Objective To compare the clinical efficacy and safety differences between the triple immunosuppressive regimen of mizoribine (MZR) or mycophenolate mofetil (MMF) combined with tacrolimus (Tac) and glucocorticoids of kidney transplant recipients in one year after transplantation. Methods A single-center retrospective cohort study design was adopted. The clinical data of 156 patients who underwent the first allogeneic kidney transplantation at the Third Hospital of Peking University from January 2022 to December 2024 were included. The patients were divided into the MZR group (78 cases) and the MMF group (78 cases) based on the initial immunosuppressive regimen after transplantation. The baseline data, medication use in one year after transplantation, blood routine indicators, adverse events and clinical outcomes were compared between the two groups. For the repeated-measurement longitudinal data, repeated-measurement analysis of variance was used to evaluate the main effects of the groups, time and their interaction effects. Results At the primary efficacy endpoint, there were no statistically significant differences in the one-year survival rate, graft survival rate and incidence of acute rejection between the two groups (all P > 0.05). In terms of medication patterns and laboratory test indicators, there were significant time main effects and "time × group" interaction effects for Tac dosage (all P < 0.05). The Tac dosage in the MZR group was lower than that in the MMF group from 2 to 3 months after transplantation, and it was higher in the MZR group than in the MMF group from 7 to 12 months and one year after transplantation. White blood cell count in the MZR group was higher at one month after transplantation, and the platelet count was higher one year after transplantation (all P < 0.05). In terms of infection, the incidence of novel coronavirus and Pneumocystis jirovecii pneumonia infections in the MZR group was lower (all P < 0.05). In terms of metabolic indicators, the post-transplantation uric acid level was better in the MZR group than in the MMF group, but the total cholesterol level was higher one year after transplantation (all P < 0.05). In terms of liver function, there was a brief and mild increase in transaminase in the early stage after transplantation in the MZR group. Conclusions During the one-year follow-up after transplantation, both the MZR and MMF regimens demonstrate comparable immunosuppressive efficacy and overall safety in Chinese kidney transplant recipients. The MZR regimen shows clear advantages in reducing specific infection risks, alleviating bone marrow suppression and improving uric acid metabolism, but its potential impact on blood lipids needs to be monitored. Therefore, the MZR regimen may be an effective and safe alternative immunosuppressive option for kidney transplant recipients, especially those with high infection risk, poor hematological tolerance, or comorbid hyperuricemia.

