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.

ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug， and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups： empagliflozin group 1 and 2， donafenib group， lenvatinib group， donafenib pretreatment+empagliflozin group， lenvatinib pretreatment + empagliflozin group， empagliflozin pretreatment+donafenib group， and empagliflozin pretreatment+lenvatinib group， with 6 rats in each group. The doses of empagliflozin， donafenib， and lenvatinib were 2.5 mg/kg， 40 mg/kg， and 1.2 mg/kg， respectively. The rats in the empagliflozin group， donafenib group， and lenvatinib group were given a blank solvent by gavage for 7 consecutive days， followed by a single dose of empagliflozin， donafenib， or lenvatinib on day 7 after the administration of the blank solvent； the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days， followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points， and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib， lenvatinib， and empagliflozin， and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug （area under the plasma concentration-time curve ［AUC］， time to peak ［T_max］， peak concentration ［C_max］， and half-life time ［t_1/2］）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group， the donafenib pretreatment+empagliflozin group had significant increases in the AUC_0-t and AUC_0-∞ of empagliflozin （P=0.011 and 0.008）， while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin， with a slightly shorter T_max （P=0.019）. Compared with the donafenib group， the empagliflozin pretreatment+donafenib group had significant increases in the AUC_0-t and AUC_0-∞ of donafenib （P=0.027 and 0.025）， as well as a significant increase in C_max （P=0.015） and significant reductions in CLz/F and Vz/F （P=0.005 and 0.004）； compared with the lenvatinib group， the empagliflozin pretreatment+lenvatinib group had a reduction in the t_1/2 of lenvatinib by approximately 5 hours （P=0.002）， with a trend of reduction in AUC_0-t （P0.05）. ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs， leading to a significant increase in the exposure levels of both drugs， and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.

Objective: To investigate the spatio-temporal clustering characteristics of influenza in Ningxia Hui Autonomous Region from 2014 to 2023, so as to provide the basis for strengthening influenza prevention and control. Methods: Data pertaining to influenza cases reported in Ningxia Hui Autonomous Region from 2014 to 2023 were retrieved from the Infectious Disease Surveillance System of the Chinese Disease Prevention and Control Information System, including age, sex, current residence, onset date, and reporting date. The seasonal incidence of influenza was analyzed using seasonal index. The spatio-temporal clustering characteristics of influenza were identified using spatial autocorrelation analysis and spatio-temporal scan analysis. Results: A total of 20 377 influenza cases were reported in Ningxia Hui Autonomous Region from 2014 to 2023, with a male-to-female ratio of 1.15∶1. The majority were children under 15 years, with 10 950 cases accounting for 53.74%. Influenza was highly prevalent in January, February, March, and December, with seasonal indices of 219.06%, 111.00%, 246.65%, and 366.24%, respectively. The average annual reported incidence was 29.55/100 000, among which Pengyang County, Jinfeng District, Dawukou District, Xiji County, and Litong District had higher average annual reported incidence, at 63.99/100 000, 55.71/100 000, 55.70/100 000, 49.49/100 000, and 49.04/100 000, respectively. Spatial autocorrelation analysis showed that in 2023, there was spatial clustering of influenza cases in Ningxia Hui Autonomous Region (Moran's I=0.333, P<0.05), with a high-high cluster in Jingyuan County, while in other years, the distribution of influenza cases was random (all P>0.05). Spatio-temporal scan analysis showed that from 2014 to 2023, there were four space-time clusters in Ningxia Hui Autonomous Region, including one type Ⅰ cluster in Hongsibao District of Wuzhong City, with the clustering period from January 20 to 26, 2014; and three type Ⅱ clusters, mainly in January, February, March and December, covering one area in Shizuishan City, five areas in Guyuan City, one area in Zhongwei City, three areas in Wuzhong City, and four areas in Yinchuan City. Conclusions From 2014 to 2023, children under 15 years were the primary population affected by influenza in Ningxia Hui Autonomous Region, with distinct spatio-temporal distribution characteristics. The peak incidence occurred during the winter and spring seasons, and the main clustering areas were in the southern regions.

