Search

Abstract Yaks live in the Qinghai-Tibet Plateau for a long time where oxygen is scarce, but can ensure the smooth development of testis and spermatogenesis. The key lies in the functional regulation of the Sertoli cells under hypoxia. In this study, we sequenced yak Sertoli cells cultured in normal oxygen concentration (Normoxia) and treated with low oxygen concentration (Hypoxia) by whole transcriptomics, and screened out 194 differentially expressed mRNAs (DEmRNAs), 934 differentially expressed LncRNAs (DELncRNAs) and 129 differentially expressed miRNAs (DEmiRNAs). GO and KEGG analysis showed that these differential genes were mainly concentrated in PI3K-AKT, MAPK, RAS, and other signaling pathways, and were associated with glucose metabolism, tight junction, steroid hormone synthesis, cell fusion, and immunity of yak Sertoli cells. We constructed the gene interaction network of yak Sertoli cells in hypoxia and screened out the relationship pairs related to glucose metabolism and tight junction. The results suggested that the changes in energy metabolism, tight junction, and immune regulation of yak Sertoli cells under hypoxia might provide favorable conditions for spermatogenesis. This study provides data for further study on the role of non-coding RNA in testis development and spermatogenesis of yak.

Abstract Background The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as a novel composite lipid indicator for atherosclerosis. However, the association between NHHR and mortality in patients with diabetes or prediabetes remains unclear. Consequently, the objective of this study was to investigate the relationship between NHHR and both all-cause and cardiovascular mortality in US adults with diabetes or prediabetes. Methods This study included 12,578 adult participants with diabetes or prediabetes from the US National Health and Nutrition Examination Survey (1999–2018). Mortality outcomes were ascertained by linking to the National Death Index (NDI) record up to December 31, 2019. We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR and all-cause and cardiovascular mortality. A segmented Cox proportional hazards model was used for evaluating threshold effects. Furthermore, a competing risks analysis was performed to explore the relationship between NHHR and cardiovascular mortality. Results During a median follow-up period of 8.08 years, 2403 participants encountered all-cause mortality, with 662 of them specifically succumbing to cardiovascular mortality. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for cardiovascular mortality. The analysis of threshold effects revealed that the inflection points for NHHR and all-cause and cardiovascular mortality were 2.72 and 2.83, respectively. Specifically, when the baseline NHHR was below the inflection points, a negative correlation was observed between NHHR and both all-cause mortality (HR: 0.76, 95% CI: 0.68–0.85) and cardiovascular mortality (HR: 0.70, 95% CI: 0.57–0.85). Conversely, when the baseline NHHR exceeded the inflection points, a positive correlation was observed between NHHR and both all-cause mortality (HR: 1.11, 95% CI: 1.06–1.16) and cardiovascular mortality (HR: 1.08, 95% CI: 1.00–1.16). Conclusions Among US adults with diabetes or prediabetes, a U-shaped association was observed between NHHR and all-cause mortality, whereas an L-shaped association was identified with cardiovascular mortality. The inflection points for all-cause and cardiovascular mortality were 2.72 and 2.83, respectively.

Context: COVID-19 is a novel coronavirus pneumonia, which is related to abnormal liver function. Thus, it is important to explore the occurrences and causes of abnormal liver function with COVID-19. Methods: We chose 109 patients with COVID-19 in 2020 and studied the relationship between gender, age, basic diseases, antiviral drug treatment, disease classification, and abnormal liver function, and analyzed the causes of abnormal liver function in patients with COVID-19 Results: Among patients, 46 (42.20%) had abnormal liver function at admission; 37 (80.43%) had mild abnormal liver function; and 9 (19.57%) had severe liver function. Compared with other age groups, the abnormal rate of serum ALP in the group younger than 21 years old were the highest (P < 0.05). The abnormal rates and concentrations of serum ALT, AST and γ-GT in the male groups were higher than in female groups (P < 0.05), basic disease group were higher than those in the non-basic disease group (P < 0.05). Serum γ-GT concentration after 1 week of antiviral treatment was higher than that before treatment (P < 0.05). The abnormal rate of ALT and AST at discharge was lower than that after antiviral treatment for 1 week (P < 0.05). Serum TB and AST concentrations at discharge were lower than those before treatment (P < 0.05). Serum AST and γ-GT concentrations in severe/critical type group were higher than those in mild or ordinary type group (P < 0.05) Conclusions: In this study, we found male sex, basic diseases, antiviral drugs, and severe/critical types are related to the occurrence of abnormal liver function in COVID-19 patients.

Abstract Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers.

Abstract Background Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear. This study aims to clarify the role of REV1 in lung cancer radioresistance, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of this new target for lung cancer treatment. Methods The effect of targeting REV1 on the radiosensitivity was verified by in vivo and in vitro experiments. RNA sequencing (RNA-seq) combined with nontargeted metabolomics analysis was used to explore the downstream targets of REV1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify the content of specific amino acids. The coimmunoprecipitation (co-IP) and GST pull-down assays were used to validate the interaction between proteins. A ubiquitination library screening system was constructed to investigate the regulatory proteins upstream of REV1. Results Targeting REV1 could enhance the radiosensitivity in vivo, while this effect was not obvious in vitro. RNA sequencing combined with nontargeted metabolomics revealed that the difference result was related to metabolism, and that the expression of glycine, serine, and threonine (Gly/Ser/Thr) metabolism signaling pathways was downregulated following REV1 knockdown. LC-MS/MS demonstrated that REV1 knockdown results in reduced levels of these three amino acids and that cystathionine γ-lyase (CTH) was the key to its function. REV1 enhances the interaction of CTH with the E3 ubiquitin ligase Rad18 and promotes ubiquitination degradation of CTH by Rad18. Screening of the ubiquitination compound library revealed that the ubiquitin-specific peptidase 9 X-linked (USP9X) is the upstream regulatory protein of REV1 by the ubiquitin-proteasome system, which remodels the intracellular Gly/Ser/Thr metabolism. Conclusion USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance. A novel inhibitor of REV1, JH-RE-06, was shown to enhance lung cancer cell radiosensitivity, with good prospects for clinical translation.

