2% of patients were moderate risk or high risk; only 3 cases scored low risk. The incidence of VTE in moderate risk and high risk patients was 13.4%(18/134) and 32.1%(9/28), respectively, while it was 0(0/3) in low risk patients. Conclusion s The overall incidence of VTE after major thoracic surgeries is 13.9%, and the incidence of VTE after lung cancer surgeries was 16.4%. Most of the VTE cases occurr within one week after the surgery. Caprini risk assessment model can identify high risk patients effectively.

Objective To observe the changes of thoracic drainage volume after lung transplantation,and to explore the influencing factors and their relationship with the prognosis of lung transplantation.Methods This retrospective analysis included 46 consecutive lung transplantations in our hospital between 2005 and 2016.The volume of postoperative chest drainage was recorded and analyzed.Single factor analysis of the factors that may affect the drainage was done.The patients were divided into different groups according to different prognosis at different time points after operation,and drainage volume was compared among groups.All analyses were performed with SPPS,version 19.0.Results There were no operative deaths.The median thoracic drainage time was 9.3 days,the median total thoracic drainage volume was 4318 mL,and the average daily drainage volume was 487 mL.During the perioperative period,the use of cardiopulmonary bypass or extracorporeal membrane oxygenation increased significantly the volume of unilateral pleural drainage (P＜0.05).The average daily drainage volume and the average daily unilateral pleural drainage volume in the postoperative dead patients were significantly greater than those of survivals at 1 st month,3rd month and 1 st year after lung transplantation (P＜0.05).At 3rd month after transplantation,the total amount of postoperative thoracic drainage was significantly greater than that of survivals (P＜ 0.05).The average daily unilateral pleural drainage volume in dead patients after surgery was significantly greater than that of the survival patients 3 years after operation (P＜0.05).Conclusion Intraoperative hemostasis in patients with lung transplantation should receive considerable attention,cardiopulmonary bypass and extracorporeal membrane oxygenation should be used cautiously during perioperative period,and greater postoperative chest drainage predicated poor short-term prognosis.

Objective To observe the relationship between Toll-like receptor 4 (TLR4) and the sensitivity of PANC1 cells to gemcitabine (GEM),and to analyze the potential mechanism.Methods PANC1 cells were divided into GEM group,lipopolysaccharide (LPS) + GEM group and TLR4-siRNA + GEM group.GEM group was treated by GEM alone.LPS + GEM group was pretreated with 1 mg/L LPS for 4 h and then treated by GEM.TLR4-siRNA + GEM group was transfected with 100 pmol/mL TLR4-siRNA for 4 h and then treated by GEM.The untreated cells were used as the control group.MTT method was used to detect the cell proliferation.Morphological changes and apoptosis rate of the cells were examined by Hoechst33258 staining and flow cytometry,respectively.The protein expression of TLR4,phosphorylated AKT (p-AKT) and activated Caspase-3 were detected by Western blot.Results The median inhibition concentration (ICs0) of GEM in the GEM group,LPS + GEM group and TLR4-siRNA + GEM group was (8.9 ± 0.32),(14.21 ±0.95),(3.96 ± 0.27) mg/L,respectively.The IC50 in LPS + GEM group was significantly higher than that in GEM group (P ＜ 0.01),and the IC50 of GEM in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01).Compared with that in GEM group,the cells with typical apoptotic morphological changes were decreased in LPS + GEM group,which was increased in TLR4-siRNA + GEM group.The apoptotic rate in control group,GEM group,LPS + GEM group,TLR4-siRNA + GEM group was (2.1 ± 0.3) ％,(15.1 ± 2.3) ％,(9.8 ± 1.5) ％,(22.9 ± 3.1) ％,respectively.Compared with that in GEM group,the cells apoptotic rate was significantly reduced in LPS + GEM group (P ＜0.01),which was significantly increased in TLR4-siRNA + GEM group (P ＜0.01).TLR4 protein level in the 4 groups was 0.83 ±0.08,0.81 ±0.07,0.85 ±0.07 and 0.16 ±0.03;p-AKT protein level 0.61 ±0.05,0.36 ±0.03,0.73 ± 0.07 and 0.21 ± 0.02;activated Caspase-3 protein level was 0.66 ± 0.05,0.73 ± 0.07,0.45 ± 0.04 and 0.91 ± 0.07,respectively.The expression of TLR4 and p-AKT in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01),while the expression of activated Caspase-3 protein was increased significantly (P ＜ 0.05).Compared with the GEM group,the expression of p-AKT protein in LPS + GEM group was significantly increased (P＜0.01),and the expression of activated Caspase-3 protein was significantly decreased (P＜0.01).Conclusions TLR4 can inhibit the sensitivity of pancreatic cancer PNAC1 cells to GEM,and the mechanism is related to the activation of PI3K/AKT pathway and downregulation of activated Caspase-3.

