Comparative genomics reveals cellobiose hydrolysis mechanism of Ruminiclostridium thermocellum M3, a cellulosic saccharification bacterium.

The cellulosome of Ruminiclostridium thermocellum was one of the most efficient cellulase systems in nature. However, the product of cellulose degradation by R. thermocellum is cellobiose, which leads to the feedback inhibition of cellulosome, and it limits the R. thermocellum application in the field of cellulosic biomass consolidated bioprocessing (CBP) industry. In a previous study, R. thermocellum M3, which can hydrolyze cellulosic feedstocks into monosaccharides, was isolated from horse manure. In this study, the complete genome of R. thermocellum M3 was sequenced and assembled. The genome of R. thermocellum M3 was compared with the other R. thermocellum to reveal the mechanism of cellulosic saccharification by R. thermocellum M3. In addition, we predicted the key genes for the elimination of feedback inhibition of cellobiose in R. thermocellum. The results indicated that the whole genome sequence of R. thermocellum M3 consisted of 3.6 Mb of chromosomes with a 38.9% of GC%. To be specific, eight gene islands and 271 carbohydrate-active enzyme-encoded proteins were detected. Moreover, the results of gene function annotation showed that 2,071, 2,120, and 1,246 genes were annotated into the Clusters of Orthologous Groups (COG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, and most of the genes were involved in carbohydrate metabolism and enzymatic catalysis. Different from other R. thermocellum, strain M3 has three proteins related to ß-glucosidase, and the cellobiose hydrolysis was enhanced by the synergy of gene BglA and BglX. Meanwhile, the GH42 family, CBM36 family, and AA8 family might participate in cellobiose degradation.

Imaging Predictors for Endovascular Recanalization of Non-acute Occlusion of Internal Carotid Artery Based on 3D T1-SPACE MRI and DSA.

Objectives: To investigate the predictive factors for successful recanalization based on digital subtraction angiography and three-dimensional T1W sampling perfection with application-optimized contrasts using different flip angle evolutions (3D T1-SPACE) high-resolution magnetic resonance imaging (MRI) signal features. Methods: Consecutive internal carotid artery occlusion cases with ipsilateral ischemic stroke refractory to therapy who visited our institution between February 2017 and August 2020 were retrospectively analyzed. Epidemiology, symptomatology, imaging morphology on angiography and MRI, peri-procedural complications, technical success rate, and follow-up results were summarized. Factors related to technical success were analyzed using univariate and multivariate analyses. Results: In total, 75 cases (53 men, mean age 57.51 ± 9.71 years) were included. The total successful recanalization rate was 72.00% (54/75), with a complication rate of 13.33% (9/75). Through multivariate analysis, first ischemic stroke in <3 months (OR: 2.57; 95% CI: 1.13-4.58), tapered stump (OR: 4.31; 95% CI: 1.37-13.55), reversed flow of the ophthalmic artery (OR: 2.99; 95% CI: 1.06-8.49), high intraluminal signal on unenhanced T1-SPACE sequence (OR: 16.15; 95% CI: 3.40-76.72), no vessel wall collapse (OR: 17.00; 95% CI: 3.57-81.02), short occlusion length (OR: 9.87; 95% CI: 2.09-46.64), and primary occlusion site at the cervical internal carotid artery (OR: 8.42; 95% CI: 1.04-68.19) were associated with successful recanalization. Conclusion: Besides traditional features such as short ischemic event time, tapered stump, and distal ICA reconstitution by the ophthalmic artery, our study demonstrates that luminal and mural changes determined by 3D SPACE high-resolution MRI could also predict successful endovascular recanalization. Endovascular recanalization for non-acute internal carotid artery occlusion is feasible, but prudent case selection is mandatory considering the high periprocedural complication rate.

