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 efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Purpose/Significance To construct a specialized database for inflammatory demyelinating disease of the central nervous system(CNS),so as to contribute to clinical research and improve the diagnostic and treatment capabilities of primary healthcare institu-tions.Method/Process Using the internet to collect medical data,after processing and analysis,the CNS inflammatory demyelinating disease database is constructed.Using statistical analysis,natural language processing(NLP),artificial intelligence(AI)image recog-nition and data visualization and other technologies,the database information is integrated and analyzed.Result/Conclusion A standard-ized big database for CNS inflammatory demyelinating diseases is constructed,which enables visualization of clinical research data,pro-vides patient education and specialist training,and facilitates multi-center teleconsultations.The establishment of a specialized database for the CNS inflammatory demyelinating disease can promote the transformation of medical research achievements,provide references for future real-world clinical research,optimize the process of diagnosis and treatment,and improve the clinical capability of primary healthcare institutions.

Fatal familial insomnia,an autosomal dominant prion disease,is rare.We reported the clin-ical symptoms,examination results,diagnosis,treatment,and prognosis of a patient who was diagnosed with fatal familial insomnia.Furthermore,we described the unique clinical manifestations that involuntary movements and laryngeal stridor were significantly correlated with postural changes,aiming to provide reference for the clini-cal diagnosis,treatment,and research of the disease in the future.

Primary central nervous system vasculitis(PACNS)is a vasculitic disorder affecting small to medium-sized blood vessels primarily in the central nervous system,involving the brain,spinal cord,and me-ninges.Tumor-like PNCAS,a rare subtype of PACNS,is often misdiagnosed as intracranial malignancy,and that with spinal cord involvement is even more uncommon.The lack of specific clinical symptoms and imaging manifestations poses a challenge to the diagnosis of PACNS.This report presents a case of tumor-like PACNS with spinal cord involvement based on the pathological evidence,aiming to enrich the knowledge about this condition.

Objective To analyze the clinical features of 17 patients with primary angiitis of the central nervous system(PACNS)and thus facilitate the early diagnosis and treatment,reduce the recurrence and mortal-ity,and improve the prognoses of this disease.Methods We collected the data of patients with PACNS diag-nosed by brain biopsy from January 2009 to June 2023 and analyzed their clinical presentations,laboratory and imaging manifestations,electrophysiological and pathological changes,and treatment regimens and prognosis.Results The 17 patients diagnosed with PACNS via brain biopsy included one child and 16 adults.The subtyp-ing results showed that 10,2,3,2,1,and 1 patients had tumorous,spinal cord-involved,angiography-posi-tive,rapidly progressive,hemorrhagic,and amyloid β-related PACNS,respectively.Eleven(64.7％)of the patients were complicated with secondary epilepsy.All the patients exhibited abnormal manifestations in head MRI,with 94.1％showing lesions with uneven enhancement around the lesions or in the leptomeninges.Mag-netic resonance angiography revealed large vessel abnormalities in 3 patients,and spinal cord involvement was observed in 2 patients.Histopathological typing revealed 7(43.7％)patients with lymphocytic vasculitis and 5(31.2％)patients with necrotizing vasculitis.Eleven patients were treated with glucocorticoids and cyclophospha-mide,which resulted in partial lesion disappearance and symptom amelioration in 6 patients upon reevaluation with head MRI after 3 months of maintenance therapy.Two,1,and 3 patients experienced rapid disease progres-sion,death,and recurrence within 1 year,respectively.Three patients showed insensitivity to hormonotherapy and residual disabilities.Two patients received rituximab after relapse and remained clinically stable during a fol-low-up period of 0.5-1 year.Conclusions Tumorous PACNS was more prone to epilepsy,mainly occurring in males.The most common histopathological type was necrotizing vasculitis,which responded to hormonotherapy and had favorable outcomes.Therefore,for the young patients with epilepsy and intracranial tumorous lesions,the possibility of PACNS should be considered.Spinal cord involvement in PACNS was often located in the thorac-ic and cervical cords,suggesting a poorer prognosis.Electromyography commonly revealed neural conduction ab-normalities in the anterior horn or roots,providing clues for differential diagnosis.For suspected spinal cord in-volvement,comprehensive electromyography is recommended.Rapidly progressive PACNS often presented infrat-entorial lesions,such as lesions in the pons and medulla,with a higher mortality rate.Hemorrhagic PACNS was rare,and a multifocal hemorrhagic lesion with enhancement in the intracranial region,particularly in young pa-tients,should raise suspicion.For the patients with recurrent or progressive disease,rituximab is a recommended therapeutic option.