Objective:To explore the clinical characteristics and prognostic factors of primary bladder adenocarcinoma（ACB）.Methods:The clinical data of 33 patients with primary ACB who underwent surgical treatment in the Department of Urology of Peking University Third Hospital from July 2003 to January 2024 were retrospectively analyzed. There were 5 females and 28 males，with an average age of（61.3 ± 11.5）years. Twelve patients had comorbidities（6 hypertension，2 coronary heart disease，5 diabetes mellitus，and 3 cerebrovascular diseases）and 12 had a smoking history. The mean body mass index（BMI）was（24.8 ± 3.2）kg/m 2. The maximum tumor diameter measured by enhanced computed tomography（CT）was（29.7 ± 12.7）mm. The preoperative neutrophil-to-lymphocyte ratio（NLR）was 3.4 ± 3.2，and the systemic immune-inflammation index（SII）was（582 ± 496）× 10 9/L.Patients were divided into two groups according to the surgical approach：the radical cystectomy group（ n = 23）and the bladder-sparing group（ n = 10）. For the radical cystectomy group，there were 19 males and 4 females，with a mean age of（59.9 ± 12.6）years. Five patients had comorbidities（3 hypertension，1 coronary heart disease，1 diabetes mellitus，and 2 cerebrovascular diseases）. Eight patients had a smoking history，with a mean BMI of（25.2 ± 3.5）kg/m 2. The maximum tumor diameter was（33.6 ± 10.9）mm，the preoperative NLR was 3.5 ± 3.5，and the SII was（618 ± 558）× 10 9/L. For the bladder-sparing group，there were 9 males and 1 female，with a mean age of（64.5 ± 8.2）years. Seven patients had comorbidities（3 hypertension，1 coronary heart disease，4 diabetes mellitus，and 1 cerebrovascular diseases）. Four patients had a smoking history，with a mean BMI of（23.5 ± 2.3）kg/m 2. The maximum tumor diameter was（20.7 ± 12.5）mm，the preoperative NLR was 3.1 ± 2.2，and the SII was（501 ± 323）× 10 9/L. Statistically significant differences were observed between the two groups in terms of comorbidities（ P = 0.008）and maximum tumor diameter（ P = 0.006），while no significant differences were found in other data（ P > 0.05）. The Kaplan-Meier survival curve was drawn，and Cox regression was used to analyze the prognostic factors of progression-free survival（PFS）and overall survival（OS）of patients. Results:Among the 33 patients，low-grade adenocarcinoma and high-grade adenocarcinoma accounted for 60.6% and 39.4% respectively according to the postoperative pathology，and 3 patients had positive surgical margins. There were 22 cases of muscle-invasive bladder adenocarcinoma，5 cases of lymph node metastasis，and 1 case of distant metastasis. The patients in tumor stages Ⅰ—Ⅳ were 9 cases（27.3%），8 cases（24.2%），7 cases（21.2%），and 9 cases（27.3%）respectively. Nine patients received postoperative adjuvant therapy，including 6 with adjuvant chemotherapy，2 with adjuvant chemotherapy combined with radiotherapy，and 1 with adjuvant immunotherapy. In the radical cystectomy group（ n = 23），there were 13 cases of low-grade and 10 cases of high-grade pathological grading，2 cases with positive margins，19 cases of muscle-invasive bladder adenocarcinoma，5 cases of lymph node metastasis，1 case of distant metastasis，and 5 patients received adjuvant therapy（4 cases of adjuvant chemotherapy，and 1 case of adjuvant immunotherapy）. In the bladder-sparing group（ n = 10），there were 7 cases of low-grade，3 cases of high-grade pathological grading，1 case with positive margins，3 cases of muscle-invasive bladder adenocarcinoma，zero lymph node or distant metastasis，and 4 patients received adjuvant therapy（2 cases of adjuvant chemotherapy，and 2 cases of combined adjuvant chemotherapy and radiotherapy）. A statistically significant difference was found in the proportion of muscle-invasive bladder adenocarcinoma between the two groups（ P = 0.006），while no significant differences were observed in other data（ P > 0.05）.The median follow-up duration of the patients was 28.0 months，the median PFS was 86.0 months，and the median OS was 90.0 months. The 2-year PFS and OS were 65.4% and 73.1% respectively. The 5-year PFS and OS were 54.2% and 56.5% respectively. The Kaplan-Meier survival analysis showed that there were no significant differences in PFS（ P = 0.777）and OS（ P = 0.585）between the radical cystectomy group and the bladder-preserving group. Female（ P = 0.011），BMI < 25 kg/m2（ P = 0.038），and positive surgical margins（ P < 0.01）were associated with poorer PFS. Aged ≥ 70 years（ P = 0.003），lymph node metastasis（ P = 0.041），and positive surgical margins（ P = 0.025）were associated with poorer OS，and patients in the adjuvant therapy group had better OS（ P = 0.005）. Multivariate Cox regression analysis indicated that positive surgical margins（HR 10.2， P = 0.012）were an independent impact factor for PFS，and positive surgical margins（HR 39.8， P = 0.001）and adjuvant therapy（HR 0.12， P = 0.021）were independent impact factors for OS. Conclusions:Positive surgical margins and adjuvant therapy are independent impact factors for the prognosis of patients with primary ACB.