Chinese herbal medicine reduces mortality in patients with severe and critical Coronavirus disease 2019: a retrospective cohort study / 医学前沿

This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20, 2020. All patients were divided into an exposed group (CHM users) and a control group (non-users). After propensity score matching in a 1:1 ratio, 156 CHM users were matched by propensity score to 156 non-users. No significant differences in seven baseline clinical variables were found between the two groups of patients. All-cause mortality was reported in 13 CHM users who died and 36 non-users who died. After multivariate adjustment, the mortality risk of CHM users was reduced by 82.2% (odds ratio 0.178, 95% CI 0.076-0.418; P < 0.001) compared with the non-users. Secondly, age (odds ratio 1.053, 95% CI 1.023-1.084; P < 0.001) and the proportion of severe/critical patients (odds ratio 0.063, 95% CI 0.028-0.143; P < 0.001) were the risk factors of mortality. These results show that the use of CHM may reduce the mortality of patients with severe/critical COVID-19.

Study on role of CDH17 regulating TGF-β autocrine for affecting invasion of gastric cancer cells / 重庆医学

Objective To explore the role and possible mechanism of transforming growth factor (TGF)-β autocrine in CDH17 regulating invasion of gastric cancer cells.Methods Construction and transfection of siRNA-CDH17 into MKN-45 gastric cancer cell line to silence the expression of CDH17.Expression of TGF-β and concentrations of TGF-β in supernatants were detected before and after CDH17 silence by immunofluorescence,immunoblotting and ELISA.The autocrine situation of TGF-β was observed.Meanwhile,the activation of TGF-β/Smad3 signaling pathway was also detected by immunoblot.After giving signaling pathway inhibitor,the changes of invasion ability of MKN-45 cells were observed by Transwell invasion experiment.The role of TGF-β autocrine and related signaling pathway activation in CDH17-regulated invasion of gastric cancer cells was evaluated.Results After transfecting siRNA-CDH17 for silencing CDH17 expression in MKN-45 cells,the expression of TGF-β was significantly decreased compared with non-transfection group,its concentration in supernatants was also significantly reduced[(510 ±55)pg/mL vs.(115±20) pg/mL,P<0.01].The immunoblots revealed that phosphorylation level of Smad3 after CDH17 silence was also significantly diminished.However,giving the TGF-β/Smad3 signaling inhibitor SIS3 (10 μmol/L) could also suppress the phosphorylation level of Smad3 when CDH17 was highly expressed,meanwhile silencing CDH17 and inhibiting Smad3 phosphorylation could significantly decrease the invasion of MKN-45 gastric cancer cells (P<0.05).Conclusion CDH17 could participate in the invasion of gastric cancer cells by promoting TGF-β autocrine to activate TGF-β/Smad3 signaling pathway.

Proximal vs total gastrectomy for proximal advanced gastric cancer / 中华普通外科杂志

Objective To investigate the clinical results and prognosis between proximal and total gastrectomy in proximal advanced gastric cancer.Methods The clinicopathological data of 221 patients with proximal advanced gastric cancer who undcrwent radical gastrectomy were retrospectively analyzed.82 patients and 139 patients underwent proximal and total gastrectomy respectively.The number of dessected lymph nodes,postoperative complications and mortality were compared.Kaplan-Meier survival rate curves and Log-rank test were drawn and compared.Results A total of 1 411 (11-34) and 3 345 (14-35) lymph nodes were harvested from the surgical specimens of 82 and 139 patients with proximal and total gastrectomy respectively,the average number of harvested lymph nodes was 17 ± 11 and 24 ± 10 (t =2.586,P ＜0.05).The overall complications in proximal gastrectomy were higher than total gastrectomy (73.2％ vs.30.2％,x2 =38.291,P ＜0.01).The ratio of functional delayed gastric emptying,anastomotic leakage and stenosis,reflux esophagitis in proximal gastrectomy patients was higher than total gastrectomy.The survival rate in proximal gastrectomy were lower than total gastrectomy in proximal advanced gastric cancer (P ＜0.01).Conclusion Total gastrectomy is recommended for proximal advanced gastric cancer.

