Objective To explore the correlations between serum Mas-related G protein-coupled receptor X2 (MRGPRX2), interleukin (IL)-4, IL-5, IL-6, IL-13, IL-23 and IL-33 levels and chronic spontaneous urticaria (CSU). Methods The clinical characteristics and laboratory data from 55 patients with CSU and 21 healthy controls at Huashan Hospital, Fudan University from February 2021 to September 2023 were collected. The disease activity and severity of CSU patients were assessed. Serum level of MRGPRX2 was tested using enzyme-linked immunosorbent assay (ELISA), and levels of IL-4, IL-5, IL-6, IL-13, IL-23, and IL-33 were measured using Luminex multiplex assay in all subjects. Spearman correlation analysis was used to evaluate the correlations between biomarkers and other parameters in CSU patients, and logistic regression analysis was performed to identify factors influencing CSU. Results CSU patients exhibited significantly higher serum levels of MRGPRX2 (2.41[0, 11.51] ng/mL vs 0[0, 2.86] ng/mL, P＝0.015) and IL-23 (0.09[0.04, 0.56] pg/mL vs 0.05[0.03, 0.08] pg/mL, P＝0.033) than healthy controls. There was no difference in levels of other cytokines between the two groups. There was no difference in levels of MRGPRX2 and cytokines between severe and non-severe CSU patients. Correlation analysis showed that serum MRGPRX2 levels in CSU patients were positively correlated with IL-4 (r＝0.345, P＝0.010) and IL-6 (r＝0.395, P＝0.003) levels. Logistic regression analysis indicated that MRGPRX2≥0.055 ng/mL and IL-23≥0.135 pg/mL were independent risk factors for CSU (P＜0.05). Conclusions Serum levels of MRGPRX2 and IL-23 in CSU patients are elevated, which may be involved in the pathogenesis of CSU.

Objective To evaluate the value of a machine learning-based biparametric magnetic resonance imaging(bpMRI)radiomics model in predicting clinically significant prostate cancer(csPCa)in the transitional zone.Methods A retrospective analysis was con-ducted on 507 cases in two medical centers.All patients underwent prostate MRI examinations before surgery,with complete patho-logical data.The case distribution was as follows:256 cases of csPCa,97 cases of clinically insignificant prostate cancer(ciPCa),and 154 cases of benign prostatic hyperplasia(BPH).Using the R language,the data from Center One was randomly divided into training and test groups at a ratio of 7∶3,and the data from Center Two as an independent external validation group.The image features from T2 WI and diffusion weighted imaging(DWI)were extracted,and the least absolute shrinkage and selection operator(LASSO)was used to reduce dimensionality and filter features.Two datasets were constructed based on T2 WI features alone and combined T2 WI and DWI features.Six prediction models were established using random forest(RF),logistic regression(LR),and support vector machine(SVM).The efficacy of six models of T2 WI features and combined T2 WI and DWI features in the diagnosis of prostate dis-eases through receiver operating characteristic(ROC)curve,area under the curve(AUC),and decision curve analysis(DCA)were compared and evaluated.Results In the training group,feature screening identified 7 and 8 features from the T2WI single sequence and the T2WI with DWI dual sequence for csPCa prediction in the transitional zone.The results showed that the T2WI with DWI dual sequence RF model had the highest AUC performance.The AUC of the training,test,and validation groups were 0.950,0.866,and 0.818,respectively.The test group accuracy was 0.805,sensitivity was 0.690,and specificity was 0.920;the validation group accu-racy was 0.726,sensitivity was 0.661,and specificity was 0.793.DCA showed that within a wide probability threshold range,the T2 WI with DWI dual sequence RF model had the greatest net benefit.Conclusion Based on the bpMRI radiomics model,non-invasive prediction of csPCa in the transitional zone can be achieved before surgery,which helps to make clinical diagnosis and treatment decisions.

