BackgroundMetabolic syndrome （MetS） is highly prevalent in patients with mental disorders， including elevated diastolic or systolic blood pressure， elevated fasting glucose， hypercholesterolemia， abdominal obesity and so on. As an important component of MetS， the relationship between hypercholesterolemia and mental disorder has been extensively reported， whereas few genome-wide association studies （GWAS） have been conducted to identify the causal role of mental disorders in hypercholesterolemia. ObjectiveTo explore the potential causal relationship between mental disorders and hypercholesterolemia by two-sample Mendelian randomization （MR） method. MethodsSummary data from GWAS were analyzed. Single nucleotide polymorphisms （SNPs） strongly associated with mental disorders were chosen as instrumental variables， and hypercholesterolemia was used as outcome variable. MR analysis utilized inverse-variance weighted （IVW）， MR-Egger regression and weighted median estimation （WME） as the primary analytical tool， and supplemented by simple mode （SM） and weighted mode （WM）. The causal relationship between mental disorders and the risk of hypercholesterolemia was illustrated in terms of odds ratio （OR）. ResultsA total of 36 SNPs associated with mental disorders were identified as instrumental variables. The primary findings from IVW revealed existence of a causal relationship between mental disorders and hypercholesterolemia （IVW： OR=1.067， 95% CI： 1.026~1.109， P=0.001）. Findings from the additional methods （MR-Egger regression， WME， SM， WM） were basically consistent with those reported in IVW method. Further verification indicated that the causal relationship between mental disorders and the risk of hypercholesterolemia was not affected by genetic polymorphism （P>0.05）. The absence of heterogeneity was confirmed through Cochran's Q test and MR-Egger regression （P>0.05）. Furthermore， no causal association in the reverse direction was found （P>0.05）. ConclusionThere is a causal relationship between mental disorders and hypercholesterolemia， and patients with mental disorders may have an increased probability of suffering from hypercholesterolemia.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

After 50 years of clinical development， endoscopic retrograde cholangiopancreatography （ERCP） has become the preferred method for the clinical diagnosis and treatment of cholangio-pancreatic duct diseases； however， the major postoperative complications of ERCP， such as pancreatitis， hemorrhage， and perforation， are still a difficult issue faced by clinicians， and postoperative perforation is associated with an extremely high risk of death. Therefore， it is very important to explore the risk factors for perforation after ERCP， make a definite diagnosis of perforation in a timely manner， and formulate precise prevention and treatment measures. By reviewing a large number of articles， this article summarizes the influencing factors for perforation after ERCP and related diagnosis and treatment measures.

OBJECTIVE To prepare nanoparticle-based targeting preparation loaded with triptolide （TP）， and evaluate its quality， targeting ability and cytotoxic effects. METHODS Polymer nanoparticles carrying TP-targeted folic acid （FA） receptor （TP@PLGA-PEG-FA） were fabricated using poly （lactic-co-glycolic acid）/polyethylene glycol/FA （PLGA-PEG-FA） as the carrier by emulsion and volatilization technique. The morphology and distribution were observed， and their particle size， Zeta potential， polydispersity index （PDI）， drug loading capacity and encapsulation efficiency were measured. Their stability， blood compatibility， in vitro drug release， uptake by RAW264.7 cells （localization with fluorescent dye Cy3.5）， and in vitro cytotoxicity were evaluated. RESULTS TP@PLGA-PEG-FA exhibited spherical shape and uniform distribution， with particle size of （122.60±0.02） nm， Zeta potential of （－17.6±0.6）mV， and PDI of 0.26±0.02； drug loading capacity and encapsulation efficiency of TP were measured to be （7.78±0.05）% and （68.62±0.03）%， respectively. The hemolysis rates of 100， 200， 300， 400 µg/mL TP@PLGA- PEG-FA were 0.77%， 0.92%， 1.34% and 1.63%， respectively. There were no significant changes in particle size， PDI and Zeta potential when TP@PLGA-PEG-FA were placed in 4 ℃ water for 14 days and in DMEM culture medium containing 10% fetal bovine serum at 37 ℃ for 12 h. The cumulative release rate of TP@PLGA-PEG-FA was （84.83±0.29）% in phosphate buffer at pH5.5 for 72 h， which was significantly higher than the cumulative release rates in phosphate buffer solutions at pH7.4 and 6.5 for 72 h （[ 42.37±0.35）% and （63.83±0.29）% ， respectively] （P＜0.05）. Activated RAW264.7 cells took up significantly more Cy3.5@PLGA-PEG-FA than they took up Cy3.5@PLGA-PEG-FA+free FA and Cy3.5@PLGA-PEG. When the mass concentration of TP was≥15.63 ng/mL， the survival rates of activated cells in the TP@PLGA-PEG-FA groups were significantly lower than those of the same mass concentration of free TP groups （P＜0.05）. CONCLUSIONS The prepared TP@PLGA-PEG-FA has high stability， good blood compatibility， active targeting and cytotoxicity to inflammatory cells.

