Objective:To investigate the efficacy and prognosis of rituximab (RTX) in the treatment of M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN).Methods:It was a retrospective cohort study. The clinical data of PLA2R-associated IMN patients who received RTX treatment in the Shenzhen Second People's Hospital from September 2018 to March 2023 were collected. According to remission status of proteinuria, the patients were divided into proteinuria remission group (24-hour urinary protein quantity < 3.5 g) and non-proteinuria remission group (24-hour urinary protein quantity ≥ 3.5 g), and the clinical data between the two groups were compared. According to baseline 24-hour urinary protein quantity and estimated glomerular filtration rate (eGFR), the patients were divided into high-risk disease progression group [24-hour urinary protein quantity ≥ 8 g or eGFR < 60 ml·min -1·(1.73 m 2) -1] and non-high-risk disease progression group [24-hour urinary protein quantity < 8 g or eGFR ≥ 60 ml·min -1·(1.73 m 2) -1]. Kaplan-Meier survival curve was utilized to compare the differences of proteinuria remission rates and renal composite endpoint event survival rates between the two groups. Multivariate Cox regression analysis was utilized to identify the influencing factors of proteinuria remission and renal composite endpoint event. Results:This study included 46 PLA2R-associated IMN patients, with 31 males (67.4%). The baseline eGFR was (78.4±34.1) ml·min -1·(1.73 m 2) -1. The 24-hour urinary protein quantity was 8.33 (6.04, 12.85) g. After 14.95 (7.44, 22.15) months of follow-up, 29 patients (63.0%) achieved proteinuria remission, with remission time of 6.0 (5.0, 9.0) months. Six (20.7%) patients relapsed, with relapsed time of 17.25 (11.75, 18.28) months. CD20 in the proteinuria remission group was lower than that in the non-proteinuria remission group ( Z=2.270, P=0.023). Eleven (23.9%) patients experienced renal composite endpoint events wtih occurrence time of 16.07 (7.87, 29.63) months. Kaplan-Meier survival curve analysis indicated that there was no statistically significant difference in proteinuria remission rates (log-rank χ2=0.26, P=0.612) and renal composite endpoint event survival rates (log-rank χ2=0.25, P=0.619) between baseline 24-hour urinary protein quantity ≥ 8 g and < 8 g groups. There was no statistically significant difference in proteinuria remission rates after RTX treatment (log-rank χ2=0.77, P=0.381) and renal composite endpoint event survival rates (log-rank χ2=1.41, P=0.236) between eGFR ≥ 60 ml·min -1·(1.73 m 2) -1 and < 60 ml·min -1·(1.73 m 2) -1 groups. Multivariate Cox regression analysis showed that hypertension history ( HR=0.16, 95% CI 0.05-0.55), immunosuppressive therapy history ( HR=0.08, 95% CI 0.01-0.50), baseline eGFR < 60 ml·min -1·(1.73 m 2) -1 ( HR=0.21, 95% CI 0.05-0.92), baseline PLA2R antibody titer ≥ 100 RU/ml ( HR=0.20, 95% CI 0.06-0.69), long time between treatment and first diagnosis ( HR=1.33, 95% CI 1.12-1.57), high baseline triglyceride ( HR=1.46, 95% CI 1.02-2.08), and baseline 24-hour urinary protein quantity ≥ 8 g ( HR=8.54, 95% CI 2.08-35.12) were independent influencing factors of proteinuria remission after RTX treatment. The baseline PLA2R antibody titer ≥ 100 RU/ml was an independent influencing factor of reaching the renal composite endpoint event ( HR=7.31, 95% CI 1.23-43.62). Conclusions:The proteinuria remission rate after RTX treatment of PLA2R-associated IMN is 63.0% and the recurrence rate is 20.7%. The incidence rate of renal composite endpoint event is 23.9%. The hypertension history, immunosuppressant medication history, baseline eGFR < 60 ml·min -1·(1.73 m 2) -1, baseline PLA2R antibody titer ≥ 100 RU/ml, long time between treatment and first diagnosis, high baseline triglyceride, and baseline 24-hour urinary protein quantity ≥ 8 g are independent influencing factors of proteinuria remission, and baseline PLA2R antibody titer ≥ 100 RU/ml is an independent risk factor of renal poor prognosis in PLA2R-associated IMN patients.

