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The disease burden related to hepatocellular carcinoma (HCC) is increasing. Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them. Recently, the approval of immune checkpoint inhibitors (ICIs) has provided a new therapeutic strategy for HCC. It is noteworthy that the positive outcomes of the phase III clinical trial IMBrave150 [atezolizumab (anti-programmed cell death ligand 1 antibody) combined with bevacizumab (anti-vascular endothelial growth factor monoclonal antibody)], showed that overall survival and progression-free survival were significantly better with sorafenib. This combination therapy has become the new standard therapy for advanced HCC and has also attracted more attention in the treatment of HCC with anti-angiogenesis-immune combination therapy. Currently, the synergistic antitumor efficacy of this combination has been shown in many preclinical and clinical studies. In this review, we discuss the mechanism and clinical application of anti-angiogenics and immunotherapy in HCC, outline the relevant mechanism and rationality of the combined application of anti-angiogenics and ICIs, and point out the existing challenges of the combination therapy.

Adenosine deaminase (ADA) is a key enzyme that catalyzes the deamination of adenosine into inosine, which eventually decomposes into uric acid (UA). A body of papers have reported that adenosine and UA are closely related to cerebrovascular events. However, the association between serum ADA activity and acute cerebral infarction (ACI) remains unclear.7913 subjects were enrolled, including 3968 ACI patients and 3945 controls, in this study. An automatic biochemistry analyzer was used to determine serum activity.Serum ADA activity was found that was significantly decreased in patients with ACI (10.10 ± 3.72 U/L) compared to those without ACI (11.07 ± 2.85 U/L,Serum ADA concentrations in patients with ACI are markedly decreased, suggesting that the decreased ADA concentrations may be involved in the pathogenesis of ACI. We hypothesized that decreased ADA activity may be an adaptive mechanism to maintain adenosine levels and protect against ischemic brain injury.

Hepatitis A virus (HAV) live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans. Recently, type I interferon (IFN) receptor-deficient mice were shown to be susceptible to HAV infection. Herein, we sought to determine the infection and replication dynamics of the H2 in Ifnar

Circulating metabolites have been implicated in stroke pathogenesis, but their genetic determinants are understudied. Using a Mendelian randomization approach, our aim was to provide evidence for the relationship of circulating metabolites and the risk of stroke and its subtypes.Genetic instruments of 102 circulating metabolites were obtained from a genome-wide association study, including 24,925 European individuals. Stroke was extracted from the MEGASTROKE dataset (67,162 cases; 454,450 controls) and a lacunar stroke dataset (7338 cases; 254,798 controls). The magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury were evaluated by a genome-wide association study of white matter hyperintensities (N = 18,381), fractional anisotropy (N = 17,663), mean diffusivity (N = 17,467) and brain microbleeds (N = 25,862). The inverse-variance weighted method Mendelian randomization was used as the primary analytical method, and directional pleiotropy and heterogeneity were examined in sensitivity analyses.A genetic predisposition to a higher level of cholesterol in small and low-density lipoprotein (LDL) was associated with risk of stroke (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.08-1.21, p = 5.98 × 10Genetically determined levels of lipids in small LDL were associated with the risk of stroke, suggesting that a therapeutic strategy targeting small LDL levels may be crucial for stroke prevention. HDL-C was positively associated with the risk of intracerebral haemorrhage.

The cellular heterogeneity and genetic features of stemness of adipose-derived stromal cells (ADSCs) remain unclear. Using single-cell RNA sequencing (scRNA-seq), we investigated the genomic features of the stemness gene in ADSCs with genetic variability. We cultured the ADSCs isolated from the fat waste of a healthy adult volunteers undergoing cosmetic plastic surgery to the third generation, used the BD Rhapsody platform to perform scRNA-seq, then used Monocle2 to analyze the growth and development trajectory of ADSCs, Cellular Trajectory Reconstruction Analysis Using Gene Counts and Expression (CytoTRACE) to evaluate the stemness gene characteristics in ADSCs clusters, and Beam to analyze the expression change characteristics of the main stemness related genes of ADSCs. According to the scRNA-seq data of 5325 ADSCs, they could be classified into nine cell clusters. According to CytoTRACE analysis, Cluster 3 of ADSCs had the highest stemness, whereas Cluster 8 had the lowest stemness. Pseudotime analysis revealed that Cluster 3 of ADSCs was primarily dispersed in the middle part of the growth and development trajectory, whereas Cluster 8 was primarily distributed at the end. We summarized the stemness of Cluster 3 in ADSCs with high expression of TPM1 and CCND1 genes in the metaphase of growth and development is the strongest, whereas the stemness of Cluster 8 with high expression of FICD, CREBRF, SDF2L1, HERPUD1, and HYOU1 genes in the telophase of growth and development is the weakest, providing a theoretical basis for screening and improving the therapeutic effect of ADSCs in cell transplantation research.

Intrahepatic cholangiocarcinoma (iCCA) is a lethal hepatobiliary malignancy that arises from the epithelial cells of the intrahepatic bile ducts, accounting for approximately 10% of cholangiocarcinoma (CCA). According to the 2019 World Health Organization (WHO) classification of tumors of the digestive system, iCCA is divided into small-duct type (SD-type) and large-duct type (LD-type). However, it remains unknown which molecular events contribute to the disparity. To explore the proteomic characteristics of iCCA, we used an isobaric tag for relative and absolute quantitation (iTRAQ) based quantitative proteomics strategy to investigate stably dysregulated proteins in the SD-type and LD-type of iCCA tissues. Importantly, we found three glycolysis/gluconeogenesis-related enzymes, triosephosphate isomerize 1 (TPI1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and phosphoglycerate kinase 1 (PGK1), were significantly down-regulated in the LD-type iCCA, which were further confirmed by immunohistochemistry using tissue microarray. Moreover, we demonstrated that the knockdown of these three candidate proteins by siRNAs notably increased the ability of proliferation in two CCA cell lines (HuH28 and RBE), suggesting that effective down-regulation of the glycolysis/gluconeogenesis pathway might be an underlying novel mechanism contributing to the LD-type iCCA.

Background Although the diagnostic value of plasma heat-shock protein 90α (HSP90α) in hepatocellular carcinoma (HCC) has been previously reported, the causal effect of the plasma HSP90α levels on HCC prognosis remains largely unclear. To this extent, we sought to assess whether the plasma HSP90α acts as a prognostic factor for HCC patients. Methods A total of 2150 HCC patients were included in this retrospective study between August 2016 and July 2021. Plasma HSP90α levels were tested within a week before treatment and their association with prognosis was assessed. Results An optimal cutoff value of 143.5 for the HSP90α based on the overall survival (OS) was determined using the X-tile software. HCC patients with HSP90α p p Conclusions Our study confirmed that the plasma HSP90α level can be used as a prognostic biomarker for HCC.

Li et al delineate a novel technique for assessing measurable residual disease (MRD) by the assessment of isolated leukemia stem cells (LSCs). They report that assessment of MRD in LSCs provides a better prediction of outcome than standard multiparameter flow cytometry.

