Corrigendum to "SEMA4D acts as a novel oligogenic pathogenic gene of idiopathic hypogonadotropic hypogonadism through the PlexinB1/MET/RND1/RHOA/RAF1/MAPK signaling axis" [Genes & Diseases 10 (2023) 65-68].

[This corrects the article DOI: 10.1016/j.gendis.2022.05.030.].

Case report: A rare Salter-Harris V metaphyseal fatigue fracture of the knee in an adolescent patient with obesity.

Stress fractures are rare, occurring in 1.5/100,000 high school athletes. High impact, repetitive loading participation in woman's sports, and being a white athlete have been identified as risk factors for stress fractures. Mostly treated conservatively, they are more common in the tibia (33%). Stress fractures requiring surgery, which are extremely rare, have been reported in the scaphoid, fifth metatarsal, and neck of femur. Herein, a 16-year-old adolescent patient with obesity presented with atypical knee pain after prolonged exercise. Advanced imaging revealed a stress fracture of the left tibia with a Salter-Harris type V fracture and varus deformity of the knee. We initially managed the fatigue fracture conservatively, followed by surgical correction of the varus deformity in the knee joint. The patient made a satisfactory recovery with equal limb length and no evidence of claudication. This is the first case of a proximal tibial metaphyseal stress fracture requiring surgery. The clinical manifestations of proximal tibial metaphyseal stress fractures and potential treatment strategies and the use of magnetic resonance for tibial stress fractures have been discussed. Understanding the location of unusual stress fractures can improve early diagnostic efficiency and reduce complication rates, healthcare costs, and recovery time.

Role of histone posttranslational modifications in the regulation of ovarian function / 生理学报

The ovary is the reproductive organ of female mammals, which is responsible for producing mature eggs and secreting sex hormones. The regulation of ovarian function involves the ordered activation and repression of genes related to cell growth and differentiation. In recent years, it has been found that histone posttranslational modification can affect DNA replication, damage repair and gene transcriptional activity. Some regulatory enzymes mediating histone modification are co-activators or co-inhibitors associated with transcription factors, which play important roles in the regulation of ovarian function and the development of ovary-related diseases. Therefore, this review outlines the dynamic patterns of common histone modifications (mainly acetylation and methylation) during the reproductive cycle and their regulation of gene expression for important molecular events, focusing on the mechanisms of follicle development and sex hormone secretion and function. For example, the specific dynamics of histone acetylation are important for the arrest and resumption of meiosis in oocytes, while histone (especially H3K4) methylation affects the maturation of oocytes by regulating their chromatin transcriptional activity and meiotic progression. Besides, histone acetylation or methylation can also promote the synthesis and secretion of steroid hormones before ovulation. Finally, the abnormal histone posttranslational modifications in the development of two common ovarian diseases (premature ovarian insufficiency and polycystic ovary syndrome) are briefly described. It will provide a reference basis for understanding the complex regulation mechanism of ovarian function and further exploring the potential therapeutic targets of related diseases.

Magnetic soft robotic bladder for assisted urination.

The poor contractility of the detrusor muscle in underactive bladders (UABs) fails to increase the pressure inside the UAB, leading to strenuous and incomplete urination. However, existing therapeutic strategies by modulating/repairing detrusor muscles, e.g., neurostimulation and regenerative medicine, still have low efficacy and/or adverse effects. Here, we present an implantable magnetic soft robotic bladder (MRB) that can directly apply mechanical compression to the UAB to assist urination. Composed of a biocompatible elastomer composite with optimized magnetic domains, the MRB enables on-demand contraction of the UAB when actuated by magnetic fields. A representative MRB for a UAB in a porcine model is demonstrated, and MRB-assisted urination is validated by in situ computed tomography imaging after 14-day implantation. The urodynamic tests show a series of successful urination with a high pressure increase and fast urine flow. Our work paves the way for developing MRB to assist urination for humans with UABs.

Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways.

BACKGROUND: The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas. OBJECTIVES: To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats. MATERIALS AND METHODS: Fifty male Sprague-Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine. RESULTS: Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine-1-phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine-1-phosphate was not significant. Moreover, mitogen-activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGFß1, collagen I/IV, Bax/Bcl-2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis. CONCLUSIONS: Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine-1-phosphate/S1PR2 and mitogen-activated protein kinase pathways.

Identification of RNA-binding protein SNRPA1 for prognosis in prostate cancer.

