Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

Factors influencing TSH suppression efficacy in postoperative papillary thyroid carcinoma patients: a retrospective cohort study.

OBJECTIVES: While surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC. METHODS: This study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy. RESULTS: There were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P < 0.05), and the ROC curve analysis indicated that the area under the curve for the preoperative TSH index was 0.610 (P < 0.05). The proportion of patients in the TSH level conforming group who took oral levothyroxine sodium tablets at a dose of ≥ 1.4 µg/kg·d after surgery was higher (P < 0.05). The postoperative levels of FT3 and FT4 were higher in the TSH level conforming group (P < 0.05). The results of binary logistic regression analysis indicated that factors "Postoperative TSH level ≥ 2 mU/L", "Levothyroxine sodium tablet dose<1.4 µg/kg·d", and "Combined with Hashimoto thyroiditis" were significantly associated with an elevated risk of postoperative TSH levels failing to reach the target (P < 0.05). CONCLUSION: Optimal thyroid function in patients with PTC post-surgery is best achieved when adjusting the dose of levothyroxine sodium in a timely manner to reach the target TSH level during follow-up visits.

Ganonorsterone A, a norsteroid from the medicinal fungus Ganoderma lingzhi.

Phytochemical investigation on the fruiting bodies of the medicinal fungus Ganoderma lingzhi led to the isolation of a new norsteroid, namely ganonorsterone A (1), together with one known steroid, cyathisterol (2). The structure and absolute configuration of compound 1 were assigned by extensive analysis of MS, NMR data, and quantum-chemical calculations including electronic circular dichroism (ECD) and calculated 13C NMR-DP4+ analysis. Bioassay results showed that compound 1 displayed moderate inhibition on NO production in RAW 264.7 macrophages.

Association of composite dietary antioxidant index with prevalence of stroke: insights from NHANES 1999-2018.

Background: There is a growing acknowledgment of the potential influence of antioxidative effects resulting from dietary decisions on the occurrence of stroke. The objective of this study was to elucidate the correlation between the composite dietary antioxidant index (CDAI) and the incidence of stroke in the general population of the United States. Methods: We gathered cross-sectional data encompassing 40,320 participants from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2018. Employing weighted multivariate logistic regression, we assessed the correlation between CDAI and stroke, while also investigating potential nonlinear relationships through restricted cubic spline (RCS) regression. Further, the intake of CDAI components were then incorporated into a predictive nomogram model, subsequently evaluated for its discriminatory prowess in stroke risk assessment using the receiver operating characteristic (ROC) curve. Results: Post-adjustment for confounding variables, we found that higher CDAI score were associated with a decreased risk of stroke, the odds ratio (OR) [95% CI] of CDAI associating with prevalence was 0.96 [0.94-0.98] (P< 0.001). Moreover, the adjusted OR [95% CI] for stroke across ascending CDAI quartiles stood at 0.90 [0.74-1.09], 0.74 [0.60-0.91], and 0.61 [0.50-0.76] compared to the reference quartile, respectively. The RCS analysis indicated a nonlinear yet negative correlation between CDAI and stroke. The nomogram model, constructed based the intake of antioxidants, exhibited a significant predictive capacity for stroke risk, boasting an area under the curve (AUC) of 77.4% (76.3%-78.5%). Conclusion: Our investigation ascertained a nonlinear negative relationship between CDAI and stroke within the broader American population. However, given the inherent limitations of the cross-sectional design, further comprehensive research is imperative to establish the causative nature of this association.

[Comprehensive nursing intervention for advanced prostate cancer patients undergoing chemoradiotherapy].

