[Efficacy of plasma exchange in severe crescentic IgA nephropathy: A multicentered, cohort study].

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m2), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m2) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m2)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION: The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.

MicroRNA-20a suppresses RANKL-modulated osteoclastogenesis and prevents bone erosion in mice with rheumatoid arthritis through the TLR4/p38 pathway.

Abnormal osteoclast formation plays a significant part in rheumatoid arthritis (RA). As potent therapeutic biomarkers, microRNAs (miRNAs) have obtained increasing attention. Recently, treatment regimens regarding miRNAs have been implicated in skeletal diseases. The aim of this study is to assess the expression and function of miR-20a during osteoclast proliferation and differentiation and its correlation with bone erosion in RA mice. The expression of miR-20a was observed to be diminished in the ankle tissues of RA mice relative to that in normal controls evaluated by RT-qPCR. Hematoxylin and eosin staining, Safranin O-fast green staining, and tartrateresistant acid phosphatase staining were used to evaluate the effects of miR-20a on RA symptoms. The proliferation and differentiation of osteoclasts, and bone erosion were repressed by agomiR-20a injection. 3'UTR luciferase reporter assays were conducted to validate the putative binding between miR-20a and receptor activation of nuclear factor-κB ligand (RANKL). The protein expression and phosphorylation level of toll-like receptor4 (TLR4)/p38 pathway-related factors were detected by Western blot. miR-20a inhibited proliferation and differentiation potentials to osteoclasts partly through the TLR4/p38 pathway. The current work provides evidence that miR-20a hinders proliferation and differentiation of osteoclasts by targeting RANKL through the TLR4/p38 pathway.

[Evaluation of intervention effect in the occupational protection of glass fiber workers by occupational health education].

Objective: To understand the mastery of occupational hygienic knowledge and the implementing of occupational health protection measures in the group which were exposed to the procedure of manufacture and use in glass fiber company, and to explore the feasibility of the prevention of the skin injury by occupational health education in glass fiber workers. Methods: We selected 257 on-the-job employees as the research object in a ceramic enterprise in Nanjing from June 2018 to August 2019, with the method of cluster random sampling. According to Solomon's design, the intervention group in which we took measures with health education was divided into RG(1) (O(1)XO(2)) and RG(3) (XO(5)) group, and the control group where we didn't take any intervention was divided into RG(2) (O(3)-O(4)) and RG(4) (-O(6)) group. The intervention effect of health education on the occupational protection of glass fiber workers was evaluated by the results of questionnaire. Results: After training, the average score of occupational health knowledge in the intervention group was 27.34 points higher than that before training, the intervention index was 1.42, 23.62-27.73 points higher than the control glass fiber workers and 33.62-35.52 points higher than the control glass non-glass fiber workers; Compared with the control group, the positive attitude rate of fiber glass workers in the intervention group increased by 13.28%, 13.51%, 11.68% and 11.48%, and the intervention indexes were 1.18, 1.17, 1.14 and 1.15, which was corresponding to using protective cream, wearing gloves, wearing working clothes, washing hands and bathing after work, respectively; Compared with the control group, the implementation rate of occupational protection measures which were represented by wearing gloves、washing hands and bathing for glass fiber workers in the intervention group increased by 29.25% and 7.27% respectively, and the intervention indexes were 1.43 and 1.08 respectively; The skin injury rate of fiberglass workers in the intervention group was reduced by 11.43% comparing to the control group, the intervention index was 1.67. Conclusion: According to the occupational health education of fiberglass workers, it improves the mastery of occupational health knowledge, positive atti-tude rate and the implementation rate of occupational protection measures, meanwhile, it reduces the skin injury rate of the intervention objects to a certain extent.

[The effect of endocapillary hypercellularity lesions on the renal prognosis and response to immunosuppressive therapy in IgA nephropathy].

