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Background: Spinal muscular atrophy (SMA) is a common neuromuscular disorder, caused by absence of both copies of the survival motor neuron 1 (SMN1) gene. Population-wide SMA screening to quantify copy number of SMN1 is recommended by multiple regions. SMN1 diagnostic assay with simplified procedure, high sensitivity and throughput is still needed.Methods: Real-Time PCR with High-Resolution Melting for the quantification of the SMN1 gene exon 7 copies and SMN1 gene exon 8 copies was established and confirmed by multiplex ligation-dependent probe amplification (MLPA). The diagnosis of 2563 individuals including SMA patients, suspected cases and the general population were analyzed by the real-time PCR. The results were compared with the gold standard test MPLA. Results: In this study, the homozygous deletions, heterozygous deletions were identified by Real-Time PCR with High-Resolution Melting method with an incidence of 10.18% and 2.42%, respectively. In addition, the R value distribution (P>0.05) among the 8 replicates and the coefficient of variation (CVConclusions: The qPCR based on High-Resolution Melting provides a sensitive and high-throughput approach to large-scale SMA carrier screening with low cost and labor.

Pharmacokinetic variability in disease state is common in clinical practice, but its underlying mechanism remains unclear. Recently, gut microbiota has been considered to be pharmacokinetically equivalent to the host liver. Although some studies have explored the roles of gut microbiota and host Cyp450s in drug pharmacokinetics, few have explored their effects on pharmacokinetic variability, especially in disease states.In this study, we aim to investigate the effects of gut microbiota and host Cyp450s on pharmacokinetic variability in mice with non-alcoholic steatohepatitis (NASH), and to elucidate the contribution of gut microbiota and host Cyp450s to pharmacokinetic variability in this setting.The pharmacokinetic variability of mice with NASH was explored under intragastric and intravenous administrations of a cocktail mixture of omeprazole, phenacetin, midazolam, tolbutamide, chlorzoxazone, and metoprolol, after which the results were compared with those obtained from the control group. Thereafter, the pharmacokinetic variabilities of all drugs and their relations to the changes in gut microbiota and host Cyp450s were compared and analyzed.The exposures of all drugs, except metoprolol, significantly increased in the NASH group under intragastric administration. However, no significant increase in the exposure of all drugs, except tolbutamide, was observed in the NASH group under intravenous administration. The pharmacokinetic variabilities of phenacetin, midazolam, omeprazole, and chlorzoxazone were mainly associated with decreased elimination activity in the gut microbiota. By contrast, the pharmacokinetic variability of tolbutamide was mainly related to the change in the host Cyp2c65. Notably, gut microbiota and host Cyp450s exerted minimal effects on the pharmacokinetic variability of metoprolol.Gut microbiota and host Cyp450s co-contribute to the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug. The present findings provide new insights into the explanation of pharmacokinetic variability in disease states.

Background/Aim: Long noncoding RNA TARID (lncRNA TARID) can activate the tumor suppressor TCF21 in tumorigenesis by inducing promoter demethylation. However, the impact on lncRNA TARID and its variants of coronary artery disease (CAD) are poorly understood. Methods We performed a case-control study enrolling 949 case patients and 892 controls to assess genotype. Five variants were genotyped by TaqMan assay. 20 case patients and 20 controls were used to evaluate the expression of lncRNA TARID. The qRT-PCR and cell cycle analysis were applied to examined cell proliferation and cell distribution. Results This study indicated that rs2327433 GG genotype was associated with CAD risk adjusting for traditional risk factors (OR=2.74, 95%CI: 1.10-6.83, P=0.03). Our results analyses revealed that the genotype of rs2327433 was related to the proportion of CAD patients with left anterior descending artery disease and left circumflex artery disease (P=0.025 and P=0.025, respectively). The results showed that the minor allele frequency of rs2327433 was significantly correlated with the severity of the disease (P=0.029). The eQTL analysis showed that rs2327433 may affect the transcription factors TCF21 regulated by lncRNA TARID. We found that TARID silencing regulated the cell proliferation and altered cell cycle progression by induced upregulation of CDK1 and PCNA. Conclusions SNP rs2327433 in lncRNA TARID was associated with CAD risk and the severity of CAD in Chinese Han population. Furthermore, SNP rs2327433 may affect the expression of atherosclerosis-related transcription factor TCF21 regulated by lncRNA TARID. Finally, our study provided a new lncRNA-dictated regulatory mechanism participating in cell proliferation.

Medium voltage direct current (MVDC) shipboard power system (SPS) is the development trend of future ships. With the characteristics of compact structure and high-power density, the short circuit is much more serious than land-based power system, which seriously restricts the development of MVDC SPS. Therefore, there is an urgent need for prospective research on fault-protection. According to the fault characteristics of MVDC SPS, a DC superconducting current-limiting switch (SCLS) is proposed, so as to realize the current limiting protection of MVDC SPS. In this paper, a small-scale SCLS superconducting coil is wound, and a current limiting experiment of the prototype is completed. The results show that SCLS has a fast current-limiting response speed and a good current-limiting effect. The experiment summarizes the characteristics of the two current limiting modes of SCLS and it is concluded that R-type current limiting mode is more suitable for MVDC SPS.

Nondipping heart rate (HR), defined as a night/day HR ratio0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown.This case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months).The HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P.01) in SHPT patients (serum intact parathyroid hormone500.0 pg/mL).CKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.

B-cell acute lymphoblastic leukemia is the most common malignant tumor in children. About 10–15% of patients will relapse with a 5-year OS of 57.5% for the past 20 years. As tumor microenvironment plays an important role in the disease process, many types of immunotherapy are approached. New immunotherapies including CAR-T cells have been developed for refractory B-ALL treatment. However, CAR-T treatment faces several problems, including loss of the target antigen and in vivo T-cell persistence. Here, we analyzed the tumor microenvironment of pediatric B-ALL patients in TARGET database. Using Cox analysis and PPI network, we finally sorted out the DAP10 gene. We found that DAP10 was hardly expressed in leukemic B cells. DAP10 was downregulated in B-ALL compared with normal individuals, and low expression level of DAP10 predicted poor survival. Furthermore, we found the tumor microenvironment was different in DAP10 high and low expression children. The CD8+ T cells might be hard to activate and more likely to suffer from exhaustion in DAP10 lowly expressed children. In conclusion, our results showed that DAP10 was a well biomarker to indicate the prognosis and tumor microenvironment in pediatric B-ALL. The treatment strategy of immunotherapy for the leukemic children with DAP10 lowly expressed should be adjusted if needed.