Objective:To investigate the risk factors for the relapse of autoimmune pancreatitis (AIP) after steroid therapy.Methods:Clinical data of 72 AIP patients treated with steroids in Nanjing Drum Tower Hospital from January 2012 to December 2023 were collected retrospectively. AIP patients were divided into relapse group ( n=25) and non-relapse group ( n=47) based on the presence or absence of their relapse after steroid therapy. Patients' age of onset, gender, history of diabetes mellitus, first clinical manifestations, serum IgG4 and CA19-9 level, imaging features and other organ involvements were recorded. Oral prednisone was used at an initial dose of 0.6 mg·kg -1·d -1, gradually reduced to 5-10 mg/d and then maintained at a low dose. The follow-up period started from steroid initiation to the last follow-up or relapse. The presence of maintenance steroid treatment, time interval between onset and steroid initiation, the presence of significant IgG4 decrease and the presence of persistently enlarged pancreas after therapy were recorded. The cumulative relapse rate curve after steroid therapy was drawn by Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazard regression model. The receiver operator characteristic curves (ROC) were plotted and the area under the curve (AUC) was calculated. The Log-Rank test was used to analyze the differences on the relapse between different groups. The subgroup forest plot was drawn to assess the effect of risk factors on the relapse of AIP in different subgroups. Results:The 72 patients with AIP had a median follow-up of 42 (12-127) months. 34.7% (25/72) of patients relapsed after steroid therapy during the follow-up period. The percentages of patients whose first clinical manifestation was abdominal distension or acute pancreatitis, whose interval between onset and steroid initiation was more than 1 year and whose pancreases were persistently enlarged after steroid therapy in the relapse group were higher than those in the non-relapse group, and the differences were all statistically significant (all P value <0.05). The 1-, 3- and 5-year cumulative relapse rate after steroid therapy was 20.8%, 34.1% and 37.8%, respectively. Univariate analysis found that the first clinical manifestations of abdominal distension or acute pancreatitis, interval between onset and steroid initiation more than 1 year, and persistently enlarged pancreas after steroid therapy were all significantly associated with relapse (all P value <0.05). Multivariate analysis found that interval between onset and steroid initiation more than 1 year and persistently enlarged pancreas after steroid therapy were independent risk factors for relapse of AIP [hazard ratio ( HR)=3.606 and 6.515, 95% confidence interval (95% CI) 1.362-9.854 and 2.088-20.326]. Kaplan-Meier survival curves showed that the relapse rate after steroid therapy was higher in AIP patients whose interval between onset and steroid initiation was more than 1 year than in those whose interval was less than 1 year (55.6% versus 27.8%), and the relapse rate in AIP patients with persistently enlarged pancreas after steroid therapy was higher than that in those without it (77.8% versus 28.6%), and the differences were both statistically significant (both P<0.05). Subgroup forest plot showed that persistently enlarged pancreas after steroid therapy was an independent risk factor for relapse of AIP regardless of the presence of a diabetes mellitus history, the first manifestation of abdominal pain, the diffuse or focal type in pancreatic imaging, and the presence of dilated pancreatic duct or not (all P value <0.05). Conclusions:Time interval between onset and steroid initiation more than 1 year and persistently enlarged pancreas after steroid therapy were independent risk factors for the relapse of AIP after steroid therapy.