In the past decade, digital PCR (dPCR), as a new nucleic acid absolute quantification technology, has been widely used in clinical research. dPCR does not rely on the standard curve and has a higher tolerance to inhibitors. Therefore, it is more accurate than quantitative real-time PCR (qPCR) for the absolute quantification of target sequences. In this article, we aim to review the application of dPCR in noninvasive prenatal testing (NIPT). We focused on the progress of dPCR in screening and identifying fetal chromosome aneuploidies and monogenic mutations. We introduced some common strategies for dPCR in NIPT and analyzed the advantages and disadvantages of different methods. In addition, we compared dPCR with qPCR and next-generation sequencing, respectively, and described their superiority and shortcomings in clinical applications. Finally, we envisaged what the future of dPCR might be in NIPT. Although dPCR can provide reproducible results with improved accuracy due to the digital detection system, it is essential to combine the merits of dPCR and other molecular techniques to achieve more effective and accurate prenatal diagnostic strategies.

From the perspective of comprehensive modernization, the Sinicization and modernization of Marxism are inseparable from the popularization of Marxism, which will promote the Sinicization and modernization of Marxism and make it more practical and vital. Time has changed, and the traditional ways and methods have faced a new pattern, but they still contain the practical value worth exploring and give full play to the contemporary function of beneficial historical experience. On the basis of drawing on historical experience, we follow the idea of establishing basic principles, focusing on important ways and looking for the development prospects, and discuss the discussion layer by layer in clear guidance, grasping the key points and thinking about the future. In today’s era, with the development of the network, the popularization of Marxist philosophy has ushered in a period of opportunity for development, but at the same time, the development has also encountered some challenges. Based on the actual situation of contemporary China, in recent years, the popularization of Marxism has made great achievements, but it also presents the phenomenon of unbalanced overall development, low operation efficiency, and uneven cooling between the officials and the people. Under these conditions, popularizing network knowledge, developing network culture, improving relevant laws, and making its theories more popular are all important ways to realize the popularization of Marxist philosophy. The research on the popularization of Marxism and the academic level is more profound, while the practical practice is more lacking. In order to correct the bias of emphasizing science and theory, it is of strong practical significance to conduct in-depth theoretical research and practical discussion from the perspective of “ways and methods.”

Wistar-Kyoto (WKY) rats as an endogenous depression model partially lack a response to classic selective serotonin reuptake inhibitors (SSRIs). Thus, this strain has the potential to be established as a model of treatment-resistant depression (TRD). However, the SSRI resistance in WKY rats is still not fully understood. In this study, WKY and control rats were subjected to a series of tests, namely, a forced swim test (FST), a sucrose preference test (SPT), and an open field test (OFT), and were scanned in a 7.0-T MRI scanner before and after three-week citalopram or saline administration. Behavioral results demonstrated that WKY rats had increased immobility in the FST and decreased sucrose preference in the SPT and central time spent in the OFT. However, citalopram did not improve immobility in the FST. The amplitude of low-frequency fluctuation (ALFF) analysis showed regional changes in the striatum and hippocampus of WKY rats. However, citalopram partially reversed the ALFF value in the dorsal part of the two regions. Functional connectivity (FC) analysis showed that FC strengths were decreased in WKY rats compared with controls. Nevertheless, citalopram partially increased FC strengths in WKY rats. Based on FC, global graph analysis demonstrated decreased network efficiency in WKY + saline group compared with control + saline group, but citalopram showed weak network efficiency improvement. In conclusion, resting-state fMRI results implied widely affected brain function at both regional and global levels in WKY rats. Citalopram had only partial effects on these functional changes, indicating a potential treatment resistance mechanism.

To explore whether tai chi and Qigong can improve cognitive function in patients with neurological disorders.The PubMed, Embase, Cochrane Central Register of Controlled Trials, SinoMed Database, Chinese National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database (VIP) databases were searched from inception to December 24, 2021. The methodological quality of the included studies was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions criteria.This study included 2,754 participants from 40 randomized controlled trials (RCT)s with low to high methodological quality. Analysis of active and non-active comparisons showed significant effects for tai chi/Qigong (P0.05) on global cognitive function, executive function, memory, visuospatial ability, and cognitive processing speed.Tai chi and Qigong were effective interventions to improve cognition in patients with Parkinson's disease, stroke, mild cognitive impairment, dementia, and traumatic brain injury; however, no RCTs were performed for other neurological disorders.

RATIONALE: Genetic studies of Idiopathic Pulmonary Fibrosis (IPF) have improved our understanding of this disease, but not all causal loci have been identified. OBJECTIVE: To identify genes enriched with rare deleterious variants in IPF and familial pulmonary fibrosis. METHODS: We performed gene burden analysis of whole exome data, tested single variants for disease association, conducted KIF15 functional studies, and examined human lung single cell RNA sequencing data. MEASUREMENT AND MAIN RESULTS: Gene burden analysis of 1,725 cases and 23,509 controls identified heterozygous rare deleterious variants in KIF15, a kinesin involved in spindle separation during mitosis, and three telomere-related genes (TERT, RTEL1, PARN). KIF15 was implicated in autosomal dominant models of rare deleterious variants (OR 4.9 [95%CI 2.7, 8.8] P=2.55x10-7) and rare protein-truncating variants (OR 7.6 [3.3, 17.1], P=8.12x10-7). Meta-analysis of the discovery and replication cohorts, including 2,966 cases and 29,817 controls, confirm the involvement of KIF15, plus the three telomere-related genes. A common variant within a KIF15 intron (rs74341405, OR 1.6 [1.4, 1.9], P=5.63x10-10) is associated with IPF risk, confirming a prior report. Lymphoblastoid cells from individuals heterozygous for the common variant have decreased KIF15 and reduced rates of cell growth. Cell proliferation is dependent on KIF15 in the presence of an inhibitor of Eg5/KIF11, which has partially redundant function. KIF15 is expressed specifically in replicating human lung cells, and shows diminished expression in replicating epithelial cells of IPF patients. CONCLUSIONS: Both rare deleterious variants and common variants in KIF15 link a non-telomerase pathway of cell proliferation with IPF susceptibility.

Postoperative cognitive dysfunction (POCD) is a severe postsurgical complication, but its underlying mechanisms remain unclear. Neuroinflammation mediated by microglial activation plays a major role in POCD pathophysiology. Upregulation of vascular cell adhesion molecule 1 (VCAM1) on brain endothelial cells is closely correlated with microglial activation in the mouse hippocampus. However, the role of VCAM1 upregulation in microglial activation remains unknown. Soluble VCAM1 (sVCAM1) activates the very late antigen-4 (VLA-4) receptor under inflammatory conditions. Therefore, we hypothesized that sVCAM1 which is shed from VCAM1 contributes to POCD by triggering hippocampal microglial activation through the VLA-4 receptor. We found that VCAM1 and sVCAM1 expression in the mouse hippocampus was upregulated after surgery, and the upregulation was accompanied by hippocampal microglial activation. sVCAM1 levels in mouse and human serum were increased after surgery. Anti-VCAM1 treatment inhibited microglial activation, proinflammatory cytokine production, VLA-4 expression and P38 mitogen-associated protein kinase (MAPK) pathway activation and attenuated hippocampal-dependent cognitive dysfunction. In vitro, recombinant sVCAM1 promoted M1 polarization in BV2 cells, increased VLA-4 expression and activated the P38 MAPK pathway. These effects were reversed by VLA-4 receptor blockade. Anti-VLA-4 treatment ameliorated hippocampal-dependent cognitive dysfunction after surgery by inhibiting microglial activation, proinflammatory cytokine production and P38 pathway activation. In conclusion, increased sVCAM1 in the hippocampus is involved in microglial activation and cognitive dysfunction induced by surgery. Inhibiting the sVCAM1-VLA-4 interaction in microglia may be a therapeutic strategy for POCD.

