A growing body of evidence has linked the gut microbiota to liver metabolism. The manipulation of intestinal microflora has been considered as a promising avenue to promote liver health. However, the effects of Lactobacillus gasseri LA39, a potential probiotic, on liver metabolism remain unclear. Accumulating studies have investigated the proteomic profile for mining the host biological events affected by microbes, and used the germ-free (GF) mouse model to evaluate host-microbe interaction. Here, we explored the effects of L. gasseri LA39 gavage on the protein expression profiles of the liver of GF mice. Our results showed that a total of 128 proteins were upregulated, whereas a total of 123 proteins were downregulated by treatment with L. gasseri LA39. Further bioinformatics analyses suggested that the primary bile acid (BA) biosynthesis pathway in the liver was activated by L. gasseri LA39. Three differentially expressed proteins (cytochrome P450 family 27 subfamily A member 1 (CYP27A1), cytochrome P450 family 7 subfamily B member 1 (CYP7B1), and cytochrome P450 family 8 subfamily B member 1 (CYP8B1)) involved in the primary BA biosynthesis pathway were further validated by western blot assay. In addition, targeted metabolomic analyses demonstrated that serum and fecal β‍-muricholic acid (a primary BA), dehydrolithocholic acid (a secondary BA), and glycolithocholic acid-3-sulfate (a secondary BA) were significantly increased by L. gasseri LA39. Thus, our data revealed that L. gasseri LA39 activates the hepatic primary BA biosynthesis and promotes the intestinal secondary BA biotransformation. Based on these findings, we suggest that L. gasseri LA39 confers an important function in the gut‒liver axis through regulating BA metabolism.
Mice ; Animals ; Bile Acids and Salts/metabolism* ; Lactobacillus gasseri ; Proteomics ; Liver/metabolism* ; Biotransformation

Objective:To evaluate the efficacy and safety of nimotuzumab combined with definitive radiotherapy in the treatment of inoperable locally advanced oral and maxillofacial squamous cell carcinoma.Methods:A total of 33 patients with inoperable locally advanced oral and maxillofacial squamous cell carcinoma admitted to the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from March 2015 to December 2019 were retrospectively selected as the research objects. The treatment regimen was all targeted therapy (nimotuzumab) combined with definitive radiotherapy, with or without chemotherapy, and the efficacy and safety of the treatment were analyzed. The primary endpoints were optimal response and overall survival (OS) , and the secondary endpoints were optimal duration of response (DOR) and progression-free survival (PFS) . The survival curve was drawn using the Kaplan-Meier method, the survival rate of the patients was analyzed, and the related adverse reactions were counted.Results:Of the 33 patients, there were 20 cases of complete remission (CR) , 5 cases of partial remission (PR) , 5 cases of stable disease (SD) , 2 cases of progressive disease (PD) , and 1 case could not be evaluated. The objective response rate was 75.8% (25/33) , and the disease control rate was 90.9% (30/33) . The mean OS of all cases was 54.5 months, and the 5-year OS rate was 57.0%. The mean DOR of the overall cases was 57.2 months, and the 5-year DOR rate was 64.4%. The mean PFS of the overall cases was 54.4 months, and the 5-year PFS rate was 59.8%. The 5-year OS rates of CR, PR and SD patients were 83.6%, 20.0% and 0 ( χ2=20.07, P<0.001) , the 5-year DOR rates were 85.0%, 20.0% and 0 ( χ2=16.89, P<0.001) , and the 5-year PFS rates were 84.0%, 20.0% and 0 ( χ2=15.91, P<0.001) . The OS, DOR and PFS of patients with CR were significantly better than those of patients with PR and SD (all P<0.05) . The 5-year OS rates of patients with oropharyngeal cancer and oral cancer were 62.5% and 40.6% ( χ2=1.67, P=0.197) , the 5-year DOR rates were 73.3% and 44.0% ( χ2=1.34, P=0.247) , and the 5-year PFS rates were 68.8% and 40.9% ( χ2=1.13, P=0.289) , with no statistically significant differences, but oropharyngeal cancer patients still showed a certain advantage. Common adverse reactions included oral mucositis and hematological toxicity, most of which were grade 1-2. Two (6.1%) patients had rash, and two (6.1%) patients had nausea and vomiting, which were considered to be related to nimotuzumab. All adverse reactions were relieved after symptomatic treatments. Conclusion:For patients with locally advanced oral and maxillofacial squamous cell carcinoma who are not suitable for surgery, the choice of nimotuzumab combined with definitive radiotherapy has a relatively satisfactory efficacy and survival rate, with good safety and high clinical value.

