Objective:To investigate the mechanism of 6-sialyllactose (6-SL) in interfering the immune checkpoint inhibitor-induced colitis (ICIC) through the bacterial 16S rDNA sequencing.Methods:BALB/c mice were randomly divided into the normal control (NC) group ( n = 7), dextran sulfate sodium (DSS) group ( n = 6), ICIC group ( n = 6), and ICIC+6-SL group ( n = 6). The DSS group was continuously fed with 3.5% DSS drinking water for 7 days to induce colonic inflammation; the ICIC group was administered cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, 150 μg) intraperitoneally on days 0 and 4 in addition to 3.5% DSS drinking water to establish the ICIC mouse model; the ICIC+6-SL group was given 6-SL [150 mg/ (kg·d) ] by gavage simultaneously with the establishment of the ICIC model. Changes in mouse body weight and disease activity index (DAI) were statistically analyzed, and all mice were sacrificed on day 7 to observe gross and histopathological morphological changes in the colon and to tally histopathological scores; the fresh colonic feces were collected for 16S rDNA sequencing to statistically analyze the diversity and species differences in the microbiota of mice of each group. Results:The success rate of the ICIC model was 100%, with all mice surviving. At the endpoint of the study (day 7), compared with the NC and DSS groups, the ICIC group had lower mouse body weight ( P < 0.05), higher DAI ( P < 0.05), damaged integrity of colonic mucosal tissue, and typical ulcerative lesions; the ICIC+6-SL group showed significant alleviation of body weight loss, significantly lower DAI scores, and lower pathological scores compared to the ICIC group, with all differences being statistically significant (all P < 0.05). 16S rDNA sequencing of mouse intestinal feces indicated that the alpha diversity of colonic microbiota in the ICIC group was lower than that in the NC and DSS groups (both P < 0.05), while the ICIC+6-SL group had higher alpha diversity than the ICIC group ( P < 0.05). In beta diversity analysis, the ANOSIM statistical value R = 0.376, P = 0.001 for the PCoA analysis of colonic microbiota and a Stress value of 0.125, P = 0.001 for the NMDS analysis indicated differences in the composition of colonic microbiota among the groups, with the greatest difference between the NC and ICIC groups, and the ICIC+6-SL group's microbiota composition was closer to that of the NC group compared to the ICIC group. Lefse analysis and Kruskal-Wallis test-based differential microbiota analysis showed that at the phylum level, compared to the NC group, the abundance of Bacteroidetes was significantly reduced in the ICIC group, while Campilobacterota was increased, and 6-SL administration could increase the abundance of Bacteroidetes and Campilobacterota in the ICIC group. At the genus level, compared to other groups, the abundance of unclassified_f_Lachnospiraceae and norank_f_Muribaculaceae was the lowest in the ICIC group, while Helicobacter, Akkermansia, and Escherichia-Shigella were enriched. Compared to the ICIC group, the abundance of unclassified_f_Lachnospiraceae and norank_f_ Muribaculaceae was increased in the ICIC+6-SL group, while the abundance of Helicobacter and Escherichia-Shigella was significantly suppressed. Conclusions:6-SL, an oligosaccharide derived from human milk, alleviates intestinal inflammatory injury in ICIC mice, reducing disease activity. This beneficial effect may be related to its regulation of gut microbiota profiling, an increased diversity of microbiota, a restoration of Bacteroidetes, and an inhibition of the growth advantage of pathogenic bacteria such as Helicobacter and Escherichia-Shigella.