In this retrospective cohort study, we aim to evaluate the effect of endocapillary hypercellularity (E) lesions on the renal prognosis and response to immunosuppressive therapy, especially diffuse endocapillary hypercellularity lesion in IgA nephropathy (IgAN). A total of 365 patients with IgAN and E lesions and 31 patients with diffuse E lesions and over 12-month follow-up period were included in this study. We performed an 1∶1 propensity score to identify controls with matched clinical and pathological features from 769 IgAN patients without E lesions. The end-point was defined as a 30% decrease in estimated glomerular filtration rate (eGFR) or end-stage kidney disease. The kidney survival of the two groups was compared by Kaplan-Meier analysis. During median follow-up period of 41 months, kidney survival rates in patients with E lesions were 96.0% at 1 year, 83.6% at 3 years, 67.7% at 5 years; while they were 96.9% at 1 year, 83.6% at 3 years, and 68.7% at 5 years in patients without E lesions (P=0.265).The HR of immunosuppressive therapy was 1.038 (95%CI 0.749-1.440) and 1.113 (95%CI 0.770-1.609) in patients not receiving immunosuppressive therapy (P=0.781). (2) During median follow-up period of 52.5 months, the kidney survival rates in patients with diffuse E-lesion were 100.0% at 1 year, 96.2% at 3 years, 74.5% at 5 years; while they were 96.2% at 1 year, 82.3% at 3 years, and 63.7% at 5 years in patients without E-lesion (P=0.158). The HR of immunosuppressive therapy was 0.625 (95%CI 0.213-1.839) and 0.447 (95%CI 0.028-7.191) in patients not receiving immunosuppressive therapy (P=0.825). E lesion or diffuse E lesion may not be associated with prognosis or response to immunosuppressive therapy.

[Trans-ethnic analysis of susceptibility variants in IgA nephropathy].

OBJECTIVE: To compare the genetic architecture of susceptibility variants of IgA nephropathy (IgAN) in Chinese and Europeans. METHODS: We selected the independent genome-wide significant variants of IgAN in European population as candidate variants. Their associations, risk alleles, risk allele frequencies, odds ratios and population attributable risk scores were derived and calculated, then compared with those in the current Chinese population, including 1 194 IgAN patients and 902 controls. Using the significant variants, genetic risk scores were calculated and compared between the East Asians and the Europeans. The correlation between the genetic risk scores and clinical manifestations was also evaluated. RESULTS: There were 16 independent single nucleotide polymorphisms (SNPs) located in 11 loci showing significantly association with susceptibility to IgAN in the Europeans. 93.75% (15/16) of them also showed significant associations in the Chinese (P<0.05). The effects of all the associated SNPs were in the same direction, either risk or being protective for IgAN, between the Chinese and the Europeans. On the contrary, remarkable higher risk allelic odds ratio (P=1.94×10-2), higher risk allele frequency (P=3.09×10-2), and higher population attributable risk (P=3.03×10-4) were observed for most of the associated SNPs in the Chinese than in the Europeans. Furthermore, genetic risk scores were significantly larger in the Asian populations compared with the Europeans (P=1.78×10-163). While there was no significance among the subpopulations in both the East Asians and the Europeans. Compared with the healthy controls, the genetic risk score in the IgAN patients was significantly larger (P=3.60×10-27). Clinical analysis showed the genetic risk score was positively associated with serum levels of IgA and IgA1, phases of chronic kidney disease and Haas grades. CONCLUSION: Our study provides further evidence in the shared genetic architecture between Chinese and Europeans, while differences with respect to the effect sizes and risk allele frequencies across ethnicities, contributing partially to the differences of disease prevalence.

Development of novel polymorphic microsatellite markers for the blood clam Tegillarca granosa by pyrosequencing.

Large amounts of expressed sequence tags (ESTs) generated using next-generation sequencing technologies provide a cost-effective and valuable genomic resource for the development of microsatellite markers. In this study, we isolated 115 novel polymorphic microsatellite markers for the blood clam Tegillarca granosa from ESTs in 454 sequencing data. All the loci were characterized in 30 individual clams from a natural population in Xiangshan (Zhejiang Province, China). The number of alleles per locus varied from 2 to 10, with an average of 3.78. The observed and expected heterozygosities ranged from 0 to 1 and from 0.040 to 0.799, respectively. The polymorphic information content (PIC) ranged from 0.038 to 0.825, and 29 highly polymorphic loci (PIC ≥ 0.5) and 42 moderately polymorphic loci (0.25 < PIC < 0.5) were identified. Thirty-eight of the 115 loci deviated significantly from the Hardy-Weinberg equilibrium (P < 0.01) after a Bonferroni correction. A BlastX search revealed that 46 (40%) of the polymorphic loci identified were from transcript regions of known genes. The microsatellite markers developed in the present study will greatly enrich the microsatellite resources of T. granosa, and are available for further population genetic analysis, genetic trait mapping, and molecular-assisted selection.