Objective:To investigate the epidemiological characteristics of septic cardiomyopathy and explore the relationship between the relevant indexes measured by echocardiography and the prognosis of patients with sepsis.Methods:A case-control study was conducted. The data of patients with sepsis admitted to the department of critical care medicine of Jiangsu Subei People's Hospital Affiliated to Yangzhou University and the department of critical care medicine of Beijing Electric Power Hospital of State Grid Corporation of China from June 2018 to June 2021 were enrolled. The general information and 28-day prognosis were recorded. At the same time, ultrasonic parameters obtained by transthoracic echocardiography within 24 hours after intensive care unit (ICU) admission were recorded. The differences in ultrasound indexes between the death group and the survival group on 28 days were compared. Parameters with significant statistical differences between the death group and the survival group were included in the Logistic regression analysis to find the independent risk factors for the prognosis of patients with sepsis, the predictive value of each index for the prognosis of patients with sepsis was evaluated by receiver operator characteristic curve (ROC curve).Results:A total of 145 patients with sepsis were enrolled, including 106 patients with septic shock. Among the 145 patients, septic cardiomyopathy was found in 73 patients, with the incidence of 50.3%. The incidence of left ventricular diastolic dysfunction cardiomyopathy was 41.4% ( n = 60), the incidence of left ventricular systolic dysfunction cardiomyopathy was 24.8% ( n = 36), and the incidence of right ventricular systolic dysfunction cardiomyopathy was 12.4% ( n = 18). At 28 days, 98 patients survived and 47 died, with the mortality of 32.4%. The peak e' velocity by tissue Doppler imaging (e') and right ventricular myocardial systolic tricuspid annulus velocity (RV-Sm) of the death group were significantly lower than those of the survival group [e' (cm/s): 7.81±1.12 vs. 8.61±1.02, RV-Sm (cm/s): 12.12±2.04 vs. 13.73±1.74, both P < 0.05], left ventricular ejection fraction (LVEF) and left ventricular systolic mitral annulus velocity (LV-Sm) in the death group were slightly higher than those in the survival group [LVEF: 0.550±0.042 vs. 0.548±0.060, LV-Sm (cm/s): 8.92±2.11 vs. 8.23±1.71], without significant differences (both P > 0.05). Parameters with significant statistical differences between the two groups were included in the Logistic regression analysis and showed that e' and RV-Sm were independent risk factors for the 28-day prognosis of patients with sepsis [e': odds ratio ( OR) = 0.623, 95% confidence interval (95% CI) was 0.410-0.947, P = 0.027; RV-Sm: OR = 0.693, 95% CI was 0.525-0.914, P = 0.010]. ROC curve analysis showed that the area under the ROC curve (AUC) of e' for predicting the 28-day prognosis of patients with sepsis was 0.657, 95% CI was 0.532-0.781, P = 0.016, the best cut-off value was 8.65 cm/s, the sensitivity was 62.1%, and the specificity was 73.4%. The AUC of RV-Sm for predicting the 28-day prognosis of patients with sepsis was 0.641, 95% CI was 0.522-0.759, P = 0.030, the best cut-off value was 14.80 cm/s, the sensitivity was 96.6%, and the specificity was 26.6%. Conclusions:The incidence of septic cardiomyopathy is high. The LVEF measured by early echocardiography has no predictive value for 28-day prognosis in septic patients, while RV-Sm and e' are important predictors for 28-day prognosis.