Objective:To investigate the mechanism of 6-sialyllactose (6-SL) in interfering the immune checkpoint inhibitor-induced colitis (ICIC) through the bacterial 16S rDNA sequencing.Methods:BALB/c mice were randomly divided into the normal control (NC) group ( n = 7), dextran sulfate sodium (DSS) group ( n = 6), ICIC group ( n = 6), and ICIC+6-SL group ( n = 6). The DSS group was continuously fed with 3.5% DSS drinking water for 7 days to induce colonic inflammation; the ICIC group was administered cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, 150 μg) intraperitoneally on days 0 and 4 in addition to 3.5% DSS drinking water to establish the ICIC mouse model; the ICIC+6-SL group was given 6-SL [150 mg/ (kg·d) ] by gavage simultaneously with the establishment of the ICIC model. Changes in mouse body weight and disease activity index (DAI) were statistically analyzed, and all mice were sacrificed on day 7 to observe gross and histopathological morphological changes in the colon and to tally histopathological scores; the fresh colonic feces were collected for 16S rDNA sequencing to statistically analyze the diversity and species differences in the microbiota of mice of each group. Results:The success rate of the ICIC model was 100%, with all mice surviving. At the endpoint of the study (day 7), compared with the NC and DSS groups, the ICIC group had lower mouse body weight ( P < 0.05), higher DAI ( P < 0.05), damaged integrity of colonic mucosal tissue, and typical ulcerative lesions; the ICIC+6-SL group showed significant alleviation of body weight loss, significantly lower DAI scores, and lower pathological scores compared to the ICIC group, with all differences being statistically significant (all P < 0.05). 16S rDNA sequencing of mouse intestinal feces indicated that the alpha diversity of colonic microbiota in the ICIC group was lower than that in the NC and DSS groups (both P < 0.05), while the ICIC+6-SL group had higher alpha diversity than the ICIC group ( P < 0.05). In beta diversity analysis, the ANOSIM statistical value R = 0.376, P = 0.001 for the PCoA analysis of colonic microbiota and a Stress value of 0.125, P = 0.001 for the NMDS analysis indicated differences in the composition of colonic microbiota among the groups, with the greatest difference between the NC and ICIC groups, and the ICIC+6-SL group's microbiota composition was closer to that of the NC group compared to the ICIC group. Lefse analysis and Kruskal-Wallis test-based differential microbiota analysis showed that at the phylum level, compared to the NC group, the abundance of Bacteroidetes was significantly reduced in the ICIC group, while Campilobacterota was increased, and 6-SL administration could increase the abundance of Bacteroidetes and Campilobacterota in the ICIC group. At the genus level, compared to other groups, the abundance of unclassified_f_Lachnospiraceae and norank_f_Muribaculaceae was the lowest in the ICIC group, while Helicobacter, Akkermansia, and Escherichia-Shigella were enriched. Compared to the ICIC group, the abundance of unclassified_f_Lachnospiraceae and norank_f_ Muribaculaceae was increased in the ICIC+6-SL group, while the abundance of Helicobacter and Escherichia-Shigella was significantly suppressed. Conclusions:6-SL, an oligosaccharide derived from human milk, alleviates intestinal inflammatory injury in ICIC mice, reducing disease activity. This beneficial effect may be related to its regulation of gut microbiota profiling, an increased diversity of microbiota, a restoration of Bacteroidetes, and an inhibition of the growth advantage of pathogenic bacteria such as Helicobacter and Escherichia-Shigella.