Background Cushing’s syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters.Methods A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD.Results A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p

Objectives: The Albumin-Bilirubin (ALBI) score has been widely used to assess the prognosis in patients with cirrhosis and hepatocellular carcinoma. This study aimed to analyze the relationship between ALBI score and all-cause mortality in patients with hepatitis B virus (HBV) infection in general. Methods: Patients aged ≥ 18 years with previous or current HBV infection from the National Health and Nutrition Examination Survey (NHANES) in the United States between 1999 and 2018 were enrolled in this retrospective cohort study. Weight univariate and multivariate Cox regression models were used to assess the relationship between ALBI score and all-cause mortality. The area under the receiver operating characteristic curve (AUC) was utilized to assess the predictive effect of ALBI score for all-cause mortality. Results: A total of 3,666 patients were included, of whom 925 (23.53 %) patients died. Compared with ALBI score ≤ -2.6, HBV-infected patients with ALBI score > -2.6 [hazard ratio (HR) = 1.75; 95 % confidence interval (CI): 1.43–2.14] were corrected with a higher all-cause mortality risk after adjusting for confounders. Stratified analyses showed that higher ALBI score was related to a higher risk of all-cause mortality in different patients with HBV infection (All P

This article presents a comprehensive review of the factors influencing the efficacy of mesenchymal stem cells (MSCs) transplantation and its association with platelet concentrates (PCs). It focuses on investigating the impact of PCs’ composition, the age and health status of platelet donors, application methods, and environmental factors on the outcomes of relevant treatments. In addition, it delves into the strategies and mechanisms for optimizing MSCs transplantation with PCs, encompassing preconditioning and combined therapies. Furthermore, it provides an in-depth exploration of the signaling pathways and proteomic characteristics associated with preconditioning and emphasizes the efficacy and specific effects of combined therapy. The article also introduces the latest advancements in the application of biomaterials for optimizing regenerative medical strategies, stimulating scholarly discourse on this subject. Through this comprehensive review, the primary goal is to facilitate a more profound comprehension of the factors influencing treatment outcomes, as well as the strategies and mechanisms for optimizing MSCs transplantation and the application of biomaterials in regenerative medicine, offering theoretical guidance and practical references for related research and clinical practice.

The aim of this experiment was to investigate the effects of exogenous sprays of 5-aminolevulinic acid (5-ALA) and 2-Diethylaminoethyl hexanoate (DTA-6) on the growth and salt tolerance of rice (Oryza sativa L.) seedlings. This study was conducted in a solar greenhouse at Guangdong Ocean University, where ‘Huanghuazhan’ was selected as the test material, and 40 mg/L 5-ALA and 30 mg/L DTA-6 were applied as foliar sprays at the three-leaf-one-heart stage of rice, followed by treatment with 0.3% NaCl (W/W) 24 h later. A total of six treatments were set up as follows: (1) CK: control, (2) A: 40 mg⋅ L−1 5-ALA, (3) D: 30 mg⋅ L−1 DTA-6, (4) S: 0.3% NaCl, (5) AS: 40 mg⋅ L−1 5-ALA + 0.3% NaCl, and (6) DS: 30 mg⋅ L−1 DTA-6+0.3% NaCl. Samples were taken at 1, 4, 7, 10, and 13 d after NaCl treatment to determine the morphology and physiological and biochemical indices of rice roots. The results showed that NaCl stress significantly inhibited rice growth; disrupted the antioxidant system; increased the rates of malondialdehyde, hydrogen peroxide, and superoxide anion production; and affected the content of related hormones. Malondialdehyde content, hydrogen peroxide content, and superoxide anion production rate significantly increased from 12.57% to 21.82%, 18.12% to 63.10%, and 7.17% to 56.20%, respectively, in the S treatment group compared to the CK group. Under salt stress, foliar sprays of both 5-ALA and DTA-6 increased antioxidant enzyme activities and osmoregulatory substance content; expanded non-enzymatic antioxidant AsA and GSH content; reduced reactive oxygen species (ROS) accumulation; lowered malondialdehyde content; increased endogenous hormones GA3, JA, IAA, SA, and ZR content; and lowered ABA content in the rice root system. The MDA, H2O2, and O2− contents were reduced from 35.64% to 56.92%, 22.30% to 53.47%, and 7.06% to 20.01%, respectively, in the AS treatment group compared with the S treatment group. In the DS treatment group, the MDA, H2O2, and O2− contents were reduced from 24.60% to 51.09%, 12.14% to 59.05%, and 12.70% to 45.20%. In summary, NaCl stress exerted an inhibitory effect on the rice root system, both foliar sprays of 5-ALA and DTA-6 alleviated damage from NaCl stress on the rice root system, and the effect of 5-ALA was better than that of DTA-6.

Abstract Gastric cancer (GC) remains the third leading cause of cancer-related mortality in the world, and ninety-five percent of GC are stomach adenocarcinomas (STAD). The active ingredients of Croci Stigma, such as Isorhamnetin, Crocin, Crocetin and Kaempferol, all have antitumor activity. However, their chemical and pharmacological profiles remain to be elusive. In this study, network pharmacology was used to characterize the action mechanism of Croci Stigma. All compounds were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database, and active ingredients were selected by their oral bioavailability and drug-likeness index. The targets of Croci Stigma active ingredients were obtained from the traditional Chinese medicine integrated database (TCMID), whereas the related genes of STAD were obtained from DisGeNET platform. Cytoscape was used to undertake visual analyses of the Drug Ingredients–Gene Symbols–Disease (I–G–D) network, and 2 core genes including MAPK14, ERBB3 were obtained, which are the predicted targets of isorhamnetin (IH) and quercetin, respectively. Data analysis from TCGA platform showed that MAPK14 and ERBB3 all upregulated in STAD patients, but only the effect of MAPK14 expression on STAD patients’ survival was significant. Molecular docking showed that IH might affect the function of MAPK14 protein, and then the underlying action mechanisms of IH on STAD were experimentally validated using human gastric cancer cell line, HGC-27 cells. The results showed that IH can inhibit cell proliferation, migration, clonal formation, and arrest cell cycle, but promote the apoptosis of HGC-27 cells. qRT-PCR data demonstrated that IH downregulated the MAPK14 mRNA expression and EMT related genes. WB results showed that IH regulates MAPK/mTOR signaling pathway. These findings suggest that IH has the therapeutic potential for the treatment of STAD.