Objective:To analyze the risk factors of clinically significant bleeding in patients with severe acute pancreatitis (SAP).Methods:The clinical data of SAP patients who were managed at Changhai Hospital affiliated to Naval Medical University from January 1, 2014 to October 31, 2022 were retrospectively analyzed. Twenty-nine SAP patients with clinically significant bleeding were classified to form the bleeding group. There were 23 males and 6 females, aged (56.25±14.01) years old. Another 116 SAP patients with similar general data but with no clinically significant bleeding during the same hospitalization period were included to form the non-bleeding group based on a ratio of 1∶4. There were 94 males and 22 females, aged (56.14±13.96) years old in this non-bleeding group. The general data, modified CT severity index (MCTSI), bedside index for severity of acute pancreatitis (BISAP) and other clinical data of the two groups were collected to determine the risk factors of bleeding in SAP patients.Results:Of the 29 patients with bleeding, 6 had gastrointestinal bleeding, 14 had intra-abdominal bleeding, and 9 had mixed bleeding sites, 15 were cured and discharged, and 14 died. All the 29 SAP patients with bleeding received treatment using drugs. In addition, 8 patients underwent successful hemostasis using digital subtraction angiography, 3 underwent successful endoscopic hemostasis, 2 underwent successful surgical hemostasis, and 2 underwent successful conservative drug hemostasis. Multivariate logistic regression analysis showed that SAP patients with higher MCTSI ( OR=1.824, 95% CI: 1.187-2.802), longer prothrombin time (PT) ( OR=3.431, 95% CI: 1.470-8.007) and higher BISAP ( OR=2.286, 95% CI: 1.054-4.957) had an increased risk of bleeding (all P<0.05). Conclusion:The prognosis of SAP patients was compromised with bleeding. High MCTSI, prolonged PT, and high BISAP were independent risk factors for bleeding in SAP patients.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*

Background::The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods::In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. Results::The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions::The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration::ClinicalTrials.gov, NCT04215653.

AIM: To investigate the effect of low-dose aspirin on primary prevention of non-fatal myocardial and cerebral infarction in patients with type 2 diabetes mellitus. METHODS: From January 2015 to December 2016,40-90 years old patients with type 2 diabetes were treated in the Department of Endocrinology of Yijishan Hospital of Wannan Medical College for more than 2 times (the interval of hospitalization was more than 3 months) , we use the hospital's his system to search out-patient and in-patient files, patients were divided into aspirin group and non-aspirin group according to the use of low-dose aspirin within 1 year after the first visit, the basic data of the first visit were collected: name, sex, age, course of diabetes, systolic and diastolic blood pressure, patients were recorded for laboratory markers including fasting blood glucose, glycated hemoglobin, triglyceride, total cholesterol, Low-density lipoprotein, high-density lipoprotein, creatinine, and platelets, complications such as hypertension, coronary heart disease, atrial fibrillation, hyperlipidemia, diabetic nephropathy and arteriosclerosis were recorded. A Chi square test and a Cox proportional hazard model were used to compare baseline data and cerebrovascular disease after the first use of aspirin. RESULTS: Of the 4 176 patients, 2 137 were type 2 diabetes, 417 were eligible for admission, including 198 males, 219 females, 224 aspirin users and 193 non-users. There was no significant difference in the incidence of cerebral infarction between the aspirin group and the non-aspirin group (χ2=0.820, P=0.365). The incidence of non-fatal myocardial infarction was lower than that of the aspirin non-aspirin group (χ2=10.099, P=0.01) , the incidence of massive hemorrhage was significantly higher than that of aspirin-free group χ2=5.425, P=0.020) . In a subgroup analysis of aspirin use, patients younger than 60 years of age had a lower incidence of ischemic stroke (cerebral infarction) and a risk ratio of 0.428 (95%CI: 0.255-0.719, P=0.001) compared with patients older than 60 years of age, the incidence of cerebral infarction was higher in female patients with a risk ratio of 1.574 (95%CI: 1.018-2.434, P=0.041). CONCLUSION: In this study of patients with type 2 diabetes, low-dose aspirin reduced the incidence of nonfatal myocardial infarction but had no significant effect on the incidence of nonfatal ischemic stroke, and significantly increase the incidence of major bleeding events, we should reconsider the use of low-dose aspirin as a potential benefit of nonfatal cerebral infarction in patients with type 2 diabetes.

