AIM:To explore the mechanisms behind the inhibition of lymphangiogenesis in pregnant rats with obstructive nephropathy and assess the protective effects on kidney function.METHODS:Forty nulliparous female Wi-star rats were randomly assigned to four groups:sham operation,sham operation+pregnancy,model,and Esaxerenone groups,with 10 rats in each group.Renal injury was induced in the model and Esaxerenone groups via unilateral ureteral obstruction(UUO).The other two groups underwent ureteral dissociation without ligation.Nine weeks post-UUO,female rats in the sham operation+pregnancy,model,and Esaxerenone groups were mated with male rats(2:1 ratio)to establish a rat model of obstructive nephropathy during pregnancy.Starting the day after UUO,rats in the Esaxerenone group re-ceived Esaxerenone at 1 mg·kg-1·d-1.On the 18th day of pregnancy,24-hour urine was collected using metabolic cages.The following day,the rats were sacrificed,serum samples collected,and the contralateral kidney removed.Blood urea ni-trogen(BUN)was measured using standard biochemical methods,and endogenous creatinine clearance rate(Ccr)was calculated.Kidney tissue pathology was assessed using HE,Masson,and Sirius red staining.Serum aldosterone levels were determined via ELISA.Immunohistochemistry,real-time PCR,and Western blot were employed to assess mineralo-corticoid receptor(MR)activation,lymphangiogenesis,signaling pathways,and fibrosis-related markers.RESULTS:Renal function tests revealed increased BUN levels and decreased Ccr in the model group(P<0.01).Pathological exami-nation showed dilated renal tubules,significant collagen deposition,and inflammatory cell infiltration in the model group.ELISA results indicated a significant increase in serum aldosterone levels in the model group(P<0.01).Immunohisto-chemistry showed enhanced nuclear translocation of MR in the kidneys of the model group post-activation.Western blot and real-time PCR demonstrated a marked increase in neutrophil gelatinase-associated lipocalin(NGAL)expression in the model group(P<0.01).Additionally,the expression of vascular endothelial growth factor C(VEGF-C)and its receptor VEGFR3 was significantly elevated in the renal tubulointerstitium of the model group,as shown by both immunohistochem-istry and real-time PCR(P<0.01).The PI3K/Akt signaling pathway was activated in the model group,with significantly increased phosphorylation levels observed primarily in renal tubular epithelial and interstitial cells(P<0.01).Collagen type III(Col III)expression,primarily in the renal tubulointerstitium,was also significantly upregulated in the model group,consistent with real-time PCR results(P<0.01).Esaxerenone treatment improved renal function,reduced patho-logical damage,inhibited aldosterone secretion,and downregulated the expression of MR,NGAL,VEGF-C,VEGFR3,phosphorylated PI3K,phosphorylated Akt,and Col III(P<0.01).CONCLUSION:Esaxerenone mitigates aldosterone-induced MR activation,modulates the PI3K/Akt signaling pathway,reduces lymphangiogenesis in the contralateral kidney of pregnant rats with obstructive nephropathy,decreases collagen deposition,and delays the progression of renal intersti-tial fibrosis.

Membranous nephropathy (MN) is a type of glomerular disease characterized by diffuse thickening of glomerular basement membrane with subepithelial immune complex deposition, and traditional diagnosis of MN mainly relies on the pathological results of renal biopsy. In recent years, the emergence of biomarkers related to MN such as phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A has changed the diagnosis and treatment mode of MN, providing a new basis for the diagnosis, treatment and prognosis of MN. MN patients with positive specific target antigens exhibit different clinical manifestations and prognoses. Specific target antigens can not only guide diagnosis, but also has predictive value for prognosis. Immunosuppressive therapy is a common treatment for idiopathic MN patients, and the emergence of novel medications such as biologics represents a advance in the treatment of MN, providing a broader array of options for managing the condition. Conversely, the treatment approach for secondary MN primarily targets the management of the primary disease. Based on multiple and new literature, we reviewed the researches progress of target antigens and immunosuppressive therapy related to MN, so as to provide references for clinical diagnosis and treatment of MN.