Employees with higher career adaptability (CA) have been shown in previous research to be more likely to build high-quality social exchange relations with current employers, thereby displaying a lower intention to leave. Based on boundaryless careers and career ecosystem perspectives, this study aimed to challenge and enrich the extant understanding of this important question by examining the mixed effects of CA on turnover behavior. Results from a three-wave survey study with 179 Chinese employees show that after controlling the baseline turnover intention (Time 1), CA (Time 1) predicted both affective commitment and relative deprivation at Time 2 (6 months after Time 1), which in turn produced opposite effects on voluntary turnover behavior at Time 3 (12 months after Time 1). Moreover, the boundaryless career mindset positively moderated the relationship between CA and relative deprivation and strengthened the indirect positive effect of CA on turnover behavior via relative deprivation. These results offer a more comprehensive and balanced view of the mixed role of CA in employees' turnover behavior and carry important implications for human resource management

Alzheimer’s disease (AD) is associated with abnormal calcium signaling, a pathway regulated by the calcium-dependent protein phosphatase. This study aimed to investigate the molecular function of protein phosphatase 3 regulatory subunit B (PPP3R1) underlying AD, which may provide novel insights for the predictive diagnostics, targeted prevention, and personalization of medical services in AD by targeting PPP3R1. A total of 1860 differentially expressed genes (DEGs) from 13,049 background genes were overlapped in AD/control and PPP3R1-low/high cohorts. Based on these DEGs, six co-expression modules were constructed by weight gene correlation network analysis (WGCNA). The turquoise module had the strongest correlation with AD and low PPP3R1, in which DEGs participated in axon guidance, glutamatergic synapse, long-term potentiation (LTP), mitogen-activated protein kinase (MAPK), Ras, and hypoxia-inducible factor 1 (HIF-1) signaling pathways. Furthermore, the cross-talking pathways of PPP3R1, such as axon guidance, glutamatergic synapse, LTP, and MAPK signaling pathways, were identified in the global regulatory network. The area under the curve (AUC) analysis showed that low PPP3R1 could accurately predict the onset of AD. Therefore, our findings highlight the involvement of PPP3R1 in the pathogenesis of AD via axon guidance, glutamatergic synapse, LTP, and MAPK signaling pathways, and identify downregulation of PPP3R1 as a potential biomarker for AD treatment in the context of 3P medicine—predictive diagnostics, targeted prevention, and personalization of medical services. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00261-2.

The high temperature superconducting (HTS) cable can be used as a low-voltage tie line between substations for its characteristic of high currentdensity. In this way, the remaining capacity on the low-voltage side of the transformer can be fully utilized. Moreover, The HTS cable can run in parallel with the original tie line, forming an electromagnetic ring network, to ensure the power supply of important loads. However, the short circuit current of the distribution network is large, and the electromagnetic ring network operation results in the quench of HTS cable when the short circuit fault is outside the HTS cable. It is important to ensure the safety of HTS cable under various short circuit faults. To ensure the safe operation of HTS cable in Shenzhen Power Grid, this paper built a distribution network model with HTS cable in Matlab/Simulink. The fault current and thermal process in different fault situation were analyzed. The design of fault current limiter (FCL) which is composed of the resistive superconducting fault current limiter (R-SFCL) and a shunt reactor was completed. The model of R-SFCL using R - Q method is build, and the effectiveness of the R-SFCL design is verified.

Han Zhang,1,2 Guanhong Chen,2 Xiajie Lyu,3 Chun Rong,4 Yingzhen Wang,1 Ying Xu,2 Chengyu Lyu1 1Department of Orthopaedics, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province, People’s Republic of China; 2Department of Orthopaedics, Shanxian Central Hospital, Heze City, Shandong Province, People’s Republic of China; 3Weifang Medical University, Weifang, Shandong, People’s Republic of China; 4Department of Operation Room, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province, People’s Republic of ChinaCorrespondence: Chengyu Lyu Email 18266390138@163.comPurpose: Long non-coding RNAs (lncRNAs) have diverse roles in modulating gene expression on both transcriptional and translational levels, but their involvement in osteosarcoma (OS) metastasis remains unknown.Patients and Methods: Transcriptional and clinical data were downloaded from TARGET datasets. A total of seven lncRNAs screened by univariate cox regression, lasso regression, and multivariate cox regression analysis were used to establish the OS metastasis model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the model.Results: The established model showed exceptional predictive performance (1 year: AUC = 0.92, 95% Cl = 0.83– 0.99; 3 years: AUC = 0.87, 95% Cl = 0.79– 0.96; 5 years: AUC = 0.86, 95% Cl = 0.76– 0.96). Patients in the high group had a poor survival outcome than those in the low group (p < 0.0001). GSEA analysis revealed that “NOTCH_SIGNALING” and “WNT_BETA_CATENIN_SIGNALING” were significantly enriched and that resting dendritic cells were associated with AL512422.1, AL357507.1, and AC006033.2 (p < 0.05).Conclusion: Based on seven prognosis-related lncRNAs, we constructed a novel model with high reliability and accuracy for predicting metastasis in OS patients.Keywords: lncRNAs, osteosarcoma, tumor metastasis, prognosis

The medium voltage direct current (MVDC) is a promising direction of future shipboard power system (SPS). However, one of the main limitations encountered in its development is the fault isolation of DC side. This paper reveals the evolution process of short-circuit fault in typical MVDC SPS through equivalent circuit and transient simulation. Based on the analysis of protection needs, a superconducting current-limiting switch (SCLS) topology is proposed, which includes one superconducting coupled coil and two DC circuit breakers (DCCBs). The models of SCLS is built on MATLAB/Simulink and the current limiting principle and current sharing principle of SCLS are verified. The results show that the SCLS has effective current limiting performance and fault clearing effect.

Because the effect of low molecular heparin (LMH) on acute ulcer and bleeding complications in patients with severe acute pancreatitis (SAP) is unclear, we investigated the safety and efficacy of early intervention with LMH in patients with SAP.Using the keywords "heparin", "low molecular weight heparin", "pancreatitis", and "severe acute pancreatitis", we searched PubMed, Medline, CNKI, etc. And select the reference documents of the comparative study of traditional treatment and low molecular weight heparin intervention. RevMan was used for the meta-analysis.A total of 8 references were included in the study, and most of them were low risk bias (medium and high quality). Meta-analysis shows that, The MHS between the two groups is statistically heterogeneous. (Chi2=19.59, I2=95%, P0.00001), Fixed-effects model (FEM) analysis showed that the MHS of experimental subjects was obviously shorter than that of controls (Z=3.24, P=0.001); The acute physiology and chronic health score (APACHE II) of the two groups were heterogeneous (Chi2=7.24, I2=72%, P=0.03); No heterogeneity was found in the amount of bleeding (Chi2=5.83, I2=31%, P=0.21), FEM analysis showed the number of complications in the experimental group was significantly less than that in the control group (Z=2.70, P=0.007).LMH intervention can dramatically reduce the average hospital stay and complications of patients with SAP, improve treatment efficacy, and has high safety.

As medium voltage dc-based (MVDC) technology is widely considered in the shipboard integrated power system (IPS), the short fault protection of shipboard IPS is urgent. This paper suggests resistive type superconducting fault current limiter (R-SFCL), flux-coupling type SFCL (FC-SFCL), and a hybrid type SFCL (H-SFCL) alleviate fault current and improve the transient behaviors of shipboard MVDC IPS. All of these SFCLs are installed at the DC line. When pole to pole short fault occurs, resistive and inductive components play roles in current limiting. To evaluate these SFCLs and choose one for the system, theoretical analysis, simulation verification and experiments are done. According to the current limiting and economic cost index, H-SFCL is preferable in these SFCLs.

The development of power system has increased the level of short-circuit fault current, and flux-coupling-type superconducting fault current limiter can effectively limit short-circuit current by the increased impedance after decoupling of windings. In this paper, two prototypes of pancake-winding and layer-winding were manufactured and experiments were conducted. The results show that the current-limiting ratio of two prototypes reached more than 40%. Analysis of the control strategy indicates that two breakers of the limiter could operate at the same time or at different times, and when two breakers operated asynchronously, there would be a damping direct current in the windings. When decoupled, two prototypes had coil voltage distributions of increase and then fall off, and pancake-winding had a intercoil voltage distribution of sawtooth.

