Objective To investigate the mechanism of melezitose(MELE)on ulcerative colitis(UC)by structing a mouse model of ulcerative colitis(UC)induced by dextran sodium sulfate(DSS).Methods Forty-eight SPF grade male c57BL/6 mice were randomly divided into normal group(0.9％NaCl),model group(0.9％NaCl),control group(100 mg·kg-1 mesalazine)and experimental-L,-M,-H groups(20,40,80 mg·kg-1 melezitose solution).The UC model was induced by giving 3％DSS solution instead of drinking water,and the disease activity index(DAI)was evaluated.Serum levels of interleukin-1 β(IL-113),IL-6,IL-10 and tumor necrosis factor α(TNF-α)were detected by enzyme linked immunosorbent assay.The expression levels of major histocompatibility complex Ⅱ(MHC Ⅱ)and cluster of differentiation 4 receptors(CD4)protein were detected by Western blot.Results The levels of IL-1 β in serum in the experimental-M,-H groups,model group and normal group were(82.15±13.66),(75.56±11.07),(118.20±19.31)and(23.47±4.72)pg·mL-1;serum IL-6 levels were(71.54±16.48),(58.57±15.62),(140.60±5.76)and(30.33±4.15)pg·mL-1;serum IL-10 levels were(48.64±5.60),(52.65±7.99),(27.10±4.91)and(61.90±10.44)pg·mL-1;serum TNF-α levels were(70.33±8.51),(66.55±8.12),(90.88±4.90)and(34.18±4.15)pg·mL-1;the relative expression levels of MHC Ⅱ protein were 0.34±0.04,0.15±0.06,0.08±0.05 and 0.53±0.59;the relative expression levels of CD4 protein were 0.79±0.08,0.92±0.12,0.99±0.11 and 0.54±0.14,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups showed statistically significant differences(P＜0.05,P＜0.01).Conclusion Melezitose could effectively improve the symptoms of UC mice;the mechanism may be through down-regulating MHC Ⅱ protein and up-regulating CD4 protein to activate T cell signal pathway to play an anti-inflammatory effect.

Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)％vs.1.62(3.50)％],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P＜0.05 or＜0.01).There were no significant difference in LVEDd and LVEF between two groups,P＞0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To investigate the feasibility of Cai tube-assisted natural orifice specimen extraction surgery (NOSES) in gastrointestinal surgery. Methods: This was a descriptive case-series study. Inclusion criteria: (1) colorectal or gastric cancer diagnosed by preoperative pathological examination or redundant sigmoid or transverse colon detected by barium enema; (2) indications for laparoscopic surgery; (3) body mass index <30 kg/m² (transanal surgery) and 35 kg/m² (transvaginal surgery); (4) no vaginal stenosis or adhesions in female patients undergoing transvaginal specimen extraction; and (5) patients with redundant colon aged 18-70 years and a history of intractable constipation for more than 10 years. Exclusion criteria: (1) colorectal cancer with intestinal perforation or obstruction, or gastric cancer with gastric perforation, gastric hemorrhage, or pyloric obstruction; (2) simultaneous resection of lung, bone, or liver metastases ; (3) history of major abdominal surgery or intestinal adhesions; and (4) incomplete clinical data. From January 2014 to October 2022, 209 patients with gastrointestinal tumors and 25 with redundant colons who met the above criteria were treated by NOSES utilizing a Cai tube (China invention patent number:ZL201410168748.2) in the Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University. The procedures included eversion and pull-out NOSES radical resection in 14 patients with middle and low rectal cancer, NOSES radical left hemicolectomy in 171 patients with left-sided colorectal cancer, NOSES radical right hemicolectomy in 12 patients with right-sided colon cancer, NOSES systematic mesogastric resection in 12 patients with gastric cancer, and NOSES subtotal colectomy in 25 patients with redundant colons. All specimens were collected by using an in-house-made anal cannula (Cai tube) with no auxiliary incisions. The primary outcomes included 1-year recurrence-free survival (RFS) and postoperative complications. Results: Among 234 patients, 116 were male and 118 were female. The mean age was (56.6±10.9) years. NOSES was successfully completed in all patients without conversion to open surgery or procedure-related death. The negative rate of circumferential resection margin was 98.8% (169/171) with both two positive cases having left-sided colorectal cancer. Postoperative complications occurred in 37 patients (15.8%), including 11 cases (4.7%) of anastomotic leakage, 3 cases(1.3%) of anastomotic bleeding, 2 cases (0.9%) of intraperitoneal bleeding, 4 cases (1.7%) of abdominal infection, and 8 cases (3.4%) of pulmonary infection. Reoperations were required in 7 patients (3.0%), all of whom consented to creation of an ileostomy after anastomotic leakage. The total readmission rate within 30 days after surgery was 0.9% (2/234). After a follow-up of (18.3±3.6) months, the 1-year RFS was 94.7%. Five of 209 patients (2.4%) with gastrointestinal tumors had local recurrence, all of which was anastomotic recurrence. Sixteen patients (7.7%) developed distant metastases, including liver metastases(n=8), lung metastases(n=6), and bone metastases (n=2). Conclusion: NOSES assisted by Cai tube is feasible and safe in radical resection of gastrointestinal tumors and subtotal colectomy for redundant colon.
Humans ; Male ; Female ; Middle Aged ; Aged ; Anastomotic Leak/surgery* ; Stomach Neoplasms/surgery* ; Retrospective Studies ; Laparoscopy ; Rectal Neoplasms/surgery* ; Colectomy ; Postoperative Complications ; Liver Neoplasms/surgery* ; Treatment Outcome

Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23-9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89-26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07-2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16-2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = -0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.
Male ; Humans ; Prognosis ; Neoplasm Recurrence, Local/pathology* ; Prostatic Neoplasms/pathology* ; Prostatectomy ; Drug Resistance ; Aldehyde Dehydrogenase, Mitochondrial

Aim To investigate the effects of realgar on the proliferation, invasion and ferroptosis of esophageal cancer cells. Methods Different concentrations of realgar(0, 10,20, 40, 60, 80, 100 μmol·L-1)or realgar 1/2IC

Objective: To explore the relationship between DNA methylation and occupational noise-induced hearing loss. Methods: A case-control study was conducted. People with hearing loss induced by occupational noise were recruited as the case group and those with normal hearing but still exposed to occupational noise were recruited as the control group. A total of 60 participants were included, of which 30 participants were in the case group and 30 in the control group. The methylation level was detected by 850k genome-wide DNA methylation chip technology. The significance of differential methylated position (DMP) was tested by R-packet 'Champ'. The differential methylated region (DMR) was analyzed by using Champ's Bumphunter algorithm. Cluster profiler was used to analyze the gene list for GO and KEGG pathway enrichment. Results: There was significant difference between two groups in binaural high-frequency average hearing threshold (P<0.05), but there was no significant difference in age, smoking, drinking, hypertension, physical exercise and cumulative noise exposure. The results of DMP and DMR analysis showed that 713875 sites were detected in the case group and the control group, and 439 methylation sites with significant difference, accounting for 0.06%; 650 regions were detected, and 72 methylation regions with significant differences, accounting for 11.08%. Compared with the control group, the results of GO enrichment analysis showed that the case group had statistically significant differences in four pathways: axogenesis of projection neurons in the central nervous system, neuronal development in the central nervous system, axogenesis of neurons in the central nervous system and neuronal differentiation in the central nervous system. KEGG enrichment analysis showed that there were significant differences in sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis pathway between the case group and the control group. Conclusion: The occurrence of occupational noise-induced hearing loss may be related to the regulation of gene expression related to axogenesis of projection neurons in the central nervous system, development of neurons in the central nervous system, axogenesis of neurons in the central nervous system, differentiation of neurons in the central nervous system, sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis and gene methylation related to metabolism.
Aldosterone ; Bile Acids and Salts ; Case-Control Studies ; DNA Methylation ; Hearing Loss, Noise-Induced/genetics* ; Humans ; Noise, Occupational/adverse effects* ; Occupational Diseases ; Occupational Exposure ; Sphingolipids

