Diabetic kidney disease （DKD） is a microvascular complication of diabetes， with a complex pathogenesis， in which mitochondrial dysfunction is considered to be the core of DKD development. Taking mitochondria as a target to regulate mitochondrial energy metabolism， mitochondrial oxidative stress， mitophagy， and mitochondrial dynamic function represents a promising strategy for the DKD prevention and treatment， with good prospects in clinical application. Traditional Chinese medicine （TCM） has great potential to mediate mitochondrial dysfunction in the DKD prevention and treatment. This article deeply explores the intrinsic relationship between various forms of mitochondrial dysfunction and DKD， and summarizes the current research status of various Chinese herbal compounds and Chinese herbal formulas in targeting mitochondrial dysfunction for the DKD prevention and treatment. This article aims to provide new targets and strategies for the DKD prevention and treatment， and the research and development of TCM.

Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

To evaluate the application value of the Peyton four-step teaching method in the standardized training of intestinal ultrasound and compare it with traditional teaching methods, so as to provide an optimized approach for clinical ultrasound training.

OBJECTIVE To systematically evaluate the influential factors for all-cause mortality in patients with carbapenem-resistant Gram-negative bacteria （CR-GNB） treated with polymyxin B. METHODS PubMed， Embase， the Cochrane Library， Web of Science， Wanfang Data， VIP， CBM and CNKI were searched to collect clinical studies on all-cause death within 30 days or 28 days after treatment with polymyxin B in patients with CR-GNB infection from database establishment to July 2025. After literature screening， data extraction and evaluation of literature quality， meta-analysis was performed using RevMan 5.4 software. RESULTS A total of 12 studies were included， involving 1 326 patients， among whom 529 patients died， with a mortality rate of 39.89%. Meta-analysis results showed that combined with cardiovascular disease [OR＝2.06， 95%CI （1.37， 3.09）， P ＝0.005 ] ， increased Sequential Organ Failure Assessment （SOFA） score [OR＝1.20， 95%CI （1.07， 1.35）， P ＝0.003 ] ， mechanical ventilation [OR＝2.35， 95%CI （1.65， 3.34）， P ＜0.001 ] ， continuous renal replacement therapy （CRRT） [OR＝2.58， 95%CI （1.67， 3.97）， P ＜0.001 ] ， bloodstream infection [OR＝3.24， 95%CI （2.19， 4.78）， P ＜0.001 ] ， multiple-site infection [OR＝1.51， 95%CI （1.03， 2.20）， P ＝0.03 ] ， septic shock [OR＝3.19， 95%CI （1.94， 5.24）， P ＜0.001 ] ， use of vasoactive drugs [OR＝2.90， 95%CI （1.97， 4.27）， P ＜0.001 ] ， and the occurrence of acute kidney injury （AKI） [OR＝2.17， 95%CI （1.41， 3.36）， P ＜0.001 ] were risk factors for all-cause mortality in patients with CR-GNB infection treated with polymyxin B. Conversely， an extended duration of polymy xin B treatment [OR＝0.92， 95%CI （0.86， 0.99）， P ＝0.03 ] and early administration after CR-GNB infection [OR＝0.47， 95%CI （0.25， 0.85）， P ＝0.01 ] were protective factors. CONCLUSIONS Patients with cardiovascular disease， receiving mechanical ventilation or CRRT， having bloodstream infection， multiple-site infection or septic shock， combining with vasoactive drugs， with AKI and increased SOFA scores have a higher risk of all-cause mortality. Conversely， extending the duration of polymyxin B treatment （beyond 7 days） and early administration within 48 hours after confirmed CR-GNB infection can significantly reduce the risk of all-cause mortality.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Combined Modality Therapy ; Radiotherapy/methods*

OBJECTIVE: To explore the clinical features of patients with necrotizing soft tissue infection (NSTI) and the related factors for sepsis, so as to provide a basis for early intervention and improvement of patients' prognosis. METHODS: A retrospective case series study was conducted to analyze the clinical data of NSTI patients admitted to the department of burns and wound repair surgery of Guangdong Provincial People's Hospital from October 2021 to December 2024. Demographic information, underlying diseases, infection characteristics, laboratory test results and etiological findings at admission, treatment status, occurrence of complications (including sepsis) and prognosis were collected. Univariate and multivariate Logistic regression analyses were used to identify the associated factors for sepsis in NSTI patients. Receiver operator characteristic curves (ROC curves) were plotted to evaluate the predictive value of individual and combined factors for sepsis. RESULTS: A total of 159 NSTI patients were enrolled, mainly middle-aged and elderly males. Most patients had comorbidities, including diabetes mellitus (110 cases, 69.2%) and hypertension (67 cases, 42.1%). The main infection site was the lower extremities (104 cases, 65.4%). Common symptoms included redness (96 cases, 60.4%), swelling (129 cases, 81.1%), local heat (60 cases, 37.7%), pain (100 cases, 62.9%), and skin ulceration or necrosis (9 cases, 5.7%). Imaging findings included soft tissue swelling (66 cases, 57.9%), gas accumulation (41 cases, 36.0%), and abnormal signal/density shadows (50 cases, 43.9%). Staphylococcus aureus was the main pathogenic bacterium [12.0% (31/259)], and drug-resistant Escherichia coli had the highest detection rate among drug-resistant bacteria [35.1% (13/37)]. Regarding debridement and repair, most patients (80 cases, 50.3%) underwent debridement ≥ 72 hours after admission, while only 10.1% (16 cases) received debridement within 6 hours. Most patients underwent multiple debridements, with 2 times of debridements being the most common (68 cases, 42.8%), and the maximum times of debridements reached 6. The largest number of patients received secondary suture (44 cases, 27.7%). In terms of complications, sepsis was the most common (66 cases, 41.51%), followed by acute kidney injury, respiratory failure requiring mechanical ventilation, and multiple organ dysfunction syndrome (MODS), while disseminated intravascular coagulation (DIC) was the least common. During the follow-up period, 9 patients (5.66%) were readmitted within 90 days, and 11 patients died, with a mortality rate of 6.92%. Univariate analysis showed that diabetes, coronary heart disease, gout, body temperature, heart rate, C-reactive protein, platelet count, total bilirubin, albumin, creatinine, out-of-hospital treatment, and out-of-hospital use of antimicrobial agents were significantly associated with sepsis in NSTI patients (all P < 0.05). Multivariate Logistic regression analysis showed that coronary heart disease [odds ratio (OR) = 30.085, 95% confidence interval (95%CI) was 2.105-956.935], C-reactive protein (OR = 1.026, 95%CI was 1.009-1.054), and total bilirubin (OR = 1.436, 95%CI was 1.188-1.948) were independent associated factors for sepsis in NSTI patients (all P < 0.05). ROC curve analysis revealed that the combination of the three predictors yielded the highest AUC for predicting sepsis in NSTI patients compared to any individual predictor [area under the curve (AUC) = 0.799 (95%CI was 0.721-0.878)]. CONCLUSIONS The clinical features of NSTI patients show certain regularity. Coronary heart disease, C-reactive protein, and total bilirubin are independent associated factors for sepsis in NSTI patients.
Humans ; Retrospective Studies ; Male ; Sepsis ; Soft Tissue Infections/microbiology* ; Female ; Middle Aged ; Aged ; Adult ; Prognosis ; Risk Factors ; Necrosis ; Logistic Models ; Fasciitis, Necrotizing

