This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Objective To explore the clinical efficacy of Liuwei Dihuang Capsules for type 2 diabetes mellitus(T2DM)with yin deficiency syndrome and the effects on intestinal flora and inflammatory factors.Methods Totally 60 patients of T2DM with yin deficiency syndrome in Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2022 to June 2023 were selected as the study objects,and were divided into control group and observation group according to the method of block randomization,with 30 cases in each group.Both groups received basic treatment.The control group was given a simulated agent of Liuwei Dihuang Capsules,while the observation group was given Liuwei Dihuang Capsules.The treatment course for both groups was 4 weeks.Clinical efficacy,blood glucose levels[fasting plasma glucose(FPG),2-hour postprandial plasma glucose(2 hPG),glycated albumin(GA)],serum insulin levels[fasting insulin(FINS)and insulin resistance index(HOMA-IR)],changes in gut microbiota,and serum inflammatory cytokine levels[interleukin(IL)-6,tumor necrosis factor(TNF)-α]of both groups were compared.Results The total effective rate of the observation group(76.67%)was better than that of the control group(50.00%)(P<0.05).Compared with before treatment,the FPG,2 hPG,GA,FINS and HOMA-IR decreased in the observation group,while the FPG,2 hPG and FINS decreased in the control group(P<0.05);after treatment,the Shannon index of the observation group increased after treatment(P<0.05),and the diversity of the microbiota increased;the abundance of the microbial communities such as Coprococcus 3,Cutibacterium,Pseudomonas,Faecalibaculum,Dubosiella and Mucispirillum significantly increased(P<0.05);the abundance of Sphingomonas,Corynebacterium 1,Ileibacterium,Ruminiclostridium and other microbiota communities significantly decreased(P<0.05).Compared with before treatment,the levels of IL-6 and TNF-α in both groups were significantly reduced after treatment(P<0.01,P<0.05).After treatment,the levels of IL-6 and TNF-α in the observation group were significantly lower than those in the control group(P<0.05).Conclusion Liuwei Dihuang Capsules can effectively reduce blood glucose levels in patients of T2DM with yin deficiency syndrome,improve insulin resistance,increase gut microbiota diversity,increase beneficial bacterial abundance,reduce harmful bacterial abundance,and alleviate inflammatory cytokine levels.

Objective To predict the value of admission dehydration state combined with fluid accumulation index for post-operative prognosis in elderly patients with intracerebral hemorrhage(ICH).Methods A retrospective study was conducted on 320 elderly ICH patients receiving surgical treatment in Department of Neurosurgery and then admitted to its Intensive Care Unit of the Affiliated Hospital of North China University of Science and Technology from May 2023 to March 2024.According to the survival status at 30 d after onset,they were divided into a survival group(202 cases)and a death group(118 cases).Clinical data such as basic information,admission vital signs,laboratory indicators,and fluid supplementation were compared between the two groups.ROC curve was plotted.Results The death group exhibited significantly advanced age,more bleeding sites,higher 7-day fluid accumulation index,and larger proportions of ventricular rupture,midline displacement and admission dehydration status,but lower uric acid level than the the survival group(P＜0.05,P＜0.01).Binary logistic regression analysis showed that admission dehydration status and 7-day fluid accumulation index were risk factors for 30-day mortality in elderly ICH patients after surgery(P＜0.01).ROC curve analysis showed that the AUC value of admission dehydration status combined with 7-day fluid accumulation index in predicting 30-day death of elderly ICH patients after surgery was 0.774(95％CI:0.722-0.825),and that of the combination was better than that of each indicator alone(P＜0.05).Conclusion Hospital dehydration status combined with 7-day fluid accumulation index has the best effectiveness in predicting 30-day mortality in elderly ICH patients after surgical treatment.