Timely evaluation of the protective effects of Coronavirus Disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is urgently needed to inform pandemic control planning. Based on 78 vaccine efficacy or effectiveness (VE) data from 49 studies and 1,984,241 SARS-CoV-2 sequences collected from 31 regions, we analyzed the relationship between genetic distance (GD) of circulating viruses against the vaccine strain and VE against symptomatic infection. We found that the GD of the receptor-binding domain of the SARS-CoV-2 spike protein is highly predictive of vaccine protection and accounted for 86.3% (P = 0.038) of the VE change in a vaccine platform-based mixed-effects model and 87.9% (P = 0.006) in a manufacturer-based model. We applied the VE-GD model to predict protection mediated by existing vaccines against new genetic variants and validated the results by published real-world and clinical trial data, finding high concordance of predicted VE with observed VE. We estimated the VE against the Delta variant to be 82.8% (95% prediction interval: 68.7–96.0) using the mRNA vaccine platform, closely matching the reported VE of 83.0% from an observational study. Among the four sublineages of Omicron, the predicted VE varied between 11.9% and 33.3%, with the highest VE predicted against BA.1 and the lowest against BA.2, using the mRNA vaccine platform. The VE-GD framework enables predictions of vaccine protection in real time and offers a rapid evaluation method against novel variants that may inform vaccine deployment and public health responses.

Genome-wide rare variant studies of IPF patients of non-European ancestry have been understudied. Here, we evaluate the enrichment of rare genetic variants of 241 unrelated non-European cases, representing individuals of Latino, African, South Asian, East Asian, and Other Admixed ancestry. Gene burden analysis of deleterious rare (protein-truncating and missense) variants demonstrate an excess of TERT rare damaging variants (OR 67.1, 95% CI [23.1, 195.0], P = 9.4 x 10-14) in non-European subjects. Analysis by ancestry demonstrated an excess of rare, damaging TERT variants in the Latino subgroup (OR 80.9, 95% CI [17.3, 383.8], P = 2.6 x 10-8). Although the non-European group did not show enrichment of PARN, RTEL1, and KIF15 rare deleterious variants, these groups all showed a trend in the same direction as the European ancestry group. For TERT and KIF15, the inclusion of IPF patients of non-European ancestry led to a higher odds ratios and increased evidence in favor of rare deleterious variant contributions, thus demonstrating the increased power of multi-ethnic studies over single-ethnicity studies. To our knowledge, this is the first study that confirms the involvement of rare deleterious TERT variants for IPF patients of Latino and non-European ancestry. To better understand the genetic underpinnings of IPF patients of all ancestries, additional work will be needed to broaden patient recruitment to normalize imbalances.

Due to the paucity of data and controversy regarding the etiology and surgical approach for managing anorectal prolapse (ARP) after anorectoplasty, we sought to investigate the underlying anatomic disorder and the surgical outcome in managing this challenging complication.We performed a retrospective study on 83 patients with ARP related to anorectal malformations (ARM). Logistic regression analyses were performed to detect the risk factors for the ARP severity. Surgical procedures were stratified according to identified anatomical abnormalities and surgical outcomes were analyzed.50 patients (62.7%) had high-type ARM. The original anorectoplasty had a higher rate of ARP in laparoscopic-assisted anorectoplasty (n = 49, 59.0%) versus posterior sagittal anorectoplasty (n = 11, 13.3%). ARP was associated with rectal fat hyperplasia (67.5%), dilated muscular tunnel (79.5%), longitudinal muscle (LM) discontinuity (16.9%), rectal dilation (22.9%), mislocated anus (7.2%), and excessive mobile mesorectum (3.6%). Based on the ARP severity, the patients were divided into a severe group (Group 1, n = 38) and a moderate group (Group 2, n = 45). Binary logistic regression analysis showed that hyperplasia rectal fat (OR 4.55, 95% CI 1.16-17.84), rectal dilation (OR 4.21, 95% CI 1.05-16.94), and high-type ARM (OR 2.90, 95% CI 1.14-7.39) were independent risk factors for the development of severe ARP. Complications after stratified surgical repair included wound infection in six patients (7.2%), anal stenosis in one patient (1.2%), and ARP recurrence in two patients (2.4%). Twenty-six patients without colostomy before prolapse repair were followed up for 2 to 12 years. All the patients maintained voluntary bowel movements. Following ARP repair, there was an overall higher rate of no soiling or grade 1 soiling (88.5 vs. 65.4%), but 3 of 12 patients with grade 2 constipation were upgraded to grade 3.Our study shows that ARM-related anorectal prolapse is associated with excessive rectum, hyperplasia of rectal fat, mobile mesorectum, loose muscular tunnel, LM discontinuity, and anal mislocation. Surgical repair with techniques stratified according to the patients' underlying risk factors is effective to prevent recurrence and improve the soiling continence.

Bladder cancer is the most prevalent tumor of the urinary tract, ranking seventh in males and seventeenth in women. The gold standard for the definitive diagnosis and initial treatment of non-muscle-invasive bladder cancer is transurethral resection (TUR) of the bladder tumor. The ability to accurately detect disease, typically in the presence of hematuria as well as to detect early recurrent tumors in patients with a history of NMIBC, is critical to the successful treatment of non-muscle-invasive bladder cancer (NMIBC). Unfortunately, the current biomarker landscape for NMIBC is still evolving. Cystoscopy remains the gold standard, but it can still miss 10% of tumors. As a result, physicians frequently employ additional diagnostic tools to aid in the diagnosis of bladder cancer. The efficacy of transurethral bipolar plasma needle electrodes and ring electrodes in the treatment of non-muscle-invasive bladder cancer was compared and analyzed in this study. During our study, 100 patients with non-muscle-invasive bladder cancer admitted to our hospital between June 2019 and June 2020 were randomly assigned to a control group and an observation group, with 50 cases in each group. The observation group was given a bipolar plasma needle electrode, while the control group was given a bipolar plasma ring. Patients continued to receive bladder irrigation chemotherapy as well as traditional Chinese medicine (TCM) treatment as part of our treatment plan, while the control group received only bladder irrigation chemotherapy. Clinical factors such as operational blood loss, catheter indention time, length of hospital stay, and others were compared between the two groups. When the risk grades in the two groups were compared, the observation group had fewer medium- and high-risk grades than the control group, but the control group had more low-risk grades, with statistical significance (P

Purpose. To explore the relationship between craniomaxillofacial features and psychological distress among adult pretreatment orthodontic patients. Methods. A group of 190 patients (95 males and 95 females) was included. Questionnaires including the Kessler psychological distress scale (K10) were sent to patients, and cephalograms were collected. Patients were divided into two groups according to K10 score: psychological distress group ( score ≥ 20 ) and no psychological distress group ( score < 20 ). Nineteen hard tissue and thirteen soft tissue parameters were traced on cephalograms to characterize the craniomaxillofacial features. Results. There was no significant difference in gender or age distribution between the two groups. Male patients with psychological distress showed statistically significantly larger anterior facial height (AFH) (126.62 mm vs. 120.97 mm), upper lip length (25.11 mm vs. 23.26 mm), and smaller overbite (1.21 mm vs. 2.75 mm) than patients without psychological distress. Male patients with hyperdivergent pattern and open bite were more likely to have psychological distress. None of the parameters showed statistical differences across groups in females. Frankfort-mandibular plane angle ( r = 0.235 ), Bjork’s sum ( r = 0.311 ), AFH ( r = 0.322 ), overbite ( r = − 0.238 ), AFH/posterior facial height ( r = 0.251 ), and upper anterior facial height (UAFH)/lower anterior facial height (LAFH) ( r = − 0.230 ) were correlated with K10 score in males. After adjusting gender and age, the AFH ( B = 0.147 ) and UAFH/LAFH ( B = − 14.923 ) were significantly related with the K10 score. Conclusion. Psychological distress was mainly correlated with hyperdivergent pattern, open bite, and larger lower anterior facial height proportion in pretreatment orthodontic patients. Orthodontists should be aware of the possible underlying psychological distress in patients with specific craniomaxillofacial features. Clinical assessment of psychological distress may need to take into account gender differences in patients.

