[Association Between TAB2 Gene Polymorphisms and Susceptibility to Cryptorchidism in Han Chinese Population in Southwest China].

Objective: To conduct preliminary investigation into the correlation between transforming growth factor beta-activated protein kinase 1-binding protein 2 ( TAB2) gene and the incidence of cryptorchidism in Han Chinese population in Southwest China. Methods: A total of 259 patients with cryptorchidism and 355 healthy controls from Southwest China were enrolled for the study. Polymerase chain reaction-restriction fragment length polymorphism method was used to analyze the genotype of the 3 tag single nucleotide polymorphisms (SNPs) of TAB2 gene, i.e., rs237028, rs521845 and rs652921. The Chi-square test was used to analyze the relationship between the genotype frequency of the three tag SNPs and the incidence of cryptorchidism. Results: The distribution of the 3 tag SNPs' alleles and genotypes were in agreement with the Hardy-Weinberg equilibrium, and the genotype results of polymerase chain reaction-restriction fragment length polymorphism assay were consistent with those of Sanger sequencing. The frequency of the G allele at TAB 2 rs237028 was significantly higher in the cryptorchidism group than that in the control group (30.9% vs. 25.6%, P=0.04, OR=1.31, 95% CI: 1.01-1.70). In the dominant model, the risk of cryptorchidism was significantly higher in AG/GG genotype carriers ( P=0.006, OR=1.57, 95% CI: 1.14-2.17). In the cryptorchidism group, the TC/CC genotype frequency of the rs652921 locus were significantly higher than that of the control group (75.3% vs. 67.0%, P=0.03, OR=1.50, 95% CI: 1.05-2.14). Correlation between rs521845 and susceptibility to cryptorchidism was not observed in the Han Chinese population. Conclusion: The AG/GG genotype of rs237028 locus and the TC/CC genotype of rs652921 locus of the TAB2 gene may be associated with increased risks of cryptorchidism in Han Chinese population in southwest China.

RIP1 promotes proliferation through G2/M checkpoint progression and mediates cisplatin-induced apoptosis and necroptosis in human ovarian cancer cells.

Receptor-interacting protein 1 (RIP1, also known as RIPK1) is not only a tumor-promoting factor in several cancers but also mediates either apoptosis or necroptosis in certain circumstances. In this study we investigated what role RIP1 plays in human ovarian cancer cells. We showed that knockout (KO) of RIP1 substantially suppressed cell proliferation, accompanied by the G2/M checkpoint arrest in two human ovarian cancer cell lines SKOV3 and A2780. On the other hand, RIP1 KO remarkably attenuated cisplatin-induced cytotoxicity, which was associated with reduction of the apoptosis markers PARP cleavage and the necroptosis marker phospho-MLKL. We found that RIP1 KO suppressed cisplatin-induced ROS accumulation in both SKOV3 and A2780 cells. ROS scavenger BHA, apoptosis inhibitor Z-VAD or necroptosis inhibitor NSA could effectively suppress cisplatin's cytotoxicity in the control cells, suggesting that ROS-mediated apoptosis and necroptosis were involved in cisplatin-induced cell death. In addition, blocking necroptosis with MLKL siRNA effectively attenuated cisplatin-induced cytotoxicity. In human ovarian cancer A2780 cell line xenograft nude mice, RIP1 KO not only significantly suppressed the tumor growth but also greatly attenuated cisplatin's anticancer activity. Our results demonstrate a dual role of RIP1 in human ovarian cancer: it acts as either a tumor-promoting factor to promote cancer cell proliferation or a tumor-suppressing factor to facilitate anticancer effects of chemotherapeutics such as cisplatin.

A Novel Approach of Urinary Monohydroxyphenyl Metabolites Assay in Cancer Screening.