DEFA gene variants associated with IgA nephropathy in a Chinese population.

IgA nephropathy (IgAN) is a complex syndrome with high genetic heterogeneity. More recently, a genome-wide association study (GWAS) from Southern Han population revealed that variants within 8p23.1, where the DEFA genes encoding a-defensins assembled, were associated with susceptibility to IgAN. To replicate the association and fine-map the genetic variants, a case-control genetic study from an independent Northern Han cohort was conducted. A total of 60 single-nucleotide polymorphisms in a region spanning 350 kb encompassing the DEFA genes cluster were analyzed in 2096 individuals. Copy number variations of DEFA1A3 within the loci were also checked for the independent association. Functional significance of the associated variants was further examined by the in silico method as well as by cis-acting expression quantitative trait loci analysis with mRNA. It showed that 17 out of 60 (28.3%) variants were associated with susceptibility to IgAN. Two independent signals with functional potentials were discovered (rs2738058, P=4.64 × 10(-5), odds ratio (OR)=0.76, 95% confidence interval (CI) 0.66-0.87 and rs9644778, P=4.78 × 10(-3), OR=1.21, 95% CI 1.06-1.39). Besides, marginally significant association of rs9644778 risk genotype with lower proportion of gross hematuria (CC+CA vs AA 35.2% vs 30.2%, P=0.073) was observed. In conclusion, DEFA gene polymorphisms have potentially pathogenic roles in IgAN, and the role of mucosal immunity in the pathogenesis of IgAN has to be emphasized.

Optimizing broadband terahertz modulation with hybrid graphene/metasurface structures.

We demonstrate efficient terahertz (THz) modulation by coupling graphene strongly with a broadband THz metasurface device. This THz metasurface, made of periodic gold slit arrays, shows near unity broadband transmission, which arises from coherent radiation of the enhanced local-field in the slits. Utilizing graphene as an active load with tunable conductivity, we can significantly modify the local-field enhancement and strongly modulate the THz wave transmission. This hybrid device also provides a new platform for future nonlinear THz spectroscopy study of graphene.

Controlling graphene ultrafast hot carrier response from metal-like to semiconductor-like by electrostatic gating.

We investigate the ultrafast terahertz response of electrostatically gated graphene upon optical excitation. We observe that the photoinduced terahertz absorption increases in charge neutral graphene but decreases in highly doped graphene. We show that this transition from semiconductor-like to metal-like response is unique for zero bandgap materials such as graphene. In charge neutral graphene photoexcited hot carriers effectively increase electron and hole densities and increase the conductivity. In highly doped graphene, however, photoexcitation does not change net conducting carrier concentration. Instead, it mainly increases electron scattering rate and reduce the conductivity.

Plasmon resonance in individual nanogap electrodes studied using graphene nanoconstrictions as photodetectors.

We achieve direct electrical readout of the wavelength and polarization dependence of the plasmon resonance in individual gold nanogap antennas by positioning a graphene nanoconstriction within the gap as a localized photodetector. The polarization sensitivities can be as large as 99%, while the plasmon-induced photocurrent enhancement is 2-100. The plasmon peak frequency, polarization sensitivity, and photocurrent enhancement all vary between devices, indicating the degree to which the plasmon resonance is sensitive to nanometer-scale irregularities.

Multiple factor analysis of metachronous upper urinary tract transitional cell carcinoma after radical cystectomy.

Transitional cell carcinoma (TCC) of the urothelium is often multifocal and subsequent tumors may occur anywhere in the urinary tract after the treatment of a primary carcinoma. Patients initially presenting a bladder cancer are at significant risk of developing metachronous tumors in the upper urinary tract (UUT). We evaluated the prognostic factors of primary invasive bladder cancer that may predict a metachronous UUT TCC after radical cystectomy. The records of 476 patients who underwent radical cystectomy for primary invasive bladder TCC from 1989 to 2001 were reviewed retrospectively. The prognostic factors of UUT TCC were determined by multivariate analysis using the COX proportional hazards regression model. Kaplan-Meier analysis was also used to assess the variable incidence of UUT TCC according to different risk factors. Twenty-two patients (4.6%). developed metachronous UUT TCC. Multiplicity, prostatic urethral involvement by the bladder cancer and the associated carcinoma in situ (CIS) were significant and independent factors affecting the occurrence of metachronous UUT TCC (P = 0.0425, 0.0082, and 0.0006, respectively). These results were supported, to some extent, by analysis of the UUT TCC disease-free rate by the Kaplan-Meier method, whereby patients with prostatic urethral involvement or with associated CIS demonstrated a significantly lower metachronous UUT TCC disease-free rate than patients without prostatic urethral involvement or without associated CIS (log-rank test, P = 0.0116 and 0.0075, respectively). Multiple tumors, prostatic urethral involvement and associated CIS were risk factors for metachronous UUT TCC, a conclusion that may be useful for designing follow-up strategies for primary invasive bladder cancer after radical cystectomy.