OBJECTIVE: To explore the effect of comprehensive nursing intervention in advanced PCa patients receiving chemoradiotherapy. METHODS: This study included 70 patients with advanced PCa undergoing chemoradiotherapy in our department from January 2020 to April 2022, who were randomly divided into a control (n = 35) and an intervention group (n = 35), the former receiving routine nursing care while the latter comprehensive nursing intervention, including such measures as health education, psychological care, radiotherapy care, chemotherapy care, and complication care. After intervention, comparisons were made between the two groups of patients in the Expanded Prostate Cancer Index Composite (EPIC) scores and incidence of adverse reactions to chemoradiotherapy. RESULTS: The scores on all the dimensions of EPIC were significantly higher in the intervention than in the control group (P < 0.05) and the incidence rate of radiation-induced proctitis and cystitis remarkably lower in the former than in the latter (36.11% vs 71.43%, P < 0.05). CONCLUSION: Comprehensive nursing intervention can improve the quality of life of the PCa patients undergoing chemoradiotherapy, increase their compliance with treatment and reduce their adverse reactions, and therefore deserves clinical promotion.

Search for serum biomarkers in patients with bipolar disorder and major depressive disorder using metabolome analysis.

Objective: Bipolar disorder (BD) and major depressive disorder (MDD) are two common psychiatric disorders. Due to the overlapping clinical symptoms and the lack of objective diagnostic biomarkers, bipolar disorder (BD) is easily misdiagnosed as major depressive disorder (MDD), which in turn affects treatment decisions and prognosis. This study aimed to investigate biomarkers that could be used to differentiate BD from MDD. Methods: Nuclear magnetic resonance (NMR) spectroscopy was performed to assess serum metabolic profiles in depressed patients with BD (n = 59), patients with MDD (n = 14), and healthy controls (n = 10). Data was analyzed using partial least squares discriminant analysis, orthogonal partial least squares discriminant analysis and t-tests. Different metabolites (VIP > 1 and p < 0.05) were identified and further analyzed using Metabo Analyst 5.0 to identify relevant metabolic pathways. Results: The metabolic phenotypes of the BD and MDD groups were significantly different from those of the healthy controls, and there were different metabolite differences between them. In the BD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, ß-glucose, pantothenic acid, mannose, glycerol, and lipids were significantly higher than those in the healthy control group, and the levels of lactate and acetoacetate were significantly lower than those in the healthy control group. In the MDD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, pyruvate, choline, acetoacetic acid, and lipids were significantly higher than those of healthy controls, and the levels of acetic acid and glycerol were significantly lower than those of healthy controls. Conclusion: Glycerolipid metabolism is significantly involved in BD and MDD. Pyruvate metabolism is significantly involved in MDD. Pyruvate, choline, and acetate may be potential biomarkers for MDD to distinguish from BD, and pantothenic acid may be a potential biomarker for BD to distinguish from MDD.

Identifying potential insecticide resistance markers through genomic-level comparison of Bemisia tabaci (Gennadius) lines.

The invasive whitefly (Bemisia tabaci) MED is one of the most economically damaging plant pests. The extensive use of insecticide over decades has led to that the invasive B. tabaci MED has developed resistance to a wide range of insecticide classes, but little is known about the genetic background associated with resistance. To this end, we conducted a comparative genome-wide analysis of single-base nucleotide polymorphisms between MED whitefly lines collected from fields that were recently infested and an insecticide-susceptible MED whitefly line collected in 1976. First, low-coverage genome sequencings were conducted on DNA isolated from individual whiteflies. The sequencing results were evaluated using an available B. tabaci MED genome as a reference. Significant genetic differences were discovered between MED whitefly lines collected from fields that were recently infested and an insecticide-susceptible MED whitefly line based on the principal component analyses. Top GO categories and KEGG pathways that might be involved in insecticide resistance development were identified, and several of them have not been previously associated with resistance. Additionally, we identified several genetic loci with novel variations including Cytochrome P450 monooxygenases (P450s), UDP-glucuronosyltransferases (UGTs), Glutathione S-transferases (GSTs), esterase, carboxyl-esterases (COE), ABC transporters, fatty acyl-CoA reductase, voltage-gated sodium channels, GABA receptor, and cuticle proteins (CPs) that were previously reported to have close associations with pesticide resistance in well-studied insect groups that provide an essential resource for the design of insecticide resistance-linked loci arrays insecticide. Our results was obtained solely on resequencing genome data sets, more pesticide bio-assays combined with omics datasets should be further used to verify the markers identified here.

Lanostane triterpenoids with anti-proliferative and anti-inflammatory activities from medicinal mushroom Ganoderma lingzhi.