Objective:To investigate the role of autophagy mediated by mTOR signaling pathway in the inhibition of osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by cadmium.Methods:HBMSCs were divided into 0, 2.5 or 5.0 μmol/L groups according to the exposure dose of cadmium chloride (CdCl 2), and each group was treated for 1 day, 4 days and (or) 7 days. The ALP activity and mRNA and protein expression levels of osteogenesis markers (ALP, RUNX2 and OSTERIX), autophagy-related proteins (LC3 and Beclin-1) and mTOR signaling pathway related proteins (mTOR, p-mTOR and p-p70S6K) expression, alkaline phosphatase staining and alizarin red staining were detected. MHY 1485 was selected as the signaling pathway activator. The control group, CdCl 2 group (5.0 μmol/L), MHY 1485 group and CdCl 2+MHY 1485 combined treatment group were set. After 7 days of treatment, the expression levels of autophagy related proteins and mTOR signaling pathway related proteins of hBMSCs in each group were detected. Results:There was no significant difference in ALP activity between 0, 2.5 and 5.0 μmol/L groups on day 1 and 4 ( P>0.05); On day 7, compared with the 0 μmol/L group, the ALP activity, expression of osteogenic markers (ALP, RUNX2, OSTERIX) and mTOR signaling pathway related proteins (mTOR, p-mTOR, p-p70S6K) expression decreased in the 2.5 and 5.0 μmol/L group ( P<0.05). Compared with the 0 μmol/L group, the staining of the 2.5 and 5.0 μmol/L groups became lighter, and the formation of ALP and mineralized nodules was reduced. Compared with the CdCl 2 group, the autophagy related protein expression in the CdCl 2+MHY 1485 combined treatment group decreased, and the mTOR signaling pathway related protein expression increased. The difference was statistically significant ( P<0.05). Conclusion:The inhibition of osteogenic differentiation of hBMSCs by cadmium may be related to autophagy mediated by mTOR signaling pathway.

Objective:To investigate the role of autophagy mediated by mTOR signaling pathway in the inhibition of osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by cadmium.Methods:HBMSCs were divided into 0, 2.5 or 5.0 μmol/L groups according to the exposure dose of cadmium chloride (CdCl 2), and each group was treated for 1 day, 4 days and (or) 7 days. The ALP activity and mRNA and protein expression levels of osteogenesis markers (ALP, RUNX2 and OSTERIX), autophagy-related proteins (LC3 and Beclin-1) and mTOR signaling pathway related proteins (mTOR, p-mTOR and p-p70S6K) expression, alkaline phosphatase staining and alizarin red staining were detected. MHY 1485 was selected as the signaling pathway activator. The control group, CdCl 2 group (5.0 μmol/L), MHY 1485 group and CdCl 2+MHY 1485 combined treatment group were set. After 7 days of treatment, the expression levels of autophagy related proteins and mTOR signaling pathway related proteins of hBMSCs in each group were detected. Results:There was no significant difference in ALP activity between 0, 2.5 and 5.0 μmol/L groups on day 1 and 4 ( P>0.05); On day 7, compared with the 0 μmol/L group, the ALP activity, expression of osteogenic markers (ALP, RUNX2, OSTERIX) and mTOR signaling pathway related proteins (mTOR, p-mTOR, p-p70S6K) expression decreased in the 2.5 and 5.0 μmol/L group ( P<0.05). Compared with the 0 μmol/L group, the staining of the 2.5 and 5.0 μmol/L groups became lighter, and the formation of ALP and mineralized nodules was reduced. Compared with the CdCl 2 group, the autophagy related protein expression in the CdCl 2+MHY 1485 combined treatment group decreased, and the mTOR signaling pathway related protein expression increased. The difference was statistically significant ( P<0.05). Conclusion:The inhibition of osteogenic differentiation of hBMSCs by cadmium may be related to autophagy mediated by mTOR signaling pathway.

OBJECTIVETo analyze the clinical and molecular features of a child with carnitine palmitoyltransferase 1A (CPT1A) deficiency.

METHODSClinical data of the child was collected. Blood acylcarnitine was determined with tandem mass spectrometry. DNA was extracted from the child and his parents. All exons and flanking regions of the CPT1A gene were analyzed by PCR and Sanger sequencing.

RESULTSAnalysis showed that the patient carried compound heterozygous mutations c.1787T>C and c.2201T>C of the CPT1A gene, which derived his father and mother, respectively. Both mutations were verified as novel through the retrieval of dbSNP, HGMD and 1000 genome databases. Bioinformatic analysis suggested that the mutations can affect protein function.

CONCLUSIONAcyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency. The c.1787T>C and c.2201T>C mutations of the CPT1A gene probably underlie the disease in this patient. Gene testing can provide important clues for genetic counseling and prenatal diagnosis.

Base Sequence ; Carnitine O-Palmitoyltransferase ; deficiency ; genetics ; Exons ; Female ; Humans ; Hypoglycemia ; enzymology ; genetics ; Infant ; Lipid Metabolism, Inborn Errors ; enzymology ; genetics ; Male ; Molecular Sequence Data ; Point Mutation ; Pregnancy

Objective To perform a risk factor analysis of central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO),and compare the difference in risk factors between CRVO and BRVO.Methods Retrospective observational casecontrol study included 46 CRVO patients,33 BRVO patients and 79 control subjects with senile cataract or refractive error,the risk factors and blood lipid spectrum analysis were performed and compared.Results Multivariate linear regression analysis showed that higher serum levels of homocysteine (P ＜ 0.000 1),total cholesterol (P =0.003 0),lipoprotein (a) (P =0.027 0),hypertension (P =0.022 0) and shorter axial length (P ＜0.000 1) were significantly correlated with CRVO.BRVO was associated with higher serum levels of homocysteine (P ＜0.000 1),total cholesterol (P =0.008 0),hypertension (P =0.002 0),body mass index (P =0.004 0) and shorter axial length (P =0.001 0).There was no significant difference in risk factors between CRVO and BRVO patients on multivariate analysis.Conclusion Multiple systemic (hyperlipidemia,hypertension and hyperhomocystinemia) and ocular (shorter axial length) risk factors are associated with both CRVO and BRVO,but these risk factors are not different between CRVO and BRVO.

Objective To evaluate the effects of electrocautery assisted uvalopalatopharyngoplasty (UPPP) for obstructive sleep apnea and hyponea syndrome(OSAHS) .Methods Patients with OSAHS were randomly divided into two groups ,with 14 cases in each group .Group A was operated on with electrocautery ,while group B was operated on with the traditional method .The operative blood loss ,the operation time ,the tunica albuginea off time ,post operative pain ,surgical outcomes and complications were compared between two groups .Results The operative blood loss and the operation time of group A were much less than in group B (all P<0 .05) ,while no difference in the tunica albuginea off time ,post operative pain and surgical outcomes was found (P>0 .05) .Two groups of patients both had no serious complications .Conclusion The advantages of electrocautery assisted UPPP consists of less operative blood loss and less operation time .It deserves to generalize and apply in the future clinical treatments .

OBJECTIVETo investigate the expression and significance of CCL5 in patients with esophageal carcinoma.

METHODSUsing reverse transcriptase polymerase chain reaction (RT-PCR), the expressions of CCL5/CD8/granzyme B/perforin in tumor and corresponding adjacent tissues from esophageal carcinoma patients were examined. Flow cytometry (FACS) was used to detect the percentages of CD8(+) T cells and CCR5(+)CD8(+) T cells in TIL and PBMC from the patients. Transwell assay was performed to study the effect of CCL5 on the migration of T cells in vitro. T test and Spearman correlation analysis were performed.

RESULTSThe mRNA expressions of CCL5 and perforin were 0.348 2 ± 0.300 1 and 0.181 9 ± 0.118 6, respectively, in the tumor samples, while their expressions in adjacent samples were 0.279 6 ± 0.138 0 and 0.118 0 ± 0.109 8, respectively, with no statistically significant differences between them (P > 0.05 for both). The mRNA expressions of CD8 and granzyme B were significantly higher in the tumor tissues than in adjacent tissues (0.464 9 ± 0.300 8 vs. 0.279 0 ± 0.173 4, 0.648 7 ± 0.516 0 vs. 0.469 7 ± 0.259 1; P < 0.05 for both). The relative expression of CCL5 was positively correlated with that of CD8, perforin and granzyme B (r(CD8) = 0.272, P = 0.034; r(perforin) = 0.305, P = 0.026; r(granzymeB) = 0.108, P = 0.012) in the tumor sites. FACS data revealed that the proportions of CD8(+) T cells in TIL and PBMC were (45.86 ± 16.09)% and (34.05 ± 15.07)%, respectively, showing a significant difference (P = 0.022). Similarly, CCR5(+)CD8(+) T cells fraction in TIL (48.12 ± 26.75)% was much higher than that in PBMC (19.53 ± 13.67) % (P < 0.001). Transwell assay showed that CCL5 protein enhanced the migration of T cells, supporting that CCL5 is crucial for CD8(+) T cells recruitment in vivo. Intriguingly, CCL5 expression was down-regulated in advanced patients (stage IIb-IV). The accumulation of CD8(+) T cells and CCR5(+)CD8(+) T cells was strongly reduced in advanced patients, suggesting that CCL5 expression may be involved in the local control of the disease and its reduction may be involved in disease progression.