Background We prospectively examined the association between serum uric acid (SUA) levels and chronic kidney disease (CKD) in China and updated the evidence through a comprehensive meta-analysis of prospective studies worldwide. Methods Our original analyses were based on data from the China Health and Retirement Longitudinal Study. The primary exposure of interest was SUA at baseline, and the main outcome was incident CKD. Logistic regression models were used to examine the association between SUA levels and incident CKD. A meta-analysis was performed to pool our effect estimate and those from other cohort studies. Results During a 4-year follow-up, 180 participants developed incident CKD. Participants in the highest SUA quartile were 2.73 times as likely to develop incident CKD compared to those in the lowest quartile (multivariable-adjusted OR, 2.73; 95% CI, 1.65–4.50). Each 1 mg/dL increment in the SUA levels was associated with a 49% increased risk of incident CKD (multivariable-adjusted OR, 1.49; 95% CI, 1.28–1.74). In the meta-analysis of 30 cohort studies (including the current study), pooled relative risks (95% CIs) of incident CKD were 1.15 (1.10–1.21) for SUA each 1 mg/dL increment, 1.22 (1.14–1.30) for the highest versus lowest SUA group, and 1.17 (1.12–1.23) for hyperuricemia versus no hyperuricemia. Conclusions Baseline SUA levels were associated with higher risk of incident CKD in middle-aged and elderly Chinese adults, and this positive association was confirmed in the meta-analysis of multiple cohort studies. Our findings may imply that SUA levels need to be routinely monitored for future CKD risk.

A quick and accurate extraction of dominant colors of background images is the basis of adaptive camouflage design. This paper proposes a Color Image Quick Fuzzy C-Means (CIQFCM) clustering algorithm based on clustering spatial mapping. First, the clustering sample space was mapped from the image pixels to the quantized color space, and several methods were adopted to compress the amount of clustering samples. Then, an improved pedigree clustering algorithm was applied to obtain the initial class centers. Finally, CIQFCM clustering algorithm was used for quick extraction of dominant colors of background image. After theoretical analysis of the effect and efficiency of the CIQFCM algorithm, several experiments were carried out to discuss the selection of proper quantization intervals and to verify the effect and efficiency of the CIQFCM algorithm. The results indicated that the value of quantization intervals should be set to 4, and the proposed algorithm could improve the clustering efficiency while maintaining the clustering effect. In addition, as the image size increased from 128 × 128 to 1024 × 1024, the efficiency improvement of CIQFCM algorithm was increased from 6.44 times to 36.42 times, which demonstrated the significant advantage of CIQFCM algorithm in dominant colors extraction of large-size images.

Background: Previous studies revealed that abnormal blood pressure (BP) plays an important role in the pathogenesis of Alzheimer’s disease (AD). However, little is known about the ambulatory BP characteristics of AD in the mild or severe stage. Objective: We explored the ambulatory BP characteristics of AD in the mild or severe stage. Methods: In the present study, 106 AD patients (42.5%male, average age 81.6 years) were enrolled from three centers in China. Clinal BP measurements at the supine and standing positions, neurological evaluations, and the 24 h ambulatory BP monitoring were performed. Results: In the 106 AD patients, 49.2%, 36.8%, and 70%of patients had 24 h, daytime, and nighttime systolic hypertension, respectively, while 19.8%, 29.2%, and 5.7%had 24 h, daytime, and nighttime diastolic hypotension. The prevalence of the reduced and reverse dipping pattern was 34.0%and 48.1%for systolic BP and 32.1%and 45.3%for diastolic BP, respectively. The daytime diastolic BP was significantly correlated with cognitive performance. After adjustment for age, sex, and body mass index, only daytime diastolic BP was associated with remarkable cognitive deterioration (p≤0.008). Further, AD patients in the severe stage had significantly lower levels of the 24 h, daytime, and nighttime diastolic BP, compared with those in the mild stage. Conclusion: In general, AD patients were featured with high nighttime systolic BP, low daytime diastolic BP, and abnormal circadian BP rhythm of reduced and reverse dipping. The diastolic BP, especially daytime diastolic BP, was adversely correlated with the cognitive deterioration in AD.

Objective The aim of this study was to investigate the effectiveness of occupational therapist-/physiotherapist-guided fatigue self-management for individuals with chronic conditions. Methods Eight databases, including MEDLINE and EMBASE, were searched until September 2019 to identify relevant studies. Randomised controlled trials and quasi-experimental studies of self-management interventions specifically developed or delivered by occupational therapists/physiotherapists to improve fatigue symptoms of individuals with chronic conditions were included. A narrative synthesis and meta-analysis were conducted to determine the effectiveness of fatigue self-management. Results Thirty-eight studies were included, and fatigue self-management approaches led by occupational therapists/physiotherapists were divided into six categories based on the intervention focus: exercise, energy conservation, multimodal programmes, activity pacing, cognitive-behavioural therapy, and comprehensive fatigue management. While all exercise programmes reported significant improvement in fatigue, other categories showed both significant improvement and no improvement in fatigue. Meta-analysis yielded a standardised mean difference of the overall 13 studies: 0.42 (95% confidence interval:−0.62 to − 0.21); standardised mean difference of the seven exercise studies was −0.55 (95% confidence interval: −0.78 to −0.31). Discussion Physical exercises inspired by the self-management principles may have positive impacts on fatigue symptoms, quality of life, and other functional abilities.

Objectives To map and characterize the nature of the evidence on the use of digital rectal stimulation for bowel management in individuals with spinal cord injury (SCI). Data Sources Five electronic databases were searched (ie, MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, and Cochrane Incontinence Group) from 1990 to November 2019. Study Selection Articles that provided information on the use of digital rectal stimulation either alone or in combination with treatments were included. Title and abstract screening was split between 2 reviewers after reaching consensus on the first 100 studies screened. Full-texts were reviewed independently by 2 reviewers. Discrepancies were resolved by a third reviewer. Data Extraction The data extraction form was developed by 2 reviewers and piloted. Data were extracted by one reviewer and checked for accuracy by a second reviewer. Data Synthesis A total of 4841 studies were screened, including 425 full text articles; 33 articles were identified. Thirty-two studies focused solely on individuals with SCI and 1 study explored the experiences of caregivers of individuals with SCI. The majority of participants were aged between 30 and 59 years old. Most studies used quantitative methods (n=30, 91%). Fourteen of the studies (42%) were cross-sectional. Within experimental or quasiexperimental designs, digital rectal stimulation was commonly studied as an adjunct to other methods such as suppositories or enemas. Incontinence and defecation time were the most commonly examined outcomes. Conclusion There were few studies found that focus on digital rectal stimulation. Further studies examining experience, effectiveness, complications, and long-term outcomes are warranted.