Objective:To explore the clinical characteristics and prognostic factors of primary bladder adenocarcinoma（ACB）.Methods:The clinical data of 33 patients with primary ACB who underwent surgical treatment in the Department of Urology of Peking University Third Hospital from July 2003 to January 2024 were retrospectively analyzed. There were 5 females and 28 males，with an average age of（61.3 ± 11.5）years. Twelve patients had comorbidities（6 hypertension，2 coronary heart disease，5 diabetes mellitus，and 3 cerebrovascular diseases）and 12 had a smoking history. The mean body mass index（BMI）was（24.8 ± 3.2）kg/m 2. The maximum tumor diameter measured by enhanced computed tomography（CT）was（29.7 ± 12.7）mm. The preoperative neutrophil-to-lymphocyte ratio（NLR）was 3.4 ± 3.2，and the systemic immune-inflammation index（SII）was（582 ± 496）× 10 9/L.Patients were divided into two groups according to the surgical approach：the radical cystectomy group（ n = 23）and the bladder-sparing group（ n = 10）. For the radical cystectomy group，there were 19 males and 4 females，with a mean age of（59.9 ± 12.6）years. Five patients had comorbidities（3 hypertension，1 coronary heart disease，1 diabetes mellitus，and 2 cerebrovascular diseases）. Eight patients had a smoking history，with a mean BMI of（25.2 ± 3.5）kg/m 2. The maximum tumor diameter was（33.6 ± 10.9）mm，the preoperative NLR was 3.5 ± 3.5，and the SII was（618 ± 558）× 10 9/L. For the bladder-sparing group，there were 9 males and 1 female，with a mean age of（64.5 ± 8.2）years. Seven patients had comorbidities（3 hypertension，1 coronary heart disease，4 diabetes mellitus，and 1 cerebrovascular diseases）. Four patients had a smoking history，with a mean BMI of（23.5 ± 2.3）kg/m 2. The maximum tumor diameter was（20.7 ± 12.5）mm，the preoperative NLR was 3.1 ± 2.2，and the SII was（501 ± 323）× 10 9/L. Statistically significant differences were observed between the two groups in terms of comorbidities（ P = 0.008）and maximum tumor diameter（ P = 0.006），while no significant differences were found in other data（ P > 0.05）. The Kaplan-Meier survival curve was drawn，and Cox regression was used to analyze the prognostic factors of progression-free survival（PFS）and overall survival（OS）of patients. Results:Among the 33 patients，low-grade adenocarcinoma and high-grade adenocarcinoma accounted for 60.6% and 39.4% respectively according to the postoperative pathology，and 3 patients had positive surgical margins. There were 22 cases of muscle-invasive bladder adenocarcinoma，5 cases of lymph node metastasis，and 1 case of distant metastasis. The patients in tumor stages Ⅰ—Ⅳ were 9 cases（27.3%），8 cases（24.2%），7 cases（21.2%），and 9 cases（27.3%）respectively. Nine patients received postoperative adjuvant therapy，including 6 with adjuvant chemotherapy，2 with adjuvant chemotherapy combined with radiotherapy，and 1 with adjuvant immunotherapy. In the radical cystectomy group（ n = 23），there were 13 cases of low-grade and 10 cases of high-grade pathological grading，2 cases with positive margins，19 cases of muscle-invasive bladder adenocarcinoma，5 cases of lymph node metastasis，1 case of distant metastasis，and 5 patients received adjuvant therapy（4 cases of adjuvant chemotherapy，and 1 case of adjuvant immunotherapy）. In the bladder-sparing group（ n = 10），there were 7 cases of low-grade，3 cases of high-grade pathological grading，1 case with positive margins，3 cases of muscle-invasive bladder adenocarcinoma，zero lymph node or distant metastasis，and 4 patients received adjuvant therapy（2 cases of adjuvant chemotherapy，and 2 cases of combined adjuvant chemotherapy and radiotherapy）. A statistically significant difference was found in the proportion of muscle-invasive bladder adenocarcinoma between the two groups（ P = 0.006），while no significant differences were observed in other data（ P > 0.05）.The median follow-up duration of the patients was 28.0 months，the median PFS was 86.0 months，and the median OS was 90.0 months. The 2-year PFS and OS were 65.4% and 73.1% respectively. The 5-year PFS and OS were 54.2% and 56.5% respectively. The Kaplan-Meier survival analysis showed that there were no significant differences in PFS（ P = 0.777）and OS（ P = 0.585）between the radical cystectomy group and the bladder-preserving group. Female（ P = 0.011），BMI < 25 kg/m2（ P = 0.038），and positive surgical margins（ P < 0.01）were associated with poorer PFS. Aged ≥ 70 years（ P = 0.003），lymph node metastasis（ P = 0.041），and positive surgical margins（ P = 0.025）were associated with poorer OS，and patients in the adjuvant therapy group had better OS（ P = 0.005）. Multivariate Cox regression analysis indicated that positive surgical margins（HR 10.2， P = 0.012）were an independent impact factor for PFS，and positive surgical margins（HR 39.8， P = 0.001）and adjuvant therapy（HR 0.12， P = 0.021）were independent impact factors for OS. Conclusions:Positive surgical margins and adjuvant therapy are independent impact factors for the prognosis of patients with primary ACB.