Objective:To understand the residents' cognition of commercial long-term insurance in Tianjin so as to provide a reference for improving service effect and quality of long-term insurance.Methods:A total of 31 residents from six districts of Tianjin were selected for semi-structured interviews from December 2022 to February 2023 by the convenient sampling method, and the data were analyzed by Colaizzi 7-step analysis method.Results:Three themes were extracted, namely, inadequate interpretation and promotion of commercial long-term insurance, immature development of commercial long-term insurance, and the ability of commercial long-term insurance to help caregivers reduce their family burden.Conclusions:The residents of Tianjin have a low awareness of commercial long-term insurance, which cannot meet the needs of most residents. It is urgent to strengthen their publicity further and improve their system.

To investigate the effects of ORF9 gene of porcine circovirus type 2(PCV2)on PK-15,eu-karyotic expression plasmid was constructed and transfected into PK-15 cells,and the effects of overexpression of ORF9 on proliferation,apoptosis and immunization of PK-15 cells were exam-ined by flow cytometry and qRT-PCR.The results showed that ORF9 gene overexpression signifi-cantly up-regulated the expression levels of the ER stress marker gene GRP78,increased the num-ber of S phase cells,accelerated cell cycle progression,increased the apoptosis rate of PK-15 cells,up-regulated the expression levels of apoptosis-related genes caspase-3,caspase-8,caspase-9,p53 and Bax(P＜0.01),down-regulated the expression levels of apoptosis-related genes Bcl-2,up-reg-ulated the expression levels of immune-related genes 1L-8,IL-10,NF-κB and TNF-α(P＜0.01),and down-regulated the expression levels of immune-related genes IL-2,IFN-β and IL-12(P＜0.01).The above results indicate that ORF9 gene may promote the proliferation and apoptosis of PK-15 cells and play a role in the escape process of PK-15 cells.

Objective:To evaluate the efficacy and safety of 308-nm excimer lamp and 308-nm excimer laser in the treatment of pediatric vitiligo.Methods:Clinical data were collected from children with stable vitiligo who received targeted phototherapy at the Department of Dermatology of Xijing Hospital from 2010 to 2015, and retrospectively analyzed. The patients were treated with either 308-nm excimer laser or 308-nm excimer lamp, and all were given topical drugs. The treatment lasted for at least 3 months, and follow-up for at least 6 months. The severity of vitiligo was assessed using the Vitiligo Area and Severity Index (VASI) score. The efficacy was evaluated after 3 months of treatment, and at least a 50% reduction in the VASI score (VASI50) was defined as "effectiveness". A logistic regression model was constructed using treatment efficacy as the dependent variable to screen factors related to the treatment outcome. The Wilcoxon signed-rank test was used to compare skewed data before and after treatment. Adverse reactions during treatment were recorded to evaluate the safety of targeted phototherapy.Results:A total of 194 children with stable vitiligo were included, comprising 103 males (53.1%) and 91 females (46.9%), with the age being 6 to 14 (10.2 ± 2.3) years. Among them, 138 (71.1%) received 308-nm excimer laser therapy, while 56 (28.9%) received 308-nm excimer lamp therapy. The VASI score ( M [ Q1, Q3]) was 0.12 (0.05, 0.40) at the baseline, significantly decreased to 0.06 (0.02, 0.19) after 3 months of treatment ( Z = 12.02, P < 0.001). After 3 months of treatment, 52 patients achieved VASI50, and 30 achieved VASI75, resulting in an overall response rate of 42.3% (82/194). Specifically, in the 308-nm excimer laser group, 38 patients achieved VASI50 and 26 achieved VASI75, with a response rate of 46.4% (64/138) ; in the 308-nm excimer lamp group, 14 patients achieved VASI50 and 4 achieved VASI75, yielding a response rate of 32.1% (18/56). Univariate logistic regression analysis indicated that lesions located on the head and neck or the trunk were more prone to repigmentation compared with those on the limbs ( OR = 3.56, 95% CI: 1.15 - 11.02, P = 0.027; OR = 6.58, 95% CI: 1.81 - 23.96, P = 0.004, respectively) ; additionally, facial lesions around the eyes were more prone to repigmentation compared with lesions on other facial areas ( OR = 4.58, 95% CI: 1.10 - 19.11, P = 0.037), and hair involvement in vitiligo lesions on the head and neck made repigmentation less likely to occur compared with lesions without hair involvement ( OR = 0.31, 95% CI: 0.13 - 0.75, P = 0.010). Multivariate logistic regression analysis revealed that the periorbital region was the most favorable site for repigmentation among facial areas ( OR = 5.37, 95% CI: 1.18 - 24.34, P = 0.029), and hair involvement in vitiligo lesions on the head and neck was an independent risk factor for phototherapy-induced repigmentation ( OR = 0.28, 95% CI: 0.08 - 0.96, P = 0.042). Among the 194 patients treated with targeted phototherapy for 3 months, 33 experienced short-term treatment-related adverse reactions, including erythema, blisters, desquamation, itching, and pain; most adverse reactions were mild, and no severe adverse reactions were observed. Conclusion:Targeted phototherapy using 308-nm excimer laser or 308-nm excimer lamp was safe and effective for the treatment of pediatric vitiligo.

