OBJECTIVES: To investigate the regulatory role of the NLRP3 signaling pathway in hepatocyte pyroptosis in nonalcoholic steatohepatitis (NASH) under hypoxia. METHODS: Twenty-four male C57BL/6 mice were randomized equally into hypoxic control (A), hypoxic NASH model (B), hypoxic NASH+NLRP3 inhibitor (C), and hypoxic NASH+caspase-1 inhibitor (D) groups. In groups B-D, the mice were fed a methionine choline-deficient (MCD) diet under hypoxic conditions (to simulate a 5000 m altitude) for 6 weeks; the mice in groups C and D received intraperitoneal injections of the respective inhibitors every other day. RESULTS: Compared with those in group A, the mice in group B showed significantly elevated serum levels of FBG, TC, TG, ALT and AST, increased liver lipid content, inflammatory cell infiltration and collagen fiber deposition, and enhanced hepatic expressions of NLRP3, caspase-1, IL-1β and GSDMD proteins, with obvious swelling, cristae breakage, vacuolization, and outer membrane disruption of the mitochondria, ribosome loss in the cytoplasm, destruction of the nuclear membrane, and pathological changes of the rough endoplasmic reticulum. Treatment with NLRP3 inhibitor and caspase-1 inhibitor both significantly lowered serum levels of TC, TG, ALT and AST (but without significantly affecting FBG) in the mouse models, and reduced liver lipid content, inflammatory cell infiltration, collagen deposition, and expression levels of NLRP3, caspase-1, GSDMD and IL-1β. The treatments also significantly improved pathological changes in the mitochondria, ribosomes and endoplasmic reticulum in liver tissues of the mice. CONCLUSIONS NLRP3 signaling pathway plays a key role in promoting hepatocyte pyroptosis in NASH mice under hypoxic condition, and inhibiting this pathway can effectively reduce liver inflammation, suggesting its potential as a therapeutic target for NASH treatment.
Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Mice, Inbred C57BL ; Male ; Hepatocytes/pathology* ; Signal Transduction ; Mice ; Hypoxia/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

With the development of clinical related disciplines, the update and establishment of relevant standards/guidelines at home and abroad, GBZ 185-2006 Diagnostic Criteria for Occupational Medicamentose-like Dermatitis due to Trichloroethylene (hereinafter referred to as “GBZ 185-2006”) was unable to meet clinical needs. Therefore, the GBZ 185-2006 was revised based on the principles of evidence-based medicine, in accordance with relevant laws/regulations and relevant standards/guidelines in combination with review of research data on occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) home and abroad, and the development of clinical practice and clinical related disciplines. The main modifications include: adding terms and definitions of OMDT, modifying the description of clinical manifestations of the diagnostic principles, adjusting the description of latency, deleting the diagnostic requirement of the incidence probability, adding the specific allergen patch test as the etiological diagnostic index, standardizing the application scope, operating procedure and precautions of the specific allergen patch test. In addition, the relevant content of “Basic Characteristics and Clinical Types of Skin Damage of Medicamentose-like Dermatitis due to Trichloroethylene” in Appendix A is improved, the treatment principles are revised, and the content of new progress in treatment, artificial liver application, are added. The revised GBZ 185-2024 Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene is more scientific and practical, and can provide technical basis for the standardized diagnosis and treatment of OMDT in medical and health institutions.

Objective To analyze risk factors of acute respiratory failure(ARF)in patients with hypertriglyceridemia acute pancreatitis(HTG-AP)and construct a risk prediction model.Methods A total of 222 HTG-AP patients were included in this study and divided into the non-ARF group(176 cases)and the ARF group(46 cases)according to diagnostic guidelines for ARF.Clinical data of the two groups were compared and the predictive factors were screened.These selected factors were then utilized in a multivariate Logistic regression analysis to construct a Logistic regression model.Subsequent evaluation of the model′s predictive ability,accuracy and clinical utility was conducted through ROC,curve analysis,calibration plot examination and decision curve analysis(DCA),respectively.Results Compared with the non-ARF group,the levels of high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL)-C and albumin(ALB)were decreased in the ARF group(P＜0.05),while the levels of creatinine(Cr),urea nitrogen(BUN),aspartate aminotransferase(AST)and C-reactive protein(CRP)were increased,and the incidence of pleural fluid and ascites was also increased(P＜0.05).Multivariate Logistic regression analysis showed that higher levels of Cr and AST,lower levels of ALB,HDL-C and ascites were independent risk factors for HTG-AP complicated ARF(P＜0.05).Based on these results,a column-line prediction model for HTG-AP complicated ARF was established.After internal verification,the area under curve(AUC)of receiver operating characteristic(ROC)curve of the nomogram model was 0.952(95%CI:0.923-0.981),the Youden index was 0.808 and the sensitivity and specificity were 93.33%and 87.43%,respectively.The calibration curve showed that the probability of HTG-AP concurrent ARF predicted by the model was in good agreement with the actual probability.The DCA curve showed that the model had certain clinical value.Conclusion The nomogram prediction model combined could provide a scheme for the clinical prevention of HTG-AP complicated with ARF.

