Objective:To analyze the prognostic factors of patients with liver cirrhosis and portal vein thrombosis (PVT), and to construct a prognostic prediction model based on machine learning methods.Methods:The clinical data of 388 patients with liver cirrhosis and PVT admitted to the Fifth Medical Center of PLA General Hospital from January 2022 to April 2024 were retrospectively collected and analyzed, including 243 males and 145 females, aged (56.9±10.9) years. A total of 388 patients were randomly divided into the training set ( n=310) and the testing set ( n=78) in a 4∶1 ratio. The Boruta algorithm was used to screen the key features in the training set, and then four machine learning algorithms, including random forest, support vector machine, generalized linear model and Bayesian, were used to establish a survival prediction model. Model performance was evaluated by the receiver operating characteristic (ROC) curves of the test set and the training set. The patients were followed up for 1 year for survival. Sort the importance of features based on the SHAP value. Results:There were 250 patients (80.6%) who survived and 60 (19.4%) who died. The model for end-stage liver disease score, total bilirubin, serum creatinine, prothrombin time, international normalized ratio, D-dimer, white blood cell count, severe ascites ratio, and Child-Pugh grade C ratio of liver function in the death group were higher than those in the survival group, and the red blood cell count and hematocrit were lower than those in the survival group, and the differences were statistically significant (all P<0.05). The areas under the ROC curve for predicting survival by random forest, support vector machine, generalized linear model and Bayesian model were 0.92, 0.78, 0.81 and 0.71 in the training set, and the area under the ROC curve in the testing set were 0.81, 0.72, 0.67 and 0.68, respectively. Random forest had the best prediction performance, with an accuracy of 81.7%, a sensitivity of 84.6%, and a specificity of 76.9% in the testing set. In the analysis of the importance of characteristic parameters of the random forest model, total bilirubin, red blood cells, hematocrit, serum creatinine, ascites classification, etc. had a relatively high contribution to the model. Conclusion:In the survival prediction model of patients with liver cirrhosis and PVT based on machine learning algorithm, the random forest model had high prediction performance, and total bilirubin may be the most important factor affecting the survival prognosis of patients.

Objective:To investigate the feasibility and optimal expansion width of replacing the left anterior descending coronary artery (LADCA) with the region of heart sparing (RHS) to reduce cardiac radiation dose during breast cancer radiotherapy.Methods:Retrospective analysis was conducted on data from 88 patients with left-sided breast cancer who underwent radiotherapy at 2 centers: Nanfang Hospital of Southern Medical University (50 cases for the training set, 15 cases for the internal test set) and Ganzhou Hospital of Nanfang Hospital (23 cases for the external test set) from March 2022 to January 2024. All patients had left-sided invasive ductal carcinoma with axillary lymph node metastasis, and had undergone modified radical mastectomy and chemotherapy. Based on simulation CT images, 2 radiation oncologists delineated the LADCA and 8 RHSs. The RHSs were delineated by expanding the LADCA contour by 0.5 cm increments, totaling 8 expansions. The RHS widths were defined as 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 cm. The nnU-Net model was trained for 3D automatic segmentation of the LADCA and RHSs. Model performance was evaluated using the Dice similarity coefficient (DSC), relative volume error (RVE), sensitivity, specificity, and 95% Hausdorff distance (HD95). Additionally, the minimum, maximum, and average relative dose variations (RDV) as well as V5% and V20% indicators were calculated for the LADCA and each RHS. Correlation analysis was performed using the least squares regression, with the slope and coefficient of determination ( R2) employed to evaluate the accuracy of the model fitting, the relationship between the LADCA and RHS, and the degree of their correlation, thereby assessing the substitutive effect of the RHS for the LADCA. Results:The DSC for the LADCA was 0.415, while the DSCs for RHS widths of 0.5 cm and 4.0 cm were 0.718 and 0.835, respectively. Overall, the automatic segmentation performance improved with increasing RHS width. The DSC, RVE, sensitivity, specificity, and HD95 for the external test set were largely consistent with those of the internal test set, demonstrating the model's good robustness across different datasets. All RDVmin values were negative, while RDVmax and RDVmean showed a positive correlation with RHS width. RDVmean increased from 39.01% to 75.89% as the RHS width increased. In the correlation analysis, the slopes for RHS widths of 1.5 cm and 2.0 cm were 0.95 and 1.05, respectively, with R2 values and coefficients of variation of 0.79 and 0.73, and 21.11% and 24.03%, respectively. Conclusions:The automatic segmentation model trained on nnU-Net can accurately segment RHSs. Based on geometric and dosimetric indicators, a 1.5 cm-wide RHS is the most suitable substitute for the LADCA, effectively limiting the radiation dose to the LADCA without compromising target dose coverage.