Power generation through harvesting human thermal energy provides an ideal strategy for self-powered wearable design. However, existing thermoelectric fibers, films, and blocks have small power generation capacity and poor flexibility, which hinders the development of self-powered wearable electronics. Here, we report a multifunctional superelastic graphene-based thermoelectric (TE) sponge for wearable electronics and thermal management. The sponge has a high Seebeck coefficient of 49.2 μV/K and a large compressive strain of 98%. After 10 000 cyclic compressions at 30% strain, the sponge shows excellent mechanical and TE stability. A wearable sponge array TE device was designed to drive medical equipment for monitoring physiological signals by harvesting human thermal energy. Furthermore, a 4 × 4 array TE device placed on the surface of a normal working Central Processing Unit (CPU) can generate a stable voltage and reduce the CPU temperature by 8 K, providing a feasible strategy for simultaneous power generation and thermal management.

Repeated outbreaks of coronavirus disease 2019 (COVID-19) have forced people to shift most of their work and life activities from offline to online, leading to a growing problem of Internet dependence and even Internet addiction. However, the mechanism of the association between COVID-19-related intolerance of uncertainty (COVID-19 IU) and Internet addiction during the second wave of COVID-19 is still unclear. The current study explored the association between COVID-19 IU and Internet addiction as mediated by depression and risk perception based on the Uncertainty-Depression-Perception-Addiction model (UDPA). A total of 1,137 adult participants were recruited, and COVID-19 IU, depression, risk perception, Internet addiction, and demographic variables were analyzed. The results showed that COVID-19 IU was significantly and positively associated with Internet addiction and that this relationship was mediated in parallel by depression and risk perception. Our findings further extend the Interaction of Person-Affect-Cognition-Execution (I-PACE) model from the perspective of applicability in the unique context of COVID-19. Furthermore, the study suggests that individuals could decrease their dependence on the Internet to prevent Internet addiction during the second wave of the pandemic through effective interventions that include lowering COVID-19 IU, improving emotion regulation, and developing reasonable perceptions of risk.

Globally, nonpharmaceutical interventions for COVID-19, including stay-at-home policies, limitations on gatherings and closure of public spaces, are being lifted. We explored the effect of lifting a stay-at-home policy on virus resurgence under different conditions.Using confirmed case data from Toronto, Canada, between Feb. 24 and June 24, 2020, we ran a compartmental model with household structure to simulate the impact of the stay-at-home policy considering different levels of compliance. We estimated threshold values for the maximum number of contacts, probability of transmission and testing rates required for the safe reopening of the community.After the implementation of the stay-at-home policy, the contact rate outside the household fell by 39% (from 11.58 daily contacts to 7.11). The effective reproductive number decreased from 3.56 (95% confidence interval [CI] 3.02-4.14) on Mar. 12 to 0.84 (95% CI 0.79-0.89) on May 6. Strong adherence to stay-at-home policies appeared to prevent SARS-CoV-2 resurgence, but extending the duration of stay-at-home policies beyond 2 months had little added effect on cumulative cases (25 958 for 65 days of a stay-at-home policy and 23 461 for 95 days, by July 2, 2020) and deaths (1404 for 65 days and 1353 for 95 days). To avoid a resurgence, the average number of contacts per person per day should be kept below 9, with strict nonpharmaceutical interventions in place.Our study demonstrates that the stay-at-home policy implemented in Toronto in March 2020 had a substantial impact on mitigating the spread of SARS-CoV-2. In the context of the early pandemic, before the emergence of variants of concern, reopening schools and workplaces was possible only with other nonpharmaceutical interventions in place.

Objective To develop and validate a magnetic resonance imaging (MRI)-based machine learning classifier for evaluating the tumor-stroma ratio (TSR) in patients with pancreatic ductal adenocarcinoma (PDAC). Materials and Methods In this retrospective study, 148 patients with PDAC underwent an MR scan and surgical resection. We used hematoxylin and eosin to quantify the TSR. For each patient, we extracted 1,409 radiomics features and reduced them using the least absolute shrinkage and selection operator logistic regression algorithm. The extreme gradient boosting (XGBoost) classifier was developed using a training set comprising 110 consecutive patients, admitted between December 2016 and December 2017. The model was validated in 38 consecutive patients, admitted between January 2018 and April 2018. We determined the performance of the XGBoost classifier based on its discriminative ability, calibration, and clinical utility. Results A log-rank test revealed significantly longer survival in the TSR-low group. The prediction model displayed good discrimination in the training (area under the curve [AUC], 0.82) and validation set (AUC, 0.78). While the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the training set were 77.14%, 75.00%, 0.76%, 0.84%, and 0.65%, respectively, those for the validation set were 58.33%, 92.86%, 0.71%, 0.93%, and 0.57%, respectively. Conclusion We developed an XGBoost classifier based on MRI radiomics features, a non-invasive prediction tool that can evaluate the TSR of patients with PDAC. Moreover, it will provide a basis for interstitial targeted therapy selection and monitoring.

The clinical success of the percutaneous coronary intervention (PCI) is highly dependent on endovascular manipulation skills and dexterous manipulation strategies of interventionalists. However, the analysis of endovascular manipulations and related discussion for technical skill assessment are limited. In this study, a multilayer and multimodal-fusion architecture is proposed to recognize six typical endovascular manipulations. The synchronously acquired multimodal motion signals from ten subjects are used as the inputs of the architecture independently. Six classification-based and two rule-based fusion algorithms are evaluated for performance comparisons. The recognition metrics under the determined architecture are further used to assess technical skills. The experimental results indicate that the proposed architecture can achieve the overall accuracy of 96.41%, much higher than that of a single-layer recognition architecture (92.85%). In addition, the multimodal fusion brings significant performance improvement in comparison with single-modal schemes. Furthermore, the K -means-based skill assessment can obtain an accuracy of 95% to cluster the attempts made by different skill-level groups. These hopeful results indicate the great possibility of the architecture to facilitate clinical skill assessment and skill learning.

Purpose. We aimed to explore the relationship between temporomandibular disorders (TMDs) and craniofacial morphology in orthodontic patients. Methods. Altogether, 262 orthodontic patients were included and divided into two groups according to their Fonseca Anamnestic Index (FAI) scores: a no-TMD group (control group, FAI

The aberrant expression of miRNA is strongly linked to numerous stages of triple-negative breast cancer (TNBC) progression, and it plays an indispensable role in the process from tumor onset and progress to invasion and metastasis. In this study, we first transfected miR-129-1-3p mimics and inhibitor into MDA-MB-231 TNBC cells, respectively. Then, we assessed the pathological role of miR-129-1-3p in MDA-MB-231 cells. The results showed that miR-129-1-3p were successfully inserted into MDA-MB-231 cells. Besides, miR-129-1-3p could distinctively repress the growth, migration along with infiltration of MDA-MB-231 cells, which might be related to the inhibition of GRIN2D expression. Our results indicate that miR-129-1-3p was illustrated to serve as a tumor repressor via targeting GRIN2D in TNBC cells and highlight that the restoration of miR-129-1-3p might be a new treatment target for TNBC.