In recent years, China attaches great importance to the prevention and treatment of rare diseases. As one of the representative diseases of rare diseases, management of Hemophilia has made great progress in China. From 1986 to 1989, the National Hemophilia Cooperative Group conducted China's hemophilia epidemiological survey according to the unified method and standard, and the results showed that the prevalence of hemophilia was 2.73/100 000, and there was no statistical difference in prevalence among different regions. In 2014, Meta-analysis showed that the prevalence of hemophilia in China was 2.8/100 000, and in 2018, based on the data of the urban population of Tianjin, the local prevalence of hemophilia was estimated to be 3.09/100 000. With the comprehensive promotion of the construction of hemophilia hierarchical diagnosis and treatment system, China requires that hospitals applying for hemophilia comprehensive management centers and diagnosis and treatment centers must be able to independently carry out screening tests and confirmatory tests related to hemophilia diagnosis. For diagnosis of hemophilia, most laboratories in China usually adopt the one-stage method (coagulation method) based on the activated partial thromboplastin time (APTT) for the determination of coagulation factor activity, but it should be noted that more than two activity detection methods are required for some special types of hemophilia. The types of each mutation in the F8 gene of patients in China are similar to those reported in international data, and the mutations in the F9 gene of our patients are mainly single base point mutations, with no mutation hotspots found. As of June 2023, a total of more than 40 000 cases with inherited bleeding disorders registered in 261 centers in China (including hemophilia), through the National Hemophilia Registration System. The history of hemophilia treatment in China has been explored through inadequate on-demand and low-dose prophylaxis, and is now moving towards higher-dose prophylaxis and individualized prophylaxis with higher efficacy. Based on the above registry data and literature, this report comprehensively summarizes the progress of basic and clinical research and medical protection in the field of hemophilia in China, and analyzes the shortcomings for further improvement of hemophilia diagnosis and treatment in China.

Abstract An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Dihydroflavonol 4-reductase (DFR; EC1.1.1.219) is an important rate-limiting enzyme in the plant flavonoid pathway toward both anthocyanins and proanthocyanidins. Although DFR genes have been isolated from multiple plants and their functions have been well characterized in some plants, little is known about DFRs in Solanaceae species. Therefore, in this study, we performed genome-wide analysis and identified 6, 5, 4, 5, 5, 6, 6 and 5 DFR gene family members in eight Solanaceae species (S. lycopersicum, S. pennellii, S. tuberosum, S. melongena, C. annuum, N. tabacum, P. inflata, and P. axillaris) respectively. The putative DFR genes were systematically identified using bioinformatics to predict their protein properties, cellular location, phylogenetic relationships, gene structure, conserved motifs, and cis-acting elements in the promoters. Furthermore, quantitative real-time PCR (qRT-PCR) was used to identify the expression pattern of DFRs in tomato. We classified all DFRs into five groups based on their phylogenetic features. Sequence analysis showed that all encoded DFR protein sequences possess a highly conserved NAD-dependent epimerase/dehydratase. In addition, almost all the members of each group displayed similar gene structures and motif distributions, which might be related to their identical executive functions. All 42 DFRs possess a series of light-responsive, phytohormone-responsive, MYB-responsive, stress-responsive, and tissue-specific expression-related cis-elements in the promoter sequences. qRT-PCR analysis showed that tomato DFRs were expressed in many different organs. This study will provide a theoretical basis for further investigation of the function of DFRs in Solanaceae.

Background To clarify clinical importance of serum CA19-9, CA-125, and plasma D-dimer (D-D) levels in detecting spontaneously ruptured ovarian endometriosis (OE).Materials and Methods We retrospectively examined 173 patients with endometriosis out of 735 cases of OE between 2013 and 2019. Among these, 21 cases were diagnosed as “spontaneously ruptured” after surgery, while the remaining cases were unruptured. Venous blood was collected pre-operatively to detect CA19-9, CA-125, and D-D levels. A receiver operating characteristic curve analysis was applied to test clinical value of each marker.Results Among the 21 patients with ruptured OE, 16 had a history of pelvic cysts, 19 claimed sudden onsets of lower abdominal pain, and fluid accumulation were detected in cul-de-sac in only six participants by ultrasound. For serological investigation, both CA19-9 and D-D were significantly elevated in the ruptured OE group (343.09 ± 367.67 U/ml vs. 36.84 ± 40.01 U/ml, 3.39 ± 4.90 mg/L vs. 0.43 ± 0.29 mg/L, both p

Abstract Immune checkpoint inhibitors (ICIs) change the prognosis of many cancer patients. With the increasing use of ICIs, immune-related adverse events are occurring, including acute kidney injury (AKI). This study aimed to assess the incidence of AKI during ICI treatment and its risk factors and impact on mortality. Patients treated with ICIs at the First Medical Center of the Chinese PLA General Hospital from January 1, 2014, to December 30, 2019, were consecutively enrolled, and risk factors affecting AKI development in patients treated with ICIs were analyzed using univariate and multivariate logistic regression. Medical record surveys and telephone inquiry were used for follow-up, and Kaplan–Meier survival analysis and Cox regression were used to analyze independent risk factors for death. Among 1615 patients, 114 (7.1%) had AKI. Multivariate logistic regression analysis showed that anemia, Alb

Hemophilia is an inherited bleeding disorder and a type of rare disease that is hereditary, lifelong and disabling. The establishment of a National Hemophilia Registry is foundational to treating hemophilia. The initial registry of hemophilia in China was first established using the paper form in 1996 and upgraded to online system in 2007. Following the China's Ministry of Health's decision to establish a national hemophilia case information management system in 2009, China has officially established a National Hemophilia Registry based on previous work. More than 200 hospitals have been involved in this work. The National Hemophilia Registry also provides the basis for the study of hemophilia epidemiology, disease characteristics and related policy formulation.

Hemophilia B is a genetic disorder caused by coagulation factor Ⅸ(FⅨ) deficiency, mainly manifesting as joint, muscle and deep tissue bleeding. Hemophilia pseudotumor is a mass formed by soft tissue liquefaction and necrosis caused by repeated bleeding. Most pseudotumors occur in the bone and muscle. We report a case of hemophilia B with pseudotumor formation in the pelvis and abdomen, where lesion location is relatively rare. After active and effective hemostasis, the patient's hematuria symptom gradually improved. This case suggests that early and timely hemostatic treatment is crucial for patients with hemophilia.

Objective To explore the regulation and clinical significance of miR-486 in patients with sleep apnea-hypopnea syndrome (OSAHS) and secondary polycythemia. Methods Twenty-five healthy subjects who visited Outpatient Department and Health Examination Center of Qinghai Provincial People's Hospital from May 2020 to April 2021 were elected as the control group, and thirty cases of OSAHS patients with secondary polycythemia diagnosed by polysomnography and laboratory examination were selected as the OSAHS+SP group. Peripheral blood mononuclear cell (PBMC) miR-486, Sirt1 and GATA-1 expression were measured by RT-qPCR, and the concen- tration of plasma Sirt1 was measured by ELISA. In addition, RT-qPCR was used for the miR-486,Sirt1 or expression in K562 cells after the IH treatment, miR-486 over-expression or miR-486 inhibition. The Sirt1 expression was measured by RT-qPCR and Western blot. GATA-1 mRNA expression was checked by RT-qPCR in Sirt1 inhibited K562 cells. Results 1)Body mass index, red blood cells, hemoglobin (HB) and sleep apnea index(AHI) in OSAHS+SP group were significantly higher than those of control group(P＜0.001); 2)The expression of miR-486, Sirt1, and GATA-1 were significantly increased and plasma Sirt1 concentration was significantly decreased in OSAHS+SP patients PBMC(P＜0.001); 3)PBMC miR-486 and GATA-1 expression were positively correlated with AHI and HB(P＜0.05). PBMC Sirt1 expression and plasma Sirt1 level were negatively correlated with plasma Sirt1 concentration in OSAHS+SP group(P＜0.05); 4)IH promoted the expression of miR-486(P＜0.01) and inhibited Sirt1 expression in K562 cells(P＜0.01). RT-qPCR and Western blot showed that over-expression of miR-486 decreased Sirt1 expression(P＜0.01), whereas miR-486 inhibition increased the expression of Sirt1(P＜0.001). The GATA-1 expression was increased after the inhibition of Sirt1(P＜0.01). Conclusions miR-486 regulates the biological process of OSAHS patients with secondary polycythemia by targeting at Sirt1.

