Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Objective:To explore the efficacy and its related factors of rituximab (RTX) in the treatment of children with frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS).Methods:It was a single-center retrospective study. The clinical data of FRNS/SDNS children first treated with RTX in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2016 to September 1, 2023 were collected. The number of relapse within 1 year before and after RTX treatment, the time to first relapse after RTX treatment, and the time to B-cell reconstitution were analyzed. At the first treatment, a single dose of RTX was given at 375 mg/m 2, with a maximum dose of 500 mg, once a week, for 1 to 4 doses. The count of CD19 + lymphocytes in the peripheral blood of the children was continuously monitored. If B-cell reconstruction was performed, the decision on whether to proceed to the next course of RTX treatment was made based on clinical manifestations. Kaplan-Meier method was used to analyze relapse-free survival rate after receiving RTX. Cox proportional hazards regression model was used to analyze the related factors of relapse after RTX treatment. Results:A total of 98 FRNS/SDNS children receiving RTX treatment were enrolled, including 75 males (76.5%). The age at onset was 4.0 (1.9, 7.1) years and age of receiving RTX was 11.3 (8.5, 13.5) years. There were 90 children (91.8%) achieving complete remission, while 8 patients (8.2%) did not respond to RTX treatment, and 3 patients (3.1%) progressed to end-stage kidney disease after receiving RTX. The relapse-free survival rates at 6 months and 1 year after RTX treatment were 83.3% (75/90) and 57.9% (22/38), respectively. The frequency of relapse 1 year after RTX treatment decreased compared to 1 year before RTX treatment ( Z=-7.398, P<0.001). Compared with children without relapse during the period of B-cell depletion, relapsed children had a higher number of relapse within one year after RTX treatment ( Z=5.246, P<0.001). The time to first relapse after RTX treatment was 8.3 (4.6, 13.9) months in 51 relapse patients. Compared with children receiving 1 dose of RTX in the first course, those receiving 2 or more doses had a longer time to the first relapse ( Z=2.983, P=0.003). There was no statistically significant difference in time to the first relapse between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). The reconstruction time of B cells after the first course of RTX was 6.9 (5.3, 9.0) months. Compared to children receiving one dose of RTX in the first course, those receiving two or more doses had a longer B-cell reconstitution time ( Z=2.739, P=0.006). There was no statistically significant difference in B-cell reconstitution time between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). Univariate Cox regression analysis showed that recurrence after calcineurin inhibitor (CNI) treatment before RTX treatment and the number of recurrence in one year before RTX treatment were correlated factors of recurrence after RTX treatment (both P<0.05). Multivariate Cox regression analysis showed that recurrence after CNI treatment before RTX treatment was an independent correlated factor of relapse after RTX therapy ( HR=3.496, 95% CI 1.245-9.818, P=0.018). Infusion reactions occurred in 10 patients (10.2%) and infections were observed in 24 patients (24.5%) during B cell depletion. No serious adverse events occurred. Conclusions:RTX is well tolerated and effective in treating FRNS/SDNS. Recurrence after CNI treatment before RTX treatment may be an independent related factor of relapse after RTX treatment.

Purpose To compare the similarity between the short-axis left ventricular cavity fractional area change measured by cardiac magnetic resonance and myocardial circumferential strain.Materials and Methods Forty cases of cardiomyopathy with different phenotypes and high-quality cardiac magnetic resonance images in PACS data center of the Sixth Medical Center of Chinese PLA General Hospital were retrospectively selected.All patients underwent cine imaging on a 3.0T MRI scanner.The endocardial and epicardial areas of each short-axis left ventricular slice were measured using Medviso Segment software to calculate slice-level fractional area change and global fractional area change.Slice circumferential strain and global circumferential strain were measured using Circle CVI42 software.Linear regression analysis was performed to assess correlations between global circumferential strain and global fractional area change,as well as slice circumferential strain and slice-level fractional area change.Results Both global circumferential strain and global fractional area change,as well as slice circumferential strain and slice-level fractional area change,exhibited positive correlations(all r>0.95).Linear regression demonstrated significant relationships(regression coefficients:2.40-3.16,P<0.05),with coefficient magnitudes related to left ventricular cavity radius.After normalization,circumferential strain and fractional area change curves showed identical standard deviations.Conclusion Short-axis left ventricular cavity fractional area change and myocardial circumferential strain display significant positive correlations at both slice and global levels,with similar curve morphology.These findings suggest that circumferential strain and fractional area change possess comparable statistical value in assessing cardiac function.