Preoperative oral carbohydrate alleviates postoperative insulin resistance and inflammatory reaction / 中华内分泌外科杂志

Objective To observe the effect of preoperative oral administration of carbohydrate on blood glucose,insulin resistance(IR) and inflammatory reaction after gastrointestinal operation.Methods 48 patients receiving gastrointestinal operation were randomly divided into the study group(n =23)and the control group(n =25).Patients in the study group were orally given 25％ glucose solution 300 ml 3 hours before operation.Before anesthesia induction,gastric contents were aspirated through nasogastric tube to examine its volume and pH.Serum high sensitivity C-reactive protein(hsCRP),fasting blood glucose,insulin level and homeostasis model assessment-insulin resistance(HOMA-IR) were detected before operation and on the first morning after operation between the two groups.Results No anesthesia or operation related complications occurred in either groups.Patients had similar gastric contents volume and the PH value of gastric contents.There was no significant difference in serum hsCRP,fasting blood glucose and HOMA-IR between the two groups before operation.But on the first day,fasting blood glucose,HOMA-IR and hsCRP were significantly lower in the study group than in the control group(6.51 ±1.15 vs 7.49 ±0.57 mmol/L,P =0.038;4.34 ± 1.60 vs 6.09 ±2.81,P =0.043;40.45 ± 27.02 vs 80.02 ± 38.98 mg/L,P =0.03).Conclusion Preoperative oral administration of carbohydrate can obviously lower the postoperative blood glucose level and insulin resistance and alleviate postoperative inflammatory reaction.

Correlation analysis between prognostic nutritional index and clinicopathological features and long-term prognosis of resectable gastric cancer / 中华普通外科杂志

Objective To investigate the correlation between the prognostic nutritional index (PNI) and clinicopathological features and long-term prognosis of gastric cancer patients after radical gastrectomy.Methods The clinical data of 135 gastric cancer patients who underwent radical gastrectomy in this hospital from 2002 to 2006 was analyzed retrospectively.The PNI value was calculated by serum albumin (g/L) + 5 x lymphocyte count (× 109/L).The receiver operating characteristic (ROC) curve and Youden index was used to determine the cutoff value of the PNI.Survival curves were described by the Kaplan-Meier method and compared by the Log-rank test.The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the prognostic factors.Result The mean PNI value was 47.3 ± 5.9.The mean values of the PNI in age (t =2.909,P =0.004),tumor size (t =2.227,P =0.028),tumor depth (t =3.314,P =0.001),negative lymph node (t =2.381,P =0.019),negative lymphovascular invasion (t =2.781,P =0.006) were significantly higher than those in patients without such factors.When the PNI was 47,the Youden index was maximal,with a sensitivity of 70％ and specificity of 63％.The mean age in high PNI group was significantly lower than that in low PNI group (x2 =6.443,P =0.011).Tumor infiltration depth in high PNI group was less than in low PNI group (x2 =7.394,P =0.007).The proportion of lymphovascular invasion in high PNI group was significantly lower than in low PNI group (x2 =4.540,P =0.033).The overall survival rate in high PNI group was higher than in low PNI group (P =0.002).The univariate and multivariate analyses showed that tumor location (OR,2.144 ; 95 ％ CI 1.239-3.712 ; P =0.006),lymph node metastasis (OR,4.887 ; 95 ％ CI 1.856-12.866 ; P =0.001),lymphovascular invasion (OR,1.842 ; 95％ CI 1.078-3.145 ; P =0.025) and the PNI value (OR,2.282 ; 95 ％ CI 1.344-3.874 ; P =0.002) were independent factors for predicting overall survival rate.Conclusions The PNI value is a simple and useful tool to predict the prognosis of patients with gastric cancer.

Advances in research on molecular design of antimicrobial peptides / 军事医学

Antimicrobial peptides ( AMPs) are a kind of micromolecular peptides with antibacterial , antivirus and anti-tumor activities.Unlike conventional antibiotics , acquisition of resistance by a sensitive microbial strain against AMPs is surprisingly improbable .AMPs are not widely used clinically due to their toxicity , susceptibility to proteolysis and high manufacturing cost .Researchers have obtained some AMPs with high activity and low toxicity by structure modifications . The molecular design of AMPs as well as their development in the future are reviewed .