Hui Huang,1,2 Qinhui Liu,1 Ting Zhang,2 Jinhang Zhang,1,2 Jian Zhou,1,2 Xiandan Jing,2 Qin Tang,1 Cuiyuan Huang,1,2 Zijing Zhang,1 Yingnan Zhao,1,2 Guorong Zhang,1,2 Jiamin Yan,1,2 Yan Xia,1,2 Ying Xu,1,2 Jiahui Li,1,2 Yanping Li,1 Jinhan He1,2 1Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Yanping LiLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86-28-85164128Email liyanping_512@163.comJinhan HeDepartment of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86-28-85426416Email jinhanhe@scu.edu.cnBackground: Renal fibrosis is the common pathway in chronic kidney diseases progression to end-stage renal disease, but to date, no clinical drug for its treatment is approved. It has been demonstrated that the inhibitor of proto-oncogene Ras, farnesylthiosalicylic acid (FTS), shows therapeutic potential for renal fibrosis, but its application was hindered by the water-insolubility and low bioavailability. Hence, in this study, we improved these properties of FTS by encapsulating it into bovine serum albumin nanoparticles (AN-FTS) and tested its therapeutic effect in renal fibrosis.Methods: AN-FTS was developed using a classic emulsification-solvent ultrasonication. The pharmacokinetics of DiD-loaded albumin nanoparticle were investigated in SD rats. The biodistribution and therapeutic efficacy of AN-FTS was assessed in a mouse model of renal fibrosis induced by unilateral ureteral obstruction (UUO).Results: AN-FTS showed a uniform spherical shape with the size of 100.6 ± 1.12 nm and PDI < 0.25. In vitro, AN-FTS displayed stronger inhibitory effects on the activation of renal fibroblasts cells NRK-49F than free FTS. In vivo, AN-FTS showed significantly higher peak concentration and area under the concentration-time curve. After intravenous administration to UUO-induced renal fibrosis mice, AN-FTS accumulated preferentially in the fibrotic kidney, and alleviated renal fibrosis and inflammation significantly more than the free drug. Mechanistically, the improved anti-fibrosis effect of AN-FTS was associated with greater inhibition in renal epithelial-to-mesenchymal transformation process via Ras/Raf1/p38 signaling pathway.Conclusion: The study reveals that AN-FTS is capable of delivering FTS to fibrotic kidney and showed superior therapeutic efficacy for renal fibrosis.Keywords: albumin nanoparticle, epithelial–mesenchymal transition, farnesylthiosalicylic acid, Ras, renal fibrosis

Few studies have characterized the clinical outcomes of 45S5 Bioglass® applied as a bone graft to that of allogeneic bone applied in calcaneal open curettage. Therefore, the purpose of the present investigation was to compare the outcomes of patients with calcaneal tumors and tumor-like lesions treated by open curettage with 45S5 Bioglass® or allogeneic bone. Of the 31 patients who underwent open curettage (18 cases of unicameral bone cysts, 7 cases of aneurysmal bone cysts, and 6 cases of intraosseous lipoma), 16 (52%) received grafts with 45S5 Bioglass® and 15 (48%) with allogeneic bone. All the feet achieved bone fusion according to the modified Neer radiographic classification system at the last follow-up examination. The mean bone ingrowth time for the grafts with 45S5 Bioglass® versus allogeneic bone was 3.71 ± 0.86 versus 4.46 ± 1.04 months (p = .038), the mean bone healing time was 4.86 ± 0.93 versus 5.73 ± 1.07 months (p = .021), and the mean incision drying time was 7.2 ± 1.8 versus 8.2 ± 1.5 days (p = .047), respectively. No differences were found in the postoperative American Orthopaedic Foot and Ankle Society ankle-hindfoot scale scores between the 2 groups (p = .213). These results show that 45S5 Bioglass® can better facilitate the formation of new bone with a faster drying time of the incision than allogeneic bone. Although both materials can benefit the clinical outcomes of calcaneal tumors and tumor-like lesions, further studies are needed to observe the long-term complications and lesion recurrence rates.

We designed a study to compare the newly developed 5-mg flunarizine hydrochloride capsules (test) to that of its marketed counterpart (5-mg; reference) among healthy adult Chinese volunteers. We performed an open-label, single-center study that consisted of 2 randomized, crossover trials, including a fasting trial and a fed trial. In each part of the study, the subjects were randomly assigned to either receive the test or reference products (5-mg flunarizine) in a 1:1 ratio. Subjects then received the alternative products, following a 14-day washout period. Concentrations of plasma flunarizine were analyzed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters (noncompartmental model) were evaluated using the WinNonlin software. The analysis of variance and Food and Drug Administration bioequivalence statistical criterion of 90% confidence interval for 80% to 125% range (set at P ≤ .05) of geometric means ratios of test: reference product for peak plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, and AUC from time 0 to infinity were determined. Tolerability was evaluated during the entire study period. Overall, 23 volunteers completed the fasting study, while 40 volunteers completed the fed study. The test formulation was found to be bioequivalent to the marketed formulation, as the 90% confidence interval for the ratio of geometric means of peak plasma concentration (fasting: 87.61%-101.67%; fed: 87.38%-104.06%), AUC from time 0 to time t (fasting: 89.44%-99.92%; fed: 92.65%-98.28%), and AUC from time 0 to infinity (fasting: 95.02%-104.33%; fed: 90.41%-96.96%) were within equivalence limits (80-125%) under both the fasting and fed conditions. When flunarizine was given alongside high-fat meals, time to maximum concentration was delayed ≈3.5 hours compared to fasting conditions. Meantime, high-fat meals increased its exposure by nearly 50%. Furthermore, there were no serious adverse events found among the subjects. This study confirmed that test and reference flunarizine hydrochloride capsules were bioequivalent under fasting and postprandial conditions.

Objectives To determine the safety and efficacy of bedaquiline for Chinese patients with multidrug-resistant tuberculosis (MDR-TB) based on serum concentration monitoring and to identify factors associated with QTc prolongation occurring during treatment. Methods Data were collected from 35 patients who received treatment regimens containing bedaquiline for MDR-TB from May 2018 to December 2020. Blood samples were collected, and serum concentrations of bedaquiline were measured using high-performance liquid chromatography–mass spectrometry. Results After completing the 24-week bedaquiline treatment course, 80.0% of the patients’ sputum cultures turned negative. The median time to sputum culture conversion was 75.5 days (interquartile range 52–126 days). The mean serum concentration of bedaquiline was 0.586 ± 0.288 µg/ml during treatment and 0.205 ± 0.145 µg/ml at 16 weeks after bedaquiline discontinuation. Bedaquiline remained detectable 52 weeks after discontinuation. Combination with clofazimine during bedaquiline treatment significantly increased cardiac QTc prolongation. When QTc prolongation occurred, serum potassium levels decreased by 10.71% from baseline, while serum sodium levels increased by 1.07% from baseline. Conclusions Good treatment outcomes were obtained with bedaquiline treatment in Chinese patients with MDR-TB. Combination with clofazimine increased the risk of QTc prolongation. Serum electrolytes (potassium and sodium) should be measured regularly during treatment of MDR-TB with regimens containing bedaquiline.