Obstructive sleep apnea (OSA) is associated with increases in QT interval corrected for heart rate (QTc interval) and QT variability index (QTVI) and sleep bruxism (SB) is prevalent in OSA patients.To examine whether QTc interval and QT variability were changed during episodes of rhythmic masticatory muscle activities (RMMAs)/SB in SB patients with and without OSA.The RR and QTc intervals, and QTVI during RMMAs with or without accompanied limb movements (RMMAs/LMs) in 10 normal controls and 10 SB patients without OSA and during apneic and recovery periods of OSA in 10 SB patients with OSA were analysed.In the SB patients without OSA and controls, QTc intervals and QTVI were significantly increased during RMMAs/LMs compared with those during the 10 s periods (from 10OSA and RMMAs/LMs events were associated with longer QTc intervals and higher QTVI, and RMMAs/LMs might contribute to these changes associated with OSA events accompanied with RMMAs/LMs.

The decreased expression of tumour suppressor candidate 3 (TUSC3) is associated with proliferation in several types of cancer, leading to an unfavourable prognosis. The present study aimed to assess the cellular and molecular function of TUSC3 in patients with cervical squamous cell carcinoma (CSCC). Levels of mRNA expressions of TUSC3 were analysed in CSCC tissues and six cell lines using qRT-PCR. Immunohistochemistry(IHC) was used to evaluate the protein expression level of TUSC3 in four paired specimens, 220 paraffin-embedded CSCC specimens and 60 cases of normal cervical tissues(NCTs), respectively. Short hairpin RNA interference was employed for TUSC3 knockdown. Cell proliferation, migration and invasion were evaluated using growth curve, MTT assay, wound healing, transwell assay and xenograft tumour model, respectively. The results demonstrated that TUSC3 mRNA and protein expression levels were downregulated in CSCC samples. Multivariate and univariate analyses indicated that TUSC3 was an independent prognostic factor for patients with CSCC. Decreased TUSC3 expression levels were significantly associated with proliferation and an aggressive phenotype of cervical cancer cells both in vitro and in vivo. Moreover, the knockdown of TUSC3 promoted migration and invasion of cancer cells, while the increased expression of TUSC3 exhibited the opposite effects. The downregulation of TUSC3 facilitated proliferation and invasion of CSCC cells through the activation of the AKT signalling pathway. Our data demonstrated that the downregulation of TUSC3 promoted CSCC cell metastasis via the AKT signalling pathway. Therefore, TUSC3 may serve as a novel prognostic marker and potential target for CSCC.

Contrast-enhanced ultrasound (CEUS) for the differentiation of benign and malignant peripheral pulmonary lesions has been considered experimental for many years. This study was aimed at evaluating the feasibility of CEUS as a diagnostic modality in this area of discussion. CEUS diagnostic accuracy was explored by comparison with contrast-enhanced computed tomography (CECT). The collective included 449 patients with 449 definitive diagnoses (benign, 178; malignant, 271). Logistic regression analysis of CEUS data revealed that delayed time to enhancement, chaotic pattern of distribution of vessels and mild extent of enhancement were independent risk factors for predicting malignancy. Time to wash-out and homogeneity of enhancement did not differ between the two groups (p > 0.05). Based on histopathology or clinical follow-up as a reference standard, CEUS and CECT had similar diagnostic accuracies of 80.16% and 81.75%, respectively. CEUS is a potentially useful imaging tool for diagnosing peripheral pulmonary lesions.

Background : To systematically evaluate the prevalence of post-sequelae and chronic obstructive pulmonary disease assessment test (CAT) scoring one year after hospital discharge among older COVID-19 patients, as well as potential risk factors. Methods : A multi-center prospective cohort study involving 1,233 eligible older COVID-19 patients was conducted. All patients were followed-up between Mar 1, 2021 and Mar 20, 2021. CAT scoring was adopted to measure symptom burden in COVID-19 patients. Results : Of the 1233 eligible cases, 630 (51.1%) reported at least one sequelae. The top six post-sequelae included fatigue (32.4%), sweating (20.0%), chest tightness (15.8%), anxiety (11.4%), myalgia (9.0%), and cough (5.8%). Severe patients had significantly higher percentage of fatigue, sweating, chest tightness, myalgia, and cough (P

Diatom test has been widely used in the diagnosis of drowning and inferring the drowning site. One of the issues is whether the concordance of the diatom types and patterns between the drowning victim's organs and media should be considered an essential requirement for the diagnosis of drowning. In this study, lung tissues from 20 rabbits and drowning media were studied by the Microwave Digestion-Vacuum Filtration-Automated Scanning Electron Microscopy method, and four methods, type consistency, coefficient of similarity, squared-chord distance, and cluster analysis, were introduced to analyze the diatom types and patterns for evaluating the value of diatom consistency in drowning cases. The results showed that diatom types and patterns in lung tissues do not perfectly match the drowning medium, and they are sometimes concordant with the drowning medium sampled from other than drowning site. We should be cautious when using diatom detection to infer drowning sites.

Objective To compare the effects of repairing and not repairing the lateral ulnar collateral ligament (LUCL) when surgically treating elbow varus posteromedial rotatory instability (PMRI). Methods In this retrospective study spanning June 2014 to February 2019, 24 patients with elbow PMRI who were treated surgically were assigned to group RL (Repair LUCL) or group NL (Non‐repair LUCL) depending on whether the LUCL was repaired. Hospitalization time, operation time, intraoperative blood loss, and related complications were reviewed. The elbow range of motion (ROM), the visual analog scale (VAS), the Mayo elbow performance score (MEPS), and the disabilities of the arm, shoulder, and hand (DASH) score were used for functional assessment. Results Among the 24 patients with PMRI, 15 were assigned to group RL and nine were assigned to group NL. The mean blood loss (184.66 ± 20.3 vs 207.33 ± 19.447, P, Schematic drawings for the surgical technique. (A) Surgical diagram of group NL with reconstruct the anteromedial facet coronoid fracture. (B) Surgical diagram of group RL with reconstruct the anteromedial facet coronoid fracture and repair of the lateral ulnar collateral ligament.

Background Hospital and ICU structural factors are key factors affecting the quality of care as well as ICU patient outcomes. However, the data from China are scarce. This study was designed to investigate how differences in patient outcomes are associated with differences in hospital and ICU structure variables in China throughout 2019. Methods This was a multicenter observational study. Data from a total of 2820 hospitals were collected using the National Clinical Improvement System Data that reports ICU information in China. Data collection consisted of a) information on the hospital and ICU structural factors, including the hospital type, number of beds, staffing, among others, and b) ICU patient outcomes, including the mortality rate as well as the incidence of ventilator-associated pneumonia (VAP), catheter-related bloodstream infections (CRBSIs), and catheter-associated urinary tract infections (CAUTIs). Generalized linear mixed models were used to analyse the association between hospital and ICU structural factors and patient outcomes. Results The median ICU patient mortality was 8.02% (3.78%, 14.35%), and the incidences of VAP, CRBSI, and CAUTI were 5.58 (1.55, 11.67) per 1000 ventilator days, 0.63 (0, 2.01) per 1000 catheter days, and 1.42 (0.37, 3.40) per 1000 catheter days, respectively. Mortality was significantly lower in public hospitals (β = − 0.018 (− 0.031, − 0.005), p = 0.006), hospitals with an ICU-to-hospital bed percentage of more than 2% (β = − 0.027 (− 0.034, -0.019), p β = 0.009 (0.001, 0.017), p = 0.027). The incidence of VAP was lower in public hospitals (β = − 0.036 (− 0.054, − 0.018), p β = − 0.008 (− 0.014, − 0.002), p = 0.011) and higher in secondary hospitals (β = 0.005 (0.001, 0.009), p = 0.010), while the incidence of CAUTIs was higher in secondary hospitals (β = 0.010 (0.002, 0.018), p = 0.015). Conclusion This study highlights the association between specific ICU structural factors and patient outcomes. Modifying structural factors is a potential opportunity that could improve patient outcomes in ICUs.

