ObjectiveTo provide a clinical reference for rational selection of the methods for common bile duct closure after laparoscopic common bile duct exploration （LCBDE） in patients with recurrent choledocholithiasis （RCL）. MethodsA retrospective analysis was performed for the clinical data of 121 patients with RCL who underwent LCBDE in the Department of Hepatopancreatobiliary Surgery， The Affiliated Hospital of North China University of Science and Technology， from February 2022 to December 2025， and according to the method for common bile duct closure， the patients were divided into primary duct closure group （PDC group with 58 patients） and T-tube drainage group （TTD group with 63 patients）. The two groups were compared in terms of time of operation， drainage volume on day 1 after surgery， total bilirubin level on day 3 after surgery， time to diet after surgery， time to drainage tube removal after surgery， common bile duct diameter at 1 week after surgery， length of postoperative hospital stay， total hospitalization costs， and complications， and the risk factors for postoperative complications were analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The multivariate Logistic regression analysis was used to identify influencing factors for postoperative complications. ResultsCompared with the TTD group， the PDC group had a significantly shorter time of operation ［48.50 （39.00 — 59.25） min vs 55.00 （46.00 — 69.00） min， Z=-2.726， P=0.006］， a significantly lower level of total bilirubin on day 3 after surgery ［17.25 （14.43 — 21.30） μmol/L vs 20.06 （16.40 — 29.30） μmol/L， Z=-2.950， P=0.003］， a significantly shorter time to diet after surgery ［1 （1 — 1） d vs 1 （1 — 2） d， Z=-4.506， P<0.001］， a significantly shorter time to drainage tube removal after surgery ［7 （7 — 7） d vs 8 （8 — 9） d， Z=-9.693， P<0.001］， a significantly shorter length of postoperative hospital stay ［8 （8 — 8） d vs 10 （9 — 11） d， Z=-8.960， P<0.001］， and significantly lower total hospitalization costs ［21 750 （20 369 — 23 310） yuan vs 24 889 （23 438 — 26 920） yuan， Z=-5.572， P<0.001］， and common bile duct diameter at 1 week after surgery in the PDC group was closer to the normal physiological anatomical structure of the biliary tract compared with that in the TTD group ［1.0 （0.9 — 1.1） cm vs 1.0 （1.0 — 1.1） cm， Z=-2.064， P=0.039］. Compared with the TTD group， the PDC group had significantly lower incidence rates of total complications （10.34% vs 26.98%， P=0.024） and electrolyte disturbance （1.72% vs 15.87%， P=0.006）. The multivariate logistic regression analysis showed that common bile duct diameter <1.3 cm before surgery and total bilirubin level ≥21.0 μmol/L before surgery were independent risk factors for postoperative complications， while primary duct closure was an independent protective factor against postoperative complications （P<0.05）. ConclusionUnder the premise of strict control of indications， PDC after LCBDE for RCL patients can accelerate recovery and reduce complications and hospitalization costs， thereby demonstrating greater advantages in clinical application.

Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

OBJECTIVE: A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study. METHODS: From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test. RESULTS: A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency. CONCLUSION The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans ; Male ; Female ; Posterior Cruciate Ligament/surgery* ; Adult ; Tibial Fractures/classification* ; Tomography, X-Ray Computed ; Middle Aged ; Retrospective Studies ; Fractures, Avulsion/classification* ; Imaging, Three-Dimensional ; Young Adult

OBJECTIVE: To analyze the RHD genotyping and sequencing results of RhD serology negative samples in the clinic, and to further explore the laboratory methods for RhD detection, in order to provide a basis for clinical precision blood transfusion. METHODS: A total of 27 200 whole blood samples were screened for RhD blood group antigen using microcolumn gel card method.Serologic RhD-negative confirmation tests were performed on blood samples that were negative for RhD on initial screening using three different clonal strains of IgG anti-D reagents. The 10 exons of the RHD gene on chromosome 1 were also analyzed by PCR-SSP to determine RHD genotyping.When the PCR-SSP method did not yield definitive results, the RHD gene of the sample was analyzed by the third-generation sequencing. RESULTS: The results of the initial screening test by the microcolumn gel card method showed that 136 of the 27 200 samples were RhD-negative, of which 86 underwent RhD-negative confirmation testing and RHD genotyping, 88.37% (76/86 cases) of the RhD-negative confirmation test results were negative for the three anti-D reagents, and the results of RHD genotyping showed that 67.44% (58/86 cases) of the cases had a complete deletion of 10 exons, and the remaining 28 cases were RHD*711delC (1 case), RHD*D-CE(1-9)-D (1 case), RHD*D-CE(2-9-)D (2 cases), RHD*D-CE(3-9)-D (4 cases), RHD*DEL1 (c.1227G >A) mutation (16 cases), RHD*weak partial 15(845G >A) mutation (3 cases), and a mutation of c.165C >T base was found in 1 sample by three-generation sequencing. CONCLUSION RHD genotype testing of samples that are serologically negative for RhD antigen shows that some of the samples have RHD gene variants, not all of which are total deletions of RHD, suggesting that there are some limitations of the serologic method for RhD detection. Due to the polymorphism of the RHD gene structure, different RhD variants present different serologic features, which need to be further detected in combination with molecular biology testing, especially for the identification of Asian-type DELs, which is important for clinical precision blood transfusion.
Humans ; Rh-Hr Blood-Group System/genetics* ; Genotype ; Polymerase Chain Reaction ; Exons ; Blood Grouping and Crossmatching