BACKGROUND: A noninvasive, fast, highly sensitive and simple test is needed for cancer screening in addition to the detection of biomarkers in blood. Recently, the patent (CN102565055A) for the Urinary Monohydroxyphenyl Metabolites Assay (UMM-A) was authorized, and the effectiveness of clinical application has yet to be studied further. METHODS: A retrospective study was conducted consisting of 432 cancer patients, 28 benign tumor patients, 117 non-cancerous diseases patients, and 120 healthy donors to analyze the levels of monohydroxyphenyl metabolites in the urine sample. A logistic regression model was used to study the possible confounding factors affecting the diagnostic performance and to test the probability of a case to be positive for UMM-A. RESULTS: Compared with healthy donors, non-cancerous disease, and benign tumor subjects, the positive rate and MM level of UMM-A in cancer patients have significantly increased. After the 246 retreated cancer patients were excluded, and 186 untreated cancer patients were included, with the same specificity to 77.0%, the sensitivity improved from 66.7 to 89.8%, the negative predictive value improved from 58.6 to 91.4%. CONCLUSIONS: The present study has provided important information on the diagnostic characteristics of UMM-A for untreated cancer and its potential application in cancer screening.

IgG4-related kidney disease (IgG4-RKD) with membranous nephropathy as its initial manifestation: report of one case and literature review.

BACKGROUND: IgG4-related disease (IgG4-RD) often affects multiple organs and tissues, especially the kidneys, and is characterized by interstitial nephritis, obstructive nephropathy, and in rare cases glomerulopathy (including membranous nephropathy). CASE PRESENTATION: In this article, we report a patient with nephrotic syndrome as the only initial manifestation. Membranous nephropathy was confirmed by renal biopsy, but without any renal interstitial lesions. The nephrotic syndrome completely resolved after treatment with immunosuppressants but recurred after drug withdrawal, which was accompanied by acute kidney injury. Ultimately, IgG4-related interstitial nephritis with membranous nephropathy was confirmed by a second renal biopsy. After routine administration of steroids and cyclophosphamide, renal function returned to normal after 2 months, and nephrotic syndrome was ameliorated after 5 months. CONCLUSION: Special attention should be paid to this rare condition in the clinical setting. In patients with membranous nephropathy (MN) that is accompanied by multi-system damage, impaired renal function, elevated IgG4 levels (absolute or relative value), negative PLA2R, and/or renal interstitial plasma cell infiltration, the possibility of IgG4-related kidney disease (IgG4-RKD) should be carefully assessed.

Response of Soil Fungi Community Structure to Salt Vegetation Succession in the Yellow River Delta.

High-throughput sequencing technology was used to reveal the composition and distribution of fungal community structure in the Yellow River Delta under bare land and four kinds of halophyte vegetation (saline seepweed, Angiospermae, Imperata and Apocynum venetum [A. venetum]). The results showed that the soil quality continuously improved with the succession of salt vegetation types. The soil fungi richness of mild-salt communities (Imperata and A. venetum) was relatively higher, with Shannon index values of 5.21 and 5.84, respectively. The soil fungi richness of severe-salt-tolerant communities (saline seepweed, Angiospermae) was relatively lower, with Shannon index values of 4.64 and 4.66, respectively. The UniFrac metric values ranged from 0.48 to 0.67 when the vegetation was in different succession stages. A total of 60,174 valid sequences were obtained for the five vegetation types, and they were classified into Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota and Mucoromycotina. Ascomycota had the greatest advantage among plant communities of Imperata and A. venetum, as indicated by relative abundances of 2.69 and 69.97 %, respectively. Basidiomycota had the greatest advantage among mild-salt communities of saline seepweed and Angiospermae, with relative abundances of 9.43 and 6.64 %, respectively. Soil physical and chemical properties were correlated with the distribution of the fungi, and Mucor was significantly correlated with soil moisture (r = 0.985; P < 0.01). Soil quality, salt vegetation and soil fungi were influenced by each other.

[Study on protective and haemodynamic effects of Danshen Tongluo capsule on rats with myocardial infarction].