Introduction Neoadjuvant chemotherapy (NACT) is an emerging approach for locally advanced cervical cancer (LACC). However, the clinical response and postoperative adjuvant radiation or chemoradiation trimodality treatment resulted in controversy. PD-1 inhibitors have shown promising role in recurrent or metastatic cervical cancer, and there is preclinical evidence of the activation and synergistic effects of NACT on PD-1 inhibitors. This study aims to evaluate the efficacy and safety of the preoperative PD-1 inhibitor camrelizumab combined with NACT for LACC.Methods and analysis The study is designed as a multicentre, open-label, single-arm, prospective phase II study. A total of 82 patients will receive neoadjuvant chemo-immunotherapy, defined as one cycle of cisplatin (75–80 mg/m2, intravenously) plus nab-paclitaxel (260 mg/m2, intravenously) NACT and subsequent two cycles of camrelizumab (200 mg, intravenously) combined with NACT. After neoadjuvant chemo-immunotherapy, patients exhibiting complete response and partial response will undergo radical surgery and subsequent adjuvant therapy. In contrast, patients with stable disease and progressive disease will transfer to concurrent chemoradiotherapy (CCRT). Following surgery, patients will receive adjuvant CCRT or radiotherapy. The primary endpoint is the objective response rate. The secondary endpoints are the pathological complete response, patients requiring postoperative adjuvant therapy, safety of neoadjuvant chemo-immunotherapy, surgical complication, event-free survival, and overall survival. An additional aim is to dynamically evaluate peripheral immune responses and local immunological microenvironments and their association with neoadjuvant immunotherapy.Ethics and dissemination This trial was approved by the Medical Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (S2020-112). This study is among the first to evaluate the efficacy and safety of neoadjuvant chemo-immunotherapy in LACC. The findings of this research will promote neoadjuvant anti-PD-1 immunotherapy with radical surgery as a new therapeutic strategy.Trial registration number ClinicalTrials.gov Registry (NCT04516616).

Summary: Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of chemotherapy and remains a huge clinical challenge. Here, we explore the role of microcirculation hypoxia induced by neutrophil extracellular traps (NETs) in the development of CIPN and look for potential treatment. Methods: The expression of NETs in plasma and dorsal root ganglion (DRG) are examined by ELISA, IHC, IF and Western blotting. IVIS Spectrum imaging and Laser Doppler Flow Metry are applied to explore the microcirculation hypoxia induced by NETs in the development of CIPN. Stroke Homing peptide (SHp)-guided deoxyribonuclease 1 (DNase1) is used to degrade NETs. Findings: The level of NETs in patients received chemotherapy increases significantly. And NETs accumulate in the DRG and limbs in CIPN mice. It leads to disturbed microcirculation and ischemic status in limbs and sciatic nerves treated with oxaliplatin (L-OHP). Furthermore, targeting NETs with DNase1 significantly reduces the chemotherapy-induced mechanical hyperalgesia. The pharmacological or genetic inhibition on myeloperoxidase (MPO) or peptidyl arginine deiminase-4 (PAD4) dramatically improves microcirculation disturbance caused by L-OHP and prevents the development of CIPN in mice. Interpretation: In addition to uncovering the role of NETs as a key element in the development of CIPN, our finding provides a potential therapeutic strategy that targeted degradation of NETs by SHp-guided DNase1 could be an effective treatment for CIPN. Funding: This study was funded by the National Natural Science Foundation of China 81870870, 81971047, 81773798, 82271252; Natural Science Foundation of Jiangsu Province BK20191253; Major Project of “Science and Technology Innovation Fund” of Nanjing Medical University 2017NJMUCX004; Key R&D Program (Social Development) Project of Jiangsu Province BE2019732; Nanjing Special Fund for Health Science and Technology Development YKK19170.

BackgroundIschemic heart disease (IHD) has a high mortality in the population. Although serum creatinine (Cr) and serum total bilirubin (TBil) are rapid and readily available biomarkers in routine blood tests, there is a lack of literature on the prognostic value of combined Cr and TBil tests for IHD. This study aimed to evaluate a combined equation based on Cr and TBil to predict the long-term risk of death in IHD and to find indicators sensitive to the prognosis of IHD patients.MethodIn this study, 2625 patients with IHD were included, and the combined value and combined equations of Cr and TBil were obtained by logistic regression analysis based on Cr and TBil collected at the time of admission. Patients were divided into four groups according to the quartiles of the combined value. COX proportional hazard regression model was used to analyze the risk factors for long-term death in IHD patients. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic effect of Cr, TBil and combined value on long-term death events.ResultsLogistic regression analysis was performed for long-term death events with Cr and TBil as independent variables, and the logit regression model was Logit(P) = 0.0129×TBil+0.007×Cr-0.417. Multifactorial Cox regression analysis showed that high values of the equation were independent risk factors for long-term death events (all-cause death: HR 1.457, 95% CI 1.256-1.689, PConclusionCombined Cr and TBil assay is superior to single biomarkers for predicting long-term death in patients with IHD. High values of the equation are independent predictors of long-term death and can be used to identify patients at high risk for IHD.