Objective To study the diagnostic value of narrow-band imaging ( NBI) combined with endoscopic ultrasonography ( EUS) for ampullary tumors. Methods A total of 21 patients suspected with ampullary lesions by imaging or endoscopic examination from December 2015 to March 2017 were enrolled in this prospective study. All patients underwent NBI and EUS, and 20 patients underwent biopsy. The type of ampullary tumor was predicted by preoperative examination, and appropriate treatment methods were chosen. The final diagnosis was confirmed by biopsy, surgical pathology, and clinical follow-up for more than 6 months. The accuracy of NBI combined with EUS and biopsy in diagnosis of ampullary malignant tumors was calculated according to the gold standard. The Chi-square test was used to compare diagnostic accuracies. Results The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of NBI combined with EUS in diagnosis of ampullary malignancies were 94. 1％ (16/17), 100. 0％ (4/4), 95. 2％ (20/21), 100. 0％ (16/16), and 80. 0％ (4/5), respectively. The corresponding indicators of preoperative biopsy were 41. 2％ ( 7/17) , 100. 0％ ( 3/3) , 50. 0％ ( 10/20) , 100. 0％ ( 7/7) , and 23. 1％( 3/13) , respectively. The accuracy of NBI combined with EUS in diagnosing ampullary malignant tumor was significantly higher compared with preoperative biopsy ( P=0. 004) . Conclusion NBI combined with EUS can more accurately predict benign or malignant ampullary tumor, and better guide the choice of surgical methods compared with preoperative biopsy.

Objective To evaluate measurement of the submucosal thickness with endoscopic ultrasonography (EUS) for activity of Crohn disease (CD).Methods Ten patients with active stage of CD and 10 healthy controls (HC) underwent EUS.Simple endoscopic score for Crohn disease(SES-CD)and submucosal thickness at the most severe lesions were measured and recorded.Submucosal thickness of the same region in CD patients were measured at remissive stage.In order to analyze the relationship between submucosal thickness and the stage of CD, submucosal thickness were compared among patients at active stage of CD, remissive stage of CD and HC.And the cut-off value of submucosal thickness was calculated to diagnose the stage of CD.Results The mean submucosal thicknesses of active stage and remissive stage of CD were 6.48±1.95 mm and 2.47±1.08 mm,respectively (P<0.01).The correlation analysis showed that submucosal thickness had a positive correlation with Crohn disease activity index(CDAI)(r=0.708,P<0.01) and SES-CD(r=0.807,P<0.01).Receiver operating characteristic curve analysis was used for 10 cases of CD patients and the area under the curve was 0.985(P<0.01).The cut-off value of submucosal thickness to diagnose active stage of CD was 3.85 mm, and the sensitivity and specificity reached 100% and 90% respectively.The Youden index was 0.9.Conclusion Measurement of gastrointestinal submucosal thickness by EUS could contribute to evaluate the stage of CD and to guide clinical treatment.