Eight previously undescribed lanostane triterpenoids and nine known ones were identified from the fruiting bodies of Ganoderma lingzhi S.H. Wu, Y. Cao & Y.C. Dai. Their structures were determined based on spectroscopic data and quantum chemical calculations. Structurally, ganoderane GL-1, featuring a hydrogenated tetramethyls-phenanthraquinone, represents the first example in lanostane nor-triterpenoid group. Biologically, ganoderanes GL-2 and GL-3, distinguished by the presence of a rare "1,11-epoxy" moiety, exhibited significant inhibition against nitric oxide production induced by lipopolysaccharide in RAW264.7 macrophage cells, while ganoderanes GL-4 and GL-8 exhibited bifunctional activities of anti-proliferation and anti-inflammation.

Structurally Diverse Phenolic Amides from the Fruits of Lycium barbarum with Potent α-Glucosidase, Dipeptidyl Peptidase-4 Inhibitory, and PPAR-γ Agonistic Activities.

A total of nine new phenolic amides (1-9), including four pairs of enantiomeric mixtures (3-5 and 8), along with ten known analogues (10-19) were identified from the fruits of Lycium barbarum using bioassay-guided chromatographic fractionation. Their structures were elucidated by comprehensive spectroscopic and spectrometric analyses, chiral HPLC analyses, and quantum NMR, and electronic circular dichroism calculations. Compounds 5-7 are the first example of feruloyl tyramine dimers fused through a cyclobutane ring. The activity results indicated that compounds 1, 11, and 13-17 exhibited remarkable inhibition against α-glucosidase with IC50 of 1.11-33.53 µM, 5-150 times stronger than acarbose (IC50 = 169.78 µM). Meanwhile, compounds 4a, 4b, 5a, 5b, 13, and 14 exerted moderate agonistic activities for peroxisome proliferator-activated receptor (PPAR-γ), with EC50 values of 10.09-44.26 µM. Especially,compound 14 also presented inhibitory activity on dipeptidyl peptidase-4 (DPPIV), with an IC50 value of 47.13 µM. Furthermore, the banding manner of compounds 14 and 17 with the active site of α-glucosidase, DPPIV, and PPAR-γ was explored by employing molecular docking analysis.

Pyrrole alkaloids from the fruiting bodies of edible mushroom Lentinula edodes.

Nine pyrrole alkaloid derivatives, including four new ones (1-4), were isolated from the wild mushroom Lentinula edodes for the first time. Their chemical structures were determined using UV-Vis spectroscopy, IR spectroscopy, MS, NMR spectroscopy, and single-crystal X-ray diffraction techniques. Compound 1, a previously unreported bicylo-pyrrole aldehyde homologue, was found to be a major component, approximately 8.2 µg g -1 in the dry powder of L. edodes. Compound 1 showed cytotoxicity against SMMC-772 (IC50 15.8 µM) without any cytotoxic effect on LO2, a normal hepatic cell line; compounds 1 and 2 displayed weak immunosuppressive activities by inhibiting the proliferation of induced T cells; compound 3 showed inhibition activity on the proliferation of HaCaT cell line (IC50 25.4 µM) and weak antioxidant activity at a concentration of 50 µM.

Common and unique alterations of functional connectivity in major depressive disorder and bipolar disorder.

OBJECTIVE: Major depressive disorder (MDD) and bipolar disorder (BD) are considered whole-brain disorders with some common clinical and neurobiological features. It is important to investigate neural mechanisms to distinguish between the two disorders. However, few studies have explored the functional dysconnectivity between the two disorders from the whole brain level. METHODS: In this study, 117 patients with MDD, 65 patients with BD, and 116 healthy controls completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Both edge-based network construction and large-scale network analyses were applied. RESULTS: Results found that both the BD and MDD groups showed decreased FC in the whole brain network. The shared aberrant network across patients involves the visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and ventral attention network (VAN), which is related to the processing of external stimuli. The default mode network (DMN) and the limbic network (LN) abnormalities were only found in patients with MDD. Furthermore, results showed the highest decrease in edges of patients with MDD in between-network FC in SMN-VN, whereas in VAN-VN of patients with BD. CONCLUSIONS: Our findings indicated that both MDD and BD are extensive abnormal brain network diseases, mainly aberrant in those brain networks correlated to the processing of external stimuli, especially the attention network. Specific altered functional connectivity also was found in MDD and BD groups, respectively. These results may provide possible trait markers to distinguish the two disorders.