Discoidin domain receptor 1 (DDR1) is overexpressed in various tumors, such as triple-negative breast cancer (TNBC), and is rarely expressed in normal tissues. These characteristics make DDR1 a preferable target candidate for the construction of an antibody-drug conjugate (ADC) for targeted therapy. Here, we investigated the preparation and preclinical efficacy of DDR1-DX8951, an ADC that includes an anti-DDR1 monoclonal antibody conjugated to DX8951 by a cleavable Gly-Gly-Phe-Gly (GGFG) linker. The anti-DDR1 monoclonal antibody was coupled to DX8951 (i.e., DDR1-DX8951), producing the targeted therapy ADC. The antitumor activities of DDR1-DX8951 monotherapy or DDR1-DX8951 plus pembrolizumab were assessed in TNBC mouse models. DDR1-DX8951 can specifically target DDR1, be quickly internalized by TNBC cells, and reduce the viability of TNBC cells in vitro. The potent antitumor activity of DDR1-DX8951 was revealed in TNBC xenograft models. Importantly, our investigation demonstrated that DDR1-DX8951 plus pembrolizumab not only revealed the inhibitory efficacy on tumor growth and metastasis but also played an important role in improving the immunosuppressive tumor microenvironment (TME) of TNBC. Taken together, this investigation provides justification for large-sample studies to further assess the safety and efficacy of DDR1-DX8951 plus pembrolizumab for TNBC clinical trials.

Objective Based on the process theory of stress effect,the structural equation model of the influencing factors of self-regulatory fatigue in maintenance hemodialysis patients is constructed,which provides theoretical bases and references for the formulation of intervention programs to relieve self-regulatory fatigue in patients.Method A total of 420 maintenance hemodialysis patients were surveyed using General Information Questionnaire,Self-Regulatory Fatigue Scale,Dialysis Symptom Index,Life Orientation Test-Revised,Perceived Social Support Scale,Brief Illness Perception Questionnaire and Medical Coping Styles Questionnaire.Results Total score of self-regulatory fatigue in maintenance hemodialysis patients was(49.52±10.93),and self-regulatory fatigue showed significant positive correlation with symptom distress,the illness perception,avoidance coping style,yieldly coping(r=0.476,0.428,0.303,0.611,all P＜0.01);self-regulatory fatigue showed significant negative correlation with perceived social support and dispositional optimism(r=-0.410,-0.652,all P＜0.01);it showed no significant correlation with facing coping(r=-0.032,P＞0.05).The Bootstrap analysis revealed that the mediation effect of yielding coping,dispositional optimism,perceived social support,and illness perception between symptom distress and self-regulatory fatigue was significant(95％CI:0.027～0.203).The overall effect of symptom distress on self-regulatory fatigue was(P＜0.001,95％CI:0.576～0.751);the direct effect was(P＜0.001,95％CI:0.170～0.357);the indirect effect was(P＜0.001,95％CI:0.332～0.485);the mediation effect accounted for 61.1％of the total effect value.Conclusion Maintenance hemodialysis patients have a high degree of self-regulatory fatigue,which needs to be further improved.Medical staff should timely identify and evaluate the symptom distress of patients,focus on guiding patients to adjust optimistic disease,provide patients with psychological guidance and stress coping strategies,reduce the negative coping behavior tendency,guide the patients correctly perceive support and care in social relations,help patients set up the correct disease cognition,thus reducing the patient's self-regulatory fatigue.

Purpose To evaluate the short-term efficacy of Gefitinib based on the non-contrast CT radiomics model in patients with advanced lung adenocarcinoma before treatment.Materials and Methods Seventy-one patients with advanced lung adenocarcinoma and treated with Gefitinib in the First Affiliated Hospital of Harbin Medical University from January 2020 to May 2022 were retrospectively analyzed,the efficacy of the treatment was evaluated in the third month after receiving the treatment,and all patients were divided into the treatment-effective group(n=41)and the treatment-ineffective group(n=30)according to the criteria for evaluating the efficacy of solid tumors.All patients were randomized into the training group and the validation group according to 7∶3,the least absolute shrinkage and selection operator were used in the training group to screen the best radiomics features,and eight models were established,including K-proximity,Logistic regression,support vector machine,adaptive enhancement,gradient boosting,random forest,ensemble algorithm and Gaussian naive Bayes.The optimal model was selected by comparing the area under the receiver operating characteristic curve(AUC)and accuracy.The optimal model performance was tested in the validation group,the clinical usability of the best model was tested using decision curves,the accuracy of the predictive models was visualized using calibration curves.Results The seven best radiomics features were obtained by least absolute shrinkage and selection operator regression screening,the best model Logistic regression was selected in a variety of models,the AUC value of Logistic regression in the validation group was 0.774(95%CI 0.536-0.951),with a sensitivity of 0.846,a specificity of 0.556,an accuracy of 0.727,a recall of 0.846,and an F1-score of 0.733.Conclusion It is possible to screen out the sensitive population of advanced lung adenocarcinoma for targeted therapy based on CT radiomics models.