Objective To evaluate the safety and efficacy of endoscopic ultrasound (EUS) guided ethanol ablation of benign insulinoma and compare its' advantages and disadvantages with surgical treatment. Methods From April 2011 to February 2016, clinical data of 38 patients with benign insulinoma treated by EUS-guided ethanol ablation or surgical treatment were retrospectively analyzed. Results 97.4% (37/38) patients had a typical clinical manifestation of Whipple's triad, and the I/G ratio of 82.9% patients (29/35) was more than 0.3 with their onset of hypoglycemia. The positive preoperative etiologic diagnosis rates of transabdominal ultrasonography, CT, MRI, PET/CT and EUS were 50.0%, 67.6%, 66.7%, 75.0%, 89.7% respectively. In the current study, 18 patients underwent EUS-guided ethanol ablation (EUS-FNI group) and 20 patients received surgicaltreatment (surgical group). Compared with the surgical group, the operation time, intraoperative hemorrhage volume, postoperative complications, length of stay and hospitalization costs were significantly reduced in the EUS-FNI group (P < 0.05). No treatment-related complications was observed in EUS-FNI group, while 40.0% (8/20) patients in surgical group had complications. During the follow-up period, all these patients maintained stable blood glucose without taking medication, and there's no recurrence of insulinoma in EUS-FNI group after the last treatment with alcohol injection; In surgical group, only 90.0% (18/20) patients had no recurrence, episode of hypoglycemia was less after the operation in 10.0% (2/20) patients. Conclusion EUS-guided ethanol ablation of benign insulinoma is safe and effective, compared with traditional surgical treatment, EUS-guided ethanol ablation is minimally invasive, costs less, recovers fast after treatment and has fewer complications.

Objective To evaluate the therapeutic effect of endoscopic management of plastic stents of post-liver transplantation anastomotic biliary stricture. Methods From January 2010 to October 2015, clinical data of patients with post-liver transplantation anastomotic biliary stricture and received endoscopic retrograde cholangiopancreatog﹣raphy and plastic stents management was collected. The technical success rate, ERCP-related complications, clinical remission rate and long-term complications were main outcome measurements to compare the efficacy and safety of different number of stents in managing post-liver transplantation anastomotic biliary stricture. Results Among the 18 patients (0.5 ~ 60.0 months) with post-liver transplantation ABSs, seven patients received less plastic stents treat﹣ment (< 3 stents), nine patients with persistent anastomotic or recurrent stricture received multiple plastic stents treatment (≥ 3 stents), two patients received multiple plastic stents treatment once suffered with post-liver trans﹣plantation ABSs. The endoscopic technical success rate was seventy-six over eighty (95.0 %). Among the seven pa﹣tients received less plastic stents treatment, one loss to follow-up, two were still under treatment, one died of acute hepatic failure, one died of septic stock, one combined with biliary fistula resulted in treatment failure, one achieved clinical remission, the clinical remission rate was one third (33.3 %). Among the eleven patients received multiple plastic stents treatment, two loss to follow-up, one was still under treatment, two received surgery because of failed treatment, six achieved clinical remission, the clinical remission rate was 75.0 % (6/8). The average diameters and stent durations of management of 1 stent, 2 stents, 3 stents, 4 stents, 5 stents, 7 stents were 8.5 F, 17.0 F, 24.0 F, 28.0 F, 36.0 F, 50.0 F. Among the six early postoperative complications, five cases occurred in less stent manage﹣ment and one occurred in MPSs management, the early postoperative complication rate was 7.5 %(6/80). No severe ERCP-related complications and procedure-related deaths. Conclusions Endoscopic management of plastic stents is safe and effective for post-liver transplantation ABSs. Providing larger biliary support, the multiple plastic stents treatment was superior to less plastic stents treatment in view of clinical remission rate, especially for refractory one. Multiple plastic stents did not increase the incidence of complications, it could be used as the first-line treatment of post-liver transplantation duct-to-duct biliary anastomosis for its safety and effectivity.

Objective To evaluate the safety and efficacy of endoscopic ultrasonography(EUS) guided ethanol ablation in patients with insulinoma. Methods The data of 10 patients with insulinoma trea-ted at the First Affiliated Hospital of Guangxi Medical University from December 2013 to January 2015 were prospectively analyzed. Results The patients were given EUS-guided ethanol ablation with dose of 0. 10 to 2. 00 ml(average 0. 70 ± 0. 62 ml)in pancreatic lesions for 15 times. No complications were observed dur-ing and after the procedure. The blood glucose improved after the procedure[4. 8(3. 9-5. 5)mmol/ L VS 2. 4 (1. 9-2. 5)mmol/ L,P < 0. 05]and the serum insulin level significantly decreased[83. 7(40. 1-143. 5) pmol/ L VS 177. 3(66. 5-200. 6)pmol/ L,P<0. 05]. The average hospital stay was(4. 3±1. 5)days. The patients were followed up for 6-12 months. EUS indicated that the echo of pancreatic lesions changed from high to low. CE-EUS revealed low enhancement and lack of blood supply. Conclusion EUS-guided ethanol ablation may become a promising minimally invasive treatment for insulinoma because of its safety,efficacy and low price. Trail registration Clinical Trial.gov,NCT02121366.