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BACKGROUND: Computer tomography (CT)-guided lung biopsy carries the risk of pneumothorax. A variety of other risk factors affect the occurrence of pneumothorax. OBJECTIVE: Assess the incidence and risk factors associated with pneumothorax complications in CT-guided lung biopsy, and to conduct a quantitative analysis of the variables among the significant risk factors to identify more effective indicators for predicting pneumothorax complications. DESIGN: Retrospective logistic SETTING: Single center in China PATIENTS AND METHODS: From June 2017 to May 2021, consecutive patients who underwent CT-guided lung biopsy were identified from the medical record system. Binary logistic regression analysis was used to identify potential risk factors for pneumothorax. Receiver operating characteristic (ROC) curves were constructed for continuous variables to determine cutoff values that optimized sensitivity and specificity. MAIN OUTCOME MEASURES: The incidence and risk factors of pneumothorax in CT-guided lung biopsy. SAMPLE SIZE: 132 patients RESULTS: The incidence of pneumothorax was 28.9% (38/132), with 6.8% (9/132) of patients requiring chest tube insertion. Results indicated that smaller lesion size (OR 0.724; 95% CI 0.619-0.848; P=.0001), longer needle tract length (OR 1.320; 95% CI 1.145-1.521; P=.001), multiple passes through the pleura (OR 4.618; 95% CI 1.378-15.467; P=.013), and needle tract length/lesion diameter (L/D) ratio (OR 0.028; 95% CI 0.002-0.732; P=.007) were independent risk factors for pneumothorax. ROC curve analysis determined a cut-off value of 0.81 for the L/D ratio (sensitivity=89.5%, specificity=71.3%). The area under the ROC curve (AUC) values of maximum diameter, needle tract length, and L/D ratio for pneumothorax were 0.749, 0.812, and 0.850, respectively. CONCLUSIONS: The L/D ratio, multiple passes through the pleura, longer needle tract length, and smaller lesions were independent risk factors for pneumothorax. A L/D ratio of less than 0.81 may indicate a pneumothorax. It may be necessary to use the proper sealing procedure for this patient group. LIMITATIONS: Due to its retrospective nature, there may be inherent selection bias.

Abstract This study explores the bidirectional association between multimorbidity and falls in Chinese middle-aged and elderly adults. Participants aged 45 and above from the China Health and Retirement Longitudinal Study were included. Binary logistic regression assessed the impact of chronic conditions on fall incidence (stage I), while multinomial logistic regression examined the relationship between baseline falls and multimorbidity (stage II). The fully adjusted odds ratios (ORs) for one, two, or three or more chronic conditions were 1.34, 1.65, and 2.02, respectively. Among participants without baseline falls, 28.61% developed two or more chronic conditions during follow-up, compared to 37.4% of those with a history of falls. Fully adjusted ORs for one, two, or three or more chronic conditions in those with a history of falls were 1.21, 1.38 and 1.70, respectively. The bidirectional relationship held in sensitivity and subgroup analyses. A bidirectional relationship exists between multimorbidity and falls in Chinese middle-aged and elderly adults. Strengthening chronic condition screening and treatment in primary healthcare may reduce falls risk, and prioritizing fall prevention and intervention in daily life is recommended.

Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.

Objective To investigate the population data of human immunodeficiency virus (HIV) infections among voluntary blood donors in Guangzhou between 2012 and 2022, and analyze its characteristics and trends, so as to provide valuable data for formulating targeted prevention and ensuring blood safety. Methods Voluntary blood donors samples from 2012 to 2022 were screened for p24 antigen and anti-HIV by two ELISA diagnostic kits and HIV RNA by nucleic acid test(NAT). The reactive blood samples were sent to the Disease Control and Prevention Center of Guangzhou for anti-HIV confirmatory test by Western blot. The population characteristics of blood donors with confirmed-positive HIV were subsequently analyzed. Results There were a total of 3 351 596 blood samples from voluntary blood donors in Guangzhou from 2012 to 2022, of which 708 samples were confirmed-positive of anti-HIV, with a total positive rate of 21.12/100 000, showing a decreasing trend (P

Abstract Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and alpha-fetoprotein (AFP) are widely used tumor markers for colorectal cancer (CRC), but their clinical significance is unknown when the levels of these tumor markers were within the normal range. This retrospective study included 2145 CRC patients. The entire cohort was randomly divided into training and validation datasets. The optimal cut-off values of tumor markers were calculated using X-tile software, and univariate and multivariate analyses were performed to assess its association with overall survival (OS). The nomogram model was constructed and validated. The entire cohort was randomly divided into a training dataset (1502 cases, 70%) and a validation dataset (643 cases,30%). Calculated from the training dataset, the optimal cut-off value was 2.9 ng/mL for CEA, 10.1 ng/mL for CA19-9, 13.4 U/mL for CA125, and 1.8 ng/mL for AFP, respectively. Multivariate analysis revealed that age, tumor location, T stage, N stage, preoperative CA19-9, and CA125 levels were independent prognostic predictors. Even within the normal range, CRC patients with relatively high levels of CA19-9 or CA125 worse OS compared to those with relatively low levels. Then, based on the independent prognostic predictors from multivariate analysis, two models with/without (model I/II) CA19-9 and CA125 were built, model I showed better prediction and reliability than model II. Within the normal range, relatively high levels of preoperative CA19-9 and CA125 were significantly associated with poor OS in CRC patients. The nomogram based on CA19-9 and CA125 levels showed improved predictive accuracy ability for CRC.