Objective:To investigate the clinical application of internal mammary perforator (IMP) as recipient vessels in immediate breast reconstruction using deep inferior epigastric perforator (DIEP) flap.Methods:The clinical data of 10 patients with early breast cancer who underwent DIEP for immediate breast reconstruction using IMP as the recipient vessels from January 2022 to December 2023 were analyzed. The number, position, and diameter of IMP, diameter of DIEP, the size of the flap, the operation time, surgical complications, cosmetic effect of breast, and patients' satisfaction were summarized and analyzed.Results:The number of IMPs was 2-3, and they were distributed in the second to the fourth ribs. The diameter of the IMP artery was (1.15±0.22) mm, and the diameter of the vein was (1.35±0.19) mm. The diameter of the DIEP was (1.55±0.28) mm, and that of its accompanying vein was (1.50±0.23) mm. The sizes of the flaps ranged from 10.0 cm×8.0 cm×3.0 cm to 12.0 cm×22.0 cm×4.0 cm, with an average of 20.5 cm×11.2 cm×2.8 cm. The weight of the flap was (389.1±51.5) g. The operation time was (574.8±68.1) min. All 10 cases of flaps survived. The reconstructed breasts were natural, soft, and symmetrical to the healthy side breasts. There was no obvious operative complication. The average BREAST-Q score of the patients was 93.5. No recurrence or metastasis was found during follow-up.Conclusions:Although technically difficult, using IMP as recipient vessels in DIEP flats for immediate breast reconstruction results in a low complication rate of the injuries in the internal mammary region. Under the premise of strictly adhering to the surgical indications, satisfactory results can be achieved, and it is safe and reliable.

Objective:To evaluate the clinical efficacy of proximal femoral reconstruction osteotomy (PFRO) in hip revision arthroplasty.Methods:A retrospective analysis was conducted of the 92 patients (93 hips) who had undergone PFRO in hip revision arthroplasty at Department of Orthopedics, The First Affiliated Hospital, University of Science and Technology of China from January 2019 to December 2023. The cohort included 50 males (51 hips) and 42 females (42 hips), with an age of (64.5±11.7) years and a body mass index of (23.7±2.9) kg/m 2. Surgical procedures were performed under general anesthesia via a posterolateral approach. Biologic prostheses were used in femoral reconstruction, and PFRO fragments repositioned and fixed using cerclage wires. The data collected were operative time, intraoperative blood loss, length of osteotomy fragments, healing at the osteotomy site, intraoperative and follow-up complications, as well as Harris hip score (HHS) and leg length discrepancy (LLD) at the last follow-up. Results:For this cohort, operative time was (174.9±45.6) minutes, intraoperative blood loss (594.6±206.6) mL, and length of osteotomy fragments (12.3±2.3) mm. The 92 patients were followed up for (35.8±12.3) months. For them, HHS improved from preoperative (38.3±8.5) points to (80.5±12.8) points at the last follow-up, and LLD decreased from preoperative (21.2±13.0) mm to 2.0(0.0, 5.0) mm at the last follow-up, showing significant differences ( P<0.05). The osteotomy sites healed in 89 cases (90 hips), with a displacement of the greater trochanter <5 mm; 3 cases (3 hips) experienced nonunion with wire loosening and a displacement of the greater trochanter >10 mm. The osteotomy fragment of the greater trochanter got fractured in 2 patients (2 hips) and a fracture of the medial cortex of the proximal femur occurred in 11 patients (11 hips), but follow-ups observed healing of all the fractures. One patient (1 hip) developed postoperative posterior dislocation of the hip which was treated conservatively. One patient (1 hip) developed postoperative periprosthetic infection which did not recur after twice of debridement followed by prosthetic revision of the proximal femoral tumor. Conclusion:In hip revision arthroplasty, as PFRO demonstrates a low incidence of fragment fractures of the greater trochanter and a high rate of healing at the osteotomy site, its short-term clinical outcomes are satisfactory.