Objective:To investigate the changes of regulatory B cells (Bregs) and lymphocyte subsets in children with primary immune thrombocytopenia (ITP), and to analyze their relationship with ITP duration and remission time.Methods:Proportion of different immune cell subsets were detected in the peripheral blood of 88 ITP children before treatmen, 84 ITP children after treatmen and 45 normal controls by flow cytometry. The treatments included glucocorticoids, intravenous IgG as first-line treatment. The changes of lymphocyte subsets in ITP children with different remission time after treatment were compared.Results:The Th, natural killer (NK), Breg cell counts and Th/Tc ratio in all children with ITP were significantly lower than those in the control group ( P<0.05), while the Tc and CD19 + B cells were significantly higher than those in the control group ( P<0.05). The Breg cell count in the persistent and chronic ITP groups was significantly lower than that in the newly diagnosed ITP ( P<0.05). A total of 84 children with ITP were relieved after treatment: 58 cases (69.1%) achieved long-term remission, and 26 cases (30.9%) had short-term remission. The Breg and lymphocyte subsets in the short-term remission ITP group after treatment were not significantly different from those before treatment, but there were still significant differences from the control group ( P<0.05); The Breg and lymphocyte subpopulations in the long-term remission ITP group after treatment were not significantly different from those in the control group, but compared with those before treatment, other cell subpopulations except Tc were significantly increased ( P<0.05); The NK cells and Breg cells in the long-term remission ITP group were significantly higher than those in the short-term remission ITP group ( P<0.05). Conclusions:The Bregs in peripheral blood of long-duration ITP children significantly decrease. After treatment, the Bregs in ITP children with long-term remission increase significantly, indicating that the restoration of the immune mechanism of Bregs may be related to the long-term remission of children with ITP.

Objective:To investigate the anti-leukemia effect of icaritin on 697 cells of children relapsed acute lymphoblastic leukemia in vitro, and to analyze its possible mechanism. Methods:697 cells were cultured in vitro and divided into control group and icariin groups (5, 10, 20 μmol/L). After treated with icaritin, the cell proliferation was detected with cell counting kit-8 (CCK-8) method, and apoptosis was measured with Hoechst 33258 staining and Flow Cytometry Assay. Expression of Bcl-2, Cyt-C, Bax and Caspase3 proteins in 697 cell were detected by Western blot. Results:After treatment with various concentrations (5-20 μmol/L) of icaritin for different time-points (24, 48, 72 h), the growth inhibition rate exhibited a dose and time-dependent manner ( r=0.76, r=0.89); the apoptotic rate exhibited significant increase for 48 h ( P<0.05). Bcl-2 protein decreased significantly ( P<0.05), while Bax, Cyt-C and Caspase3 cleavage protein increased significantly in icaritin treated group for 48 h compared with control group ( P<0.05). Conclusions:Icaritin shows the effects of anti-leukemia by inducing apoptosis and inhibiting proliferation of 697 cell. Icaritin maybe induce apoptosis of 697 cell by down-regulation of Bcl-2 expression and up-regulation of the Bax, Cyt-C and cleaved Caspase 3 expression.

Objective To investigate the diagnosis and treatment of upper gastrointestinal hemorrhage caused by pancreatic segmental portal hypertension.Methods The clinical diagnosis and follow-up data of 13 patients with upper gastrointestinal hemorrhage caused by pancreatic segmental portal hypertension from Jan 2010 to Dec 2017 were retrospectively analyzed.Results Of the 13 patients,5 had pancreatic pseudocysts and 8 had chronic pancreatitis.All of them had a history of hematemesis or (and) tarry feces,and 2 of them had a history of hemorrhagic shock.13 patients had isolated gastric varices,and 5 of them had varicose veins in the lower esophagus.13 patients had splenomegaly and hypersplenism,and all patients underwent splenectomy.All patients were followed up,and the varicose veins were significantly improved or disappeared.During 1 year to 8 years of follow-up,there was no rebleeding.Conclusion Splenectomy cures upper gastrointestinal hemorrhage caused by rupture of the varicose veins in patients of pancreatic segmental portal hypertension.Preoperative interventional spleen artery embolization can reduce the difficulty of spleen resection.