To assess and compare the therapeutic effects of Anterior Cervical Discectomy and Fusion (ACDF) and Cervical Laminectomy and Fusion (CLF) in the treatment of 4-level cervical.We performed a retrospective review on 39 patients with 4-level CSM who underwent ACDF or CLF in the Third Hospital of Hebei Medical University from January 2010 to December 2018. The patients were divided into ACDF group and CLF group according to the treatment. The operative index was evaluated based on intraoperative blood loss and operation time. The functional outcomes including Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) of axial pain were compared. The Cobb angle, Cobb angle improvement rate, range of motion (ROM) and ROM loss ratio were measured for radiographic evaluation.No major complications or deaths occurred. The average age at baseline was 55 years. There was no significant difference between the ACDF and CLF group in follow-up time (26.29 months, 25.39 months, P 0.05). The intraoperative blood loss was higher in the CLF group than in the ACDF group (692.67 ± 38.68 vs 392.14 ± 128.06, P 0.05). The operation time was longer in the CLF group than in the ACDF group (206.60 ± 49.37 vs 172.64 ± 31.96, P 0.05). Significant improvements in the VAS and JOA scores were observed in both groups (P 0.05). No significant difference in VAS was found between the ACDF and CLF groups (P 0.05). There was a significantly larger improvement rate of JOA score in the ACDF group than in the CLF group (60.9% ± 9.57% vs 31.5% ± 15.70%, P 0.05). There were two (9.6%) cases with complications In the ACDF group, including one (4.8%) case of dysphagia and one (4.8%) case of pharyngodynia. In the CLF group, two patients (11.1%) developed CBoth ACDF and CLF were effective in the treatment of multi-level cervical spondylosis and ACDF is more suitable for patients with 4-level CSM.

Background Segond fracture may be identified when an anterior cruciate ligament (ACL) tear is diagnosed, and it has historically been considered a sign of significant knee trauma indicating intra-articular injury. There are few studies on the correlation between a Segond fracture and meniscus injury. The purpose of this study was to evaluate the relationship between a Segond fracture and meniscus injury in patients with ACL tears. Methods A retrospective review of all patients undergoing acute ACL reconstruction (less than 1 month from the time of injury) between 2013 and 2020 was performed. The absence or presence of a Segond fracture was confirmed using preoperative radiographs. Demographic data (age, sex and body mass index), injury variables (time from injury and mechanism of injury) and arthroscopic features (meniscal or chondral injury) were analysed to investigate the relationship between a Segond fracture and meniscus injury. Results A total of 427 patients were included in the study. The incidence of Segond fractures was 12.4%. Among the patients with a Segond fracture, 15 patients were injured playing soccer (28.3%), 11 patients were injured playing basketball (20.8%), eight patients sustained the injury during racquet sports (15.1%), five patients (9.4%) were injured during less popular sports (such as skiing, ice-skating and boxing), and 14 patients (26.4%) were injured by contact mode of injury. A Segond fracture was a significant risk factor for lateral meniscus tears in patients with ACL tears (adjusted odds ratio, 1.938; 95% confidence interval, 1.078–3.481; P = 0.027). Conclusion The incidence of Segond fractures in patients with acute ACL tears was higher than that reported in previous studies. A Segond fracture could increase the risk of a lateral meniscus tear in patients with an ACL tear.

Lung carcinoma is the primary reason for cancer-associated mortality, and it exhibits the highest mortality and incidence in developed and developing countries. Non-small cell lung cancer (NSCLC) and SCLC are the 2 main types of lung cancer, with NSCLC contributing to 85% of all lung carcinoma cases. Conventional treatment mainly involves surgery, chemoradiotherapy, and immunotherapy, but has a dismal prognosis for many patients. Therefore, identifying an effective adjuvant therapy is urgent. Historically, traditional herbal medicine has been an essential part of complementary and alternative medicine, due to its numerous targets, few side effects and substantial therapeutic benefits. In China and other East Asian countries, traditional herbal medicine is increasingly popular, and is highly accepted by patients as a clinical adjuvant therapy. Numerous studies have reported that herbal extracts and prescription medications are effective at combating tumors. It emphasizes that, by mainly regulating the P13K/AKT signaling pathway, the Wnt signaling pathway, and the NF-κB signaling pathway, herbal medicine induces apoptosis and inhibits the proliferation and migration of tumor cells. The present review discusses the anti-NSCLC mechanisms of herbal medicines and provides options for future adjuvant therapy in patients with NSCLC.

Background Varicocele is a high incidence and is considered to be the most common and correctable cause of male infertility. Oxidative stress (OS) plays a central role in the pathogenesis of varicocele-related male infertility. In addition to varicocelectomy, antioxidant supplementation seems to be an effective scheme for the treatment of varicocele-related male infertility, but it is still controversial. The purpose of this study is to determine the effects of alpha-lipoic acid (ALA) supplementation on sperm quality in patients with varicocele-related male infertility. Methods In this randomized controlled clinical trial, we will randomize 80 patients with varicocele-related male infertility from Guilin People’s Hospital. The non-surgical observation group (n = 20) will receive ALA, the non-surgical control group (n = 20) will receive vitamin E, the surgical observation group (n = 20) will receive ALA after the operation, and the surgical control group (n = 20) will receive vitamin E after the operation. The course of treatment will be 3 months. The results will compare the changes in semen parameters, sex hormones, testicular volume, sperm DNA fragment index (DFI), seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) between the groups at baseline and after 3 months of antioxidant supplementation. Discussion Whether it is necessary to use antioxidants in varicocele-related male infertility, how potent antioxidants should be used, postoperative application or non-surgical independent application still needs to be explored. This study attempts to compare the effects of two antioxidants (ALA and vitamin E) on sperm quality in patients with varicocele-related male infertility (surgical or non-surgical) and attempted to answer the above questions. Trial registration Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100054958. Registered on 29 December 2021

To compare the clinical efficacy among different acupuncture and moxibustion therapies on stable angina pectoris (SAP) of coronary heart disease by means of network Meta-analysis. The articles of randomized controlled trial (RCT) for SAP of coronary heart disease treated with acupuncture and moxibustion therapies were searched from PubMed, Web of Science, Cochrane Library, CNKI, Wanfang database and VIP database from May 1, 2002 to May 1, 2022. The quality of them was assessed with the risk of bias assessment tool of Cochrane 5.3, and the network Meta-analysis was undertaken with Stata 13.1 software. A total of 29 articles were included with the acupuncture and moxibustion therapies involved, e.g. acupuncture, acupoint application and moxibustion. In comparison with the simple routine western medication, the effective rate was better on SAP treated with the combined treatments, in which, acupoint application, moxibustion, acupuncture and intradermal needling were combined with routine western medication (运用网状Meta分析方法比较不同针灸疗法治疗冠心病稳定型心绞痛（SAP）的临床疗效。计算机检索PubMed、Web of Science、Cochrane Library、中国期刊全文数据库（CNKI）、万方数据知识服务平台（Wanfang）、 维普资讯中文期刊服务平台（VIP）2002年5月1日至2022年5月1日针灸治疗冠心病SAP的随机对照试验文献，运用Cochrane 5.3偏倚风险评估工具进行质量评价，Stata 13.1进行网状Meta分析。共纳入29篇文献，涉及针刺、穴位贴敷、艾灸等针灸疗法。穴位贴敷、艾灸、针刺、皮内针联合常规西药治疗改善心绞痛有效率优于单独常规西药治疗（