It was a single-center cross-sectional study to investigate the association of serum C3 level with blood pressure and estimated glomerular filtration rate (eGFR) in patients with idiopathic membranous nephropathy (IMN). The clinical and pathological data of 98 patients with IMN diagnosed by renal biopsy in the Department of Nephrology of East Hospital Affiliated to Tongji University from August 1, 2018 to October 31, 2023 were retrospectively analyzed. The demographic characteristics, serum complement C3 and other clinical data were compared between the non-hypertension group ( n=37) and hypertension group ( n=61). Pearson or Spearman correlation analysis method was used to analyze the correlation between serum C3 and eGFR in IMN patients and IMN patients with hypertension. Multiple linear regression analysis was used to analyze the related factors of eGFR in IMN patients with chronic kidney disease stage 1-3 in hypertension group. The results showed that compared with the non-hypertension group, the patients in hypertension group were older, and had higher levels of serum creatinine, cystatin C, urinary microalbumin to creatinine ratio, serum C3 and C4, and lower eGFR (all P<0.05). The correlation analysis showed that there was no correlation between serum C3 level and eGFR in IMN patients ( r=0.118, P=0.247). However, serum C3 level was positively correlated with eGFR in IMN patients with hypertension ( r=0.325, P=0.011). Multiple linear regression analysis showed that eGFR was negatively correlated with age ( β=-0.328, P=0.013), and positively correlated with serum C3 level ( β=0.228, P=0.048). The study shows that serum C3 level in hypertension group is higher than that in non-hypertension group in IMN patients. Moreover, serum C3 is positively correlated with eGFR.

Objective:To explore the characteristics of cerebellar metabolites of autistic children using the magnetic resonance spectrum (MRS) and analyze their correlation with clinical symptoms.Methods:An autism group ( n=14) and a control group ( n=8) both underwent bilateral MRS scans of their cerebella. The NAA, Cho and Cr absolute values were recorded along with the NAA/Cr and Cho/Cr ratios. Those values were correlated with clinical symptoms of autism (the CARS and ABC scales), as well as with age. Results:There were no significant differences between the two groups in cerebellar metabolite levels, but the autism group exhibited significantly higher Cho/Cr ratios in the right cerebellum than in the left. There was a significant positive correlation between the Cho/Cr ratio in the right cerebellum and CARS scores, and between the NAA/Cr ratio in the right cerebellum and age.Conclusions:There is metabolic abnormality in the left and right cerebellar hemispheres of autistic children. The metabolic abnormality is related to the severity of clinical symptoms. However, metabolism in the cerebellum improves gradually with age.

Objective:The results of the two interferon-gamma release assay tests were compared, so as to provide reference for the laboratory to choose the detection method.Methods:Double blood samples of 96 suspected TB patients hospitalized in Civil Aviation General Hospital from July 2018 to December 2019 were collected, providing for TB specific antigen stimulation test by QIAGEN kit and Autobio kit respectively. ELISA and chemiluminescence were used to detect interferon-gamma, and the results were determined according to the manufacturer′s instructions. Based on the clinical or bacteriological evidence for diagnosis of tuberculosis, the consistency of the two kits was compared, and the diagnostic efficacy of tuberculosis was evaluated. At the same time, 60 samples of plasma stimulated by TB specific antigen in QIAGEN kit were randomly selected to detect interferon-gamma by ELISA and chemiluminescence respectively, and the consistency between the two interferon-gamma detection systems was compared. The Kappa coefficient were used to measure the consistency of the results. The ordinary linear regression and Bland-Altman plots were performed to show the differences of IFN-γ data between assays.Result:In 96 samples, the sensitivity and specificity of QIAGEN test were 81.82% (18/22) and 74.32% (55/74), and that of Autobio test were 72.73% (16/22) and 70.27% (52/74), respectively. The results of the two systems were consistent, Kappa value was 0.847, P<0.05. The area under ROC curve of QIAGEN test for diagnosis of tuberculosis was 0.807 (95% confidence interval: 0.702-0.911), while that of Autobio test was 0.765 (95% confidence interval: 0.640-0.889). Comparing the results of two systems for detecting interferon-gamma in the same plasma, the results of two systems were in good agreement ( R2=0.97, P<0.05); but there were significant differences in the levels of interferon-gamma in the same patient sample after stimulation with different negative and positive tubes ( R2=0.41, P<0.05). Conclusion:The results of γ-interferon release assay test of Autobio system and QIAGEN system are in good agreement, and the results of γ-interferon release assay test of the two systems are also in good agreement. Different amount of antigen coating, titer and test system may be responsible for the different release of interferon-gamma.