Objectives There was no evidence regarding the relationship between septic shock and tracheal injury scores. Investigate whether septic shock was independently associated with tracheal injury scores in intensive care unit (ICU) patients with invasive ventilation.Design Prospective observational cohort study.Setting Our study was conducted in a Class III hospital in Hebei province, China.Participants Patients over 18 years of age admitted to the ICU between 31 May 2020 and 3 May 2022 with a tracheal tube and expected to be on the tube for more than 24 hours.Primary and secondary outcome measures Tracheal injuries were evaluated by examining hyperaemia, ischaemia, ulcers and tracheal perforation by fiberoptic bronchoscope. Depending on the number of lesions, the lesions were further classified as moderate, severe or confluent.Results Among the 97 selected participants, the average age was 56.6±16.5 years, with approximately 64.9% being men. The results of adjusted linear regression showed that septic shock was associated with tracheal injury scores (β: 2.99; 95% CI 0.70 to 5.29). Subgroup analysis revealed a stronger association with a duration of intubation ≥8 days (p=0.013).Conclusion Patients with septic shock exhibit significantly higher tracheal injury scores compared with those without septic shock, suggesting that septic shock may serve as an independent risk factor for tracheal injury.Trial registration number ChiCTR2000037842, registered 03 September 2020. Retrospectively registered, https://www.chictr.org.cn/edit.aspx?pid=57011&htm=4.

Background Ischemic stroke (IS) is the main cause of death and adult disability. However, the pathogenesis of this complicated disease is unknown. The present study aimed to assess the relationship between ITLN1 single nucleotide polymorphisms (SNPs) and the susceptibility to IS in Xi’an population, Shaanxi province. Methods In this study, we designed polymerase chain reaction (PCR) primers located at −3,308 bp upstream of the transcription initiation site within promoter region of the ITLN1 gene. The target fragment was amplified by PCR and identified by agarose gel electrophoresis. Sanger sequencing was then performed in the samples extracted from a cohort comprising 1,272 participants (636 controls and 636 cases), and the obtained sequences were compared with the reference sequences available on the National Center for Biotechnology Information (NCBI) website to detect SNPs in the ITLN1 gene promoter region. Logistic regression analysis was employed to assess the relationship between ITLN1 polymorphisms and IS risk, with adjustments for age and gender. Significant positive results were tested by false-positive report probability (FPRP) and false discovery rate (FDR). The interaction among noteworthy SNPs and their predictive relationship with IS risk were explored using the Multi-Factor Dimensionality Reduction (MDR) software. Results The results of Sanger sequencing were compared with the reference sequences on the NCBI website, and we found 14 SNPs in ITLN1 gene promoter satisfied Hardy-Weinberg equilibrium (HWE). Logistic regression analysis showed that ITLN1 was associated with a decreased risk of IS (rs6427553: Homozygous C/C: adjusted OR: 0.69, 95% CI [0.48–0.97]; Log-additive: adjusted OR: 0.83, 95% CI [0.70–0.98]; rs7411035: Homozygous G/G: adjusted OR: 0.66, 95% CI [0.47–0.94]; Dominant G/T-G/G: adjusted OR: 0.78, 95% CI [0.62–0.98]; Log-additive: adjusted OR: 0.81, 95% CI [0.69–0.96]; rs4656958: Heterozygous G/A: adjusted OR: 0.74, 95% CI [0.59–0.94]; Homozygous A/A: adjusted OR: 0.51, 95% CI [0.31–0.84]; Dominant G/A-A/A: adjusted OR: 0.71, 95% CI [0.57–0.89]; Recessive A/A: adjusted OR: 0.59, 95% CI [0.36–0.96]; Log-additive: adjusted OR: 0.73, 95% CI [0.61–0.88]), especially in people aged less than 60 years and males. Conclusions In short, our study revealed a correlation between ITLN1 variants (rs6427553, rs7411035 and rs4656958) and IS risk in Xi’an population, Shaanxi province, laying a foundation for ITLN1 gene as a potential biomarker for predicting susceptibility to IS.

Abstract This paper presents comprehensive research of the advantages and applicability of various concrete carbonation detection methods. Employing a combination of Phenolphthalein indicator (PI), Thermogravimetric analysis (TGA), X-ray phase analysis (XRD), Fourier transform infrared spectroscopy (FTIR), and Quantitative calcium carbonate analysis (CA), a detailed comparison to determine the carbonation depth in the partial carbonation zone of concrete specimens is conducted. Among the quantitative analysis methods, CA measures CaCO3 content based on chemical reactions, while TGA obtains the concentration distribution of Ca(OH)2 and CaCO3. Among qualitative analysis methods, XRD tested the intensity distribution of Ca(OH)2 and CaCO3, while FTIR traced the characteristic peaks of C-O functional groups in a specific spectral range to determine the depth of carbonation of concrete. Results indicate that the depth of carbonation values measured by CA, TGA, XRDA, and FTIR are 2–3 times higher than those measured by PI. This research may provide valuable insights for the design of carbonation detection in concrete.