Objective:To analyze the characteristics of peripheral blood lymphocyte subsets in patients with relapsed neuromyelitis optica spectrum disorder (NMOSD) during rituximab (RTX) treatment and to clarify the influence of these lymphocyte subsets in NMOSD relapse.Methods:The monitoring data of lymphocyte subsets (175 times) in 76 patients diagnosed as having aquaporin-4-immunoglobulin G (AQP4-IgG)-seropositive NMOSD during RTX treatment at Department of Neurology, General Hospital of Chinese People's Liberation Army from August 2018 to August 2023 were collected. A relapse group ( n=26) and a non-relapse group ( n=149) were divided based on states at data collection (relapse or not). Two-sample t-test or Mann-Whitney U test were used to compare the differences in RTX administration intervals and lymphocyte subsets between the 2 groups. Additionally, a point biserial correlation analysis was performed to investigate the correlations of lymphocyte subsets and RTX administration intervals with NMOSD relapse. Results:The relapse group had significantly longer RTX administration intervals (10.00 [6.73, 14.37] months vs. 7.27[6.30, 9.10] months), statistically lower percentage of CD3 -CD56 + natural killer lymphocytes (10.72% [7.06%, 15.34%) vs. 13.85% [9.42%, 20.13%]), and significantly higher CD19 + B lymphocytes (7.41% [1.18%, 15.70%] vs. 3.55% [0.38%, 8.74%]) than the non-relapse group ( P<0.05). Positive correlations were noted between RTX administration intervals and NMOSD relapse and between CD3 -D19 +B lymphocytes and NMOSD relapse ( r=0.363, P<0.001; r=0.218, P=0.004); negative correlation was noted between CD3 -CD56 + NK lymphocytes and NMOSD relapse ( r=-0.193, P=0.011). Conclusion:Extended RTX administration interval can increase NMOSD relapse; CD3 -CD56 + natural killer lymphocytes and CD19 +B lymphocytes may regulate the disease states of NMOSD patients.

Objective:To explore the relationship between hemoglobin variability (Hb-var) and risk of all-cause death and cardiovascular death in patients with peritoneal dialysis (PD), and to provide basis for reducing the risk of death in PD patients.Methods:It was a multicenter retrospective cohort study. The clinical data of regular PD patients from Nanfang Hospital of Southern Medical University, Shunde Hospital of Southern Medical University, Foshan First People's Hospital and Ganzhou People's Hospital from July 1, 2008 to December 31, 2019 were collected. Hb-var was calculated based on hemoglobin at baseline before PD and in the first year after PD. The patients were divided into low Hb-var group, moderate Hb-var group and high Hb-var group according to the tertiles of first year Hb-var, and the differences of baseline clinical data among three groups were compared. Follow-up endpoints included death, transfer to hemodialysis, transfer to kidney transplantation, transfer to other centers, loss of follow-up, or on December 31, 2021. Cox regression analysis model was used to analyze the association of the first-year Hb-var with all-cause death and cardiovascular death. Fine-Gray competitive risk regression model was used to evaluate the impact of competitive events on mortality risk.Results:A total of 1 562 patients with PD were included in the study, aged (47.6±13.8) years old, with 821 males (52.6%) and baseline hemoglobin of 81 (69, 94) g/L. Hb-var in the first year of PD was 26.6 (16.7, 40.3) g/L. There were statistically significant differences in age, body mass index, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, intact parathyroid hormone and the proportion of renin-angiotensin system inhibitors among low Hb-var group (<20.0 g/L), moderate Hb-var group (20.0-35.5 g/L) and high Hb-var group (≥35.5 g/L, all P<0.05). The follow-up time was 33 (19, 51) months, and 208 patients (13.3%) died, among which 111 patients (53.4%) died of cardiovascular death. Multivariate Cox regression analysis showed that the higher Hb-var in the first year, the lower the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.018) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) in PD patients. Compared with low Hb-var group, the risk of all-cause death ( HR=0.56, 95% CI 0.37-0.82, P=0.003) and cardiovascular death ( HR=0.54, 95% CI 0.31-0.95, P=0.032) was lowest in the high Hb-var group. The competitive risk regression model analysis showed that Hb-var in the first year was still negatively correlated with the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.039). Conclusion:High Hb-var in the first year is associated with low risk of all-cause death and cardiovascular death in PD patients with severe anemia at baseline.

Objective:To evaluate the clinical efficacy of intermittent theta burst stimulation (iTBS) of the bilateral cerebellum in treating post-stroke dysphagia.Methods:Forty patients with dysphagia after a cerebral infarction were randomly divided into a control group and an iTBS group, with 20 cases in each group. In addition to routine swallowing rehabilitation training and nutritional guidance, the iTBS group underwent daily bilateral cerebellar iTBS 6 times a week for 3 weeks, while the control group was given sham stimulation. Before and after the treatment, both groups were evaluated by using the water-swallowing test and the standardized swallowing assessment (SSA), and the latency and amplitude of the mylohyoid muscle′s motor evoked potential (MEP) were also recorded. The SSA scores and MEP amplitudes of the mylohyoid muscle after treatment were tested for any correlation.Results:The treatment improved the water-swallowing test results in both groups, with that of the iTBS group significantly better than that of the control group. The clinical efficacy in the iTBS group was 95%, significantly higher than the control group′s 80%. The SSA scores decreased significantly in both groups after the treatment, with the iTBS group′s average score then significantly lower than that of the control group. The average latency and amplitude of the mylohyoid muscle′s MEP was also significantly better in the iTBS group after the treatment. In the control group only the average amplitude was significantly greater than before the treatment. Pearson correlation analysis showed that the SSA scores and the MEP amplitudes of the mylohyoid muscle after treatment were uncorrelated in both groups.Conclusions:Bilateral intermittent theta burst stimulation can effectively improve the swallowing of patients with post-stroke dysphagia.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.