Objective To investigate the predictive value of early fluid balance combined with daily average fluid intake on the prognosis of patients who received hematoma evacuation for spontaneous intracerebral hemorrhage(sICH).Methods This study retrospectively and consecutively enrolled patients who underwent hematoma evacuation for sICH admitted to the Neurosurgical Intensive Care Unit of North China University of Science and Technology Affiliated Hospital between January 2023 and January 2025.Patients'baseline and clinical data were collected,including gender,age,admission vital signs(body temperature,respiratory rate,heart rate,systolic and diastolic blood pressure),medical history(hypertension,diabetes mellitus,coronary heart disease),admission Glasgow coma scale(GCS)score,admission laboratory parameters(including white blood cell count,red blood cell count,platelet count,urine bacterial levels,urine ketones,urine pH,homocysteine),hemorrhage location,hemorrhage volume,time from ictus to surgery,and hematoma evacuation rate(hematoma evacuation rate[％]=[preoperative hematoma volume-postoperative hematoma volume]/preoperative hematoma volume × 100％).Fluid intake,output,balance,daily average intake,and cumulative fluid balance during the early postoperative period(the first to seventh 24-hour periods)were assessed and recorded.Fluid intake comprised the sum of intravenously administered fluids(crystalloids,hypertonic fluids,colloids,blood products,and parenteral nutrition),enteral nutrition(nasogastric feeding solutions and water),and renal replacement therapy fluids.Fluid output comprised the sum of urine volume,vomitus,drainage fluid,and dialysis fluid losses.Fluid balance was defined as the difference between fluid intake and output.Daily average intake was calculated as the average of the fluid intake over the first seven postoperative 24-hour periods.Cumulative fluid balance was the sum of the fluid balances over the first seven postoperative 24-hour periods.Patient outcomes were assessed at 30 days postoperatively.Discharged patients underwent outpatient review or telephone follow-up,while inpatients were evaluated by neurosurgeons.Prognosis was evaluated using the 30-day modified Rankin scale(mRS)score:mRS scores 0-3 were classified as favorable prognosis,and mRS scores 4-6 as poor prognosis.Patients were subsequently divided into favorable prognosis and poor prognosis groups based on mRS scores.Factors with P＜0.05 in univariate comparisons and without collinearity(multicollinearity was defined by:tolerance＜0.1 and variance inflation factor＞10)were included in multivariate Logistic regression analysis to identify independent risk factors for poor 30-day prognosis after hematoma evacuation in sICH patients.Receiver operating characteristic(ROC)curve analysis was employed to evaluate the predictive value of relevant factors for poor 30-day prognosis after hematoma evacuation in sICH patients.Results A total of 320 patients who underwent hematoma evacuation for sICH were enrolled,including 192 males and 128 females,with an age range of 20-91 years(median age 62[53,68]years).Among them,144 patients were assigned to the favorable prognosis group and 176 to the poor prognosis group.The poor prognosis group exhibited significantly higher hemorrhage volume,homocysteine level,fluid intake at the 3rd,5th,6th,and 7th 24-hour periods,fluid balance at the 3rd,5th,6th,and 7th 24-hour periods,daily average intake,and cumulative fluid balance compared to the favorable prognosis group(all P＜0.05).The favorable prognosis group had a significantly higher hematoma evacuation rate,GCS score,proportion of supratentorial hemorrhage and negative urine ketones than the poor prognosis group(all P＜0.05).No significant differences were found in other clinical data(all P＞0.05).Fluid balance over the first seven postoperative 24-hour periods displayed a rise-decline-rise pattern in the poor prognosis group and a rise-decline pattern in the favorable prognosis group.Both groups peaked at the 3rd 24-hour period.Multivariate Logistic regression analysis identified fluid balance at the 3rd 24-hour period(OR,2.013,95％CI 1.386-2.922,P＜0.01)and daily average intake(OR,3.583,95％CI 1.793-7.161,P＜0.01)as independent influencing factors for poor 30-day prognosis after hematoma evacuation in sICH patients.ROC curve analysis revealed that the area under the curve(AUC)for fluid balance at the 3rd 24-hour period and daily average intake in predicting poor 30-day prognosis were 0.699(95％CI 0.642-0.757)and 0.765(95％CI 0.712-0.819),respectively.The combined model of fluid balance at the 3rd 24-hour period and daily average intake achieved an AUC of 0.804(95％CI 0.756-0.853),demonstrating significantly superior predictive performance compared to either variable alone(both P＜0.05).Conclusions The combination of fluid balance at the 3rd 24-hour period and daily average intake demonstrates modest predictive value for poor 30-day prognosis after hematoma evacuation in sICH patients.These findings require validation through multicenter,large-scale,prospective studies.