Objective To evaluate the characteristics of preoperative corneal astigmatism in cataract surgery candi-dates with high myopia.Methods In this observational study,medical records of consecutive patients who underwent cataract surgery in our hospital between January 2014 and December 2023 were reviewed retrospectively.Biometric param-eters of eyes were measured preoperatively by IOL-Master optical biometry.The cataract patients were classified into a high myopia group[defined as axial length(AL)≥26.00 mm]and a control group(normal ALs,22.00 mm ≤ AL ≤25.00 mm).The characteristics of corneal astigmatism were compared between the two groups.Results Among 17 325 cataract pa-tients(17 325 eyes),2 206 patients(2 206 eyes)had high myopia and 13 429 patients(13 429 eyes)had no high myopia.In the high myopia group,1 822 eyes(82.6％)had corneal astigmatism ≥0.50 D,1 138 eyes(51.6％)had corneal astig-matism ≥1.00 D,623 eyes(28.2％)had corneal astigmatism ≥1.50 D and 314 eyes(14.2％)had corneal astigmatism ≥2.00 D.These proportions were significantly higher than those in the control group(71.9％,35.9％,15.9％and 7.3％,re-spectively;all P＜0.001).In the high myopia group,1 340 eyes(60.7％)had moderate astigmatism,147 eyes(6.7％)had high astigmatism and 922 eyes(41.8％)had with-the-rule(WTR)astigmatism.These 3 proportions were all significantly higher than those in the control group(48.9％,3.3％and 28.2％,respectively;all P＜0.001).Among high-myopia pa-tients,the corneal astigmatism was statistically greater in women than that in men(P=0.001),and the proportion of ob-lique astigmatism was higher in women than that in men(19.3％vs.15.8％,P=0.034).The proportion of against-the-rule(ATR)astigmatism increased significantly with age.In the high myopia group,the corneal astigmatism of eyes with WTR,ATR and oblique astigmatism was(1.26±0.85)D,(1.28±0.81)D and(0.89±0.71)D,respectively.They were signifi-cantly greater than those in the control group[(0.82±0.71)D,(1.06±0.68)D and(0.67±0.53)D,respectively;all P＜0.001].In the high myopia group,there were 31.8％,12.3％and 4.1％of eyes with corneal astigmatism ≥1.00 D,≥1.50 D and ≥2.00 D,respectively.All of these 3 proportions were significantly lower than those of eyes with WTR or ATR astig-matism(all P＜0.05).This finding is consistent with the tendency in the control group.Conclusion A significant bur-den of preoperative corneal astigmatism is observed in cataract surgery candidates with high myopia,with more than 50％of the patients having corneal astigmatism ≥1.00 D.The corneal astigmatism of patients with high myopia is significantly greater than that of patients with normal ALs.The proportion of moderate-to-high astigmatism is significantly higher in high-myopia patients than that in patients with normal ALs.

Heart failure,as a global public health challenge,is experiencing an increasingly severe disease burden.Given the close relationship be-tween the Nitric Oxide-Soluble Guanylate Cyclase-Cyclic Guanosine Monophosphate(NO-sGC-cGMP)signaling pathway and heart failure,this study,through a comprehensive search and review of re-cent literature on the NO-sGC-cGMP pathway and heart failure,aims to outline the mechanism of ac-tion of this signaling pathway and its connection with heart failure,in order to explore new avenues for the treatment of heart failure.

This study aims to establish an indirect ELISA method for detecting RVFV antibodies u-sing recombinant proteins of Rift Valley fever virus(RVFV)Gn protein Ⅱ-Ⅲ structural domains as the encapsulated antigen which was expressed by the Escherichia coli(E.coli)expression sys-tem.The gene sequences encoding the Ⅱ and Ⅲ subdomains of RVFV Gn protein were inserted in-to pET-30a(+)to construct the recombinant plasmid pET-RVFV Gn-D Ⅱ-Ⅲ.After transforma-tion of the recombinant plasmid into DE3(BL21)competent cells,the recombinant Gn-D Ⅱ-Ⅲ protein was induced with IPTG and purified using affinity chromatography.An indirect ELISA method for the detection of RVFV antibodies was developed using purified recombinant protein as coating antigen and SPA-HRP as the enzyme-labelled secondary antibody.Western blot analysis confirmed that the RVFV Gn-D Ⅱ-Ⅲ protein was successfully expressed.The optimal expression conditions for RVFV Gn-D Ⅱ-Ⅲ protein were induced with 0.8 mmol/L IPTG at 37 ℃ for 5 h.The Gn-D Ⅱ-Ⅲ protein was purified using affinity chromatography with a purity of 91.9％,and the purified protein was used as the encapsulated antigen to develop an ELISA assay for RVFV anti-bodies.The specificity evaluation showed that the method specifically detected RVFV-positive sera and did not cross-react with sera positive for West Nile virus(WNV),Ebola virus(EBOV),Mar-burg virus(MARV)and tick-borne encephalitis virus(TBEV).When the RVFV Gn-D Ⅲ-Ⅲ posi-tive serum was diluted to 6 400 times,the test result still showed positive results,demonstrating the method had good sensitivity.The repeatability evaluation results indicated that the variation co-efficients for both intra-and inter-batch responses was less than 10％,indicating that the method had good repeatability.In conclusion,the RVFV Gn-D Ⅱ-Ⅲ protein was successfully expressed u-sing the E.coli expression system.The purified recombinant Gn-D Ⅱ-Ⅲ protein was used as the encapsulated antigen to develop an indirect ELISA assay for RVFV antibodies,which provides a preliminary basis for the diagnosis of RVF and the research and development of RVF vaccines.