OBJECTIVE: To investigate the effect of Arsenic trioxide (ATO) combined with Norcantharidin (NCTD) on the proliferation and apoptosis of Jurkat cells, and to evaluate its effect on the proliferation and apoptosis of acute T-lymphoblastic leukemia (T-ALL) based on the Wnt/β-catenin signaling pathway. METHODS: Jurkat cell lines were used as the study subjects and treated with different concentrations of ATO (0, 2, 4, 8, 16 μmol/L) and NCTD (0, 10, 25, 50, 100 μmol/L) for 72 hours, and the cell proliferation was detected by CCK-8. Meanwhile, flow cytometry was used to detect the apoptosis rate, EdU staining to detect cell proliferation viability, cell clone formation assay to assess cell cloning ability, Transwell assay to assess cell invasion ability, and Western blot to detect apoptosis and the expression of Wnt/β-catenin signaling pathway-related proteins. RESULTS: Compared with the control group, both ATO and NCTD effectively inhibited Jurkat cell proliferation when used alone, and the inhibition effect was more significant when used in combination ( P < 0.05). The combination significantly increased the apoptosis rate of Jurkat cells ( P < 0.05). Meanwhile, the combination significantly decreased the proliferation vitality and clone formation ability of the cells ( P < 0.05), and inhibited the invasion ability of Jurkat cells ( P < 0.05). Western blot analysis showed that the combination of ATO and NCTD significantly up-regulated the expression of pro-apoptotic proteins Bax and E-cadherin, and down-regulated the expression of anti-apoptotic proteins Bcl-2, c-myc and Cyclin D1 ( P < 0.05). CONCLUSION The combination of ATO and NCTD had a synergistic effect in inhibiting proliferation and promoting apoptosis in Jurkat cells, which may be related to the inhibition of Wnt/β-catenin signaling pathway.
Humans ; Apoptosis/drug effects* ; Jurkat Cells ; Cell Proliferation/drug effects* ; Arsenic Trioxide ; Wnt Signaling Pathway/drug effects* ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; beta Catenin/metabolism* ; Arsenicals/pharmacology* ; Oxides/pharmacology*

Objective:To analyze the blood-transition prototype components and metabolites of Fengliaoxing Fengshi Dieda medicinal liquor.Methods:Ultra-high performance liquid chromatographyquadrupole/electrostatic field orbital trap high resolution mass spectrometry (UHPLC-Q Exactive Focus MS/MS) technique was used to compare the chromatogram differences of Fengliaoxing Fengshi Dieda medicinal liquor extract, blank serum and drug-containing serum. According to the retention time, relative molecular weight and the ratio with primary and secondary ion fragments provided by MS, the prototype components and metabolites of Fengliaoxing Fengshi Dieda medicinal liquor extract were analyzed in serum of rats after oral administration. The detection conditions were as follows: the mobile phase of methanol (A)-0.1% formic acid solution (B) for elution gradient (0-5 min, 5%A; 5-60 min, 5%-95%A; 60-65 min, 95%A), the flow rate of 0.3 ml/min, heated electrospray ionization, detection range of m/z 80-1 200, positive and negative ion scanning modes.Results:A total of 31 transitional components were detected in the serum, of which 9 were prototype components and 22 were metabolites. The 9 prototype components were identified as phenylacetaldehyde, baogongteng C/ erycibellin, p-coumaric acid, 5-Hydroxymethylfurfural, quinic acid, paeonol, 3-Hydroxybenzaldehyde, salicylic acid, and isourecumenol. The 22 metabolites mainly consist of 11 organic acid components, 3 indole components, 2 organic phenolic components, 2 alkaloid components, 1 nucleoside component, 1 amino acid component, 1 lactone component, and 1 sulfonic component. The metabolic pathways were mainly glucuronidation, sulfation and others, which by phase Ⅱ metabolism.Conclusion:Organic phenols and organic acids are the main components that enter the body of Fengliaoxing Fengshi Dieda Medicinal Liquor, while alkaloid compounds and organic acid components may be potential active ingredients for its pharmacological effects.

This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Objective:This study aims to provide insights into the clinical features of anti-melanoma differentiation-associated protein-5(MDA5)-positive dermatomyositis (MDA5-DM) patients with fatal outcomes, leveraging pathogenic microbiota metagenomic analysis, to guide the clinical assessment and treatment choices.Methods:From January 2020 to August 2023, deceased patients diagnosed with MDA5-DM were identified at the Department of Rheumatology and Immunology, the Second Affiliated Hospital of Xi ′an Jiaotong University. Clinical data were retrospectively collected and analyzed using Mann Whitney U test and Fisher ′s exact test to summarize risk factors and treatment assessment for MDA5-DM patients with fatal outcomes. Results:①The proportion of male patients was higher than females among MDA5-DM patients with fatal outcomes, which differed from the incidence pattern, possibly associated with smoking and gender proportions (6/11 vs. 0/7, P=0.037). ②94%(17/18) patients presented initially with elevated ferritin levels [(1 350±942)ng/ml] and CRP [(47±36)mg/L]. ③All patients (18/18) exhibited early involvement of the upper lung lobes, including multiple nodules in 9/18, ground-glass opacities in 5/18, and solitary nodules in 4/18. ④Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid was negative in 4/16 cases, with cytomegalovirus and pneumocystis jirovecii being the most commonly detected pathogens in 5/16 cases each. ⑤89%(16/18) of patients continued to have lymphocyte counts persistently <0.5×10 9/L irrespective of treatment. Conclusion:Smoking may have adverse effects on male MDA5 patients. Early involvement of the upper lobe of the lungs is more common in MDA5 antibody positive deaths, and persistent lymphocyte depletion is an important factor in poor response. Enhancing mNGS analysis of bronchoalveolar lavage fluid and vigilance towards cytomegalovirusand Pneumocystis jirovecii could provide valuable clinical guidance.