BACKGROUND:Traditional methods of urinary tract reconstruction are limited by donor scarcity,high complication rates,and suboptimal functional recovery.Tissue engineering strategies offer new directions in this field.Since the urinary tract is mainly composed of muscle tissue,the key is to find suitable seed cells and efficiently induce them to differentiate into smooth muscle cells.Comparative studies on the efficacy of different smooth muscle cell induction regimens are still lacking. OBJECTIVE:To isolate,culture,and identify human urine-derived stem cells,and to compare the effects of two different induction protocols. METHODS:Human urine-derived stem cells were isolated from urine samples of 11 healthy adult volunteers by multiple centrifugations.Surface markers were identified by flow cytometry.The multi-directional differentiation potential of human urine-derived stem cells was verified through osteogenic and adipogenic differentiation.Differentiation was induced by transforming growth factor-β1 or transforming growth factor-β1 combined with platelet derived growth factor for 14 days.Immunofluorescence staining and western blot assay were employed to compare the expression differences of smooth muscle-specific proteins(α-SMA and SM22). RESULTS AND CONCLUSION:(1)Urine-derived stem cells were successfully isolated from the eight urine samples of healthy people.These cells exhibit a"rice grain"-like morphology and possess a robust proliferative capacity.(2)Urine-derived stem cells exhibited high expression of mesenchymal stem cell surface markers(CD73,CD90,and CD44)and extremely low expression of hematopoietic stem cell surface markers(CD34 and CD45).These cells did not express CD19,CD105,and HLA-DR.(3)After osteogenic and adipogenic differentiation,the formation of calcium nodules and lipid droplets was observed,with positive staining results from Alizarin Red S and Oil Red O staining.(4)After 14 days of smooth muscle induction culture,immunofluorescence staining revealed that the smooth muscle differentiation rate of urine-derived stem cells treated with a combination of transforming growth factor-β1 and platelet derived growth factor was significantly higher compared to those treated with transforming growth factor-β1 alone(P<0.005).(5)After 14 days of smooth muscle induction culture,western blot assay further demonstrated that the expression levels of α-SMA and SM22 in the transforming growth factor-β1/platelet derived growth factor group were significantly elevated compared to those in the transforming growth factor-β1 only group(P<0.005).These findings confirm that urine-derived stem cells can be non-invasively isolated using multiple rounds of centrifugation.Compared with transforming growth factor-β1 alone,the combination of transforming growth factor-β1 and platelet derived growth factor can improve the efficiency of inducing urine-derived stem cells to differentiate into smooth muscle cells.

Objective : To explore the role and mechanism of 25-hydroxycholesterol (25-HC) in inflammatory bow- el disease (IBD) in mice． Methods : All mice were divided into three groups : the control group was fed normally ; the DSS model group was fed with 2. 5% dextran sulfate sodium (DSS) solution ; the DSS + 25-HC experimental group was fed with 2. 5% DSS solution and he mice in the experimental group were intraperitoneally injected with 25-HC．The symptom changes of the mice were evaluated by assessing the disease activity index(DAI) ，and the tis- sue changes were judged by histological scoring．The expression of interleukin-17 and its signaling pathways in the mice were detected by Western blot，qRT-PCR, immunohistochemistry /fluorescence，and flow cytometry．Combined with the detection of tight junction proteins in the intestinal epithelium of the mice，the mechanism by which 25-HC affects IBD in mice was explored． Results : In comparison to the DSS control group，The DSS + 25-HC experimen- tal group mice exhibited a reduction in body weight ( F = 30. 1，P ＜0. 000 1) ，a shortened colon ( F = 63. 8，P < 0. 05) ，and elevated DAI(F = 774. 5，P＜0. 000 1) and histopathological scores(F = 141. 5，P＜0. 05) ．Addition- ally，the expression of tight junction-associated proteins(ZO-2，Occludin，JAM and Claudin-4) was found to be sig- nificantly reduced．The level of IL-17 significantly decreased，and its expression level was positively correlated with tight junction proteins． Conclusion 25-HC inhibited IL-17 production by colonic γδ T cells through the RORγt pathway，aggravated mucosal injury，and promoted the development of DSS-induced acute colitis in mice．