Objective To develop a method for the determination of five furostanol saponins(timosaponin N,timosaponin L, timosaponin BⅡ,25R-timosaponin BⅡ,and 25S-officinalisnin-Ⅰ)in rhizome and fibrous root of Anemarrhena asphodeloides Bge. by HPLC with the charged aerosol detector(CAD). Methods The analysis was performed on TechMate C18-ST-II(250 mm×4.6 mm,5μm)with acetonitrile:water(22:78,V/V),the flow rate of 1.0 ml/min and column temperature at 30℃. The Corona parameters were as follows:sampling rate 10 Hz,filter 5 s,and the nebulizer temperature 55℃. Results The approach showed good linearity for five saponins. The correlation coefficients(r2)for calibration curves varied from 0.9992 to 0.9998. The limits of detection(LOD)were 0.28,0.92,0.92,0.92 and 0.92 ng for five steroidal saponins,respectively. The limits of quantitation(LOQ)were found to be 0.92, 2.77,2.77,2.77 and 2.76 ng,respectively. RSD calculated from peak area of precision,repeatability and stability in 48 h were all less than 3.0%. The average recoveries of timosaponin N,timosaponin L,timosaponin BⅡ,25R-timosaponinBⅡ,and 25S-officinalis-nin-Ⅰwere 98.17%,101.37%,98.53%,97.63%,and 98.17%,respectively. Conclusion The developed method is accurate,reli-able,which could be applied to the quality control of multiple components in A. asphodeloides Bge.

Objective To design and synthesize compounds with protein tyrosine kinase(PTK)inhibitory activity with L029 as the lead compound. Methods L029 derivatives were designed and synthesized from L029 by reduction and/or substitution with the 3-dimethylamino-1-propyl,methyl acetate,methyl propionate in its active H and other sites. PTK activity was measured by enzyme-linked immunosorbent assay(ELISA). The inhibitory rate was calculated to screen out the compounds with PTK inhibitory activity. Re-sults Five target compounds were synthesized and their structures were confirmed by 1H NMR and MS. Three compounds T2,T3 and T5 were screened out with strong PTK inhibitory activity. Conclusion The synthetic routes of the target compounds are simple with mild reaction condition,and 3 compounds show strong inhibitory activity by ELISA. These results can provide reference for the further design and synthesis of this kind of molecules.

Objective To design and synthesize novel 2-indolone derivatives as the c-Met kinase inhibitors. Methods With c-Met kinase inhibitor SU11274 as lead compound,a series of 2-indolone derivatives were designed according to the concept of bioiso-sterism. Then the target compounds(10a-10r)were synthesized from 2-indolone through 5-chlorosulfonation with chlorosulfonic acid, sulfonamidation with intermediate 3,condensation with 6a-6h,7a-7h and 4a-4b,respectively. Their inhibitory activity against c-Met and proliferation of MCF-7 cells were evaluated. Results and Conclusion The designed compounds were successfully prepared and their structures were confirmed by 1H NMR and ESI-MS. Some compounds had certain inhibitory activity against c-Met and prolif-eration of MCF-7 cells. An initial structure-activity relationship analysis of these compounds was performed to provide useful informa-tion for further optimization of their structures.

Objective To explore the influence factors for femoral head necrosis after treatment of femoral neck fractures with dynamic hip screw (DHS) and anti-rotation screw.Methods A retrospective case series analysis was made on the clinical data of 106 cases of femoral neck fractures who had undergone fixation with DHS and anti-rotation screw between May 2010 and May 2015.There were 59 males and 47 females,with an average age of 57.0 years (range,27-76 years).By Garden classification,there were 27 cases of type Ⅱ,51 cases of type Ⅲ and 28 cases of type Ⅳ.All cases were divided into femoral head necrosis group (18 cases) and none-necrosis group (88 cases) according to the radiographs of the fractured hip at the follow-up.Univariate analyses and a multivariate logistic regression analysis were made to test whether the following factors were significantly associated with femoral neck necrosis:sex,age,Garden classification,Pauwels classification,Singh index,injury-to-surgery time interval,reduction methods,reduction quality,complete weight-bearing time,implant removal and the time cost of implant removal surgery.Results All the 106 patients obtained a mean follow-up of 49 months (range,26-76 months).Femoral head necrosis occurred in 18 cases (17.0％).In univariate analyses,Garden classification,reduction quality,implant removal and long time of the implant removal surgery were significantly associated with femoral head necrosis (P ＜ 0.01).In multivariate logistic regression analysis,high level of Garden classification(95％ CI 0.008,0.998,P ＜ 0.05),implant removal and long time of the implant removal surgery (95％ CI 0.000,0.143,P ＜ 0.01) were found to have a significant effect on femoral head necrosis development.Conclusions Fracture displacement,removal of internal fixation and broadening the screw canal,which cand hinder the blood supply of femoral head,will enhance the rate of femoral head necrosis.As a result,it needs prudent consideration to remove internal fixation after internal fixation with DHS combined with anti-rotation screw for femoral neck fractures.When it is difficult to remove the anti-rotation screw,it is better to give up,rather than to force a removal.