Objective:To analyze the relationship between the expression level of calumenin(CALU)and the prognosis of hepatocellular carcinoma(HCC)patients by bioinformatics tools and establish the prognostic prediction nomogram,and to clarify its possible mechanism.Methods:The data of 374 HCC tissue samples were downloaded from The Cancer Genome Atlas(TCGA)database and the data of 160 normal tissue samples were down loaded from Genotype-Tissue Expression(GTEx)database.Paired sample t-test was used to analyze the difference in CALU expression between the HCC tissue samples and the paired adjacent normal tissue samples.Human Protein Atlas(HPA)database was used to verify the results.DESeq2 package was used to screen the differentially expressed genes(DEGs)between CALU low expression group and CALU high expression group in the HCC tissue samples.R package pROC was used to analyze the receiver operating characteristic(ROC)curve.Univariate and multivariate Cox regression analyses were used to confirm the prognosis value of CALU in the HCC patients with different clinicopathological characteristics,and ggplot2 package was used to construct the forest plot.R packages rms and survival were used to construct the nomogram and its calibration curve,and the diagnostic value of CALU in distinguishing HCC tissue from normal tissue was analyzed.The data from Kaplan-Meier Plotter database were used to further verify the relationship between CALU and the prognosis of HCC patients.The gene transcriptional expression data of 216 HCC samples obtained from GSE14520 dataset were used to verify the prediction accuracy of the nomogram.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were used to determine the function and enrichment pathways of the DEGs,and Gene Set Enrichment Analysis(GSEA)was used to obtain the significantly enriched gene sets of the DEGs.Single-cell sequencing data of 10 HCC tissue samples and 8 adjacent normal tissue samples obtained from GSE149614 dataset were used to verify the relationship between CALU and the prognosis of HCC patients and its mechanism.Results:Compared with normal tissue,the expression level of CALU mRNA in HCC tissue was significantly increased(P＜0.001),and the expression level of CALU protein in HCC samples was also increased.A total of 928 DEGs were identified between CALU low expression group and CALU high expression group in the HCC samples,including 784 upregulated DEGs and 144 downregulated DEGs.The ROC analysis results indicated that CALU showed high diagnostic value in distinguishing cancer tissue from adjacent non-cancer tissue with an area under curve(AUC)of 0.839.Kaplan-Meier survival analysis showed that the survival rate of HCC patients in CALU high expression group was significantly lower than that in CALU group low expression(P＜0.001).Univariate and multivariate Cox regression analyses results demonstrated that high expression of CALU was an independent risk factor of the prognosis in HCC patients,and a prognosis prediction nomogram was constructed.The applicability of nomogram on the prognosis of HCC was verified by GSE14520 dataset.The GO enrichment analysis results showed that DEGs were mainly enriched in pathways related to the oxidative stress,ferroptosis and cuproptosis(P＜0.05).The KEGG enrichment analysis results showed that DEGs were mainly enriched in the pathways related to extracellular matrix(ECM)receptor interaction,linoleic acid metabolism and neuroactive ligand receptor interaction(P＜0.05).The GSEA results showed that high expression of CALU may promote the G1-S phase transition of the cell cycle,ubiquitination protein polymerization and HCC progression,while low expression of CALU may activate oxidative stress,ferroptosis and cuproptosis in HCC cells.Single-cell sequencing analysis results showed that the expression level of CALU mRNA was significantly increased in HCC cells with advanced tumor stages.HCC_CALU_High cell subset was mainly related to ubiquitination,p53 and cell cycle(P＜0.01),and HCC_CALU_Low cell subset was mainly related to oxidative stress,ferroptosis,and histone binding(P＜0.01).Conclusion:The high expression of CALU may be related to the poor prognosis of HCC patients.The constructed nomogram of HCC prognosis shows favourable effect in predicting the survival rate of the HCC patients.The up-regulation of CALU may promote HCC progression by regulating the G1-S phase of the cell cycle and ubiquitination of protein,while down-regulation of CALU may inhibit HCC progression by inducing oxidative stress,ferroptosis and cuproptosis in cells.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.