A popular use of marginal donor organs requires an optimization of organ preservation strategies. The current standards of organ preservation and static cold storage are insufficient to fulfill the demands of marginal donor organ preservation. Machine perfusion has been a primary development direction in organ preservation. Capable of improving preservation effectiveness and prolonging preservation time, it has the potential of becoming a practical platform for ex-vivo organ assessment and injury restoring. This review summarized the latest advances in organ preservation and restoration techniques.

Objective:To evaluate the efficacy of individualized removal therapeutic regimen for donor-specific antibodies (DSA) and examine its related influencing factors.Method:From January 2016 to January 2021, 34 recipients of kidney transplant (KT) underwent regular DSA testing and the results were positive. DSA removal therapy based upon rituximab (RTX) plus intravenous immune globulin (IVIG) was offered. Correlation between DSA negative conversion rate and DSA types, time from start of treatment to transplantation, HLA loci targeted by DSA and DSA mean fluorescent intensity (MFI) were analyzed retrospectively. Changes of immunedominant DSA (iDSA) and serum creatinine in individuals with de novo DSA (dnDSA) before and after treatment were also examined.Results:At Month 3 post-treatment, antibodies turned negative in 17/34(50.0%) patients and DSA became negative in 19/34(55.9%) at the last follow-up. Then we identified 78 DSA from all patients. No significant difference existed in negative conversion rate of pfDSA and dnDSA at Month 3 post-treatment [62.9%(39/62) vs 37.5%(6/16)] and at the last follow-up [4.2%(46/62) vs 56.3%(9/16)]( P=0.067, 0.219). For pfDSA, negative conversion rate of pfDSA with different MFIs after 3-month treatment varied significantly [negative conversion rate of weak positive DSA was 78.6%(33/42) and positive and above DSA 30%(6/20), P<0.001]. It was an independent related factor of whether or not pfDSA could turn negative (48.6%, 95% CI: 22.3%-66.8%, P=0.001). At the last follow-up, negative conversion rate of pfDSA differed markedly at different timepoints from start of treatment to transplantation [treated within 30 days post-operation was 79.2%(42/53) and over 30 days post-operation was 44.4%(4/9), P=0.042] and among different DSA MFI [88.1%(37/42) of weakly positive DSA and 45%(9/20) of positive and above DSA, P<0.001] and they were independent related factors for negative conversion of pfDSA (34.8%, 95% CI: 3.2%-61.8%, P=0.008; 43.1%, 95% CI: 18.5%-63.4%, P=0.001). Mean decline rate in iDSA was 66.67% at Month 3 post-treatment and 77.90% at the last follow-up. The difference was statistically significant ( P=0.035). Serum level of creatinine of 9 patients with dnDSA was (110.2±26.9) μmol/L pre-treatment, (178.8±90.5) μmol/L during treatment, (153.9±72.8) μmol/L at Month 3 post-treatment and (213.6±185.8) μmol/L at the last follow-up. Serum creatinine rose during treatment ( t=-2.794, P=0.023), declined at Month 3 post-treatment ( t=3.430, P=0.009) and spiked again at the last follow-up ( P=0.028). Conclusion:After DSA removal therapy based upon RTX plus IVIG, negative conversion rate of pfDSA is correlated with its MFI and time from start of treatment to transplantation. There is no significant rebound in DSA MFI and graft function of dnDSA patients improves immediately after treatment.