Objective: To evaluate the mid-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using the Cai tube in the treatment of left colorectal cancer. Methods: A prospective randomized control trial (China Clinical Trials Registration Number: ChiCTR-OOR-15007060) was performed. Sixty patients with left colorectal cancer at Department of Gastrointestinal Surgery of Zhongshan Hospital from September 2015 to August 2017 were prospectively enrolled. Case inclusion criteria: (1) left colorectal adenocarcinoma (rectal cancer with distance ≥ 8 cm from tumor low margin to anal edge, sigmoid colon cancer, descending colon cancer and left transverse colon cancer) confirmed by preoperative pathology; (2) satisfactory conditions of conventional laparoscopic surgery; (3) maximum diameter of the tumor < 4.5 cm confirmed by preoperative abdominal and pelvic CT or MRI; (4) BMI < 30 kg/m². Case exclusion criteria: (1) benign lesions, mucinous adenocarcinoma, signet-ring cell carcinoma and other special pathological types of tumors confirmed by preoperative pathological examination; (2) multiple or recurrent cancers; (3) with a history of neoadjuvant chemoradiotherapy; (4) obvious regional infiltration or distant metastasis indicated by preoperative imaging examination; (5) intestinal obstruction, intestinal perforation, etc. Participants were randomly assigned to NOSES group (using the Cai tube) and conventional laparoscopy (CL) group by random number table method. Clinical data between two groups were compared and analyzed, including perioperative conditions, tumor exfoliation cell detection and bacterial culture results of intraperitoneal lavage fluid, postoperative complications (Clavien-Dindo grading), postoperative pain [visual simulation scoring (VAS) assessment], anal function (Kirwan anal function grading assessment), and postoperative 3-year disease-free survival (DFS), overall survival (OS), overall recurrence rate, and local recurrence rate. Results: A total of 60 patients were enrolled, with 30 in the NOSES group and 30 in the CL group. All the patients in the NOSES group successfully completed operation with Cai tube. Baseline data between the two groups were not significantly different (all P>0.05). There were no statistically significant differences between two groups in conversion rate to open surgery, number of lymph node harivested, proximal and distal resection margin of tumor, negative rate of circumferential margin, operation time, blood loss, inflammatory indexes, postoperative anal function, postoperative hospital stay, hospitalization cost, morbidity of postoperative complications (Clavien-Dindo grade II or above) (all P>0.05). Compared to the CL group, the NOSES group had lower maximum postoperative VAS score (2.5±0.3 vs. 5.1±0.4, t=3.187, P<0.01), and fewer use of additional postoperative analgesia [6.7% (2/30) vs. 33.3% (10/30),χ²=6.670, P=0.02]. The postoperative time to gas passage was shorter in the NOSES group [(2.2±1.4) days vs. (3.1±1.2) days,P=0.026]. No tumor cells and bacterial contamination were found in abdominal lavage fluid before and after operation in either group. The anal function at postoperative 3-month of all the patients in the NOSES group was Kirwan grade I to II, while in the CL group, anal function of 2 cases (6.7%) was Kirwan grade III, and of 28 cases was also Kirwan grade I to II, whose difference was not statistically significant (P>0.05). In the NOSES group and the CL group, 3-year DFS was 96.7% and 83.3% (P=0.090), OS was 100% and 90% (P=0.096), overall recurrence rate was 3.3% and 10.0% (P=0.166), and local recurrence rate was 3.3% and 3.3% (P=0.999), respectively, whose differences were not statistically significant (all P>0.05). Conclusions: In the treatment of left colorectal cancer, compared with conventional laparoscopic colectomy, NOSES colectomy using Cai tube exhibits less scar, less postoperative pain, shorter recovery of gastrointestinal function, and similar mid-term outcomes. Given proper surgical indications, the surgical procedure is safe and feasible.
Follow-Up Studies ; Humans ; Laparoscopy ; Pain, Postoperative ; Postoperative Complications/surgery* ; Prospective Studies ; Rectal Neoplasms/surgery* ; Retrospective Studies ; Sigmoid Neoplasms/surgery* ; Treatment Outcome

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
Animals ; Anxiety/etiology* ; Chronic Pain/etiology* ; GABAergic Neurons ; Gyrus Cinguli/metabolism* ; Hyperalgesia/metabolism* ; Pancreatitis, Chronic/pathology* ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Trinitrobenzenesulfonic Acid/toxicity*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors