OBJECTIVE To investigate the regulatory effects of couplet medicinals of Atractylodes macrocephala-Aucklandia lappa on gut microbiota and short-chain fatty acids （SCFAs） in the diarrhea-type irritable bowel syndrome （IBS-D） rats with spleen deficiency. METHODS The IBS-D rat model with spleen deficiency was induced by intragastric administration of Senna alexandrina combined with restraint stimulation. The model rats were divided into model group， positive control group （pinaverium bromide 1.5 mg/kg）， A. macrocephala-A. lappa low-dose， medium-dose and high-dose groups （0.7， 1.4， 2.8 g/kg）， with 6 rats in each group. Another 6 healthy rats were taken as the blank control group. The blank control group and the model group were given normal saline intragastrically， and other groups were given relevant drug liquid intragastrically， once a day， for consecutive 14 days. The general characteristics of rats and fecal water content were observed， and intestinal sensitivity [evaluating by abdominal wall withdrawal reflex （AWR） threshold] and the intestinal propulsion rate were determined. The serum levels of 5- hydroxytryptamine（5-HT）and SP were detected， and the pathological changes of colon tissue were observed； the protein expressions of 5-HT-3 receptor（5-HT3R）， 5-HT4R and 5-HT transporter（SERT） in colon tissue of rats were detected. 16S rRNA sequencing was performed for the feces of rats in blank control group， model group and A. macrocephala-A. lappa high-dose group； the contents of acetic acid， propionic acid and butyric acid in the feces of the rats were determined. RESULTS Compared with the model group， the body weight after 7 and 14 days of medication， fecal water content， AWR threshold， and the protein expressions of 5-HT4R and SERT in colon tissue were increased significantly in the A. macrocephala-A. lappa medium-dose and high-dose groups （P＜0.05 or P＜0.01）； serum contents of 5-HT and SP， intestinal propulsion rate （except for A. macrocephala-A. lappa medium-dose group）， the protein expression of 5-HT3R in colon tissue were decreased significantly （P＜0.01）； diarrhea relief， mental state recovery， and partially recovery of the structure of colon tissue were all found； moreover， the diversity and species number of gut microbiota were reduced in A. macrocephala-A. lappa high-dose group and the content of butyric acid in fecal samples was significantly reduced （P＜0.05）. CONCLUSIONS The compatibility of A. macrocephala and A. lappa can improve intestinal motility and sensitivity of IBS-D model rats with spleen deficiency， and alleviate diarrhea. This may be related to improving changes in intestinal microbiota structure， reducing 5-HT expression and butyric acid content， and increasing 5-HT4R and SERT expression.

Objective To investigate the mechanism of Guizhi Tongluo Tablets(GZTLP)on improving atherosclerosis in APOE knockout mice by regulating neutrophil extracellular trapping nets(NETs).Methods After modeling,24 APOE knockout mice aged 8 weeks were randomly divided into 4 groups:GZTLP high-dose group,low-dose group,model control group and normal control group,with 6 mice in each group.GZTLP was given 1.87 mg·g-1 and 0.47 mg·g-1 intragastric administration in high-dose group and low-dose group,respectively.The normal control group and model control group were given 0.9%sodium chloride solution intragastric administration for 6 weeks,and the lipid plaque deposition in aorta was observed by gross oil red O staining.Lipid deposition in aortic root was observed by oil red O staining.The pathological changes of lipid plaques in aortic root were observed by HE staining.The levels of interleukin-1β(IL-1β)and tumor necrosis factor α(TNF-α)in peripheral blood of mice were detected by enzyme-linked immunosorbent assay(ELISA).The expression of lymphocyte antigen 6G(Ly6G),myeloperoxidase(MPO)and citrulinated histone(Cit-H3)in plaques of the aortic arch and the colocalization of Ly6G,MPO and Cit-H3 were detected by immunofluorescence assay.Results Compared with the normal control group,the aorta of mice in the model control group showed serious lipid plaque deposition,morphological damage,and a large number of inflammatory cells infiltration,the contents of serum inflammatory factors IL-1β and TNF-α were increased,and the protein expressions of Ly6G,Cit-H3 and MPO were significantly increased.Compared with model control group,GZTLP group reduced the amount of lipid plaque deposition in aorta,the arrangement of aortic cells was more regular,the inflammatory cell infiltration was improved,and the contents of serum inflammatory factors IL-1β and TNF-α were significantly decreased(P<0.05).The colocalization and the protein expression of Ly6G,MPO and Cit-H3 were significantly decreased in aortic tissues(P<0.01).Conclusions GZTLP can improve atherosclerosis,and its mechanism may be related to the inhibition of neutrophil extracellular trapping nets.

Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

OBJECTIVE To explore the therapeutic effect and safety of Maiwei Yangfei Decoction(MWYF)in the treatment of idiopathic pulmonary fibrosis of qi-yin deficiency type.METHODS A total of 58 patients with idiopathic pulmonary fibrosis of qi-yin deficiency type were randomly divided into an experimental group and a control group with 29 cases in each group according to a 1:1 ratio.Two cases dropped out of the experimental group and three cases dropped out of the control group.The control group received standardized treatment of Western medicine,and the experimental group received MWYF on the basis of the treatment of the control group.The treatment course of both groups was 3 months.The TCM syndrome score,lung function,6-minute walking distance(6MWD),transcutaneous blood oxygen saturation(SpO2),high-resolution computed tomography(HRCT)score,St.George's respir-atory questionnaire(SGRQ)score and serum sialoglycoprotein antigen(KL-6)level of the two groups were compared before and after treatment.Blood routine and liver and kidney function of the two groups were detected before and after treatment,and the occurrence of adverse reactions during treatment was recorded.RESULTS After treatment,the total score of TCM syndrome of the two groups was significantly improved(P<0.01),and the experimental group was better than the control group(P<0.01);the DLCO%of the experi-mental group increased(P<0.05),and the experimental group was higher than the control group(P<0.05).The experimental group showed significant improvement in 6MWD,HRCT grid shadow,SGRQ symptom score and total score,and serum KL-6 level(P<0.05,P<0.01),which was better than the control group(P<0.05,P<0.01).No serious adverse events occurred in either group dur-ing the treatment.CONCLUSION MWYF combined with standardized Western medicine treatment can effectively improve the clini-cal symptoms of patients with idiopathic pulmonary fibrosis of qi-yin deficiency type,reduce the expression level of serum KL-6,and has a definite effect and good safety.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Endometrial cancer has been identified by The Cancer Genome Atlas program with four molecular subtypes by genome sequence analysis. Clinical trials to select suitable immunotherapeutic agents based on the different immune characteristics of each subtype have been conducted in several countries and have made important progress. The main clinical applications of immune checkpoint inhibitors include anti-programmed cell death protein-1/programmed death-ligand 1 antibodies and poly ADP-ribose polymerase inhibitors. Optimizing drug selection and drug combination based on the target characteristics of different immune checkpoint inhibitors may provide new opportunities for immunotherapy of endometrial cancer and bring new light to improve survival rates.

Background: There is still controversy whether the existence of esophageal heterotopic gastric mucosa (EHGM) and its histological type are related to the laryngopharyngeal symptoms. Aims: To analyze the clinical and histological characteristics of EHGM and its correlation with gastroesophageal reflux. Methods: A retrospective study was conducted in consecutive gastroscopy-proved EHGM cases from September 2018 to January 2020 at the Second Affiliated Hospital of Baotou Medical College. Besides clinical data review and questionnaire survey on reflux symptoms, histological typing of EHGM and immunohistochemistry were also performed in some cases. Results: A total of 1 229 cases of EHGM were recruited. The male-to-female ratio was 1.67:1, and middle-aged people were predominant. Most of the heterotopic mucosa were located 15-18 cm away from the incisors, and were mainly single. Two hundred and ninety-four cases (23.9%) were complicated with reflux esophagitis (RE), of which Los Angeles grade A and B accounted for 96.6%. Regurgitation/acid reflux (15.5 %) and heartburn (12.3%) were the most common esophageal symptoms, while extraesophageal symptoms were rare. Histological typing was obtained in 57 cases, of which, 37 (64.9%) were cardia-type, 18 (31.6%) were fundic-type, and 2 (3.5%) were mixed type. There were no significant differences in gender, age, location and number of EHGM, expression levels of H

Nodular gastritis is directly related to Helicobacter pylori (Hp) infection. Refractory Hp infection has significant impact on the treatment efficacy and prognosis of nodular gastritis. Aims: To analyze the spheroidization and antibiotic resistance of refractory Hp and PPI drug metabolic enzyme CYP2C19 gene polymorphism in patients with nodular gastritis, so as to promote the eradication rate of refractory Hp infection in patients with nodular gastritis. Methods: Refractory Hp infection patients with nodular gastritis from Oct. 2019 to Nov. 2020 at the Second Affiliated Hospital of Baotou Medical College were enrolled. Hp strains were cultured in microaerophilic environment. Immunohistochemistry was used to detect Hp spheroidization. Mutation sites of antibiotic resistance genes and host CYP2C19 gene polymorphism were detected by PCR. According to the results of genetic testing, individualized therapy was given and follow up was performed, the eradication rate of intention-to-treat was calculated. Results: A total of 42 patients with refractory Hp nodular gastritis were enrolled. Among them, lymphocyte accumulation was found in 33.3% patients. Hp spheroidization was found in 2 patients, and the spheroidization rates were 20% and 10%, respectively. There were 25 intensive metabolizer, 15 intermediate metabolizer and 2 poor metabolizer of CYP2C19. Antibiotic resistance gene detection showed that the drug resistance rate of amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline, metronidazole were 4.8%, 38.1%, 35.7%, 47.6%, 42.9% and 61.9%, respectively. Twenty-two (52.4%) of the patients developed resistance to 3 or more antibiotics. The total eradication rate of intention-to-treat was 83.3%, of which high-dose dual therapy was 88.9%. Conclusions: Multi-antibiotic resistance and CYP2C19 may be the main reason for the failure of eradication of refractory Hp in nodular gastritis. Hp spheroidization has little effect on the efficacy of eradication therapy. The amoxicillin resistance rate is still significantly lower than that of other antibiotics, and high-dose dual therapy is a better option.