Prostate cancer is one of the deadliest cancers in men. RNA-binding proteins play a critical role in human cancers; however, whether they have a significant effect on the prognosis of prostate cancer has yet to be elucidated. In the present study, we performed a comprehensive analysis of RNA sequencing and clinical data from the Cancer Genome Atlas dataset and obtained differentially expressed RNA-binding proteins between prostate cancer and benign tissues. We constructed a protein-protein interaction network and Cox regression analyses were conducted to identify prognostic hub RNA-binding proteins. SNRPA1 was associated with the highest risk of poor prognosis and was therefore selected for further analysis. SNRPA1 expression was positively correlated with Gleason score and pathological TNM stage in prostate cancer patients. Furthermore, the expression profile of SNRPA1 was validated using the Oncomine, Human Protein Atlas, and Cancer Cell Line Encyclopedia databases. Meanwhile, the prognostic profile of SNRPA1 was successfully verified in GSE70769. Additionally, the results of molecular experiments revealed the proliferative role of SNRPA1 in prostate cancer cells. In summary, our findings evidenced a relationship between RNA-binding proteins and prostate cancer and indicated the prognostic significance of SNRPA1 in prostate cancer.

A four-gene signature associated with clinical features can better predict prognosis in prostate cancer.

Prostate cancer (PCa) is one of the most deadly urinary tumors in men globally, and the 5-year over survival is poor due to metastasis of tumor. It is significant to explore potential biomarkers for early diagnosis and personalized therapy of PCa. In the present study, we performed an integrated analysis based on multiple microarrays in the Gene Expression Omnibus (GEO) dataset and obtained differentially expressed genes (DEGs) between 510 PCa and 259 benign issues. The weighted correlation network analysis indicated that prognostic profile was the most relevant to DEGs. Then, univariate and multivariate COX regression analyses were conducted and four prognostic genes were obtained to establish a four-gene prognostic model. And the predictive effect and expression profiles of the four genes were well validated in another GEO dataset, The Cancer Genome Atlas and the Human Protein Atlas datasets. Furthermore, combination of four-gene model and clinical features was analyzed systematically to guide the prognosis of patients with PCa to a largest extent. In summary, our findings indicate that four genes had important prognostic significance in PCa and combination of four-gene model and clinical features could achieve a better prediction to guide the prognosis of patients with PCa.

Combined in vitro and in silico analyses of FGFR1 variants: genotype-phenotype study in idiopathic hypogonadotropic hypogonadism.

Fibroblast growth factor receptor 1 (FGFR1) is an idiopathic hypogonadotropic hypogonadism (IHH)-associated gene, mutated in approximately 10% of the patients with this condition. Through targeted gene sequencing of 153 males with IHH and 100 healthy controls, we identified 10 mutations in FGFR1 from IHH patients with a frequency of 5.9% in the Chinese population of central China. These included nine missense mutations(NM_023110.2, p.Gly687Arg, p.Ala608Asp, p.Gly348Glu, p.Asn296Ser, p.Gly226Asp, p.Arg209Cys, p.Gly97Arg, p.Val71Met, p.Gly70Arg) and a splicing mutation c.1430 + 1G > T. in vitro and in silico analyses of FGFR1 variants were conducted to study the impact of the identified mutations. Our findings indicated that the splicing mutation dramatically affected premRNA processing, causing exon 10 and 6 nucleotides in the 3' end of exon 9 to be completely skipped. Two variants (p.Gly687Arg and p.Ala608Asp) markedly impaired tyrosine kinase activity, while the other variants had limited impact on the mitogen-activated protein kinase (MAPK) signaling pathway. However, the functional impairment of the mutant receptors was not always consistent with the phenotypes, indicating that FGFR1 mutations might cause IHH in conjunction with other mutant genes. In this study, we expanded the knowledge on the mutation spectrum of FGFR1 in IHH patients and explored the genotype-phenotype relationship.

The relation between positive rate of autoantibodies against beta1 and M2-adrenergic receptors and urinary albumin excretion rate in the type 2 diabetes mellitus with refractory hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relation between the positive rates of autoantibodies against beta(1) adrenergic receptor (beta1-receptor)and (M2-receptor) with urinary albumin excretion rate (UAER) in type 2 diabetes patients with refractory hypertension.</p><p><b>METHODS</b>Autoantibodies against beta(1)- and M(2)-receptor as well as autoantibodies were determined in type 2 diabetes patients with (n = 136) or without (n = 111) refractory hypertension, hypertensive patients without renal failure (n = 60) and healthy control subjects (n = 40, control) by ELISA.</p><p><b>RESULTS</b>The positive rates of the autoantibodies against beta1-receptors (44.9%) and M(2)-receptor (37.5%) in patients with type 2 diabetes with refractory hypertension were significantly higher than those in patients with type 2 diabetes without refractory hypertension (27.9% and 24.3%, respectively, all P < 0.05), in patients with hypertension without renal failure (11.7% and 15.0%, all P < 0.01) and in healthy controls (8.3% and 7.5%, all P < 0.01). In type 2 diabetes patients with refractory hypertension and renal failure (UAER > or = 200 microg/min), the positive rates of the autoantibodies against beta(1)-receptor (87.1%, 27/31) and against M(2)-receptor (67.7%, 21/31) were significantly higher than those in type 2 diabetes patients with refractory hypertension but without renal failure (UAER 20 - 199 microg /min, 46.7%, 28/60 and 41.7%, 25/60, respectively, all P < 0.05).</p><p><b>CONCLUSION</b>The serum beta(1)- and M (2)-receptor autoantibodies are positively associated with the UAER level and suggest that these autoantibodies against beta(1) and M(2)-receptor may play important roles in the pathogenesis of the type 2 diabetes with refractory hypertension.</p>

