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.

[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

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

Objective:To investigate the relationship between the Palatopharyngeal Arch Staging System（PASS） and the severity of Obstructive Sleep Apnea（OSA）, as well as the patterns of airway collapse, while further assessing its clinical applicability. Methods:A total of 98 patients diagnosed with OSA at the Department of Otorhinolaryngology Head and Neck Surgery, Shenzhen University Affiliated Shenzhen Hospital, were recruited for this study. Data collected included basic demographic information, oropharyngeal laryngoscopy videos, results from awake laryngoscopy Muller tests, and indicators from sleep respiratory monitoring. The distribution of each PASS stage among patients with varying severities of OSA was compared. Additionally, both objective and subjective sleep indicators along with occurrences of airway collapse in OSA patients across different PASS stages were analyzed. Results:In total, 98 patients participated in this study. Statistically significant differences were observed in neck circumference, weight, Body Mass Index（BMI）, tongue position, and PASS stage when comparing mild-to-moderate OSA patients to those with severe OSA（P<0.05）. Furthermore, there were statistically significant variations in Apnea-Hypopnea Index（AHI）, minimum blood oxygen saturation levels, average blood oxygen saturation levels, oxygen desaturation index values, and total oxygen desaturation indices among OSA patients categorized by different PASS stages. Multiple comparisons revealed statistically significant differences in AHI as well as minimum and average blood oxygen saturation levels between patients at PASS 1 versus those at PASS 3（P<0.05）. Additionally, notable differences regarding oropharyngeal collapse rates among OSA patients across various PASS stages were identified; specifically between those at PASS stage 1 and those at PASS stage 3. Conclusion:The proportion of PASS stages for OSA varies across different severity levels. The severity of OSA and the degree of airway collapse in patients with varying PASS stages also exhibit significant differences. Patients classified as PASS 3 demonstrate a more severe form of OSA compared to those at PASS 1, with stage 3 being more susceptible to oropharyngeal collapse than its stage 1 counterpart. This assessment system is anticipated to address the current limitations in evaluating the lateral pharyngeal wall within the oropharynx.
Humans ; Sleep Apnea, Obstructive/pathology* ; Male ; Severity of Illness Index ; Female ; Middle Aged ; Polysomnography ; Adult ; Pharynx/physiopathology* ; Aged

Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

Objective To analyze the characteristics of HIV-1 pretreatment drug resistance(PDR)and molecular transmission networks in Yubei District,Chongqing,providing evidence for targeted interventions.Methods Using a cross-sectional design,plasma samples were collected from HIV/AIDS patients receiving antiretroviral therapy(ART)in Yubei District from January 2022 to December 2023.Pol gene fragments were extracted and amplified for HIV-1 genotyping and drug resistance analysis.Molecular transmission networks were constructed based on genetic distance calculations.Results Among 478 HIV-1 pol sequences,eight geno-types were identified:with CRF07_BC(60.4%,289/478),CRF08_BC(15.5%,74/478),CRF01_AE(11.7%,56/478),and CRF85_BC(5.9%,28/478).The overall PDR rate was 6.3%(30/478),with resistance to nucleoside reverse transcriptase inhibitors(NRTIs)and non-nucleoside reverse transcriptase inhibitors(NNRTIs)at 1.7%(8/478)and 5.2%(25/478),respectively.No protease inhibitor(PI)resistance was de-tected.The molecular network included 177 cases(37.0%network entry rate),forming 53 clusters with 198 connections.Cluster sizes ranged from 2 to 17 nodes,and 75.3%(149/198)of connections were associated with five subdistricts/towns:Shuanglonghu Street,Huixing Street,Luoqi Town,Gulu Town,and Baoshenghu Street.Conclusion HIV-1 genotypes in Yubei District exhibit diversity and complexity,with moderate PDR prevalence.Regional clustering of transmission networks suggests the need for enhanced molecular surveil-lance and targeted interventions based on analytical findings.

Objective To explore the effectiveness and safety of hypofractionated radiotherapy(HFRT)combined with transcatheter arterial chemoembolization(TACE)for metachronous hepatic oligometastasis from nasopharyngeal carcinoma(NPC).Methods The clinical data of patients with metachronous hepatic oligometastasis from NPC,who received HFRT combined with TACE treatment at the Sichuan Provincial Cancer Hospital of China from January 2012 to October 2022,were retrospectively analyzed.The 3-year and 5-year overall survival(OS),progression-free survival(PFS),local recurrence-free survival(LRFS),no extrahepatic distant metastasis survival(EMFS),and treatment-related adverse reactions were analyzed.Results A total of 55 patients were enrolled in this study,including 36 males and 19 females,the median age at the time of occurring metachronous hepatic oligometastasis was 44(27-75)years.The 3-year and 5-year OS,PFS,LRFS,EMFS were 67.8％and 40.0％,55.8％and 30.0％,72.7％and 56.5％,63.6％and 56.5％,respectively.The subgroup analysis indicated that the treatment course of TACE ≥3 cycles could significantly improve the PFS of patients with oligometastasis.HFRT combined with TACE treatment was well tolerated by all patients,and the incidence of Grade Ⅲ-Ⅳadverse reactions was quite low.Conclusion For the treatment of metachronous hepatic oligometastasis from NPC,HFRT combined with TACE is clinically effective,besides,the patients can well tolerate the therapeutic scheme.

Objective:To investigate the incidence of radiation pneumonitis (RP) induced by 125I seed implantation for the treatment of malignant lung tumors and analyze related dosimetric parameters. Methods:A retrospective analysis was conducted on 31 cases of malignant lung tumors treated with 125I seed implantation from January 2017 to December 2022 at Hebei Provincial Tumor Radioactive Seeds Implantation Diagnosis and Treatment Center. These cases consisted of eight patients with squamous cell carcinoma, 10 patients with adenocarcinoma, and 13 patients with metastatic cancer in other sites. At 1-6 months after treatment, these patients received postoperative chest CT scans, with the efficacy evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), including the objective response rate (ORR) and the disease control rate (DCR). The efficacy of RP was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Postoperative dosimetric parameters, including D90 (minimum peripheral dose received by 90% of the target volume), V8 (percentage of lung volume receiving 8 Gy), V32 (percentage of lung volume receiving 32 Gy), and Dmean (mean radiation dose) of the affected lung, were statistically analyzed. The relationships of the RP occurrence with postoperative D90, V8, V32, and Dmean were analyzed by comparison with relevant external radiotherapy data, to identify the parameters that are correlated closely with RP occurrence. Results:All the patients underwent successful surgeries. The postoperative efficacy evaluation after six months showed complete response (CR) in 11 cases, partial response (PR) in 11 cases, stable disease (SD) in eight cases, and progressive disease (PD) in one case, with an overall response rate (ORR) of 71.0%, and a disease control rate (DCR) of 96.8%. Three patients suffered RP, with an incidence rate of 9.7%. Postoperative V8, V32, and Dmean could not serve as predictive indicators for RP. Follow-up observation revealed that three RP cases (3/5) exhibited postoperative D90 exceeding 170 Gy and no RP cases (0/26) showed postoperative D90 below 170 Gy. Conclusions:In the treatment of malignant lung tumors with 125I seed implantation, there is a certain correlation between RP and postoperative D90, while there is no correlation between it and V8, V32, and Dmean.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To identify the association between CD4 +T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods:From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition.Results:The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×10 7 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [ OR (95% CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [ OR (95% CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group ( Pinteraction<0.05). Conclusion:The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.