Objective:To investigate the clinical efficacy of acupoint pressing acupuncture combined with moxibustion at Baihui acupoint on infantile cold and nasal obstruction caused by exogenous wind and cold. Methods:This study included a total of 120 children with exogenous wind and cold-induced infantile cold and nasal obstruction who were treated at the Jinhua Maternal & Child Health Care Hospital from February 2021 to May 2022. They were divided into three groups using a random number table method, namely the acupoint pressing acupuncture group, the moxibustion group, and the combined therapy group, each containing 40 children. Based on routine treatment, children in the acupoint pressing acupuncture group received acupoint ( Yintang, Shuangyingxiang, Shuangbitong) pressing acupuncture treatment, while those in the moxibustion group underwent mild moxibustion at Baihui acupoint, and those in the combined therapy group underwent acupoint ( Yintang, Shuangyingxiang, Shuangbitong) pressing acupuncture Baihui combined with mild moxibustion at Baihui acupoint. The clinical efficacy of each group was evaluated. At 2, 24, 48, and 72 hours after treatment, differences in nasal congestion symptom scores were compared among the three groups. Sleep quality was also compared among the three groups before and after treatment. Results:The response rate in the combined therapy group was 92.5% (37/40), which was significantly higher than 75% (30/40) in the acupoint pressing acupuncture group and 65% (26/40) in the moxibustion group ( χ2 = 4.50, 9.04, both P < 0.05). At 2, 24, 48, and 72 hours after treatment, the nasal congestion symptom score in the combined therapy group was (2.05 ± 0.55) points, (1.80 ± 0.64) points, (1.33 ± 0.59) points, and (0.90 ± 0.18) points, respectively, while it was (2.43 ± 0.59) points, (2.15 ± 0.57) points, (1.73 ± 0.84) points, and (1.18 ± 0.80) points, respectively, in the acupoint pressing acupuncture group, and (2.50 ± 0.59) points, (2.13 ± 0.78) points, (1.88 ± 0.81) points, and (1.45 ± 0.81) points, respectively, in the moxibustion group. At the above-mentioned time points, the nasal congestion symptom score was statistically significant among the three groups ( F = 3.15, 9.27, 16.17, 20.22, all P < 0.05). After treatment, daytime sleep duration and nocturnal sleep duration in the combined therapy group were (3.41 ± 0.31) hours and (12.36 ± 1.17) hours, respectively, which were significantly longer than (2.95 ± 1.07) hours and (11.33 ± 1.38) hours in the acupoint pressing acupuncture group and (2.93 ± 0.98) hours and (11.21 ± 1.93) hours in the moxibustion group ( F = 6.37, 12.31, both P < 0.05). Nocturnal wake time, the number of night wakings, and sleep onset time in the combined therapy group were (18.74 ± 2.21) minutes, (1.64 ± 0.18) times, and (15.43 ± 2.03) minutes, respectively, which were significantly shorter or less than (21.13 ± 3.78) minutes, (2.15 ± 0.66) times, and (17.63 ± 5.24) minutes in the acupoint pressing acupuncture group, and (20.53 ± 2.90) minutes, (2.11 ± 0.32) times, and (17.22 ± 2.88) minutes in the moxibustion group ( F = 15.93, 15.36, 10.11, all P < 0.05). There was a significant difference in sleep quality score among the three groups ( F = 23.45, P < 0.05). Conclusion:The combination of acupoint pressing acupuncture and moxibustion at Baihui acupoint is highly effective against infantile cold and nasal obstruction caused by exogenous wind and cold. The combined therapy can alleviate the symptoms of nasal congestion in children and improve sleep quality.