Background Hypertensive disorders of pregnancy (HDP) are a growing concern and a challenge for maternity care providers as the prevalence of hypertension continues to increase. However, optimal management of HDP is unclear. Therefore, we aimed to explore the differences in adverse fetal outcomes among women with different subtypes of HDP and different blood pressure (BP) levels, to provide evidence-based management of HDP. Methods We obtained data from China’s National Maternal Near-Miss Surveillance System from 2012 to 2020. Associations between BP management and adverse fetal outcomes, stratified by the four subtypes of HDP, were assessed using logistic regression analysis with a robust variance estimator. Results For the period, a total of 393,353 pregnant women with HDP were included in the study; 8.51% had chronic hypertension, 2.27% had superimposed preeclampsia, 50.17% had preeclampsia or eclampsia, and 39.04% had gestational hypertension. The BP levels at delivery admission were mostly (61.14%) of non-severe stage 2 (systolic BP 140–159 mm Hg and/or diastolic BP 90–109 mm Hg) hypertension by American Heart Association classification. A high rate of adverse fetal outcomes was observed among women with HDP, especially among those aged 35 y or those diagnosed with superimposed preeclampsia. Compared with those with normal BP levels at delivery admission, we found an upward curve with increased risk among pregnant women with more severe BP levels, including the risk of preterm birth and small for gestational age (SGA) fetus. The odds ratios (ORs) of stillbirth, neonatal death, and low Apgar scores associated with severe stage 2 hypertension increased significantly. In addition, the association between BP at admission and fetal outcomes differed among women with varying HDP subtypes. Pregnant women with preeclampsia or eclampsia had an increased risk for preterm birth (adjusted OR [aOR], 1.33 [95% confidence interval {CI}, 1.07 ~ 1.65]) and SGA (aOR, 1.37 [95% CI, 1.10 ~ 1.71]) even when the admission BP was at stage 1 level. Conclusion Greater attention should be paid to cases involving preeclampsia superimposed on chronic hypertension and pregnant women aged 35 y to mitigate the burden of adverse fetal outcomes caused by HDP.

Castration-resistant prostate cancer (CRPC) is a highly malignant type of advanced cancer resistant to androgen deprivation therapy. One of the important mechanisms for the development of CRPC is the persistent imbalanced regulation of AR and AR splice variants (AR/AR-Vs). In this study, we reported KDM4A-AS1, a recently discovered lncRNA, as a tumor promoter that was significantly increased in CRPC cell lines and cancer tissues. Depletion of KDM4A-AS1 significantly reduced cell viability, proliferation, migration in vitro, and tumor growth in vivo. We found that by binding to the NTD domain, KDM4A-AS1 enhances the stability of USP14-AR/AR-Vs complex, and promoted AR/AR-Vs deubiquitination to protect it from MDM2-mediated ubiquitin-proteasome degradation. Moreover, KDM4A-AS1 was found to enhance CRPC drug resistance to enzalutamide by repressing AR/AR-Vs degradation; antisense oligonucleotide drugs targeting KDM4A-AS1 significantly reduced the growth of tumors with enzalutamide resistance. Taken together, our results indicated that KDM4A-AS1 played an important role in the progression of CRPC and enzalutamide resistance by regulating AR/AR-Vs deubiquitination; targeting KDM4A-AS1 has broad clinical application potential.

Background The gain or loss of large chromosomal regions or even whole chromosomes is termed as genomic scarring and can be observed as copy number variations resulting from the failure of DNA damage repair. Results In this study, a new algorithm called genomic scar analysis (GSA) has developed and validated to calculate homologous recombination deficiency (HRD) score. The two critical submodules were tree recursion (TR) segmentation and filtering, and the estimation and correction of the tumor purity and ploidy. Then, this study evaluated the rationality of segmentation and genotype identification by the GSA algorithm and compared with other two algorithms, PureCN and ASCAT, found that the segmentation result of GSA algorithm was more logical. In addition, the results indicated that the GSA algorithm had an excellent predictive effect on tumor purity and ploidy, if the tumor purity was more than 20%. Furtherly, this study evaluated the HRD scores and BRCA1/2 deficiency status of 195 clinical samples, and the results indicated that the accuracy was 0.98 (comparing with Affymetrix OncoScan™ assay) and the sensitivity was 95.2% (comparing with BRCA1/2 deficiency status), both were well-behaved. Finally, HRD scores and 16 genes mutations (TP53 and 15 HRR pathway genes) were analyzed in 17 cell lines, the results showed that there was higher frequency in HRR pathway genes in high HRD score samples. Conclusions This new algorithm, named as GSA, could effectively and accurately calculate the purity and ploidy of tumor samples through NGS data, and then reflect the degree of genomic instability and large-scale copy number variations of tumor samples.

As a means to aid in the investigation of viral infection mechanisms and identification of more effective antivirus targets, the availability of a source which continually collects and updates information on the virus and host ncRNA-associated interaction resources is essential. Here, we update the ViRBase database to version 3.0 (http://www.virbase.org/ or http://www.rna-society.org/virbase/). This update represents a major revision: (i) the total number of interaction entries is now greater than 820,000, an approximately 70-fold increment, involving 116 virus and 36 host organisms, (ii) it supplements and provides more details on RNA annotations (including RNA editing, RNA localization and RNA modification), ncRNA SNP and ncRNA-drug related information and (iii) it provides two additional tools for predicting binding sites (IntaRNA and PRIdictor), a visual plug-in to display interactions and a website which is optimized for more practical and user-friendly operation. Overall, ViRBase v3.0 provides a more comprehensive resource for virus and host ncRNA-associated interactions enabling researchers a more effective means for investigation of viral infections.

OBJECTIVE Myasthenia gravis (MG) is an autoimmune disorder whose main symptoms are muscle weakness and fatigue. Irisin is a novel skeletal muscle-derived myokine participating in several physiological and pathological processes. The initial objective of the project was to explore serum levels of irisin in patients with MG, as well as its correlation with disease severity. METHODS We retrospectively evaluated serum levels of irisin in 77 MG patients and 57 healthy controls (HCs) by enzyme-linked immunosorbent assay. Further, clinical parameters were measured properly. RESULTS Serum irisin levels were significantly elevated in MG patients compared with HCs (p

The treatment for severe hemifacial microsomia (HFM), especially type III case, is extremely difficult. Mandibular distraction osteogenesis (MDO) was rarely used as the primary choice in the treatment of severe type cases. The authors sought to observe the short-term therapeutic outcomes of patients with severe unilateral HFM who underwent MDO first.A retrospective study of children underwent MDO or later received costochondral graft (CCG) for severe unilateral HFM from 2009 to 2019 was conducted. Cephalometric measurements and clinical variables were analyzed to evaluate the effectiveness of MDO first strategy for severe cases and compare disparity between Pruzansky-Kaban classification type IIb and type III groups.Thirty-six patients (23 males and 13 females) underwent MDO first for severe HFM were included for analysis in the present study. The average age at MDO was 8.33 ± 2.03 years. At the last follow-up, MDO acquired significant improvement in mandibular height, maxillary cant, chin deviation, lip commissural line tilt, and clinical chin deviation (P 0.05). Distraction results were stable during the short-term follow-up in terms of the mandibular height ratio and maxillary cant (P 0.05).MDO is a proper primary method for suitable type IIb and type III HFM cases. MDO can immediately and significantly improve the facial skeleton deficiency, extend the associated soft tissue at the same time, and lay foundation for secondary surgery. MDO can achieve the downgrade of HFM deficiency severity. MDO followed by costochondral graft can get satisfactory esthetic and structural consequence for type III patients.