Epidemiology investigation of allergic rhinitis in urban and rural areas of Ningbo and Yongzhou / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the epidemiological characteristics of allergic rhinitis (AR) in urban and rural areas of Ningbo and Yongzhou.@*METHOD@#Fifteen fields in the two cities from October 2006 to June 2007 were randomly selected. Cases suspected with symptoms of AR by a self-administered and interview questionnaire were recommended to special examinations for confirmed diagnosis.@*RESULT@#1. A total of 9969 individuals from 3803 families were surveyed, of whom 303 suffered with AR. 2. The prevalence rate was 4.10% in Ningbo and 1.65% in Yongzhou (the sex-adjusted rate was 4.10% and 1.64% respectively, and the age-adjusted rate was 4.33% and 1.58%); the population of island inhabitants had the lowest prevalence rate of 0.73%. 3. The prevalence rate in patients with asthma and that with family genetic history was 8% and 12% respectively.@*CONCLUSION@#It demonstrates that the prevalence rate is higher in Ningbo than in Yongzhou, in urban than in rural and in adolescent than in other ages. Allergic rhinitis may be associated with asthma and related to genetic factors. Allergic rhinitis may be curable.

Link of autoantibodies against ?_1 receptor with hypertension-related renal failure / 中国医师进修杂志

Objective To explore the role of the autoantibodies against ?_1-adrenergic receptor(?_1-receptor)in the development of hypertension with renal failure.Methods The epitopes of the second extracellular loop of ?_1-receptor were synthesized and used respectively to screen sera autoantibodies from patients with hypertension with renal failure(61 cases),hypertension without renal failure(58 cases) and healthy blood donors(40 cases,control) by ELISA method.Results The positive rates of the autoantibodies ?_1-receptor(69%,42/61) in patients with hypertension with renal failure were higher than those of patients with hypertension without renal failure(19%,11/58) respectively(P

Autoantibodies against beta1 and M2 receptor in diabetic patients with refractory hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the role of the autoantibodies against M(2)-muscarinic receptor (M(2)-receptor), beta(1)-adrenergic receptor (beta(1)-receptor) in the development of diabetic with refractory hypertension.</p><p><b>METHODS</b>Serum autoantibodies against M(2) and beta(1) were detected by ELISA using synthesized epitopes of the second extracellular loop of M(2) receptor (169 - 193) and beta(1) receptor (197 - 222) in healthy controls (n = 40), diabetic patients (n = 62), diabetic patients with non-refractory hypertension (n = 55) and diabetic patients with refractory hypertension (n = 81).</p><p><b>RESULTS</b>The positive rates of the autoantibodies against M(2) receptor and beta(1) receptor were similar among healthy controls (15.0% and 17. 5%), diabetes mellitus patients (17.7% and 14.5%) and diabetic patients with non-refractory hypertension (16.4% and 12.7%) but are significantly higher in diabetic patients with refractory hypertension (64.2% and 55.6%, P < 0.01 vs. other 3 groups).</p><p><b>CONCLUSION</b>This finding suggests that autoimmune mechanisms might play a role in the pathogenesis of diabetic patients with refractory hypertension.</p>

Study on the roles of autoantibodies against ?1 adrenoceptor and M2 cholinergic receptor in patients with chronic renal insufficiency / 中国医师杂志

Objective To explore the roles of autoantibodies against ?1 adrenoceptor(?1-receptor)and M2 cholinergic receptor(M2-receptor)in patients with chronic renal insufficiency.Methods The epitopes of the second extracellular loop of ?1 receptor and M2 receptor were synthesized and used respectively to detect the sera autoantibodies against ?1 receptor and M2 receptor by enzyme linked immunosorbent assay(ELISA) in 76 patients with chronic renal insufficiency,60 cases with hypertension and 40 healthy controls.Results In patients with chronic renal insufficiency,the positive rates of the autoantibodies against ?1-receptor and M2-receptor were 56.7% and 38.1% respectively,which were much higher than those of patients with hypertension(18.3% and 11.7%) and higher than those of healthy controls(17.5% and 15.0%)(all P

Association of T-786C polymorphisms of eNOS gene with diabetic nephropathy / 中华内分泌代谢杂志

PCR/ASO probes were applied to analyse the T-786C polymorphisms in 5′-flanking region of endothelial nitric oxide synthase(eNOS)gene in type 2 diabetic patients with or without nephropatby and healthy individuals.The results showed that the T-786C polymorphisms of eNOS gene seemed to be related to diabetic nephropathy in type 2 diabetes.