The present study aimed to compare the efficacy of different exercises on systolic blood pressure (SBP), diastolic blood pressure (DBP), and aortic pulse wave velocity (PWV) in postmenopausal women. We searched the China National Knowledge Infrastructure (CNKI), Wanfang database, Web of Science, PubMed, and Cochrane library databases, up to July 2022. The randomized controlled trials (RCTs) were selected following the inclusion criteria. We assessed study quality with the PEDro scale. The Stata software was used for statistical analysis. Twenty-three papers (26 RCTs) and 729 participants were included. Meta-analysis demonstrated that exercise decreased SBP (WMD = −6.74 mmHg, 95%CI: −9.08, −4.41, p = 0.000), DBP (WMD = −4.13 mmHg, 95%CI: −5.78, −2.48, p = 0.000) and aortic PWV (WMD = −0.79 m/s, 95%CI: −1.02, −0.56, p = 0.000). Aerobic exercise can significantly decrease SBP (WMD = −7.97 mmHg, 95%CI: −12.99, −2.60, p = 0.003) and DBP (WMD = −5.97 mmHg, 95%CI: −8.55, −3.39, p = 0.000). Resistance exercise can significantly decrease SBP (WMD = −5.62 mmHg, 95%CI: −9.00, −2.23, p = 0.001), DBP (WMD = −1.87 mmHg, 95%CI: −2.75, −0.99, p = 0.000) and aortic PWV (WMD = −0.67 m/s，95%CI: −0.98, −0.36, p = 0.000). Combined aerobic and resistance exercise can significantly decrease SBP (WMD = −5.42 mmHg, 95%CI: −10.17, −0.68, p = 0.025). The efficacy of mind-body exercise (Tai Chi/Yoga) on SBP, DBP, and aortic PWV were not obvious (p > 0.05). Exercise significantly improved SBP, DBP, and aortic PWV in postmenopausal women. Aerobic exercise decreased SBP and DBP. Resistance exercise decreased SBP, DBP, and aortic PWV. Additionally, further research is required to confirm the efficacy of mind-body exercise (Tai Chi/Yoga) on blood pressure and arterial stiffness.

Abstract COPD is the fourth leading cause of mortality, and is predicted to be the third leading cause of death worldwide by 2020. But few studies on Tibetan COPD of China. This study identifies distinctive miRNA signatures in Tibetan COPD patients from Tibetan healthy subjects that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. In this study, a total of 210 differentially expressed miRNAs were screened. Analysis of the functions of target genes of differentially expressed miRNAs via GO enrichment analysis revealed that they mainly influenced guanyl-nucleotide exchange factor activity, cell morphogenesis and the positive regulation of GTPase activity. KEGG pathway enrichment analysis showed that these target genes were mainly enriched in signaling by NGF, Axon guidance, developmental biology, ubiquitin mediated proteolysis, and PDGF signaling pathways. MiR-106-5p and miR-486-5p expression was validated in the complete cohort. Age, plasma miR-106-5p, miR-486-5p, SP-D protein levels, and SP-D mRNA level were also determined to be correlated with FEV1%Pred, and may as the risk factors of Tibetan COPD. The combination of plasma miR-106-5p, miR-486-5p and SP-D mRNA expression may be the best model to assist the diagnosis of Tibetan COPD.

Abstract. Background:. Minimal change nephropathy (MCD) is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury (AKI). This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome. Methods:. Patients from Chinese People's Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1, 2013 to December 31, 2017. Patients diagnosed with membranous nephropathy (MN) by renal biopsy from January 1, 2013 to December 31, 2017 are included as a control population. We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups. We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis. Results:. A total of 367 patients with MCD were included in the analysis, with a sex ratio of 1.46: 1 (male: female) and an age range of 6 to 77 years. Among all the patients, 109 developed AKI (29.7%), and of these patients, 85 were male (78.0%). In the 586 patients with MN, 27 (4.6%) patients developed AKI. The percentage of AKI in MCD patients was significantly higher than that in MN patients (χ2 = 41.063, P

Purpose: To evaluate the effectiveness of donor in vitro fertilization (IVF-D) and donor artificial insemination (AI-D) in clinical outcomes, risks, and costs. Methods: This study analyzed the cycle changes and clinical outcomes in 20,910 IVF-D and 16,850 AI-D cycles between 2013 and 2021 in the Reproductive and Genetic Hospital of CITIC-Xiangya. A cost-effectiveness analysis was performed to evaluate the costs per couple and per live birth cycle in the two treatment groups. Results: IVF-D had higher pregnancy and live birth rates than AI-D (p < 0.001). The cumulative pregnancy and live birth rates for three AI-D cycles were 41.01% and 32.42%, respectively, higher than the rates for one or two AI-D cycles. The multiple birth and birth defect rate of AI-D was lower than that of IVF-D significantly. IVF-D mean cost per couple was higher than that of AI-D (CNY32,575 vs. CNY11,062, p < 0.001), with a mean cost difference of CNY21,513 (95% confidence interval, CNY20,517–22,508). The mean costs per live birth cycle for IVF-D and AI-D were CNY49,411 and CNY31,246, respectively. Conclusion: AI-D is more cost-effective and poses a lower risk for infertility couples than IVF-D, and patients should undergo three AI-D cycles to obtain the highest success rate.

Poor compliance with multi-dose vaccine schedules by adults for whom hepatitis (Hep) A and B vaccines are recommended contributes to major Hep A and B disease burdens among high-risk U.S. adults. Evidence on hepatitis vaccine series adherence, completion, timeliness of completion, and factors associated with these outcomes, is limited and not readily generalizable for U.S. adults. This retrospective, observational study examined adherence, completion, its timeliness, and the impact of sociodemographic and clinical factors on these outcomes among a large, geographically representative sample of U.S. adults. We analyzed the Optum Clinformatics SES administrative claims database (1/1/2010-6/30/2020) for recipients of 2-dose (HepA, HepB2) or 3-dose (HepB3, HepAB) hepatitis vaccines. Adherence was defined as receipt of booster doses within specified assessment periods, per label-recommended schedules. Completion (receipt of all doses) was assessed at 6, 12, 18, and 24 months.The study included 356,828 adults ≥19 years old who were continuously enrolled in a medical benefit plan for one (HepB2), six (HepB3; HepAB), or 18 months (HepA) prior to and following the index date (first observed vaccine dose). Adherence and 24-month completion rates were: HepA (27.0%, 28.4%), HepB2 (32.2%, 44.8%), HepB3 (14.3%, 37.3%), HepAB, (15.3%, 33.8%). Kaplan-Meier completion curves plateaued after about 6 months for HepB2 and about 12 months for HepA, HepB3, and HepAB vaccines. Logistic regression analyses showed risk for low adherence/completion was generally associated with male gender, younger age, Black or Hispanic race/ethnicity, lower educational or household income attainment, and more comorbidities. Adherence and completion rates for all hepatitis vaccine series are low, especially for males, younger adults, those with lower socio-economic status and more comorbidities. To our knowledge, this is the largest claims-based analysis of adherence and completion rates for U.S. adults initiating all currently available HepA and HepB vaccines. Findings may inform hepatitis vaccination programming.