To establish an indirect enzyme linked immunosorbent assay(ELISA)method for the detection of Zaire Ebola virus(ZEBOV)specific antibodies,the full-length of ZEBOV GP1 gene was amplified by PCR and cloned into pET-30a(+)vector to generate the pET-30a(+)-GP1 plasmid.After expressed in the E.coli expression system,the purified GP1 protein was used as coating antigen to establish the indirect ELISA method for detection of ZEBOV antibody.The con-ditions including concentration of coating antigen and serum dilution were determined by chess-board titration.Specificity,sensitivity,and reproducibility of the established ELISA detection meth-od were evaluated.GP1 protein was successfully prepared by prokaryotic expression,and was used as the coatingantigen for indirect ELISA.By optimizing the reaction conditions,the optimal concen-tration of the coating antigen was determined to be 0.5 g/L;the optimal dilution of serum was cal-culated to be 1∶3 200;the optimal dilution of enzyme-labeled secondary antibody was measured to be 1∶20 000.The established method exhibited excellent specificity,sensitivity,and reproducibili-ty.In the present study,the GP1 protein was successfully expressed in the E.coli expression sys-tem and the high purity GP1 protein was used as the coating protein to establish an indirect ELISA assay for ZEBOV antibody.This method is highly specific,sensitive,and reproducible,which provides technical support for the fur-ther study of the biological function of GP1 and the detection of ZEBOV antibody in serum.

Objective To investigate the auditory effects of cochlear implantation in quiet and noisy environ-ments in children with different bilateral intervention modes,as well as the factors influencing these effects.Methods A total of 185 children with bilateral severe to profound sensorineural hearing loss were divided into three groups:bimodal hearing mode group(BIM,n=55),simultaneous bilateral cochlear implantation group(SCI,n=70),and sequential bilateral cochlear implantation group(SBCI,n=60).The Parents' Evaluation of Aural/Oral Performance of Children(PEACH)was used to assess the PEACH scores of the three groups in quiet and noisy environments one year after binaural hearing aid intervention.Additionally,the effects of cochlear implantation age,preoperative residual hearing,hearing aid usage,rehabilitation training mode,family system,and other factors on auditory per-formance in quiet and noisy environments were analyzed.Results The PEACH scores in quiet environments were higher than those in noisy environments for all three groups(all P＜0.05).The SCI group had higher PEACH scores in both quiet and noisy environments compared to the BIM group(P＜0.05).Multifactorial analysis revealed differences in factors influencing auditory performance in quiet and noisy environments among the three groups.First cochlear implantation before 3 years of age,preoperative hearing aid usage,and home-based rehabilitation training mode were common favourable influencing factors for auditory performance in both environments.Preopera-tive residual hearing below 95 dB HL was an favourable influencing factor for auditory performance in quiet environ-ments in the BIM group.The higher the level of parental education,the better auditory performance in both quiet and noisy environments for the SCI and SBCI groups.Implantation interval of 24 months or less and hearing aid usage during the inter-implantation period were favourable influencing factors for auditory performance in both envi-ronments for the SBCI group.Conclusion Children with severe to profound prelingual deafness after simultaneous bilateral CI implantation had better hearing performance than bimodal listening in quiet and noise environments.Ear-ly implantation,preoperative or inter-implantation hearing aid usage are recommended to improve auditory perform-ance in noisy environments,regardless of the bilateral intervention mode.The interval between bilateral cochlear im-plantations should be less than 12 months.