To study the protective effect of Danshen Tongluo capsule on rat hearts in the myocardial infarction (MI) model. After being fed with high fat diets for one month, the SD rats were randomly divided into the sham group and the model group according to the left ventricular ejection fraction (EF). The MI model group was duplicated by ligating coronary artery and then divided into five groups: the model group, the positive control group (model + captopril), the small dose group (model + Danshen Tongluo), the medium dose group (model + Danshen Tongluo) and the high dose group (model + Danshen Tongluo). Four weeks later, changes in myocardium ultra-structure were observed by hemodynamics, cardiac ultrasound and electron microscope. The results showed: (1) All doses of Danshen Tongluo capsule could significantly reduce the left ventricular end diastolic pressure (LVEDP) (P <0.01), increase the maximum internal pressure of the left ventricle (+ dp/dtmax), and lower the drop rate of left ventricular pressure (- dp/dtmax), with statistical significances in medium and high dose groups; (2) The B ultrasound results showed increase in EF and left ventricular shortening fraction (FS) in all dose groups of Danshen Tongluo capsule; (3) The medium dose group showed significant decrease in myocardial infarction index (P <0.01) and injured and fractured myofilament and sarcomere of ischemic myocardium in myocardial ultra-structure; All of Danshen Tongluo capsule-treated groups revealed reduction in myocardial injury and myocardial infraction area. The study preliminarily proves that Danshen Tongluo capsule can improve hemodynamic function, and has a protective effect on myocardial ischemia.

The prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

BACKGROUND: Interstitial lung disease (ILD) is the most widespread and fatal pulmonary complication of rheumatoid arthritis (RA). Existing knowledge on the prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is inconclusive. Therefore, we designed this review to address this gap. MATERIALS AND METHODS: To find relevant observational studies discussing the prevalence and/or risk factors of RA-ILD, EMBASE, Web of Science, PubMed, and the Cochrane Library were explored. The pooled odds ratios (ORs) / hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with a fixed/ random effects model. While subgroup analysis, meta-regression analysis and sensitivity analysis were carried out to determine the sources of heterogeneity, the I2 statistic was utilized to assess between-studies heterogeneity. Funnel plots and Egger's test were employed to assess publication bias. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, our review was conducted. RESULTS: A total of 56 studies with 11,851 RA-ILD patients were included in this meta-analysis. The pooled prevalence of RA-ILD was 18.7% (95% CI 15.8-21.6) with significant heterogeneity (I2 = 96.4%). The prevalence of RA-ILD was found to be more likely as a result of several identified factors, including male sex (ORs = 1.92 95% CI 1.70-2.16), older age (WMDs = 6.89, 95% CI 3.10-10.67), having a smoking history (ORs =1.91, 95% CI 1.48-2.47), pulmonary comorbidities predicted (HRs = 2.08, 95% CI 1.89-2.30), longer RA duration (ORs = 1.03, 95% CI 1.01-1.05), older age of RA onset (WMDs =4.46, 95% CI 0.63-8.29), positive RF (HRs = 1.15, 95%CI 0.75-1.77; ORs = 2.11, 95%CI 1.65-2.68), positive ACPA (ORs = 2.11, 95%CI 1.65-2.68), higher ESR (ORs = 1.008, 95%CI 1.002-1.014), moderate and high DAS28 (≥3.2) (ORs = 1.87, 95%CI 1.36-2.58), rheumatoid nodules (ORs = 1.87, 95% CI 1.18-2.98), LEF use (ORs = 1.42, 95%CI 1.08-1.87) and steroid use (HRs= 1.70, 1.13-2.55). The use of biological agents was a protective factor (HRs = 0.77, 95% CI 0.69-0.87). CONCLUSION(S): The pooled prevalence of RA-ILD in our study was approximately 18.7%. Furthermore, we identified 13 risk factors for RA-ILD, including male sex, older age, having a smoking history, pulmonary comorbidities, older age of RA onset, longer RA duration, positive RF, positive ACPA, higher ESR, moderate and high DAS28 (≥3.2), rheumatoid nodules, LEF use and steroid use. Additionally, biological agents use was a protective factor.