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious threat to human health worldwide, with a high genetic susceptibility. Rs2302685, a functional germline variant of LRP6, has been recently found to associate with NAFLD risk. This study was aimed to clarify the underlying mechanism associated with rs2302685 risk and its impact on pharmacotherapy in treatment of NAFLD. Methods: Venous blood samples were collected from NAFLD and non-NAFLD patients for SNP genotyping by using mass spectrometry. The Lrp6-floxdel mouse (Lrp6 (+/-)) was generated to model the partial function associated with human rs2302685. The liver injury and therapeutic effects of silibinin were compared between Lrp6 (+/-) and Lrp6 (+/+) mice received a methionine-choline deficient (MCD) diet or normal diet. The effect of Lrp6 functional alteration on Wnt/β-catenin-Cyp2e1 signaling activities was evaluated by a series of cellular and molecular assays. Results: The T allele of LRP6 rs2302685 was confirmed to associate with a higher risk of NAFLD in human subjects. The carriers of rs2302685 had reduced level of AST and ALT as compared with the noncarriers. The Lrp6 (+/-) mice exhibited a less severe liver injury induced by MCD but a reduced response to the treatment of silibinin in comparison to the Lrp6 (+/+) mice, suggesting Lrp6 as a target of silibinin. Wnt/β-catenin-Cyp2e1 signaling together with ROS generation could be exacerbated by the overexpression of Lrp6, while decreased in response to Lrp6 siRNA or silibinin treatment under NAFLD modeling. Conclusions: The Lrp6 function affects individual susceptibility to NAFLD and the therapeutic effect of silibinin through the Wnt/β-catenin-Cyp2e1 signaling pathway. The present work has provided an underlying mechanism for human individual susceptibility to NAFLD associated with Lrp6 polymorphisms as well as a rationale for the effective use of silibinin in NAFLD patients.

The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.

The high-frequency PWM pulse voltage of SMES power conditioning system (PCS) transmitted to the HTS magnet will influence the security of the magnet. Therefore, to analyze the dynamic response of the magnet with the interaction of the PWM pulse voltage is necessary for the SMES operation. This paper proposes a frequency-domain analysis method for the transient characteristic of the HTS magnet, which can be utilized to analyze the voltage distribution and the frequency response characteristic of the magnet. To evaluate the effectiveness of the proposed method, a sample HTS magnet is assembled to measure its voltage distribution characteristic. Furthermore, the results of amplitude-frequency characteristics coincide with the trend of magnet voltage variation.

Background Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition associated with aging, insulin resistance, metabolic syndrome, genetic factors and more. Although genetic traits are among the most important risks factors for NAFLD, the understanding of their influence is still quite limited. The present study aimed at identifying novel single nucleotide polymorphisms (SNPs) that may confer a risk for NAFLD in the Han Chinese population. Methods Based on the “two-hit hypothesis”, candidate SNPs, including Sirtuin3 rs28365927, were genotyped by MassARRAY in B-type ultrasonography-proven NAFLD patients (n = 292) and healthy controls (n = 387). Results In a model analysis of individuals matched based on gender and age that compared 223 NAFLD and 223 non-NAFLD patients, the rs28365927 GA + AA genotype was a significant risk factor for the development of NAFLD in a dominant model. Rs28365927 was significantly associated with a higher NAFLD risk in both an additive model (A vs G) and genotypic model (GA vs GG). Among the NAFLD patients, serum levels of total bilirubin (TBIL), DBIL direct bilirubin (DBIL) and glutamic-pyruvic transaminase (ALT) in rs28365927 A allele carriers (GA + AA) were 11.1, 14.7 and 41.5% higher, respectively, than in non-carriers (GG). Furthermore, among the NAFLD patients, the carriers of Rs28365927 allele A were positively correlated with higher ALT levels. Conclusion Sirtuin3 rs28365927 functional variant confers to the high risk of non-alcoholic fatty liver disease in Chinese Han population. The rs28365927 A allele significantly increased the ALT levels of NAFLD patients.

To provide a scientific basis for the policies for the development of wind energy and towards the goal of carbon neutrality in China and local governments, changes in wind energy potential over China were investigated based on the bias-corrected ensemble mean (CENS) of high-resolution dynamical downscaling projections using the RCP2.6, RCP4.5 and RCP8.5 emission scenarios. Firstly, evaluation indicated that CENS could better reproduce the long-term mean and interannual variability of surface wind speed over China compared to the original simulation outputs, providing a reliable basis for future projections. Projection of the averaged wind power density of China showed a decreasing trend during 2020–2099 in all four seasons under all three scenarios, with the significant (p

Patients with obstructive sleep apnea (OSA) frequently experience apnea-related oxygen desaturation events (ODE) accompanied by striking blood pressure (BP) fluctuations during sleep. We aimed to investigate the effects of characteristics of ODE on nocturnal BP fluctuations in OSA patients.A total of 6199 ODE were obtained from 30 patients with who underwent overnight portable monitoring and beat-to-beat BP monitoring simultaneously. The associations between nocturnal BP parameters and the characteristics of ODE were studied. The mean value of systolic BP (SBP) monitored during ODE was higher than the non-hypoxia SBP value (122.0 ± 15.9 vs. 120.4 ± 15.1 mmHg, P = 0.001) and nighttime SBP value (122.0 ± 15.9 vs. 120.8 ± 15.0 mmHg, P = 0.002). SBP variability (SBPV) during ODE was higher than the values not during ODE (14.0 ± 2.8 vs. 13.2 ± 2.6 mmHg, P = 0.043) and nighttime SBPV (14.0 ± 2.8 vs. 12.9 ± 2.3 mmHg, P 0.001). Hypoxia SBP index, defined as the percentage of SBP surge (△SBP) ≥10 mmHg to all △SBP during ODE, increased with greater respiratory event index (P = 0.01). Both the coefficient of variation for SBP values of an ODE (SBPV') and event-related SBP elevation (△SBP') increased with raised amplitude of ODE (P 0.001 for SBPV' and P 0.001 for △SBP'). Similar results were observed when the duration of events was analyzed (P 0.001 for SBPV' and P 0.001 for △SBP').BP related to ODE may be the main component of increased BP during sleep in OSA patients. In addition to the frequency of respiratory events, the amplitude and duration of ODE may have a role in nocturnal BP fluctuations in OSA patients.

Polycystic ovary syndrome (PCOS) is a neuroendocrine heterogeneous disease that frequently occurs in women of reproductive age, causing serious damage to the fertility, quality of life, and physical and mental health of patients. The current studies have proved that satisfactory endometrial receptivity is one of the conditions that must be met during the process of spermatovum position, adhesion and invasion, as well as the subsequent blastocyst division and embryo development. Women with PCOS may suffer a series of pathological processes such as changes in the expression levels of hormones and related receptors, imbalances in the proportion of miscellaneous cytokines, insulin resistance, low-grade chronic inflammation and endometrial morphological changes, which will damage endometrial receptivity from various aspects and obstruct fertilized egg nidation and embryonic development, thus causing adverse reproductive health events including infertility and abortion. This article reviews the research progress about characteristics and related influencing factors of endometrial receptivity in PCOS patients.

Background/Aims Achalasia is a rare disease, but the incidence is increasing recently. Peroral esophageal myotomy (POEM) is an effective treatment. Regurgitation is a common symptom before and after POEM. Our aim is to investigate the factors related to preoperative and postoperative reflux symptoms. Methods Our study was retrospective. The achalasia patients diagnosed by high-resolution manometry and gastroscopy were divided into reflux group and non-reflux group before and after POEM, respectively. General information, symptoms, POEM information, and manometric results were compared. Results (1) Ninety-six of 130 patients had reflux symptoms before POEM. The lower esophageal sphincter pressure (LESP) in the reflux group was significantly higher than the non-reflux group (P = 0.023), while integrated relaxation pressure (IRP) was similar. The reflux group had longer esophagus than the non-reflux group (P = 0.006). Reflux symptoms were not related to subtypes of achalasia. (2) Twenty-five of 84 patients had reflux symptoms after POEM. Postoperative Eckardt scores, LESP, and 4-second IRP (4sIRP) were significantly lower than the preoperative values (P < 0.001). The preoperative values and POEM information were similar between the postoperative 2 groups and there was no significant difference in the presence of preoperative reflux symptoms between 2 groups. The postoperative LESP and 4sIRP were similar between the 2 groups, however, the postoperative UESP was significantly higher in the reflux group than the non-reflux group (P = 0.042). The non-reflux group had more declines in Eckardt scores and LESP than the reflux group. Conclusion s The reflux symptoms of achalasia patients without treatment were mainly due to food retention. The postoperative reflux symptoms were not the sign of the excessive relaxation of lower esophageal sphincter.