High-fat diet (HFD) has been associated with neuroinflammation and apoptosis in distinct brain regions. To explore the effect of short-term (7, 14 and 21 days) high-fat overfeeding on apoptosis, inflammatory signaling proteins, APP changes and glial cell activities in cerebral cortex and cerebellum. Mice were fed with HFD for different lengths (up to 21 days) and after each time body weights of mice was tested, then the apoptotic proteins, IL-1β, APP, BACE1and MAPKs, Akt and NF-κB signaling activity were evaluated by western blots. Results demonstrate that short period of high-fat overnutrition significantly promotes apoptosis, APP expression at day 21 of cerebral cortex and at day 7 of cerebellum compared to chow diet. In addition, increased GFAP+astrocytes, Iba-1+microglia and IL-1β 30 were observed in cerebral cortex after 21 days HFD, but no changes for 7 days overfeeding of cerebellum. Serendipitously, ERK1/2 pathway was activated both in cerebral cortex and cerebellum for different time course of HFD. Furthermore, increased phospho-p38 MAPK level was observed in cerebellum only. In consistent with in vivo results, SH-SY5Y cells treatment with cholesterol (50 μM, 100 μM) for 48 h culture in vitro demonstrated that pro-apoptotic proteins were enhanced as well. In brief, short-term HFD consumption increases sensitivity to apoptosis, APP and IL-1β production as well as gliosis in cerebral cortex and cerebellum, which may be related to enhancement of ERK1/2 and p38 MAPK activation.

Background The long‐term trend in cancer death in a rapidly developing country provides information for cancer prophylaxis. Here, we aimed to identify the trends in cancer mortality in China during the 2004‐2018 period. Methods Using raw data from the national mortality surveillance system of China, we assessed the mortalities of all cancer and site‐specific cancers during the 2004‐2018 period. The participants were divided into three age groups: ≥65 years, 40‐64 years, and ≤39 years. Changing trends in cancer death by gender, residency, and tumor location were estimated using fitting joinpoint models to log‐transformed crude mortality rates (CMRs) and age‐standardized mortality rates (ASMRs). Results Cancer death accounted for 24% of all‐cause of death in China during 2014‐2018. The CMR of all cancer was 150.0 per 100,000 persons. Cancer was the leading cause of death in the population, This 15‐year longitudinal study described cancer burden of a rapid changing country with significant regional and urban‐rural disparities, which is important in evaluating the effect of population ageing, risk factor exposure, and public health efforts on cancer mortality. Lung and liver cancers were the 1st leading cause of immature death in women and men, respectively. Lung, colorectal, and pancreatic cancers kept increasing in rural areas. These findings are references for policy making to control cancer.

Background There is still a lack of clinical data in arthroscopic treatment for treating multiple ligament injuries. This study aims to evaluate the clinical outcomes of patients with multiple ligament injuries undergoing treatment based on the classification stage and type of injury. Methods A prospective, clinical trial on multiple ligament injuries was planned, which included 95 patients (58 men and 37 women; age: 42.8 ± 11.9 [range, 18–63] years) from October 2017 to June 2018. Injuries were classified into three stages (emergency stage 3 weeks) and six types (KD I–VI) based on injuries time and structures, which indicated appropriate treatments. The clinical outcomes were evaluated at 2, 4, 6, 8, and 12 weeks and at 6, 9, 12 months and 24 months after surgery. The final choices in efficacy index included International Knee Documentation Committee (IKDC) score, Lysholm score, visual analog scale (VAS) score, and range of motion. Results During the follow-up, all patients exhibited statistically significant functional improvement in the injured limb compared with their preoperative situation. The mean postoperative scores of acute stage patients at 2-year follow-up were IKDC subjective score, 77.54 ± 11.53; Lysholm score, 85.96 ± 9.39; Tegner score, 4.13 ± 1.08; and VAS score, 1.21 ± 0.76. The mean postoperative scores of chronic stage patents at 2-year follow-up were IKDC subjective score, 74.61 ± 12.38; Lysholm score, 81.71 ± 10.80; Tegner score, 3.96 ± 1.14; and VAS score, 1.71 ± 0.60. The IKDC subjective score, Lysholm score, and Tegner score were significantly improved (P P < 0.01) at 2-year follow-up. Regarding the multiple ligament injuries classification, patients with more structural damage in stages V and VI showed less progress in functional recovery than those in stages I–IV. Conclusions This new classification with three stages and six types helps to identify the severity of injury and plan the management effectively. The outcomes were encouraging and the subjective functional results showed significant improvement at 2-year follow-up. Study design Prospective clinical trial. Level of evidence II

Surgical indications for the treatment of gallbladder polyps are controversial. Evaluation of gallbladder polyps with malignant tendency and indications for cholecystectomy in patients with long diameter polyps of 10 to 15 mm require further analysis and discussion. In this study, our objective was to re-evaluate indications for the surgical resection of gallbladder polyps and construct a nomogram model for the prediction of gallbladder polyps with malignant tendency.Clinicopathologic data of 2,272 patients who had undergone cholecystectomy for gallbladder polyps were collected from 11 medical centers in China. Risk factor analyses and nomogram prediction model for gallbladder polyps with malignant tendency were conducted.Excluding 311 patients with cholelithiasis and 488 patients with long diameter polyps ≤5 and15 mm, factors that differed significantly among patients with gallbladder polyps having a long diameter of 6 to 9 mm (885 cases) and 10 to 15 mm (588 cases) were polyp detection time, CEA and CA19-9 levels, number of polyps, fundus, echogenicity, gallbladder wall thickness and postoperative pathologic features (P.05). Among 588 patients with gallbladder polyps with a long diameter of 10 of 15 mm, multivariate analysis indicated the following independent risk factors of gallbladder polyps with malignant tendency: single polyps (OR = 0.286/P.001), polyps with broad base (OR = 2.644/P = .001), polyps with medium/low echogenicity (OR = 2.387/P = .003), and polyps with short diameter of 7 to 9 or 10 to 15 mm (OR = 3.820/P = .005; OR = 2.220/P = .048, respectively). The C-index of the nomogram model and internal validation were .778 and .768, respectively. In addition, a sample online calculator for the nomogram prediction model had been created (https://docliqi.shinyapps.io/dynnom/).Indications for cholecystectomy in patients with gallbladder polyps with a long diameter of 10 to 15 mm should be assessed by combining the information on short diameter, number of polyps, fundus, and echogenicity. The nomogram model can be used to predict the risk for the development of gallbladder polyps with malignant tendency.

Coptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels., Berberine is a compound with glucose-lowering effects in mice and humans. Here, the authors show that in mice berberine has beneficial glycemic effects by promoting insulin secretion, which requires the potassium channel KCNH6 in beta cells, and that berberine can promote insulin secretion in healthy men in a phase 1 clinical trial.