Dysosmaflavonoid A-F, new flavonols with potent DPPH radical scavenging activity from Dysosma versipellis.

Six new flavonols, including four glucosylated flavonols (dysosmaflavonoid A-D), one phenylpropanoid-substituted flavonol (dysosmaflavonoid E), and one phenyl-substituted flavonol (dysosmaflavonoid F), together with five known analogues, were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by comprehensive analysis of their NMR, IR, UV, HRESIMS, and HPLC data. The antioxidant activities of all isolated compounds were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Compounds 2, 3, 5-8, and 12 exhibited significant DPPH scavenging capacity with IC50 values of 33.95, 39.02, 31.17, 32.79, 31.85, 30.48, and 23.75 µM, respectively, in comparison with Trolox (IC50, 15.80 µM). Compound 12 displayed more potent DPPH radical scavenging activity than prenylated and (or) glucosided derivatives (2-4, or 10). The preliminary structure-activity relationship showed that the catechol structure in flavonol is essential for DPPH radical scavenging effect.

Effects of water and salt stresses on plant growth and xylem hydraulic properties of tomato.

Xylem is the main tissue for water transport in plants, and the changes of hydraulic properties in which would affect plant water relations and fruit water accumulation. It remains unclear regarding the responses of xylem anatomy and hydraulic properties to water and salt stresses in tomato plants and their relationships with plant growth and fruit water content. We conducted a pot experiment in a greenhouse to investigate the responses of plant growth, fruit water content, and xylem hydraulic properties of a cherry tomato (Hong Baoshi) and a medium-fruited tomato (Beifan 501). There were three treatments, control with a soil water content (θ) of 75%-95% of field capacity (FC) and an initial electrical conductivity (EC) of 0.398 dS·m-1; water stress with θ of 75%-95% of FC (before flowering) and 45%-65% of FC (from flowering until maturity) and an EC of 0.398 dS·m-1; and salt stress with θ of 75%-95% of FC and an EC of 1.680 dS·m-1. Results showed that water and salt stresses decreased the cross-sectional stem area and xylem vessel diameter by 22.0%-40.7% and 10.0%-18.3%, respectively, and reduced the specific hydraulic conductivity of stem and the hydraulic conductivity of peduncle by 8.8%-41.1% and 12.9%-28.4%, respectively. Those changes inhibited plant growth and reduced aboveground fresh weight, fruit size, fresh weight and water content, with a more pronounced negative effect in the medium-fruited tomato. More-over, fruit water content was positively correlated with the specific hydraulic conductivity of stem and peduncle. In conclusion, water and salt stresses would inhibit plant growht, fruit fresh weight, and consequently tomato yield, due to their negative effects on xylem hydraulic properties of the tomato plant. Medium-fruited tomatoes are more susceptible to water and salt stresses than cherry tomatoes.

LSD1 inhibitors from the roots of Pueraria lobata.

One new 6a,11a-dehydropterocarpan derivative, 6-O-methyl-anhydrotuberosin (1), one new 6a-hydroxypterocarpan, (6aR,11aR,11bR)-hydroxytuberosone (7), and seven known compounds including two 6a,11a-dehydropterocarpans (2 and 4), two coumestans (3 and 5), one isoflavonoid (6) and two other phenolic compounds (8 and 9) were isolated from the roots of Pueraria lobata. The structures of the isolated compounds were elucidated with spectroscopic and spectrometric methods (1 D and 2DNMR, HRESIMS). Compounds 1, 2, 4-5 showed potent LSD1 inhibitory activities with IC50 values ranging from 1.73 to 4.99 µM. Furthermore, compound 2 showed potent cytotoxicity against gastric cancer cell lines MGC-803 and BGC-823, and lung cancer cell lines H1299 and H460.