ObjectiveTo investigate the role of serum HBV RNA in assessing antiviral therapy for patients with chronic hepatitis B， as well as its potential as a biomarker in clinical therapy， and to provide a scientific basis for the clinical treatment of chronic hepatitis B. MethodsA total of 134 patients who were diagnosed with chronic HBV infection in The Second Affiliated Hospital of Kunming Medical University from April 2023 to May 2024 were enrolled as subjects， and related examinations were performed， including HBV DNA， serum HBV RNA， liver function， HBsAg， anti-HBs， HBeAg， anti-HBe， anti-HBc， and transient elastography of the liver. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test or the continuity-adjusted chi-square test was used for comparison of categorical data between two groups. Pearson correlation analysis or Spearman correlation analysis was performed. ResultsThe 134 patients with chronic HBV infection were divided into HBeAg-positive group with 45 patients and HBeAg-negative group with 89 patients， and there were significant differences between the two groups in age， the positive rate and quantitative value of HBV DNA， the positive rate and quantitative value of serum HBV RNA， HBsAg， anti-HBe， and ALT （all P<0.05）. In the cohort study of the HBeAg negative group， there were significant differences in the levels of HBV DNA， HBsAg， and GGT between the serum HBV RNA-negative group with 14 patients and the serum HBV RNA-positive group with 75 patients （all P<0.05）. There were 28 patients in the HBeAg-positive group and 62 in the HBeAg-positive group who used antiviral drugs for ≥1 month， and the 28 HBeAg-positive patients had an HBV RNA positive rate of 100%， while for the 62 HBeAg-negative patients， there were significant differences in the positive rate and level of serum HBV RNA between the patients with different durations of medication （both P<0.05）. Among the 89 HBeAg-negative patients， there were 62 treatment-experienced patients and 27 treatment-naïve patients， and there was a significant difference between the two groups in HBV RNA level ［2.07 （1.52 — 2.82） log₁₀ copies/mL vs 2.69 （1.80 — 3.55） log₁₀ copies/mL， Z=2.034， P=0.042］. For HBeAg-negative patients， serum HBV RNA was positively correlated with HBV DNA and HBsAg （both P<0.05）， and for HBeAg-positive patients， serum HBV RNA was significantly positively correlated with HBV DNA， HBsAg， and HBeAg （all P<0.05）. ConclusionAntiviral therapy can reduce viral load， and for HBeAg-negative patients with high-sensitivity HBV DNA below the lower limit of detection， serum HBV RNA can fill the “gap” in the detection of viral replication.