Coronavirus disease 2019 (COVID-19) emerged in China in late 2019, which was manifested as fever, cough, dyspnea, normal level of white blood cells, decreased blood lymphocytes, and pulmonary opacities on CT scans. National Health Commission of the People's Republic of China has revised the recommendations on COVID-19 seven times, but there are still many challenges in the diagnosis and management of COVID-19. The radiological findings in a proportion of patients revealed diffuse interstitial opacities, mimicking interstitial pneumonia. Thus it is essential to differentiate the COVID-19 from the acute and progressive diffuse interstitial lung diseases in order to avoid misdiagnosis or overdiagnosis. Therefore, our study compared COVID-19 with interstitial pneumonia and tried to explore the differential diagnostic algorithm.

Objective The efficacy of the two teaching methods for EBUS-TBNA was evaluated by comparing the learning curve, diagnostic accuracy, and specimen acquisition for genotyping by operators and so to find a better one for training pulmonologists. Methods The first fifty patients of each operator learning EBUS-TBNA between January 2015 and June 2019 in a single center were retrospective collected and grouped by the operators training methods. The diagnosis, genotyping and clinical characters were reviewed. Results A total of 442 patients were collected and reviewed. There were two training groups: a conventional training group (232 cases) and a simulator assistant training group (210 cases). There was no statistical difference in the diagnostic yield between the groups of trainees. However, specimen from lung cancer patients in simulator training group were more adequate for gene testing than in conventional training group (86.8% vs 71.2%, P＜0.05). By comparing the learning curve among the groups, it was found that the trainees in stimulator assistant training group needed less minimum number of operations to achieved proficiency than in conventional training group. Conclusions Simulation-based training is demonstrated to be more efficient in improving the bronchoscopists'skill in terms of getting sufficient specimen for gene testing. Simulation-based training may also shorten the time needed for bronchoscopists'training and can be applied in the EBUS-TBNA training course.

Objective To investigate the effect of recombinant Newcastle disease virus expressing IL-29(rL-IL29) on the proliferation and migration with invasion of gastric cancer cells and to explore the potential mechanism. Methods Gastric cancer cell lines BGC were cultured and divided into the PBS, rL-IL29 and newcastle disease virus(NDV)groups infected by the PBS, rL-IL29 or NDV.Western blot was used to detecte the expression of NDV, IL-29,p-ERK,MMP2 and p-AKT protein in cells.The proliferation,migration and invasion of gastric cancer cell lines BGC were detected by CCK8、cell clone forming experiments、scratch test and Transwell invasion test. Results IL-29 protein was only expressed in rL-IL29 group,NDV protein were expressed both in rL-IL29 group and NDV group and was significantly higher than those of PBS group (P＜0.05). The proliferation and migration of BGC cells infected with rL-IL29 were inhibited more seriously than those infected with NDV or PBS group.The expression of p-ERK,MMP2 (66 ku/72 ku),p-AKT and P65 protein was all significantly decreased(P＜0.05). Conclusions The proliferation and migration of gastric cancer cell lines BGC were inhibited by rL-IL29 and the mechanism may be related with ERK,AKT signaling pathways.

Objective To investigate the effects of pseudolaric acid B (PAB) on the proliferation and apoptosis of HEp-2 cells. Methods Cell grouping and treatment: cells were treated with 0, 0.5, 1, 2, 4, 8 and 16 μmol/L PAB for 24, 48 and 72 h respectively; MTT assay was used to detect cell viability; flow cytometry was used to detect apoptosis; The expression of Bcl-2, Bax and caspase-3 protein and mRNA was detected by Western blot and qPCR. The expression of PARP and c-PARP was detected by immunohistochemistry. Results PAB inhibited HEp-2 proliferation in a time-concentration dependent manner. Compared with the control group, the apoptosis rate of HEp-2 cells in 4 μmol/L and 8 μmol/L PAB groups was significantly increased(P＜0.01). Compared with the control group, the expression of Bcl-2 and PARP in HEp-2 cells of 4 μmol/L and 8 μmol/L PAB groups were significantly decreased(P＜0.05), and the expression of Bax, caspase-3 and c-PARP was significantly increased(P＜0.05). Conclusions PAB can activate the mitochondrial apoptosis pathway thus induce apoptosis of HEp-2 cells and inhibit cell proliferation.

Abstract The greater wax moth, Galleria mellonella Linnaeus (Lepidoptera: Galleriinae), is a ubiquitous pest of the honeybee, and poses a serious threat to the global honeybee industry. G. mellonella pheromone system is unusual compared to other lepidopterans and provides a unique olfactory model for pheromone perception. To better understand the olfactory mechanisms in G. mellonella, we conducted a transcriptomic analysis on the antennae of both male and female adults of G. mellonella using high-throughput sequencing and annotated gene families potentially involved in chemoreception. We annotated 46 unigenes coding for odorant receptors, 25 for ionotropic receptors, two for sensory neuron membrane proteins, 22 for odorant binding proteins and 20 for chemosensory proteins. Expressed primarily in antennae were all the 46 odorant receptor unigenes, nine of the 14 ionotropic receptor unigenes, and two of the 22 unigenes coding for odorant binding proteins, suggesting their putative roles in olfaction. The expression of some of the identified unigenes were sex-specific, suggesting that they may have important functions in the reproductive behavior of the insect. Identification of the candidate unigenes and initial analyses on their expression profiles should facilitate functional studies in the future on chemoreception mechanisms in this species and related lepidopteran moths.

Meiosis is a complex process involving the expression and interaction of numerous genes in a series of highly orchestrated molecular events. Fam9b localized in Xp22.3 has been found to be expressed in testes. However, FAM9B expression, localization, and its role in meiosis have not been previously reported. In this study, FAM9B expression was evaluated in the human testes and ovaries by RT-PCR, qPCR, and western blotting. FAM9B was found in the nuclei of primary spermatocytes in testes and specifically localized in the synaptonemal complex (SC) region of spermatocytes. FAM9B was also evident in the follicle cell nuclei and diffusely dispersed in the granular cell cytoplasm. FAM9B was partly co-localized with SYCP3, which is essential for both formation and maintenance of lateral SC elements. In addition, FAM9B had a similar distribution pattern and co-localization as γH2AX, which is a novel biomarker for DNA double-strand breaks during meiosis. All results indicate that FAM9B is a novel meiosis-associated protein that is co-localized with SYCP3 and γH2AX and may play an important role in SC formation and DNA recombination during meiosis. These findings offer a new perspective for understanding the molecular mechanisms involved in meiosis of human gametogenesis.