Paper-based photodetectors have attracted extensive research interest owing to their environmentally friendly and highly deformable properties. Although perovskite crystals with outstanding optoelectronic properties have proved to be one of the most promising candidates for photodetectors, the development of paper-based photodetectors is hindered by the moisture absorptivity of paper and the instability of perovskite crystals in a humid atmosphere. In this study, we demonstrate a highly deformable and high-performance paper-based perovskite photodetector. The photodetector maintains its excellent performance even after exposure to a relative humidity of 60% for 120 h.

This meta-analysis was designed to assess the association between two loco-regional therapies, regional nodal irradiation (RNI) and axillary lymph node dissection (ALND), and breast cancer-related lymphoedema (BCRL). We searched PubMed, Science Direct, Embase, and BMJ databases for clinical studies published between January 1, 2010 and January 1, 2020, which assessed risk factors and incidence/prevalence of BCRL. Two investigators independently selected articles to extract relative data and calculate corresponding exact binomial 95% confidence intervals (CIs). In total, 93 articles were reviewed, from which 19 studies were selected. The extracted data were pooled using a random-effects mixed model. The incidence of lymphedema in the selected studies ranged from 3% to 36.7%, with a pooled incidence of 14.29% (95% CI 13.79–14.79). The summary odds ratio/risk ratio (OR/RR) of ALND vs. no-ALND was 3.67 (95% CI 2.25–5.98) with a heterogeneity (I2) of 81% (P

The power industry is changing rapidly. One approach to accommodate a part of the change is the use of energy storage, in particular superconducting magnetic storage systems (SMES). Both solenoidal and toroidal magnets storing a few megajoules have been designed and valuated for this application. Solenoidal magnets have extensive stray fields, which are one of the serious limitations. Toroidal magnets require more conductor and are more complicated in terms of construction and insulation. The existing power systems require 100 s of megawatts of power from energy storage systems, whereas the power capacity of a single SMES installation will be quite limited. Modular SMES may provide a solution to this limitation. This article describes a 3 MJ/2 MW modular toroidal SMES using YBCO tape. The design approach is aimed at the reduction of the insulation requirement; and a slit structure of the cooling plate is designed to reduce the eddy current loss. The cooling process and losses of the magnet are analyzed.

This paper proposes a routing algorithm of cluster tree network and further combines the hierarchical structure of clustering with that of neural network, and designs a data fusion algorithm based on clustering routing protocol. Then, aiming at the difficulty in selecting the weights of neural network, a weight optimization neural network based on particle swarm optimization algorithm is proposed and applied to multi-sensor fusion. The simulation results show that the number of cluster heads of ACEC protocol is more concentrated on the expected value and has good stability. The algorithm selects cluster head nodes by non-uniform clustering and dynamic threshold, which ensures the balanced distribution of cluster head nodes in the network, reduces the network energy consumption and prolongs the service life of the network. The success rate of ancec protocol is similar to debug protocol, but with the increase of transmission time, LEACH protocol and debug protocol do not consider the link quality factor when forwarding data, so the communication link quality is uneven when selecting the next hop relay point in each round, so the data transmission success rate has a relatively obvious downward trend. The fusion result is clearly better than the poor two sensors, but inferior to the best sensor. This is due to the low SNR of sensors SNL and SN2, so their recognition effect is relatively poor, which also conforms to the rule of multi-sensor fusion. The results show that the method based on qdpso-bp network fusion is feasible.

To probe the function of miR-518a-5p/Granzyme B (GZMB) in hypoxia/reoxygenation (H/R) -induced vascular endothelial cell injury.The key genes of myocardial infarction were screened by bioinformatic methods. The upstream micro RNAs (miRNAs) of GZMB were predicted by TargetScan. The binding of miR-518a-5p to GZMB was verified with luciferase reporter assay. The H/R model was constructed with human vascular endothelial cell (HUVEC) in vitro. Cell Counting Kit-8 (CCK8) assay was performed to detect cell proliferation. Western blot was utilized to evaluate the levels of indicated proteins.GZMB was up-regulated in patients with myocardial infarction and identified as the key gene by the bioinformatics analysis. Then the prediction from TargetScan indicated that miR-518a-5p, which is down-regulated in myocardial infarction patients, might be the potential upstream miRNA for GZMB. The following experiments verified that miR-518a-5p could bind to the 3'UTR of GZMB and negatively modulates GZMB expression. More importantly, the miR-518a-5p mimic enhanced cell proliferation and repressed apoptosis of H/R-injured HUVEC cells by inhibiting GZMB expression.We proved that miR-518a-5p could partly attenuate H/R-induced HUVEC cell injury by targeting GZMB, and perhaps the miR-518a-5p/GZMB axis could be potential therapeutic targets for myocardial infarction.

The aim of this study was to compare the safety and efficacy of radiofrequency ablation (RFA) with microwave ablation (MWA) for hepatocellular carcinoma (HCC) within the Milan criteria in challenging locations. This study retrospectively investigated 201 consecutive patients with Milan criteria HCCs who underwent RFA (RFA group, n = 150) or MWA (MWA group, n = 51) between January 2012 and December 2016. Overall survival (OS), recurrence-free survival (RFS), local tumor control, and treatment-related complications were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. Median follow-up duration was 36.7 months (range: 6.2–64.0 months). Cumulative 1-, 3-, and 5-year OS rates were 97.9%, 92.3%, and 80.6% in the MWA group and 96.4%, 87.4%, and 78.2% in the RFA group, respectively, (P = 0.450). Cumulative RFS rates at 1, 3, and 5 years were 93.2%, 74.4%, and 63.7% in the MWA group and 80.3%, 57.3%, and 49.6% in the RFA group, respectively, (P = 0.097). Multivariate analyses showed that variable categories “patient age above 65 years” (P = 0.004) and “more than one tumor” (P = 0.004) were associated with overall mortality, and “patient age above 65 years” (P = 0.048) and “tumor size greater than 3 cm” (P = 0.009) were associated with inferior RFS. The incidences of major complications were not significantly different between the two groups (3.3% vs 3.9%, P = 0.843). RFA and MWA were associated with comparable safety and efficacy for HCC within the Milan criteria in challenging locations. Further study in a large, multi-center patient cohort is necessary to validate the results.