Objective:To explore the application value of three-dimensional high-resolution anorectal manometry(3D-HRAM)model in the diagnosis and localization of anal sphincter injury after surgery for complex anal fistula.Methods:A prospective study was con-ducted on 92 patients who had undergone surgery for complex anal fistula in the Department of Coloproctology of The People's Hospi-tal Affiliated to Fujian University of Traditional Chinese Medicine from January 2023 to January 2024.The study was conducted in two stages.In the first stage,92 patients underwent 3D-HRAM and endoanal ultrasonography(EAUS)to examine the sphincter,and the data were compared with intraoperative records to evaluate the diagnostic efficiency and localization accuracy of 3D-HRAM and EAUS.In the second stage,92 patients who had been examined were grouped according to the presence or absence of symptoms of anal dysfunction to further verify the diagnostic and localization values of 3D-HRAM and EAUS for postoperative compensated/decompen-sated sphincter injury.Results:Among 92 patients,41 and 57 patients were diagnosed with sphincter injury through 3D-HRAM and EAUS,with a sensitivity of 61.19%and 85.07%,a specificity of 88%and 76%,an area under the curve of 0.739 and 0.813 calcu-lated by plotting the receiver operating characteristic curve,and a localization accuracy of 44.77%and 71.64%,respectively,showing significant differences between 3D-HRAM and EAUS(P=0.002),indicating that 3D-HRAM had lower diagnostic efficiency and local-ization accuracy than EAUS for anal sphincter injury after surgery for complex anal fistula.After grouping by symptoms,the diagnostic efficiency and localization accuracy of 3D-HRAM for symptomatic sphincter injury(decompensated)were significantly better than those for asymptomatic sphincter injury,and were similar to those of EAUS(P=0.763).Conclusion:The application advantage of 3D-HRAM lies in the diagnosis and localization of decompensated anal sphincter injury after surgery for complex anal fistula,which provides effective technical support for the study of anal defecation control mechanisms and injury compensation mechanisms.

OBJECTIVE To investigate the current status of contamination with carbapenem-resistant gram-negative bacteria in environment of intensive care units(ICU)of tertiary hospitals in Shanghai and find out the potential contamination sources so as to provide bases for prevention and control of multidrug-resistant organisms infec-tions in the ICUs.METHODS The surroundings of the ICU patients detected with CRGNB and environmental ob-jects surfaces in public area were sampled by mSuperCARBA chromogenic media from Dec.2024 to Jan.2025,the strains were isolated,and the targeted strains were identified by matrix-assisted laser desorption/ionization time-of-flight(MALDI-TOF)mass spectrometer.RESULTS A total of 653 samples were collected in the survey,76 of which were positive for bacterial culture,60 were detected with CRGNB,and the isolation rate of CRGNB was 9.19％.The isolation rate of CRGNB was 53.40％in the water-source group,0.91％in the non-water-source group,and there was significant difference(x2=286.450,P＜0.001).The result of whole genome sequencing for 17 strains of CRKP showed that ST11 and ST15 were the two major types of multilocus typing(MT),respective-ly carrying 2-12 types of drug resistance genes.CONCLUSIONS The CRGNB strains are detected in some environ-mental sites of the ICUs of 15 tertiary hospitals in Shanghai,and the isolation rate of CRKP is highest among them.The colonization rate of CRGNB is relatively low on the highly frequent-contact object surfaces of the ICUs,however,sink drain holes poses a risk of hospital-acquired CRGNB infections transmissions.Additionally,the ba-sins and towels of the CRGNB patients are hard to be thoroughly cleaned,disinfected and dried,resulting in a high contamination rate.

Galectin-9 (Gal-9), a member of the β-galactoside-binding lectin family, is widely expressed in various tissues and cells. It can specifically bind to multiple glycoprotein receptors, including the receptors of Tim-3, CD44, 4-1BB/CD137, and Dectin-1, thereby regulating the activity of immune cells and participating in crucial physiological and pathological processes such as immune regulation and tumor development. Given its role in immunomodulation, Gal-9 is considered a potential target for immunotherapy, showing promising prospects in the treatment of various diseases, including autoimmune disorders, transplantation rejection, pregnancy complications, inflammation, infection, and cancer. This review summarizes the biological effects mediated by Gal-9 upon binding to its receptors, which may help to explore the potential application value of Gal-9 in clinical diagnosis and therapy.