Utility, benefits, and risks of newborn genetic screening carrier reports for families.

Background: Newborn genetic screening (NBGS) based on next-generation sequencing offers enhanced disease detection and better detection rates than traditional newborn screening. However, challenges remain, especially around reporting the NBGS carrier results. Therefore, we aimed to investigate the NBGS carrier parents' views on NBGS and NBGS reports in China. Methods: We distributed a survey querying demographic information, knowledge and perceptions of NBGS, the impact of NBGS on a total of 2930 parents, and their decision-making to parents of newborns reported as carriers in NBGS in Nanjing, China in 2022. Results: The average age of the survey respondents was 30.7 years (standard deviation = 3.6). Most (68.38%) felt informed about NBGS, especially women, the highly educated, and high earners. Nearly all (98.74%) saw NBGS as crucial for early disease detection, with 73.18% believing it positively impacts their future. However, 19.16% felt it might cause anxiety, especially among the less educated. Concerns included potential discrimination due to exposed genetic data and strained family ties. Many suggested NBGS coverage by medical insurance to ease financial burdens. Conclusions: Through our study, we gained insights into parents' perspectives and concerns regarding the NBGS carrier result reporting, thus providing relevant information for further refinement and clinical promotion of the NBGS project.

Newborn genetic screening for Fabry disease: Insights from a retrospective analysis in Nanjing, China.

Fabry disease (FD), an X-linked disorder resulting from dysfunction of α-galactosidase A, can result in significant complications. Early intervention yields better outcomes, but misdiagnosis or delayed diagnosis is common, impacting prognosis. Thus, early detection is crucial in the clinical diagnosis and treatment of FD. While newborn screening for FD has been implemented in certain regions, challenges persist in enzyme activity detection techniques, particularly for female and late-onset patients. Further exploration of improved screening strategies is warranted. This study retrospectively analyzed genetic screening results for pathogenic GLA variants in 17,171 newborns. The results indicated an estimated incidence of FD in the Nanjing region of China of approximately 1 in 1321. The most prevalent pathogenic variant among potential FD patients was c.640-801G > A (46.15 %). Furthermore, the residual enzyme activity of the pathogenic variant c.911G > C was marginally higher than that of other variants, and suggesting that genetic screening may be more effective in identifying potential female and late-onset patients compared to enzyme activity testing. This research offers initial insights into the effectiveness of GLA genetic screening and serves as a reference for early diagnosis, treatment, and genetic counseling in FD.

Toxoplasma gondii: enzyme-linked immunosorbent assay based on a recombinant multi-epitope peptide for distinguishing recent from past infection in human sera.

Enzyme-linked immunosorbent assays (ELISAs) based on a recombinant multi-epitope peptide (rMEP) were used in an attempt to differentiate pregnant women with Toxoplasma serologic profiles (TSPs) indicative of recently acquired infections (acute profile) from those with TSPs indicative of infections acquired in the distant past (chronic profile). The recombinant expression vector pET-32c-MEP encoding MEP constructed previously was expressed in Escherichia coli and the rMEP was purified as a bioactive fusion protein. The IgG-ELISA and IgM-ELISA based on the purified rMEP were developed, and used to detect IgG and IgM antibodies against Toxoplasma gondii in human sera. Immunoblot assays showed that the purified rMEP could be strongly recognized by IgM antibodies in the pooled sera from women with acute profiles, and by IgG antibodies in the pooled sera from women with chronic profiles. ELISA results also proved that the reactivities of IgG and IgM antibodies differed significantly in sera from women with acute and chronic profiles. Compared with two commercial ELISA tests for seradiagnosis of toxoplasmosis, the total concordance (including positive and negative sera) of this rMEP-based assay was 93.2% and 95.7% for the detection of IgG and IgM antibodies, respectively. Our study suggests that the rMEP protein could be used as the diagnostic antigen to differentiate recent from past infections in human toxoplasmosis.