Bartter syndrome (BS, OMIM #601678) is a rare inherited salt-losing tubulopathy characterized by hypokalemia metabolic alkalosis with secondary renin-angiotensin-aldosterone system activation. As reported, BS type 1 is generally presented prenatal and neonatal period, and symptoms usually appear before and after birth or in infancy, accompanied by severe salt loss, whilst kidney function remains mostly normal. In this study, we report a case of BS type 1 with childhood onset and proteinuria and renal impairment. The child was born preterm due to hyperamniotic fluid, but there were no apparent symptoms after birth until the age of 3 when the child began to present with polydipsia, polyuria and increased nocturnal uria. At the age of 5, she had elevated serum creatinine level and proteinuria. After admission, she was diagnosed with chronic tubulointerstitial disease and stage 2 chronic kidney disease(CKD). According to the chloride clearance test, the abnormal function of medullary thick ascending limb Henle′s loop, was confirmed and BS type 1 was diagnosed by gene sequencing. After active management of complications, kidney function of the child improved. In the long-term follow-up, the urinary protein amount of the child still increased, eGFR slowly decreased, and the child was currently in the CKD2 stage. Children with prenatal BS may not present typical clinical manifestations immediately after birth until the onset of relevant clinical symptoms in childhood. BS type 1 patients may have renal impairment, which needs to be identified in time. Clinical differentiation diagnosis between BS and Gitelman syndrome can be made by chloride clearance tests. Early diagnosis and treatment are critical to improve prognosis.

OBJECTIVE The N-methyl-D-aspartate(NMDA)receptor has been shown to be strongly associ-ated with rapid antidepressant effects.GW043 is a com-pound with a novel structure that we designed and syn-thesized to act on the NMDA receptor(NMDAR).METH-ODS In this study,we first confirmed the target of GW043 using a receptor binding assay.We observed the effect of GW043 on NMDAR currents in vivo and in vitro assays using a membrane clamp technique with a view to characterizing the function of GW043.We investi-gated the antidepressant effect of GW043 in rodent behavioral models such as FST,TST and CUMS.Fur-thermore,we explored the mechanism of GW043 onset using Western blotting,BrdU staining,Golgi staining and electrophysiological techniques.RESULTS GW043 interacts with high affinity only at the NMDAR.Electro-physiological studies have indicated that GW043 is a par-tial agonist of NMDAR.Meanwhile,behavioral experi-ments were conducted to confirm the antidepressant effect of GW043 in rodents.The mechanism study found that GW043 regulate synaptic plasticity through LTP and BDNF/mTOR pathways and increase the number of new-born neurons to cause antidepressant effects.GW043,a partial agonist of NMDAR,reversed depression-like behav-ior in rats by modulating synaptic plasticity,suggesting an antidepressant effect.CONCLUSION The results suggest that GW043 is a partial agonist of NMDA recep-tors and has significant antidepressant effects.

This paper reports a case of atypical cholesterol side chain enzyme deficiency caused possibly by CYP11A1p.A359V heterozygous mutation. The patient was diagnosed as congenital adrenal hyperplasia because he was born with gonadal dysplasia and there were manifestations of salt losing and pigment changing, combined with high level of plasma ACTH. Further genetic screening revealed CYP11A1p.A359V heterozygous mutations in patients with a final diagnosis of cholesterol side chain enzyme deficiency which was treated effectively to glucocorticoid.

OBJECTIVETo analyze the hematological and genetic characteristics of unstable hemoglobin Rush (Hb Rush) and compound heterozygote of Hb Rush and thalassemia.

METHODSPeripheral blood samples and genomic DNA from three patients (including two ethnic Dai and one Han Chinese) with anemia of undetermined origin were collected. Hematological phenotypes of these patients were determined through red blood cell analysis and hemoglobin electrophoresis. Genotypes of alpha- and beta-globin genes, -158 XmnⅠ polymorphic site ofγ promoter region, and haplotypes of 7 polymorphic restriction sites in the beta-globin gene cluster were determined using PCR-based methods and DNA sequencing.