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Objective To observe the therapeutic effects and mechanisms of acupuncture at"Yanglingquan"(GB34)and"Zusanli"(ST36)on knee osteoarthritis(KOA)rats,focusing on the regulation of PTEN-induced kinase 1/Parkin(PINK1/Parkin)-mediated mitophagy in chondrocytes.Methods Ten out of 40 male SD rats were randomly selected as the normal group,and the remaining 30 rats were used to construct a KOA model.A total of 27 rats were successfully modeled.The successfully modeled rats were randomly divided into a model group,an acupuncture group(acupuncture at Yanglingquan and Zusanli),and an acupuncture+autophagy inhibitor(3-MA)group(acupuncture at Yanglingquan and Zusanli combined with intraperitoneal injection of 3-MA),with 9 rats in each group.After intervention,the morphology of cartilage tissue in each group was observed,and the Mankin's score of cartilage was assessed.The apoptosis rate of chondrocytes was calculated.Enzyme-linked immunosorbent assay(ELISA)was used to detect inflammatory factors[cyclooxygenase 2(COX-2),interleukin 1β(IL-1β),and tumor necrosis factor α(TNF-α)],oxidative damage indicators[nitric oxide(NO),superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)],and the levels of matrix metalloproteinase 3(MMP-3)and tissue inhibitor of metalloproteinase 1(TIMP-1).The DHE probe was used to measure reactive oxygen species(ROS)level.Polymerase chain reaction(PCR)was used to detect the mRNA expression levels of PTEN-induced kinase 1(PINK1),Parkin,and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)in cartilage tissue.Western blot was used to measure the protein expression levels of PINK1,Parkin,and LC3-Ⅱ in cartilage tissue.Results Compared with the normal group,the model group showed increased Mankin's score,apoptosis rate,COX-2 level,IL-1β and TNF-α levels,NO and MDA levels,MMP-3 and TIMP-1 levels,and ROS content,as well as decreased SOD and GSH-Px levels,and reduced mRNA and protein expressions of PINK1,Parkin and LC3-Ⅱ,with statistically significant differences(P＜0.05).Compared with the model group,the acupuncture group showed decreased Mankin's score,apoptosis rate,COX-2 level,IL-1β and TNF-α levels,NO and MDA levels,MMP-3 and TIMP-1 levels,and ROS content,as well as increased SOD and GSH-Px levels,and elevated mRNA and protein expressions of PINK1,Parkin and LC3-Ⅱ,with statistically significant differences(P＜0.05).Compared with the acupuncture group,the acupuncture+3-MA group showed increased Mankin's score,apoptosis rate,COX-2 level,IL-1β and TNF-α levels,NO and MDA levels,MMP-3 and TIMP-1 levels,and ROS content,as well as decreased SOD and GSH-Px levels,and mRNA and protein expressions of PINK1,Parkin and LC3-Ⅱ,with statistically significant differences(P＜0.05).Conclusion Acupuncture at"Yanglingquan"and"Zusanli"can inhibit chondrocyte apoptosis by activating PINK1/Parkin-mediated mitophagy,thus improving the condition of KOA rats.

This study summarizes Professor Qin Zhenhua's clinical experience in treating cutaneous pruritus using a modified self-prescribed formula,Yinqiao Xingzi Decoction.Following the viewpoints from the classical Chinese medical literature and after years of clinical practice,Professor Qin proposes that the onset of cutaneous pruritus is often associated with the attack of exogenous pathogens,disharmony of qi and blood,or debility due to prolonged illness.The disease primarily involves the skin,with the fundamental pathogenesis of pathogens stagnating in the muscular superficies.Clinically,the treatment is frequently conducted from the perspective of fire-heat syndrome,and the therapeutic methods of clearing heat and removing toxins,releasing muscles and dispersing pathogens from the superficies,and dispelling wind to relieve itching are utilized.The approaches aim to cool heat in the blood,expel pathogens from the muscular layer,eliminate heat for stopping itching,and extinguish wind for calming the skin.The basic prescription,Yinqiao Xingzi Decoction(composed of Lonicerae Japonicae Flos,Forsythiae Fructus,Armeniacae Semen Amarum,Arnebiae Radix,Tribuli Fructus,Dictamni Cortex,Kochiae Fructus,and Glycyrrhizae Radix et Rhizoma),is used by modification depending on the predominance of pathogenic factors of wind,heat,dryness,or dampness-toxins,and according to the various syndromes like blood-heat,yin deficiency,or qi-blood deficiency.Yinqiao Xingzi Decoction is applicable to cutaneous pruritus with the most of clinical common syndrome types,but it is unsuitable for cases caused by yang deficiency or qi stagnation with blood stasis.