Feasibility of modified endoscopic anti-reflux mucosectomy for refractory gastroesophageal reflux disease with moderate hiatus hernia / 中华消化内镜杂志

Objective:To evaluate the efficiency and safety of modified endoscopic anti-reflux mucosectomy (ARMS) for refractory gastroesophageal reflux disease (rGERD) with moderate hiatus hernia.Methods:A total of 30 patients with rGERD with moderate hiatus hernia (3-5 cm) diagnosed at the Department of Gastroenterology of Northern Jiangsu People's Hospital from June 2017 to June 2020 were randomly divided into 2/3 circumferential mucosal resection group ( n=15) and 3/4 circumferential mucosal resection group ( n=15) using random number table method, and received modified ARMS of the corresponding mucosal resection range. The GERD symptoms, esophagitis under endoscopy, 24 h pH results, and lower esophageal sphincter (LES) resting pressure were compared before and after the procedure. The therapeutic effect and complications of the two groups were analyzed. Results:In 2/3 resection group, the GERD questionnaire scores (9.53±0.36 VS 11.93±0.57, t=6.874, P<0.001), acid exposure time (19.81%±1.72% VS 31.45%±2.78%, t=8.020, P<0.001) and the DeMeester score based on 24 h esophageal pH monitoring (40.98±4.55 VS 55.33±5.65, t=6.408, P<0.001) at 6 months after the treatment showed a significant reduction compared with those before. In 3/4 resection group, the GERD questionnaire scores (9.0±0.57 VS 12.47±0.68, t=8.650, P<0.001), acid exposure time (20.07%±2.19% VS 29.96%±3.00%, t=7.444, P<0.001) and the DeMeester score (33.67±3.47 VS 51.17±6.03, t=4.973, P<0.001) at 6 months after the treatment were lower than those before. There was no significant difference in the GERD questionnaire scores ( t=0.790, P=0.436), acid exposure time ( t=0.093, P=0.926) or the DeMeester score ( t=1.278, P=0.212) between the two groups at 6 months after treatment. In the two groups, there was no significant difference in the ratio of esophagitis grade C and D (10/15 VS 5/15, χ2=3.894, P=0.063; 8/15 VS 4/15, χ2=2.778, P=0.125) or LES resting pressure [3.29 (2.66,8.29) mmHg VS 3.98 (3.67,9.43) mmHg, P=0.334;5.78 (1.9,8.46) mmHg VS 5.88 (3.28,8.99) mmHg, P=0.125] before and after the treatment. No postoperative delayed bleeding or perforation was observed. The incidence of postoperative esophageal stenosis of 2/3 resection group was lower than that of the other group (1/15 VS 6/15, χ2=4.658, P=0.021). Conclusion:Modified ARMS is effective for controlling reflux symptoms and esophageal acid exposure in rGRED patients with moderate hiatus hernia (3-5 cm), but cannot significantly increase the postoperative resting pressure of LES. Compared with 3/4 circumferential mucosal resection, 2/3 circumferential mucosal resection can reduce the incidence of postoperative esophageal stenosis.

Comparison of clinical efficacy of intravitreal injection of Conbercept and Aflibercept in the treatment of wet age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the clinical efficacy of conbercept and aflibercept in the treatment of wet age-related macular degeneration(wARMD)based on 4 consecutive intravitreal injections.METHODS: The clinical data of 108 patients(108 eyes)who were diagnosed as wARMD and treated with intravitreal injection at our hospital from January 2019 to January 2021 were retrospectively analyzed. They were divided into conbercept group(54 cases, 54 eyes)and aflibercept group(54 cases, 54 eyes)according to the different injectable drugs. All patients received intravitreal injection once a month, with four consecutive injections. Follow up for 12mo to observe best corrected visual acuity(BCVA), central macular thickness(CMT), complications and recurrence before and after injection.RESULTS: BCVA and CMT of patients in the two groups at 1, 2, 5 and 8mo after injection had no between-group differences(P&#x0026;#x003E;0.05), but both were significantly improved compared with those before injection(P&#x0026;#x003C;0.05). By the end of follow-up, conjunctival hemorrhage occurred in 2 eyes of the conbercept group at the early stage, and increased intraocular pressure and conjunctival hemorrhage occurred respectively in 2 eyes of the aflibercept group. There were no serious complications related to drug injection such as retinal detachment, complicated cataract, endophthalmitis and retinal pigment epithelial tear in the two groups, and there was no difference in the recurrence rate between the two groups(7% vs. 6%, P=1.000).CONCLUSION: On the basis of continuous 4 times of intravitreal injection, both conbercept and aflibercept are safe and effective in the treatment of wARMD, and the efficacy is even.