Multiple factor analysis of metachronous upper urinary tract transitional cell carcinoma after radical cystectomy

Transitional cell carcinoma (TCC) of the urothelium is often multifocal and subsequent tumors may occur anywhere in the urinary tract after the treatment of a primary carcinoma. Patients initially presenting a bladder cancer are at significant risk of developing metachronous tumors in the upper urinary tract (UUT). We evaluated the prognostic factors of primary invasive bladder cancer that may predict a metachronous UUT TCC after radical cystectomy. The records of 476 patients who underwent radical cystectomy for primary invasive bladder TCC from 1989 to 2001 were reviewed retrospectively. The prognostic factors of UUT TCC were determined by multivariate analysis using the COX proportional hazards regression model. Kaplan-Meier analysis was also used to assess the variable incidence of UUT TCC according to different risk factors. Twenty-two patients (4.6 percent). developed metachronous UUT TCC. Multiplicity, prostatic urethral involvement by the bladder cancer and the associated carcinoma in situ (CIS) were significant and independent factors affecting the occurrence of metachronous UUT TCC (P = 0.0425, 0.0082, and 0.0006, respectively). These results were supported, to some extent, by analysis of the UUT TCC disease-free rate by the Kaplan-Meier method, whereby patients with prostatic urethral involvement or with associated CIS demonstrated a significantly lower metachronous UUT TCC disease-free rate than patients without prostatic urethral involvement or without associated CIS (log-rank test, P = 0.0116 and 0.0075, respectively). Multiple tumors, prostatic urethral involvement and associated CIS were risk factors for metachronous UUT TCC, a conclusion that may be useful for designing follow-up strategies for primary invasive bladder cancer after radical cystectomy.

Disaster epidemiology and medical response in the Chi-Chi earthquake in Taiwan.

STUDY OBJECTIVE: We examine the mortality and morbidity associated with earthquakes in the Chi-Chi earthquake in Taiwan in 1999. METHODS: Crude casualty data were collected from the reports of the government, local health bureaus, and 97 hospitals. The demographic data from the annual report of the Department of Interior were also employed for data analysis. Cross tables showing incidence of deaths and injuries by age, sex, time, and geographic distribution were generated to compare the mortality among different subgroups. Multiple regression models were established to explore the risk factors related to the mortality caused by earthquakes. RESULTS: The following results were found: the mortality rate increased with proximity to the epicenter, mortality was higher among the elderly than among young people, 30% of the victims died from head injuries caused by the collapse of dwellings, and the peak of medical demand was 12 hours after the earthquake and significantly increased demand for care lasted as long as 3 days. Furthermore, the regression model indicated that 78.5% of the variation of locality-age-sex-specific mortality was explained by the intensity of the earthquake, age, population density, distance to epicenter, medical beds per 10,000 people, and physicians per 10,000 people. CONCLUSION: The results implied that fragile minorities, specifically the elderly and children, require special consideration and attention in regard to disaster rescue and emergency medical care allocation. Epidemiologic analysis can guide disaster response and preparation.

[Major complications after open prostatectomy: management and prevention].

From Jan. 1976 to Dec. 1989, 829 patients with benign prostatic hyperplasia (BPH) were treated. Open prostatectomy was performed successfully in 571 patients. Secondary hemorrhage was observed in 21 patients (3.7%), bladder neck or posterior urethral stricture in 10 (1.7%), and temporary incontinence in 21 (3.7%). No operative mortality was noted. The pathogenesis, management and prevention of those complications were detailed with review of the literatures. Effective hemostasis, proper enucleation of the enlarged gland and meticulous reconstruction of the bladder neck are claimed to be the key points in reducing complications and increasing cure rate in the treatment of BPH with open prostatectomy.