The 2019 Coronavirus Virus Disease (COVID-19) represents a global public health challenge in the twenty-first century. As of June 2020, the virus had spread across 216 countries across the globe. This paper aims to analyze and identify those existing comorbidities among COVID-19 patients that represent potential risk factors for COVID-19 complications, severe illness, and death. Multiple database resources were searched. The resources include the University of Saskatchewan library USearch, Google Scholar, PubMed, Medline, and the Google search engine. Thirty-seven articles, which included 15 different types of chronic diseases, were selected. Among the reviewed diseases and conditions, cancer, diabetes, lymphopenia, hypertension, kidney disease, smoking, chronic obstructive pulmonary disease (COPD), and organ transplant were found to represent potential risk factors for COVID-19 complications, severe illness, and death. Other conditions that require further research as to whether they predispose subjects to severe illness and death include coronary artery disease, cerebrovascular disease, valvular heart disease, gastrointestinal diseases, HIV/AIDS, asthma, and liver disease. In conclusion, this article explains the association between diseases mentioned above and the severity of COVID-19 and clearly shows the population at risk. This paper will help government bodies and decision-makers prioritize resources for these populations to reduce mortality rates and overall quality of life.

Purpose The Yellowknife Health Effects Monitoring Programme (YKHEMP) was established to examine the relationship of exposure to arsenic and other chemicals of potential concern such as antimony, cadmium, lead, manganese and vanadium and health outcomes.Participants A total of 2037 individuals were recruited, including children (age 3–19) and adults (age 20+), residing in Dettah, Ndilǫ and Yellowknife, in the Northwest Territories, Canada, in two waves in Fall 2017 and Spring 2018. In Yellowknife, there were 891 (675 adults, 216 children), randomly selected participants with a participation rate of 64%. In addition, we also recruited a total of 875 (669 adults, 206 children) volunteer participants. A total of 225 (137 adults, 88 children) of the Yellowknives Dene First Nation (YKDFN), and 46 (33 adults, 13 children) of the North Slave Métis Alliance participated in the study. Each participant answered a lifestyle questionnaire as well as provided toenail clippings and urine for contaminant testing and saliva samples for testing of genetic polymorphisms associated with arsenic metabolism. Participants also provided consent to have their medical records reviewed by the research team for the past 5 years to allow for the investigation between exposure and health outcomes.Findings to date The adult YKHEMP participants had lower urinary total arsenic but the children had higher inorganic arsenic than the general Canadian population. There was no difference in urinary total arsenic concentrations between adults and children, however, urinary inorganic arsenic concentrations were generally higher in children than in adults in all four YKHEMP sampling groups. The adult YKDFN participants had lower urinary total arsenic and inorganic arsenic concentrations compared with the random selected and volunteer participants.Future plans YKHEMP is designed as a prospective cohort study; the children participants will be re-examined in 2022 and both adult and children participants in 2027.

Leber congenital amaurosis (LCA) is a group of severe congenital retinal diseases. Variants in the guanylate cyclase 2D gene (GUCY2D), which encodes guanylate cyclase 1 (ROS-GC1), are associated with LCA1 and account for 6%-21% of all LCA cases. In this study, one family with LCA1 was recruited from China. A combination of next generation sequencing and Sanger sequencing was used to screen for disease-causing mutations. We found three novel mutations (c.139delC, p.Ala49Profs*36; c.835G>A, p.Asp279Asn and c.2783G>A, p.Gly928Glu) in the GUCY2D gene. Proband III-2 carries mutations c.139delC and c.2783G>A, which are inherited from the heterozygous mutation carriers, II-2 (c.139delC) and II-3 (c.2783G>A) that possess c.139delC and c.2783G>A. Additionally, II-8 carries heterozygous mutation c.835G>A. Sanger sequencing was used to confirm the presence of the three novel mutations in other family members. Mutation c.139delC results in a truncated protein. Mutations c.835G>A and c.2783G>A significantly reduce the catalytic activity of ROS-GC1. Our findings highlight the gene variants range of LCA. Moreover, HPLC-coupled tandem mass spectrometry (HPLC-MS/MS) was used to analyze the concentration of 3',5'-cyclic guanosine monophosphate (cGMP), suggesting that HPLC-MS/MS is an effective alternative method to evaluate the catalytic activity of wild-type and mutant ROS-GC1.

Osteoarthritis: Limiting tissue damage after knee surgery A potential therapeutic target identified by researchers in China could help limit damage to tissues following osteoarthritic knee surgery. A total knee arthroplasty can alleviate symptoms of end-stage osteoarthritis, but the surgery requires use of a tourniquet. This temporarily cuts blood supply to tissues and can trigger severe ischemia-reperfusion (I/R) injury, tissue damage caused by blood flow returning after oxygen deficiency. Shao-Nan Yu and co-workers at the China-Japan Union Hospital of Jilin University, Changchun, demonstrated that lowering expression of a particular RNA molecule following surgery could limit I/R damage. They found that the molecule was over-expressed in mice during I/R injury. This overexpression limited activation of a signalling pathway and an associated protein vital to the chemical balance of cell membranes and healthy muscle cell contraction.

Abstract Lead (Pb) is known to impair children’s cognitive function. It has been previously shown that developmental Pb exposure alters dendritic spine formation in hippocampal pyramidal neurons. However, the underlying mechanism has not yet been defined. In this study, a low-level gestational Pb exposure (GLE) rat model was employed to investigate the impact of Pb on the spine density of the hippocampal pyramidal neurons and its regulatory mechanism. Pb exposure resulted in impaired performance of the rats in the Morris water maze tasks, and in decreased EPSC amplitudes in hippocampal CA3-CA1 regions. With a 3D reconstruction by the Imaris software, the results from Golgi staining showed that the spine density in the CA1 region was reduced in the Pb-exposed rats in a dose-dependent manner. Decreased spine density was also observed in cultured hippocampal neurons following the Pb treatment. Furthermore, the expression level of NLGN1, a postsynaptic protein that mediates synaptogenesis, was significantly decreased following the Pb exposure both in vivo and in vitro. Up-regulation of NLGN1 in cultured primary neurons partially attenuated the impact of Pb on the spine density. Taken together, our resultssuggest that Pb exposure alters spine plasticity in the developing hippocampus by down-regulating NLGN1 protein levels.