Objective To analyze the clinical features of multiple myeloma ( MM ) with renal insufficiency as the initial manifestation, and to improve the level of clinical diagnosis of MM, and reducing misdiagnosis of this disease. Methods To retrospectively analyze the clinical data of 140 patients with MM, who were admitted in our Department of Nephrology and Hematology. They were diagnosed as MM by bone marrow aspiration biopsy. The patients were divided into renal insufficiency group and normal renal function group, based on the criterion of serum creatinine>177μmol/L. The two groups were statistically analyzed by t test, rank sum test,χ2 test and binary logistic regression analysis. Results 55.7% of the patients in the renal insufficiency group presented low level of three immunoglobulin classes ( IgG, IgA, IgM) , while in the normal?renal function group, 54. 3% of patients mainly presented IgG subtype, showing statistically significant differences between the two groups ( P<0.001) . Univariate analysis showed that IgM level (<0.4 g/L), hemoglobin, white blood cells, erythrocyte sedimentation rate (ESR), total protein, globulin, uric acid, corrected serum calcium, proteinuria and hematuria were statistically significantly different between the two groups ( P<0.05 for all) . Unconditional logistic regression analysis showed that lower level of IgM ( OR=19.992, 95% CI: 1. 327?301. 202 ) , hemoglobin, uric acid, ESR, serum total protein, proteinuria and hematuria are independent risk factors for the development of renal insufficiency in MM patients ( P<0.05 for all). Conclusions Low level of IgM (<0.4 g/L) is an important clinical characteristics of MM patients with renal insufficiency as the initial clinical manifestation. For middle?aged and elderly patients, who present as low levels of three IgG classes ( IgG, IgA, IgM) or low level of IgM, multiple myeloma should be excluded, so as to reduce the misdiagnosis.

Objective To analyze the clinical features of multiple myeloma ( MM ) with renal insufficiency as the initial manifestation, and to improve the level of clinical diagnosis of MM, and reducing misdiagnosis of this disease. Methods To retrospectively analyze the clinical data of 140 patients with MM, who were admitted in our Department of Nephrology and Hematology. They were diagnosed as MM by bone marrow aspiration biopsy. The patients were divided into renal insufficiency group and normal renal function group, based on the criterion of serum creatinine>177μmol/L. The two groups were statistically analyzed by t test, rank sum test,χ2 test and binary logistic regression analysis. Results 55.7% of the patients in the renal insufficiency group presented low level of three immunoglobulin classes ( IgG, IgA, IgM) , while in the normal?renal function group, 54. 3% of patients mainly presented IgG subtype, showing statistically significant differences between the two groups ( P<0.001) . Univariate analysis showed that IgM level (<0.4 g/L), hemoglobin, white blood cells, erythrocyte sedimentation rate (ESR), total protein, globulin, uric acid, corrected serum calcium, proteinuria and hematuria were statistically significantly different between the two groups ( P<0.05 for all) . Unconditional logistic regression analysis showed that lower level of IgM ( OR=19.992, 95% CI: 1. 327?301. 202 ) , hemoglobin, uric acid, ESR, serum total protein, proteinuria and hematuria are independent risk factors for the development of renal insufficiency in MM patients ( P<0.05 for all). Conclusions Low level of IgM (<0.4 g/L) is an important clinical characteristics of MM patients with renal insufficiency as the initial clinical manifestation. For middle?aged and elderly patients, who present as low levels of three IgG classes ( IgG, IgA, IgM) or low level of IgM, multiple myeloma should be excluded, so as to reduce the misdiagnosis.

Objective Summarize the experience of diagnosis and treatment of esophageal rupture.Methods Twelve cases of esophageal rupture were treated with surgical intervention and clinical data were analyzed retrospectively.Diagnosis was confirmed in all patients by chest X-cays,Closed thoracic drainage,upper gastrointestinal contrast,chest CT scan and gastroscopy.In this series,there were 6 cases of spontaneous esophageal rupture,2 cases of iatrogenic esophageal rupture,4 cases of foreign body in esophagus rupture.For surgical treatment of 8 cases,including emergency esophageal stitching issue and diaphragmatic muscle or greater omentum to cover 6 cases;Esophageal ligation and resection of rupture area on both closes of the near and far,phase ii gastroesophageal anastomosis of esophagus resection in 2 cases,including 1 case of esophagus repair failure after turning the operation).Esophageal resection of gastroesophageal anastomosis in 1 case (for into the outer court misdiagnosed patients);4 cases were conservative.Results Initial diagnosis of spontaneous esophageal rupture and iatrogenic esophageal rupture 7 patients were cured,17 to 53 days of hospital stay,Follow-up for 3 months to 5 years,no esophageal related complications.Exception 1 patient died of postoperative infection(misdiaguosed for a long time).4 cases of esophageal foreign bodies to rupture were cured and these cases' fissure were less than 5 mm by chest CT scan and gastroscope diagnosis.Conclusion Complete collection of medical history,chest X-cays,Closed thoracic drainage,upper gastrointestinal contrast,chest CT scan and gastroscopy may clear diagnosis.Choose the proper method according to the patients as early as possible by general closed gap is the key to the treatment,at the same time be adequate drainage,control of infection and nutrition support treatment.

Objective:To analyze survival in patients with advanced oral cancer from prospective clinical trials. Methods:From 2008 to 2010, 256 patients with oral cancer at clinical stage III/IVA were randomly categorized into two groups. Patients in the experi-mental group received neo-adjuvant chemotherapy, surgery, and post-operative radiation, and patients in the control group underwent surgery and post-operative radiation. All patients were routinely followed-up after treatments. Survival was analyzed using Kaplan–Meier method and log-rank test, and differences were considered statistically significant at P value lower than 0.05. Results: Each group was composed of 128 patients. With the median follow-up period of 60 months, the 5-year overall survival rate was 61.7%and the disease-free survival rate was 53.9%. The overall survival rate (P=0.350) and the disease-free survival rate (P=0.160) were not sig-nificantly different between the experimental and control groups. Patients with positive pathological response to neo-adjuvant chemo-therapy exhibited significantly improved overall survival (P＜0.05). Conclusion:Radical surgery should be emphasized to improve the prognosis of oral cancer. Functional reconstruction could also improve the quality of life and survival of patients. Despite that neo-adju-vant chemotherapy could not improve the survival of patients with advanced oral cancer in entirety, it could benefit patients exhibiting positive treatment responses.