ObjectiveTo investigate the expression of L1 cell adhesion molecule (L1CAM) and transforming growth factor-β1 (TGFβ1) in pancreatic cancer tissue and their association with the prognosis of pancreatic cancer. MethodsHistological specimens were collected from 125 patients with pancreatic cancer who underwent surgical resection in The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University Cancer Hospital, and Wuming Hospital of Guangxi Medical University from January 2015 to January 2018. Immunohistochemistry was used to measure the expression of L1CAM and TGFβ1 in all specimens, and the association of the expression of L1CAM and TGFβ1 with clinical indices, survival, and prognosis was analyzed. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the Cox proportional-hazards regression model was used to investigate the influencing factors for the survival of patients with pancreatic cancer; the Kaplan-Meier survival analysis was used to evaluate the survival of patients with different expression levels of L1CAM and TGFβ1. ResultsThe high protein expression rate of L1CAM in pancreatic cancer tissue was significantly higher than that in adjacent tissue (75.20% vs 20.00%, χ2=76.352, P＜0.001). The high protein expression rate of TGFβ1 in pancreatic cancer tissue was significantly higher than that in adjacent tissue (8160% vs 23.20%, χ2=85.461, P＜0.001). The protein expression of L1CAM was positively correlated with that of TGFβ1 in pancreatic cancer (r=0.492, P＜0.001). The protein expression of L1CAM and TGFβ1 were associated with tumor size, degree of tumor differentiation, TNM stage, lymph node metastasis, intravascular tumor thrombus, and perineural invasion (all P＜0.05). The patients with high protein expression of L1CAM or TGFβ1 had a significantly lower overall survival rate than those with low expression (χ2=54661 and 39597, both P＜0.001). ConclusionL1CAM and TGFβ1 proteins are highly expressed in pancreatic cancer tissue and may be associated with poor prognosis by promoting lymphatic metastasis and hematogenous metastasis. L1CAM and TGFβ1 proteins play an important role in the development, progression, and metastasis of pancreatic cancer.

Objective To evaluate the efficacy and safety of different antimicrobial regimens in patients with bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods The clinical date of patients with CRKP bloodstream infections were retrospectively analyzed at the First Affiliated Hospital of Zhejiang University Medical College between January 2017 and January 2018.All subjects were separated into three groups based on antibiotics regimens over 72 hours,including meropenem 2.0 g every 8 hours,tigecycline 200 mg as initial dose and 100 mg every 12 hours,and polymyxin B 1.25 mg/kg every 12 hours as salvage treatment of tigecycline.Results A total of 86 patients were finally recruited,including 14,52 and 20 patients in groups of meropenem,tigecycline and polymyxin B salvage,respectively.All of the strains were resistant to meropenem and susceptible to tigecycline and polymyxin B initially,while 2 of them became resistant to tigecycline during treatment.The 28-day mortality was significantly higher in meropenem group (13/14) than that in tigecycline group and polymyxin B salvage group (61.5％,32/52) and (12/20),respectively (P＜0.01),while as no significant difference was seen in the last two groups (x2=0.014,P＞0.05).The incidences of hepatic impairment [3.8％(2/52) vs.1/20] and renal dysfunction (0 vs.1/20) between tigecycline group and polymyxin B salvage group were both comparable (P＞0.05).Conclusion The meropenem-based therapy is not recommended for CRKP-related bloodstream infections.Tigecycline-based therapy is still disappointing despite salvage use of polymyxin B after 72 hours.Hepatic and nephretic toxicities caused by additional polymyxin B are acceptable.

Objective To assess the application value of NCE-MRA using iMSDE prepared bSSFP sequence in lower limb in patients with diabetes. Methods This prospective study included a total of 35 patients with type II diabetes who underwent CE-MRA on the 1.5T MR scanner after the NCE-MRA. The obtained MIP images were independently rated by two radiologist with a four score table and using CE-MRA as a reference standard to evaluate the diagnostic accuracy of NCE-MRA for the narrowed arteries. The difference of the percent age of diagnostic arterial segments between NCE-MRA and CE-MRA on diabetic patients was evaluated by the χ2 test. Results Compared with CE-MRA, the diagnostic-value arterial segment ratio of pelvic arteries on NCE-MRA is decreased significantly. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of two readers in NCE-MRA were 95%/87%, 96%/95%, 57%/72%, 99%/99%, and 96%/95%(k=0.76), respectively. Conclusions The NCE-MRA using iMSDE prepared bSSFP sequence is capable of depicting vascu-lar lesions for the lower extremities in diabetic patients with the advantages of contrast agent free, short scan times and good diagnostic value in the thigh and calves.