Abstract The Sanshandao gold deposit contains an estimated Au resource of >1500 tons, however little is known about the history of exhumation, and the magnitude of displacement on the ore-hosting fault. Structural measurement revealed two phases of normal and one phase of sinistral movement on the fault. Despite of intra-sample dispersions, (U-Th)/He ages from two sub-vertical profiles show decreasing trends from the surface down to −3560 m (zircon: 123 Ma to 55 Ma; apatite 103 Ma to 0.3 Ma). Over-dispersion of AHe ages likely reflects the presence of undetected inclusions. According to the age-depth pattern, we infer that the deposit underwent an early phase of rapid cooling in the late Early Cretaceous, which was followed by a short period of thermal stagnation and a revived rapid cooling between 75 Ma and 55 Ma in response to a combined effects of late normal movement and erosion. Since the Eocene, the deposit has experienced a slow monotonic cooling. Exhumation magnitude estimates suggest that the deposit have been denudated > 5.1 km. The two phases of normal displacement along the fault occurred in the late Early Cretaceous and Late Cretaceous to Paleocene, leading to a total offset magnitude of 0.5–2.3 km.

Abstract The axis tilt of light beam in optical system would introduce the dispersion of orbital angular momentum (OAM) spectrum. To deal with it, a two-step method is proposed and demonstrated. First, the tilt angle of optical axis is identified with a deduced relation between the tilt angle and the variation of OAM topological charges with different reference axes, which is obtained with the help of a charge coupled device (CCD) camera. In our experiments, the precision of measured tilt angle is about 10−4 rad with topological charges of −3~3. With the measured angle value, the additional phase delay due to axis tilt can be calculated so that the dispersion of OAM spectrum can be corrected with a simple formula while the optical axis is not aligned. The experimental results indicate that the original OAM spectrum has been successfully extracted for not only the pure state but also the superposed OAM states.

Abstract In this paper, a spoof surface plasmon polarions (SPPs) transmission line is designed by patterning thin metal film in open-cross shape arranged in array. Numerical simulations show the proposed open-cross array can support spoof SPPs with enlarged propagation constant and hence enhanced confinement at metal/dielectric interface as compared to the reported ultra-thin plasmonic waveguide with the rectangular groove or solid-cross. Furthermore, a differential transmission line pair is built with such two close plasmonic arrays. A narrow metal strip locates at the symmetrical plane of the two SPPs waveguides and acts as a resonator to realize common-mode rejection at specific frequency. The notch frequency for common mode can be adjusted by tuning the metal strip length of the resonator while differential mode propagation remains unaffected. Both simulated and experimental results with good agreement are given to verify the proposed idea.

Abstract Macrophages and resident microglia play an import role in the secondary neuroinflammation response following spinal cord injury. Reprogramming of macrophage/microglia polarization is an import strategy for spinal cord injury restoration. Low-level laser therapy (LLLT) is a noninvasive treatment that has been widely used in neurotrauma and neurodegenerative diseases. However, the influence of low-level laser on polarization of macrophage/microglia following spinal cord injury remains unknown. The present study applied low-level laser therapy on a crush spinal cord injury rat model. Using immunofluorescence, flow cytometry, RT-qPCR, and western blot assays, we found that low-level laser therapy altered the polarization state to a M2 tendency. A greater number of neurons survived in the pare injury site, which was accompanied by higher BBB scores in the LLLT group. Furthermore, low-level laser therapy elevated expression of interleukin 4 (IL-4) and interleukin 13 (IL-13). Results from this study show that low-level laser therapy has the potential for reducing inflammation, regulating macrophage/microglia polarization, and promoting neuronal survival. These beneficial effects demonstrate that low-level laser therapy may be an effective candidate for clinical treatment of spinal cord injury.

Background: Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death. Methods: Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality. Results: In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094–1.886), age (OR: 1.046, 95% CI: 1.036–1.057), and presence of DN (OR: 1.837, 95% CI: 1.322–2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346–0.989), hemoglobin (OR: 0.974, 95% CI: 0.967–0.981), albumin (OR: 0.939, 95% CI: 0.915–0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070–0.386) were protective factors based on a multivariate analysis. Conclusions: Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Advances in high-throughput genotyping enable the generation of genome-scale data much more easily and at lower cost than ever before. However, small-scale and cost-effective high-throughput single-nucleotide polymorphism (SNP) genotyping technologies are still under development. In this study, we compared the performances of TaqMan, KASP and rhAmp SNP genotyping platforms in terms of their assay design flexibility, assay design success rate, allele call rate and quality, ease of experiment run and cost per sample. Fifty SNP markers linked to genes governing various agronomic traits of wheat were chosen to design SNP assays. Design success rates were 39/50, 49/50, and 49/50 for TaqMan, KASP, and rhAmp, respectively, and 30 SNP assays were manufactured for genotyping comparisons across the three platforms. rhAmp showed 97% of samples amplified while TaqMan and KASP showed 93% and 93.5% of amplifications, respectively. Allele call quality of rhAmp was 97%, while it was 98% for both TaqMan and KASP. rhAmp and KASP showed significantly better (p < 0.001) allele discrimination than TaqMan; however, TaqMan showed the most compact cluster. Based on the current market, rhAmp was the least expensive technology followed by KASP. In conclusion, rhAmp provides a reliable and cost-effective option for targeted genotyping and marker-assisted selection in crop genetic improvement.

BACKGROUND:The benefits of volatile anesthetics in coronary artery bypass grafting (CABG) patients remain controversial. We aimed to conduct an updated meta-analysis to assess whether the use of volatile anesthetics during CABG could reduce mortality and other outcomes. METHODS:We searched eight databases from inception to June 2019 and included randomized controlled trials (RCTs) comparing the effects of volatile anesthetics versus total intravenous anesthesia (TIVA) in CABG patients. The primary outcomes were operative mortality and one-year mortality. The secondary outcomes included the length of stay in the intensive care unit (ICU) and hospital and postoperative safety outcomes (myocardial infarction, heart failure, arrhythmia, stroke, delirium, postoperative cognitive impairment, acute kidney injury, and the use of intra-aortic balloon pump (IABP) or other mechanical circulatory support). Trial sequential analysis (TSA) was performed to control for random errors. RESULTS:A total of 89 RCTs comprising 14,387 patients were included. There were no significant differences between the volatile anesthetics and TIVA groups in operative mortality (relative risk (RR) = 0.92, 95% confidence interval (CI): 0.68-1.24, p = 0.59, I2 = 0%), one-year mortality (RR = 0.64, 95% CI: 0.32-1.26, p = 0.19, I2 = 51%), or any of the postoperative safety outcomes. The lengths of stay in the ICU and hospital were shorter in the volatile anesthetics group than in the TIVA group. TSA revealed that the results for operative mortality, one-year mortality, length of stay in the ICU, heart failure, stroke, and the use of IABP were inconclusive. CONCLUSIONS:Conventional meta-analysis suggests that the use of volatile anesthetics during CABG is not associated with reduced risk of mortality or other postoperative safety outcomes when compared with TIVA. TSA shows that the current evidence is insufficient and inconclusive. Thus, future large RCTs are required to clarify this issue.