Background: Ultrasound-guided central venous catheter placement has significantly improved the success rate of punctures and reduced the risk of complications. However, catheterizing the internal jugular vein under ultrasound guidance in neonates remains challenging. Methods: Ninety-six patients were screened for eligibility in this randomized controlled trial between November 2018 and October 2019. After meeting the inclusion criteria, 90 term neonates undergoing cardiothoracic, general, or neurosurgery procedures were randomly assigned to the modified dynamic needle tip positioning short-axis ( n = 45) or long-axis groups ( n = 45) using a computer-generated random numbers table. The primary outcome was the first-attempt success rate. The secondary outcomes included the total success rate, cannulation time, and incidence of cannulation-related complications, including hematoma, accidental arterial puncture, or pneumothorax. Data were compared between the two groups. Results: The success rate for the first attempt was higher (88.9% vs 64.4%; p = 0.001; relative risk, 1.4; 95% confidence interval, 1.1–1.8), while the cannulation time was shorter (171.0 ± 47.8 s vs 304.4 ± 113.5 s; p = 0.001; estimated difference, −133.4; 95% confidence interval, −170.1 to −96.7), in the modified dynamic needle tip positioning short-axis group compared with the long-axis group. Six hematomas and two common carotid artery punctures were identified in the long-axis group, while none were identified in the modified dynamic needle tip positioning short-axis group. Conclusions: The modified dynamic needle tip positioning short-axis out-of-plane technique enhanced the procedural efficacy and safety of internal jugular vein catheterization in neonates.

As a kind of renewable energy, the development and utilization of solar energy is valued by many countries. To accurately provide a basis for the use of solar energy in mainland China, the optimized empirical model is adopted to analyze the variation trends and spatial patterns in solar radiation (SR) during 1961–2016 based on the data of 31 SR sites and 500 sunshine duration (SD) stations. The results indicate that there are obvious discrepancies in the variation trends of annual SR and SD during 1961–2016, with trend conversion occurring in 1992 (SR) and 1980 (SD), respectively. Overall, annual SR decreases at the rate of -3.68 MJ/m²·a in China. Notably, SR declines at the rate of -16.95 MJ/m²·a during 1961–1989 (“dimming” stage), while it increases at the rate of 5.34 MJ/m²·a for 1990–2016 (“brightening” period). In addition, all seasons show a tendency of dimming first and then brightening except for autumn. Compared with SD, SR is more sensitive to changes in pollution, leading to a marked recovery with the reduction of pollution after the 1990s. This study provides a new perspective for the trend difference between SR and SD after the 1990s.

Objective Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with reduced bone mineral density (BMD) in persons with HIV (PWH). BMD provides information only about bone mineral quantity. Trabecular bone score (TBS) is a noninvasive tool that estimates bone microarchitecture. The aim of this study is to measure BMD and TBS of Chinese PWH after one-year ART. Methods We designed a retrospective study of adult Chinese PWH. Patients with a dual-energy X-ray absorptiometry (DXA) scan prior to ART initiation, and again 48 weeks later were included. Information regarding demographic and clinical history, HIV treatment history, BMD and TBS were collected. We analyzed differences in BMD and TBS over 48 weeks and associations between key risk factors and changes in BMD and TBS. Results Our study included 233 ​PWH (mean age ​= ​36.6 ​± ​11.1 years). Before ART initiation, 19.3% of PWH had normal BMD but abnormal TBS. Both BMD and TBS decreased after one-year ART. TDF and LPV/r-containing regimens were associated with greater declines in BMD at different site. Traditional risk factors such as old age, low BMI and female sex were associated with lower baseline TBS. Greater change in TBS over one year was associated with lower BMI and lower baseline CD4+ cell count, but unlike BMD measures, it was not correlated with treatment with TDF and LPV/r in our study population. Conclusions We present the first longitudinal analysis of change in TBS over 48 weeks compared with BMD among Asian PWH receiving ART. Before ART initiation, approximately 20% of PWH with impaired bone microarchitecture would not have been identified if DXA were used alone to assess for bone damage. Both BMD and TBS decreased after one-year ART. Change in TBS was not associated with different antiretroviral agents. The translational potential of this article The trabecular microarchitecture measured indirectly by TBS may provide clinicians additional information about bone damage in PWH.

Objective An epidemic of obesity is prevalent in the world. Recent evidences have linked obesity to male infertility , but the underlying mechanisms remain to be elucidated. Although spermatozoa dysfunction is the most cause of infertility and defective mitochondrial function plays a key role in impairing the sperm quality , there was little study on the role of mitochondria within spermatozoa in obese male infertility. Methods In this study, the semen parameters in Chinese obesity (BMI ≥ 28 kg/m2, n = 51) and normal (BMI of 18.5 to 23.9 kg/m2, n = 42) volunteers were investigated. Moreover, the oxidative stress injury was explored in human spermatozoa by examining the activity of intracellular SOD and MDA in sperm and LDH release from sperm. The activity test of mitochondrial respiratory chain complexes and the mitochondrial membrane potential were also performed. Results We found that obesity had a negative influence on the quality of semen. Furthermore, oxidative stress was detected in sperm from obese males. Oxidative stress-related mitochondrial dysfunction was also observed in the spermatozoa of obese males. Conclusions In total, these results indicated that oxidative stress-related mitochondrial dysfunction might be a reason for obesity-induced infertility, which provided the insights into the pathophysiological mechanism behind obesity-induced infertility in obese human males.

Background. Allergic rhinitis (AR) affects millions of people and is lack of effective treatment. CD40 is an important costimulatory molecule in immunity. However, few studies have focused on the role of CD40 in AR. Methods. In this study, we built mouse model of chronic AR. The mice were divided into the AR, control, intravenous CD40 siRNA, and nasal CD40 siRNA groups ( n = 6 each). We detected OVA-sIgE, IL-4, IL-5, IL-13, IL-10, IFN-γ, and TGF-β levels in serum and supernatant by ELISA, CD40+ splenic DCs, and Foxp3+ Tregs by flow cytometry and CD40 mRNA by RT2-PCR. We also used PAS and MT stains to assess tissue remodelling. Results. (1) The OVA-sIgE, IL-4, IL-5, and IL-13 levels in the serum or supernatant of nasal septal membrane of AR mice were significantly higher than control. After treated with CD40 siRNA, those indicators were significantly decreased. The IFN-γ, IL-10, and TGF-β levels in AR mice were significantly lower than that in control and were increased by administration of CD40 siRNA. (2) AR mice had significantly fewer Foxp3+ Tregs in the spleen than control mice. After treated with CD40 siRNA, AR mice had significantly more Foxp3+ Tregs. (3) AR mice exhibited a significantly higher CD40 mRNA levels than control. Administration of CD40 siRNA significantly reduced the CD40 mRNA level. (4) The AR mice showed significantly greater collagen deposition than the control in MT staining. Applications of CD40 siRNA significantly reduced the collagen deposition in AR mice. Conclusion. CD40 siRNA therapy shows promise for chronic AR as it significantly attenuated allergic symptoms and Th2-related inflammation and upregulated Foxp3+ Tregs. CD40 plays a role in tissue remodelling in AR, which can be inhibited by CD40 siRNA application.