RESULTSAll patients have presented hypochromic microcytic anemia and hemoglobin fraction with significant increased measurement (30.5%-59.2%) in the region of fetal hemoglobin during alkaline medium electrophoresis. DNA analysis suggested that all patients have carried mutations leading to the unstable hemoglobin Rush (HBB codon 101, GAG>CAG, Glu>Gln). Two of them were compound heterozygotes of Hb Rush and thalassemia mutations of -α,CD17 and Hb E, respectively. Hb Rush mutation was associated with various haplotypes of the β-globin gene cluster. No significant association was found between increased abnormal hemoglobin fraction in the region of Hb F and the polymorphism ofγ promoter or large deletion of the beta-globin gene cluster.

CONCLUSIONThis study has confirmed the distribution of Hb Rush among various Chinese populations and is the third report of its kind. Hb Rush can result in increased measurement of hemoglobin fraction in the region of fetal hemoglobin (Hb F) during routine hemoglobin electrophoresis under alkaline condition. Hb Rush heterozygote alone can lead to hypochromic microcytic anemia and thalassemia-like phenotype. Prenatal diagnosis of Hb Rush is necessary for carriers.

Adult ; Base Sequence ; Blood Protein Electrophoresis ; methods ; Female ; Fetal Hemoglobin ; genetics ; metabolism ; Genotype ; Haplotypes ; Hemoglobins, Abnormal ; genetics ; metabolism ; Heterozygote ; Humans ; Infant ; Mutation ; Phenotype ; Polymorphism, Genetic ; Sequence Analysis, DNA ; methods ; Thalassemia ; blood ; diagnosis ; genetics ; Young Adult ; alpha-Globins ; genetics ; metabolism ; beta-Globins ; genetics ; metabolism

BACKGROUND:Traditional therapeutic methods of diabetes combined with lower limb artery obturation showed poor outcomes such as drug or intervention.Stem cell transplantation is a new method to treat this disease in recant years,and has obtained good outcomes in the clinic.Evaluating the therapeutic outcomes of stem cell transplantation has great damage and cost much.Thus,color Doppler ultrasound is used to examine non-invasion in the artery of the lower extremity,which shows important clinical value.OBJECTIVE:To evaluate improvement of lower extremity artery lesion following autologous peripheral blood stem cell transplantation using color Doppler ultrasound,and to compare with results of angiography.METHODS:A total of 41 patients diagnosed as having diabetes combined with lower limb artery obturation were included.Following administration of recombinant human granulocyte-colony stimulating factor(rhG-CSF)(150 μg/d)for 5 days,peripheral blood mononuclear cells(PBMNCs)were mobilized and harvested by using a separator at day 5 to prepare stem cell suspension,and which were injected intramuscularly in the diseased extremities(3×109 per limb).The clinical and laboratory findings were monitored every week for 3 months to 1 year following stem cell transplantation.RESULTS AND CONCLUSION:After stem cell transplantation,severe pain lameness,local cool-feeling and ulcer were significantly improved,and ankle-brachial index was increased obviously(P＜0.01).Color Doppler ultrasonography measurement showed that peak systolic velocity in diseased extremities was significantly increased post-transplantation(P＜0.01).Following transplantation,blood flow of the lower limb arterial canal was improved to different extents;collateral vessels were increased surrounding obstructed artery and in muscles.Spiral CT for new collateral vessel formation were showed increased.No related complication or adverse effects were observed in 41 patients during observation.Results indicated that color Doppler ultrasound can exactly rapidly examine and assess blood transport improvement in the lower limbs following stem cell transplantation,which is identical to results from angiography.It also provides reliable evidences for the diagnosis on the transplantation of stem cells for the treatment of diabetes combined with lower limb artery obturation.

Electrochemotherapy was instituted for sarcoma, and the tumor inhibitory ratio, curing ratio, vascular endothelial growth factor, microvessel density and mechanism were measured and analyzed. The results indicate that the curing ratio of electrochemotherapy for sarcoma is 84.6%. The present research provides experimental evidence for the security, mechanism and feasibility of electrochemotherapy in clinical practice.
Animals ; Antineoplastic Agents ; administration & dosage ; Bleomycin ; administration & dosage ; Drug Delivery Systems ; methods ; Electrochemotherapy ; methods ; Electroporation ; methods ; Mice ; Sarcoma 180 ; therapy ; Vascular Endothelial Growth Factor A ; analysis