Objective To explore the occurrence and related factors of diarrhea in the early stage of enternal nutrition in critically ill patients, therefore providing guidance for the optimization of enteral nutrition. Methods A prospective cross-sectional study was conducted in 29 ICUs of 28 general hospitals of Zhejiang Province between June 1 and October 1, 2016. Patients who were admitted to ICU required for enteral nutrition were included and continuously observed for over 7 days or till discharged from ICU. The patient's general characteristics, severity of disease, enteral nutrition, diarrhea-related and prognostic indicators were recorded. Multivariable logistic regression was performed to analysis risk factors associated with diarrhea and in-hospital mortality. Results A total of 533 critically ill patientswere enrolled in this study. The overall incidence of diarrhea was 30.8％ (n = 164). Diarrhea occurred most frequently on the three days after EN, with a median duration of 2 (1, 3) days. The daily incidence of diarrhea were significantly different between groups (all P< 0.05), which were gradually reduced on day 7. Multivariable logistic regression analysis showed that prokinetic drugs (OR=1.82; 95％ CI: 1.24-2.65), APACHE II score (OR=1.04; 95％ CI: 1.02-1.07), post-pylorus enteral feeding (OR=1.90; 95％ CI:1.11-3.36) were independent risk factors for diarrhea, while interruption of EN (OR=3.74; 95％ CI: 1.85-7.54), APACHE II score (OR=1.07; 95％ CI: 1.04-1.11), vasoactive agent (OR=2.31; 95％ CI: 1.42-3.77), and timing (>48 h) (OR=2.00; 95％ CI: 1.08-3.70) were independent risk factors for in-hospital mortality. Conclusions Our study showed that APACHE II score, the use of prokinetic drugs, and post-pylorus enteral feeding were risk factors for diarrhea. Patients suffering diarrhea experienced increased ICU length of stay, increased the time of mechanical ventilation and in-hospital mortality compared with patients without diarrhea. Interruption of EN induced by diarrhea significantly increased the risk of in-hospital mortality.

Objective:To investigate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of upper gastrointestinal lesions .Methods:IT knife and HOOK knife were applied in ESD for the treatment of 30 cases of upper gastrointestinal mucosal or submucosal lesions revealed by gastroscopy .The ESD procedure was conducted as follows .Firstly , 0 .9% sodium chloride solution was injected into the submucosa so as to elevate the mucosa on lesion .Secondly ,the mucosa around the lesion was pre‐cut .Thirdly ,the lesion was dissected completely from the surrounding connective tissue .Results:The diameters of the lesions ranged from 0 .8 to 4 .5 cm with mean of (2 .6 ± 1 .3) cm .As postoperative pathology confirmed , there was tumor residual on wound surface of 2 cases after ESD ,and they received extended resection .And the lesions of the other 28 cases were successfully resected by ESD .The success rate of complete dissection was 93 .3% (28/30) .The ESD procedure time (from fluid injection to complete dissection) ranged from 29 to 110 min ,with a mean of (48 ± 11 .2) min .The average amount of bleeding during operation was 45 mL and the bleeding was successfully stopped by electro‐coagulation ,argon plasma coagulation . One patient (aspirin was stopped 5 days before operation) suffered hemorrhage per‐diapedesin and recovered after conservative treatment .The bleeding rate of ESD was 3 .33% (1/30) .Perforation occurred in 3 cases during the ESD procedure ,and was closed with metallic endoclip .And no case was transferred to laparotomy .The perforation rate of ESD was 10 .0% (3/30) .After the operation ,16 cases were followed up .And the follow‐up period ranged from 3 to 6 months ,with a mean of (4 .5 ± 1 .2) months .The wound surfaces of 16 cases were healed ,and there was no residue or recurrence .Conclusions:The curative effect of ESD for the treatment of upper gastrointestinal lesions is reliable ,as it can not only wholly remove the large lesion ,but also provide with pathological proof .With ESD ,less pain ,faster rehabilitation ,and lower recurrent rate can be achieved for patients .