Objective: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with its genetic evidence widely explored. This study explored the potential the parent-of-origin (PoO) effect of WNT pathway on the risks of NSCL/P, using a case-parent trio design. Methods: Data on the single nucleotide polymorphism (SNP) of WNT genes were selected from a genome-wide association study (GWAS). A total of 806 Chinese non-syndromic cleft lip patients, with or without cleft palate (NSCL/P) case-parent trios, were gathered from an international consortium. PoO effect of WNT pathway genes and its haplotypes were explored by log-linear models. Additional Wald tests were performed to assess: a) the heterogeneity of PoO effect between different maternal exposures, b) the interaction between PoO effect, c) maternal exposure to environmental tobacco smoke (ETS), and d) multivitamin supplementation during pregnancy. The threshold for statistical significance was adjusted as 3.47×10^-4, according to Bonferroni correction. Results: After quality control, a total of 144 SNPs within seven genes were included for analyses, among which 8 SNPs were of potential PoO effect (P<0.05). However, none of them achieved the statistical significance after Bonferroni correction. The haplotype rs4074668-rs12725747 (T-A) on WNT9A showed significant PoO effect, based on the haplotype test for PoO (P=2.74×10^-4). In addition, no statistically significant interaction was found in further exploration of this haplotype under environmental exposures as ETS or multivitamin supplementation. Conclusions Genes in the WNT pathway may influence the NSCL/P risks through the potential PoO effect. Particularly, the haplotype rs4074668-rs12725747 (T-A) on WNT9A presented significant PoO effect on NSCL/P, statistically. From this current study, findings on WNT pathway related risks among the NSCL/P, need to be further validated by independent samples in the future.

Objective To investigate the complication and risk factors in elderly patients undergoing pancreaticoduodenectomy (PD).Methods From Jan 2005 to Dec 2016,358 consecutive patients undergoing PD were divided into ≥ 70 years group (98 cases) and ＜ 70 years group (260patients).Perioperative complications were compared and risk factors explored between the two groups.Results There were differences in coronary heart disease between the two groups in the preoperative medical comorbidities (P =0.008),and that of albumin,alanine aminotransferase,alkaline phosphatase and creatinine (all P ＜ 0.05).Perioperative mortality was higher in the elderly group than in the younger group (P =0.038),probably related to higher systemic complications (P =0.001).The independent risk factors influencing the postoperative medical complications were preoperative total bilirubin ≥ 171 μmol/L and intraoperative blood loss ≥ 1 000 ml.Conclusions Patients over 70 years old have a comparatively higher perioperative mortality rate after pancreaticoduodenectomy,which were probably derived from a higher postoperative vital organ dysfunction.

Objective To provide clinical evidence for the relationship between epithelial-mesenchymal transition (EMT) and colorectal cancer(CRC) by detecting the expression of TGF-β, Smad-3 and Smad-7 in serum from CRC patients. Methods We detected the expression levels of TGF-β1 , Smad-3 and Smad-7 by ELISA method. Results The expression levels of TGF-β1 , Smad-3 were significantly higher and the Smad-7 was significantly lower in CRC patients than those in control group(P<0. 01). The expression levels of TGF-β1 and Smad-3 were signifi-cantly higher in Dukes D than those in Dukes B,C. The Smad-7 was significantly lower in Dukes D than that in Dukes B,C(P<0. 01). Conclusion TGF-β1 and Smad-3 and Smad-7 may play an important role in the develop-ment of CRC.

Objective To explore the curative effectiveness of comprehensive voice training methods on teachers' voice disorders patients by using subjective and objective assessment. Methods Forty-seven teachers' voice disorders patients suffering from voice symptoms without organic disease and complete follow-up data as the research object were treated with a three-month comprehensive voice training program. Training content included relieving laryngeal muscle tension, improving the throat vocal cord movement and reconstruction methods of pronunciation. The use of voice acoustic analysis and voice handicap index(VHI) were compared before and after training. Results The jitter and shimmer were significantly decreased after comprehensive voice training from 1.06(0.79,1.38)％and 2.71(2.16,3.24)％to 0.78 (0.59, 0.99)％ and 1.64(1.03,2.45)％, the differences were significant (Z=3.249,-4.121, P<0.05). Maximum phonation time and dysphonia severity index were significantly increased obviously from (9.87 ± 2.61)s and-2.23±0.75 to (12.81±1.97)s and-0.43±1.65 respectively, the differences were significant (t=-6.057,-5.273, P<0.05). After the training, the VHI score of voice disorder index decreased from (37.41±4.96)points to (26.31± 4.29) points after the comprehensive voice training. In addition to emotional function, the difference was statistically significant(t=12.715, 5.881, 11.483, P<0.05). Conclusions Voice training can reduce the degree of voice disorders effectively, increase the power of the respiratory system, therefore improve the voice quality of teachers with voice disorders. The subjective and objective combination assessment can evaluate the quality of the patient′s voice more thoroughly and evaluate the clinical efficacy of voice training further.