The Hepatitis B (HB) vaccine is efficacious in preventing hepatitis B virus infection. However, the association between antibody response to the HB vaccine and dynamic immune repertoire changes in different cell subsets remains unclear. Nine healthy participants were administered three doses of HB vaccine following the 0, 1, 6 month schedule. Peripheral CD4(+) T, memory B (MB), naïve B (NB), and plasma cells (PCs) were sorted before vaccination and 7 days following each dose. The complementary determining region 3 of T-cell receptor β (TCRβ) chain and B-cell receptor (BCR) heavy chain (IgG, IgM, IgA) repertoires were analyzed by high-throughput sequencing. All nine participants elicited protective antibody titers to the vaccine at the end of immunization. Compared with the baseline, MB cells showed a significant increase in IgG usage and decreased IgM usage and repertoire diversity at the end of vaccination. TCRβ diversity changes were highly correlated with those of the BCR in MB cells in participants with a faster and robust antibody responses. The percentage of shared clonotypes between NB and MB cells, and MB cells and PCs were much higher than that between NB cells and PCs. The more clonotypes sharing the faster and stronger antibody responses were observed after HB vaccination. These results suggest the integral involvement of MB cells in vaccine immunization. Interaction between CD4(+) T and MB cells and B cell differentiation may improve antibody response to HB vaccine.

Litong Yao,1,2,* Xinyu Wang,2,* Yifan Zhong,3,* Yan Wang,4,* Jingyang Wu,3 Jin Geng,3 Yun Zhou,3 Jun Chen,3 Peng Guan,5 Yingying Xu,1 Lei Chen,3 Lei Liu,3 Yuedong Hu3 1Department of Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2China Medical University, Shenyang, 110001, People’s Republic of China; 3Department of Ophthalmology, First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 4Department of Radiology, General Hospital of Liaohe Oil Field, Panjin, 124010, People’s Republic of China; 5Department of Epidemiology, School of Public Health, China Medical University, Shenyang, 110122, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Liu; Yuedong HuDepartment of Ophthalmology, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning Province, People’s Republic of ChinaTel/Fax +86-24-8328-2277Email liuleijiao@163.com; laser2005sy@126.comBackground: This study aimed to investigate the association between the triglyceride–glucose (TyG) index and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes.Methods: In this nested case–control study, all diabetic participants were registered hospitalizations during 2012– 2018, including 596 with DR as cases and three matching controls per case. DR was assessed using Early Treatment Diabetic Retinopathy Study criteria. The TyG index was calculated: Ln (fasting blood glucose [mg/dL] × fasting triglycerides [mg/dL] ÷ 2). Multivariate logistic regression, a receiver-operating characteristic (ROC) curve, linear regression models, and mediation analysis were used to explore associations.Results: The TyG index was lower in DR and decreased as its severity advanced among 2,112 subjects (P=0.005). After confounders (sex, duration of diabetes, use of antidiabetic agents, heart rate, systolic blood pressure, pulse pressure, height, weight, body-mass index, and glycated hemoglobin) had been accounted for, there were significant associations between the TyG index and any-severity DR (OR 0.83, 95% CI 0.73– 0.95; P=0.006), as well as vision-threatening DR (VTDR; OR 0.53, 95% CI 0.36– 0.76; P=0.001). ROC analysis indicated that the TyG index showed significant discriminatory ability in any-severity DR (area under curve [AUC] 0.534, P=0.015) and VTDR (AUC 0.624, P=0.001).Conclusion: The TyG index was associated with the presence and severity of DR. Our findings suggest that the TyG index may become a useful biomarker in evaluating and following the presence of DR and VTDR.Keywords: diabetic retinopathy, triglyceride–glucose index, type 2 diabetes, hospital-based nested case–control study

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common disease with high mortality. Kidney involvement in AAV commonly performances as ANCA-associated glomerulonephritis (AAGN). We aimed to identify the risk factors for mortality and end-stage renal disease(ESRD) within 6 months since diagnosis in AAGN patients. A total of 350 AAGN patients were enrolled in our center between 2004 and 2017 retrospectively. We analyzed the demographic, clinical and follow-up data. Factors for mortality and ESRD were investigated with univariate and multivariate Cox regression models. The median follow-up time was 60.8 (IQR 31.2, 84.5) months and 40 (11.4%) patients died within the first 6 months. In the multivariate analysis, age ≥ 65 years (HR = 2.245, 95%CI 1.085-4.645, P = 0.029), high leukocyte counts (HR = 1.089, 95%CI 1.015-1.168, P = 0.018), high Birmingham Vasculitis Activity Score (BVAS) (HR = 1.089, 95%CI 1.017-1.165, P = 0.014), infection (HR = 2.023, 95%CI 1.013-4.042, P = 0.046) and low serum albumin (HR = 0.916, 95%CI 0.845-0.992, P = 0.030) were independent risk factors for all-cause mortality in the first 6 months. A total of 95 patients reached ESRD within the first 6 months. The renal survival rate was 72.9% at 6 months. Multivariate analysis showed that high BVAS (HR = 1.198, 95%CI 1.043-1.376, P = 0.011), high daily urine protein (HR = 1.316, 95%CI 1.046-1.656, P = 0.019) and low eGFR (HR = 0.877, 95%CI 0.804-0.957, P = 0.003) were independent risk factors for ESRD. The mortality and ESRD rates were high in the first 6 months for AAGN patients. High disease activity evaluated by BVAS impacted both on patients' survival and renal survival, while over 65 years of age and infection were risk factors for mortality.

Diabetic neuropathic pain (DNP) is a common complication of diabetes characterized by persistent pain. Emerging evidence links astrocytes to mechanical nociceptive processing, and the motor cortex (MCx) is a cerebral cortex region that is known to play a key role in pain regulation. However, the association between MCx astrocytes and DNP pathogenesis remains largely unexplored. Here, we studied this association using designer receptors exclusively activated by designer drugs to specifically manipulate MCx astrocytes. We proved that the selective inhibition of MCx astrocytes reduced DNP in streptozocin (STZ)-induced DNP models and discovered a potential mechanism by which astrocytes release cytokines, including TNF-α and IL-1β, to increase neuronal activation in the MCx, thereby regulating pain. Together, these results demonstrate a pivotal role for MCx astrocytes in DNP pathogenesis and provide new insight into DNP treatment strategies.

Background/Objectives Coexistent seizures add complexity to the burden of Alzheimer's disease (AD). We aim to estimate the incidence and prevalence of coexistent seizures and AD and summarize characteristics. Design A systematic review and meta‐analysis (PROSPERO protocol registration CRD42020150479). Setting Population‐, community‐, hospital‐, or nursing home‐based. Participants and measurements Thirty‐nine studies reporting on seizure incidence and prevalence in 21,198 and 380,777 participants with AD, respectively, and AD prevalence in 727,446 participants with seizures. When statistical heterogeneity and inconsistency (assessed by Q statistic and I2) were not shown, rates were synthesized using random effect. Results Studies were conducted in Australia, Brazil, Finland, France, Ireland, Italy, Japan, Netherlands, Portugal, Sweden, Taiwan, United Kingdom, and United States. The incidence of seizures among people with clinically diagnosed AD ranged from 4.2 to 31.5 per 1000 person‐years. Prevalence of seizures among people with clinically diagnosed AD ranged from 1.5% to 12.7% generally, but it rose to the highest (49.5% of those with early‐onset AD) in one study. Meta‐analysis reported a combined seizure prevalence rate among people with pathologically verified AD at 16% (95% confidence interval [CI] 14–19). Prevalence of seizure in autosomal dominant AD (ADAD) ranged from 2.8% to 41.7%. Being younger was associated with higher risk of seizure occurrence. Eleven percent of people with adult‐onset seizures had AD (95%CI, 7‐14). Conclusion Seizures are common in those with AD, and seizure monitoring may be particularly important for younger adults and those with ADAD.