Objective:To compare the efficacy of endoscopic submucosal dissection (ESD) and modified-endoscopic mucosal resection (M-EMR) for G1 rectal neuroendocrine tumors (RNETs) .Methods:Data of 121 patients with pathologically confirmed G1 RNETs treated with ESD ( n=105) or M-EMR ( n=16) in Nanjing Drum Tower Hospital from January 2017 to September 2020 were retrospectively analyzed. The complete resection rate, complication incidence, hospital stay, treatment cost and other indicators of the two groups were compared by using inverse probability of treatment weighting (IPTW). Results:There were significant differences in tumor number ( χ2=8.76, P=0.003), tumor invasion depth ( χ2=6.96, P=0.008), utilization of metal clips [82.9% (87/105) VS 93.8% (15/16), χ2=8.78, P=0.003], number of metal clips ( χ2=8.41, P=0.016), hemostasis using hot clamp [78.1% (82/105) VS 18.7% (3/16), χ2=20.64, P<0.001], traction procedure [2.9% (3/105) VS 18.7% (3/16), χ2=4.45, P=0.035] and treatment cost (17 568.6 ± 8 911.0 yuan VS 8 120.8±1 528.2 yuan, t=3.65, P<0.001) between the ESD group and the M-EMR group. After verifying the stability of the results using IPTW sensitivity analysis, there was still significant difference in the treatment cost ( t=2.07, P<0.001). Conclusion:Both ESD and M-EMR demonstrate comparable efficacy in treating G1 RNETs; however, M-EMR exhibites lower treatment costs.

Objective To investigate the application of endoscopic retrograde cholangiopancreatography(ERCP)in children and the risk factors for post-ERCP pancreatitis(PEP).Methods A retrospective analysis was conducted on the clinical data of 66 children,aged≤16 years,who underwent ERCP for pancreaticobiliary diseases at the Gastrointestinal Endoscopy Center of the Second Affiliated Hospital of Kunming Medical University from September 2013 to September 2023.The incidence rate of PEP and the risk factors for the development of PEP were analyzed.Results A total of 78 ERCP procedures were performed on 66 children,with 5 diagnostic ERCPs,69 therapeutic ERCPs,and 4 failed procedures.The success rate of ERCP operations was 95%(74/78).There were 17 cases of PEP in total,with an incidence rate of 22%.In the PEP group,the proportion of children with normal preoperative bilirubin and the proportion of guidewire insertion into the pancreatic duct during surgery were higher than in the non-PEP group(P<0.05).The multivariate logistic regression analysis showed that guidewire insertion into the pancreatic duct was an independent risk factor for PEP(P<0.05).Conclusions With the increasing application of ERCP in children with pancreaticobiliary diseases,it is important to select an appropriate intubation technique during surgery to avoid blindly entering the guidewire into the pancreatic duct and reduce the occurrence of PEP.