Objective:To analyze the changes and efficacy of antiviral treatment regimens in patients with chronic hepatitis C.Methods:This was a single center retrospective study. A total of 157 patients with chronic hepatitis C in Huashan Hospital, Fudan University from January 2014 to February 2019 were included. Clinical informations of antiviral treatment and follow-up were collected. The sustained virologic response (SVR) rate and adverse events in patients receiving different antiviral regimens were compared. Chi-square test was used for statistical analysis.Results:Among the 157 patients, 133 patients had sufficient follow-up data. Seventy-one patients received treatment before 2017, among which 63 patients received interferon regimens and the SVR rate was 74.65%(53/71). Sixty-two patients received treatment after 2017, among which 61 patients received direct-acting antiviral agents (DAA) regimens and the SVR rate was 98.39%(61/62). The difference in SVR rate between the two groups was statistically significant ( χ2=15.230, P<0.01). In 69 patients who received DAA regimens from 2014 to 2019, the SVR at post-treatment week 12 (SVR12) was 95.65%(66/69). Among 43 patients who received DAA regimens containing sofosbuvir, the SVR12 rates of patients with hepatitis C virus genotype 1, 3 and other genotypes were 15/15, 5/6 and 90.91%(20/22), respectively. All the 26 patients who received DAA regimens non-containing sofosbuvir achieved SVR12. The SVR12 rates of patients with different hepatitis C virus genotypes and DAA regimens were not significantly different ( χ2=5.243, P=0.263). The incidences of adverse events in pre-2017 group and post-2017 group were 84.62%(77/91) and 6.06% (4/66), respectively. The difference was statistically significant ( χ2=94.520, P<0.01). The most common adverse events were decreases in neutrophil cell count, decreases in hemoglobin level and decreases in platelet count. Treatment was ceased in six patients due to adverse events. Conclusions:After 2017, the majority of patients with chronic hepatitis C received DAA regimens instead of interferon regimens. The SVR rate increases and the incidence of adverse events decreases along with the changes of leading treatment regimens.The SVR12 rate is higher in patients receiving DAA regimens, regardless of hepatitis C virus genotypes.

Objective To assess the safety and diagnostic accuracy of manual carbon dioxide (C02) digital angiography in performing endovascular therapy (EVT) for arteriosclerosis obliterans (ASO) of lower extremity in patients who have renal insufficiency or iodine allergy. Methods The clinical data of 19 patients with lower extremity ASO complicated by renal insufficiency or iodine allergy, who were admitted to authors' hospital to receive EVT of lower extremity with intraoperative C02 angiography during the period from January 2013 to March 2015, were retrospectively analyzed. Using manual bolus injection of C02, or with additional use of minimum dose of iodinated contrast media, CO2 angiography was performed so as to guide EVT procedure. The safety and diagnostic accuracy of manual C02 angiography were evaluated. Results A total of 21 endovascular treatments were performed in 19 patients with lower extremity ASO, and a total of 28 arterial segment lesions were treated. The technical success rate was 100％. Ankle-brachial index (ABI) was improved from preoperative 0. 56±0. 08 to postoperative 0. 74±0. 07, the difference was statistically significant (t= -20. 605, P＜0. 00l). The mean serum creatinine (sCr) levels tested at 48 h and one week after the treatment were (159. 91±33. 21) μmol/L and (143. 44±43. 59) μmol/L respectively, which were not significantly different from preoperative (139. 5±37. 6) μmol/L (t=-1. 098, P=0. 285), and none of these results met the standard of contrast nephropathy. Among the 21 times of EVT procedure, additional use of iodinated contrast media was employed in 13 procedures, the average used amount of iodine contrast agent was (12±5. 5) mL. After the treatment, sCr level was elevated, the estimated glomerular filtration rates (eGFR) were lower than 50 mL· min-1 · 1. 73 m-2, which restored to preoperative level in one week. CO2 angiography showed that the image quality of all arteries above the knee joint met the requirements of treatment, except for one patient whose images could not accurately display the length and extent of the stenosis due to restenosis of the superficial femoral artery. The image quality of the arteries below the knee level was usual. Conclusion In performing EVT procedure to treat lower extremity ASO the use of C02 angiography is safe. The image quality of all arteries above the knee joint is satisfactory, it can significantly reduce, or even avoid, the use of iodine contrast agents. Therefore, this technique is especially suitable for patients who have renal insufficiency or iodine allergy. (J Intervent Radiol, 2018, 27:211-214)