To evaluate the safety and effectiveness of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions, an open, multicenter, controlled, phase Ⅳ clinical trial was conducted in the drug clinical trial centers of 16 domestic hospitals. 2 123 patients from June 10, 2011 to November 29, 2012 were enrolled in the trial. Drug clinical trial was approved by Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital Ethics Committee before implementation. Before the start of trial, subjects were selected according to the research scheme and inclusion criteria, then they would step into the 14 d study after signing Informed Consent Form. All subjects were treated according to the research scheme, evaluated the conditions and filled in CFR sheet, to provide the evaluation data and information on safety and efficacy of Shenbei Guchang capsules. Shenbei Guchang capsules were used to treat diarrhea type irritable bowel syndrome in widely used conditions (2 123 cases), and 2 029 cases of them entered FAS set, cure+markedly effective in 1 921 cases, with a comprehensive curative effect rate of 94.68%; 2 010 cases of them entered PPS set, cure+markedly effective in 1 906 cases, with a comprehensive curative effect rate of 94.83%. The primary symptoms of IBS were abdominal pain and diarrhea. After treatment, both abdominal pain and diarrhea were improved, with significant differences (P<0.000 1). There were significant differences in traditional Chinese medicine symptom scores on both post-treatment day 7 and day 14 as compared with the conditions before treatment (P<0.000 1). 35 cases of adverse events occurred during the trial with an incidence of 1.65%, including 12 cases of drug-related adverse events (adverse reaction) with an incidence of 0.57%, mainly manifested as nausea, abdominal distension and dry mouth, most of which would be spontaneously relieved without any measures. No serious adverse events occurred. The commercially available Shenbei Guchang capsules are proved safe and effective for the treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions (2 123 cases), and can be continued for clinical promotion and application.

[Objective] Probing into the effect of Changyanning syrup about colonic electrophysiology and motility of visceral hypersensitivity rat.[Methods] The test consists of the model series and the control series and the Changyanning syrup series,and the two latter rats were sensitized by intraperitoneal injection of chicken egg albumen.After two weeks,the stomach is poured 0.7ml's normal saline by blank space series,0.7ml's normal saline by model series,0.7ml's Changyanning syrup by Changyanning series.Continue to pour stomach in a month,writing colon fast wave,slow wave and the colon contraction,the observation of interdigestive myoelectric complex IMC cycle,Ⅲ times duration,fast wave and slow wave propagation rate,the largesttest amplitude,the amount of the colon contraction,the index of the colon contraction.[Result] The model series' interdigestive myoelectric complex IMC cycle prolongs,Ⅲ times duration prolongs,fast wave and slow wave propagation rate speeds up,the largesttest amplitude broadens.The slow wave propagation rate speeds up.The amount of the colon contraction speeds up,the index of the colon contraction speeds up.After Changyanning series treated,interdigestive myoelectric complex IMC cycle cuts down,Ⅲ times the duration cuts down,the largesttest amplitude decreases.[Conclusion] There are quite differencs between model group and control group in electricity and motion of visceral hypersensitivity rat.Changyanning syrup treating visceral hypersensitivity is by means of partly recovering the colon fast and slow wave and contraction wave rhythm and amplitude.

Atrial fibrillation is the most common arrhythmia disease in the clinical works,and endangers the public health seriously.With the development of AAD and ABL,we have made a great progress in AF's prevention and treatment.However,the literature and research about the non-disease causes of lone AF are very rare.So,the article will make a system review and summary about it,in order to instruct the lone AF's primary prevention.

Objective To identify the features of colon electricity activities and the motion in viscerally hypersensitive rats. Methods The rats were divided into control group and model group that was latter sensitized by chicken egg albumen.After two weeks, the colon spike potential, slow wave and the colon contraction were recorded. The interdigestive myoelectric complex cycle,the duration of phase Ⅲ,spike potential and slow wave propagation rate and average largest amplitude were observed,and then the number of the contraction, the index of contraction were recorded. Results Both IMC cycle and phase Ⅲ were prolonged, spike potential propagation frequency speeded up (P