Meta-analysis of the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates / 中华儿科杂志

Objective: To systematically evaluate the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates. Methods: Eight databases in either Chinese or English, including PubMed, the Cochrane Library, Embase, Medline, Scopus, CNKI, Wanfang and VIP, were searched to extract the studies on the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates published from the establishment of each database to December 2022. The Meta-analysis was performed using Stata 14.0 statistical software. Results: A total of 9 studies were included in this Meta-analysis, including 6 retrospective cohort studies, 2 prospective cohort studies and 1 randomized controlled trial (RCT) study, involving 9 143 premature infants. The Meta-analysis showed that prenatal steroid exposure increased the risk of late preterm neonatal hypoglycemia (RR=1.55, 95%CI 1.25-1.91, P<0.001). The similar correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates was all found in the following subgroups: North America (RR=1.57, 95%CI 1.37-1.80, P<0.001), enrolling pregnant women with gestational diabetes (RR=1.62, 95%CI 1.26-2.08, P<0.001), A-grade literature quality (RR=1.43, 95%CI 1.14-1.79, P=0.002), criteria for hypoglycemia ≤40 mg/dl (1 mg/dl=0.056 mmol/L, RR=1.49, 95%CI 1.28-1.73, P<0.001), sample size of 501-1 500 (RR=1.69, 95%CI 1.19-2.40, P=0.003) and >1 500 (RR=1.65, 95%CI 1.48-1.83, P<0.001), steroid injection dosage and frequency of 12 mg 2 times (RR=1.66, 95%CI 1.50-1.84, P<0.001), the time interval from antenatal corticosteroid administration to delivery of 24-47 h (RR=1.98, 95%CI 1.26-3.10, P=0.003), unadjusted gestational age (RR=1.78, 95%CI 1.02-3.10,P=0.043) and unadjusted birth weight (RR=1.80, 95%CI 1.22-2.66, P=0.003). Meta-regression results showed that steroid injection frequency and dose were the main sources of high heterogeneity among studies (P=0.030). Conclusion: Prenatal steroid exposure may be a risk factor for hypoglycemia in late preterm neonates.

An autophagy-related gene prognostic index predicting biochemical recurrence, metastasis, and drug resistance for prostate cancer / 亚洲男科学杂志(英文版)

Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23-9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89-26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07-2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16-2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = -0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.

Identification of senescence-related molecular subtypes and key genes for prostate cancer / 亚洲男科学杂志(英文版)

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), prostate androgen-regulated mucin-like protein 1 (PARM1), leucine zipper protein 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix protein (COMP), vestigial-like family member 3 (VGLL3), apolipoprotein E (APOE), and aldehyde dehydrogenase 2 family member (ALDH2), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96, hepatitis A virus cellular receptor 2 (HAVCR2), and neuropilin 1 (NRP1) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 (TNFSF18) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.

Circadian rhythm in prostate cancer: time to take notice of the clock / 亚洲男科学杂志(英文版)

The circadian clock is an evolutionary molecular product that is associated with better adaptation to changes in the external environment. Disruption of the circadian rhythm plays a critical role in tumorigenesis of many kinds of cancers, including prostate cancer (PCa). Integrating circadian rhythm into PCa research not only brings a closer understanding of the mechanisms of PCa but also provides new and effective options for the precise treatment of patients with PCa. This review begins with patterns of the circadian clock, highlights the role of the disruption of circadian rhythms in PCa at the epidemiological and molecular levels, and discusses possible new approaches to PCa therapy that target the circadian clock.