Objective To investigate the importance of hepatitis B virus ( HBV ) infection in the patho-genesis of cholangiocarcinoma ( CC) and further clarify the correlation between the occurrence of intrahepatic and extrahepatic cholangiocarcinoma .Methods HBV protein and gene of 52 formalin fixed,paraffin embedded tis-sues with CC were detected by immunohistochemistry and nest PCR .Results Hepatitis B virus X gene was de-tectable in 33.3%(7/21)of 21 intrahepatic cholangiocarcinoma cases .Hepatitis B surface antigen(HBsAg)was detectable in 21.7%(5/21)and hepatitis B core antigen(HBcAg)was detectable in 19.0%(4/21)of 21 intrahe-patic cholangiocarcinoma cases .In contrast,no HBsAg,HBcAg and hepatitis B virus X gene were detected in any of the 31 extrahepatic cholangiocarcinoma cases .Conclusion HBV infection is a significant risk factor for intra-hepatic cholangiocarcinoma ,but not for extrahepatic cholangiocarcinoma ,in Northeast of China .The integration of HBV gene may be involved in the carcinogenesis of intrahepatic bile duct epithelial cells .

Aim Toinvestigatetheeffectofhigh,me-dium and low doses of Mahuang decoction on the re-lease amount of rat hippocampal neural transmitter (Glu,Gly,Asp,GABA),then compare Mahuang de-contion with ephedra alkaloids and ephedra.Methods Ratswererandomlydividedinto6groupsandgiven orally with Mahuang decoction of high dose (calculated by ephedra 4 g·kg-1 ),medium dose (calculated by ephedra 2 g·kg-1 ),low dose (calculated by ephedra 1 g · kg-1 ),ephedra (calculated by ephedra 2 g · kg-1 ),ephedra alkaloids (ephedrine 7 mg · kg-1 , pseudoephedrine 2. 4 mg · kg-1 , methylephedrine 1. 12 mg · kg-1 )and blank control group.Samples were obtained from the hippocampus of conscious rat by microdialysis sampling technique.The content of ami-no acid neurotransmitters in dialysates was detected u-sing the established HPLC-ECD with OPA pre-column derivationmethod.Results Fouraminoacidneuro-transmitters could be well separated in 28 min.High, medium and low doses of Mahuang decoction,ephedra and ephedra alkaloids significantly increased the con-tent of these four amino acid neurotransmitters,com-pared with blank control group (P<0. 05 ).Ephedra alkaloids significantly reduced the levels of inhibitoryamino acid neurotransmitters GABA and Gly in 90 min,compared with the medium dose of Mahuang de-coction.Excitatory neurotransmitters of ASP and Glu in hippocampus showed the trend of increase first and then decrease after oral administration of Mahuang de-coction and ephedra. The levels of Glu and Asp reached peaks from 90 min to 120 min after treatment with Mahuang decoction,and also increased along with dose increase of Mahuang decoction.In comparison with the medium dose of Mahuang decoction group,the level of Glu reached peak at 90 min and 150 min in ephedra alkaloids group and ephedra group respective-ly,and the content of Glu significantly increased at peaktime.Conclusions Increasedcontentofexcita-tory amino acid neurotransmitters (Asp and Glu ) shows positive correlation with the dose of Mahuang de-coction.Other components in Mahuang decoction in-hibits the up-regulation effect of ephedra and ephedra alkaloids on Glu,and promotes the up-regulation effect of ephedra alkaloids on GABA and Gly.