CONCLUSIONSThe current data indicate the involvement of CCL5 in the regulation of CD8(+) T cell entry into tumor lesions in esophageal carcinoma patients. This process may affect the disease status and potentially as a prognostic factor for cancer patients. Enhancing local CCL5 expression in tumor lesions may represent a novel strategy in esophageal cancer therapy.

CD8-Positive T-Lymphocytes ; Chemokine CCL5 ; metabolism ; Disease Progression ; Esophageal Neoplasms ; metabolism ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear ; Lymphocytes, Tumor-Infiltrating

UNLABELLEDObjective To compare the impact of right ventricular apical (RVA) versus right ventricular outflow tract (RVOT) pacing on left ventricular systolic synchronization.

METHODSSixty patients were prospectively recruited and randomized into RVA group (n=30) with the right ventricle leads placed in the RVA and RVOT group (n=30) with right ventricle leads placed in the septum of the RVOT. Speckle tracking imaging was performed with 100% ventricle pacing to measure the differences in the time to maximum left ventricle (LV) radial strain.

RESULTSIn RVA group, the difference in the time to 6-segment maximum LV radial strain after pacing was 105.27 ± 19.74 ms, significantly greater than that in RVOT group (41.65 ± 12.17 ms, P<0.001). The standard difference of time to 6-segment maximum LV radial strain was also significantly greater in RVA group than in RVOT group (42.71 ± 17.63 vs 17.63 ± 5.62 ms, P<0.001).

CONCLUSIONLeft ventricle systolic synchronizaition after RVOT pacing is superior to RVA pacing.

Cardiac Pacing, Artificial ; methods ; Heart ; Heart Ventricles ; Humans ; Systole

OBJECTIVETo establish the HPLC fingerprint of Angelica polymorpha.

METHODThe 10 batches of A. polymorpha were measured by HPLC with isoimperatorin as a reference substance and the chromatographic experients were performed on Kromasil 100A C18 column (4.6 mm x 250 mm, 5 microm), eluted with acetonitrile and water as mobile phase in gradient mode. The flow rate was 1.0 m x min(-1) and the detection wavelength was 254 nm.

RESULTThe common mode of the HPLC fingerprints were set up. There were 8 common peaks in the fingerprint of 10 samples, and the similarity of the 10 samples was more than 0.9.

CONCLUSIONThe method is simple, accurate and have a good reaptability. The quality of A. polymorpha can be controlled effectively by the HPLC fingerprint.

Angelica ; chemistry ; China ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Furocoumarins ; chemistry ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Quality Control ; Reference Standards ; Reproducibility of Results

OBJECTIVE: To explore the treatment effect of H-UPPP on patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: Seventy-nine patients were enrolled in our study. Among which 49 patients were done with H-UPPP, and the other 30 patients were done with UPPP. AHI and LSaO2 were monitored by polysomnography and plasma endothelins-1 were tested with enzyme linked immunosorbent assay (ELISA) before and after operation. RESULT: Forty-one patients were improved with reduced snoring and daytime sleepiness one year after operation in H-UPPP group,and the overall efficiency was 83.7%. Twenty-six patients were improved with reduced snoring and daytime sleepiness one year after operation in UPPP group, and the overall efficiency was 86.7%. There were significant differences of AHI, LSaO2 and ET-1 before and after operation between the two groups. Negative correlation was showed between AHI and LSaO2, also between LSaO2 and ET-1. CONCLUSION Both H-UPPP and UPPP were proved to be effective to patients with OSAHS. The perioperative complications with H-UPPP was less than UPPP.
Adult ; Apnea ; blood ; surgery ; Disorders of Excessive Somnolence ; blood ; surgery ; Endothelin-1 ; blood ; Female ; Humans ; Male ; Middle Aged ; Palate, Soft ; surgery ; Pharynx ; surgery ; Polysomnography ; Sleep Apnea, Obstructive ; blood ; surgery ; Sleep Stages ; Snoring ; blood ; surgery ; Uvula ; surgery