Abstract The process of post-transcriptional regulation has been recognized to be significantly impacted by the presence of N6-methyladenosine (m6A) modification. As an m6A demethylase, ALKBH5 has been shown to contribute to the progression of different cancers by increasing expression of several oncogenes. Hence, a better understanding of the key targets of ALKBH5 in cancer cells could potentially lead to the development of new therapeutic targets. However, the specific role of ALKBH5 in pancreatic neuroendocrine neoplasms (pNENs) remains largely unknown. Here, we demonstrated that ALKBH5 was up-regulated in pNENs and played a critical role in tumor growth and lipid metabolism. Mechanistically, ALKBH5 over-expression was found to increase the expression of FABP5 in an m6A-IGF2BP2 dependent manner, leading to disorders in lipid metabolism. Additionally, ALKBH5 was found to activate PI3K/Akt/mTOR signaling pathway, resulting in enhanced lipid metabolism and proliferation abilities. In conclusion, our study uncovers the ALKBH5/IGF2BP2/FABP5/mTOR axis as a mechanism for aberrant m6A modification in lipid metabolism and highlights a new molecular basis for the development of therapeutic strategies for pNENs treatment. Graphical Abstract

Abstract Background The mechanisms whereby CYFIP2 acts in tumor development and drives immune infiltration have been poorly explored. Thus, this study aimed to identifying the role of CYFIP2 in tumors and immune response. Methods In this study, we first explored expression patterns, diagnostic role and prognostic value of CYFIP2 in cancers, particularly in lung adenocarcinoma (LUAD). Then, we performed functional enrichment, genetic alterations, DNA methylation analysis, and immune cell infiltration analysis of CYFIP2 to uncover its potential mechanisms involved in immune microenvironment. Results We found that CYFIP2 significantly differentially expressed in different tumors including LUAD compared with normal tissues. Furthermore, CYFIP2 was found to be significantly correlated with clinical parameters in LUAD. According to the diagnostic and survival analysis, CYFIP2 may be employed as a potential diagnostic and prognostic biomarker. Moreover, genetic alterations revealed that mutation of CYFIP2 was the main types of alterations in different cancers. DNA methylation analysis indicated that CYFIP2 mRNA expression correlated with hypomethylation. Afterwards, functional enrichment analysis uncovered that CYFIP2 was involved in tumor-associated and immune-related pathways. Immune infiltration analysis indicated that CYFIP2 was significantly correlated with immune cells infiltration. In particular, CYFIP2 was strongly linked with immune microenvironment scores. Additionally, CYFIP2 exhibited a significant relationship with immune regulators and immune-related genes including chemokines, chemokines receptors, and MHC genes. Conclusion Our results suggested that CYFIP2 may serve as a prognostic cancer biomarker for determining prognosis and might be a promising therapeutic strategy for tumor immunotherapy.

Abstract Background Arginase-1 (ARG1) promotes collagen synthesis and cell proliferation. ARG1 is highly expressed in various tumour cells. The mechanisms of ARG1 in epithelial-to-mesenchymal transition (EMT)-associated cataracts were studied herein. Methods C57BL/6 mice, a human lens epithelial cell line (HLEC-SRA01/04), and human lens capsule samples were used in this study. The right lens anterior capsule of the mouse eye was punctured through the central cornea with a 26-gauge hypodermic needle. Human lens epithelial cells (HLECs) were transfected with ARG1-targeted (siARG1) or negative control siRNA (siNC). For gene overexpression, HLECs were transfected with a plasmid bearing the ARG1 coding sequence or an empty vector. Medium containing 0.2% serum with or without transforming growth factor beta-2 (TGF-β2) was added for 6 or 24 h to detect mRNA or protein, respectively. The expression of related genes was measured by quantitative real-time polymerase chain reaction (RT–qPCR), western blotting, and immunohistochemical staining. Transwell assays and wound healing assays were used to determine cell migration. Cell proliferation, superoxide levels, nitric oxide (NO) levels, and arginase activity were estimated using Cell Counting Kit-8 assays, a superoxide assay kit, an NO assay kit, and an arginase activity kit. Results ARG1, alpha-smooth muscle actin (α-SMA), fibronectin, and Ki67 expression increased after lens capsular injury, while zonula occludens-1 (ZO-1) expression decreased. Fibronectin and collagen type I alpha1 chain (collagen 1A1) expression increased, and cell migration increased significantly in ARG1-overexpressing HLECs compared with those transfected with an empty vector after TGF-β2 treatment. These effects were reversed by ARG1 knockdown. The arginase-related pathway plays an important role in EMT. mRNAs of enzymes of the arginase-related pathway were highly expressed after ARG1 overexpression. ARG1 knockdown suppressed these expression changes. Numidargistat (CB-1158) dihydrochloride (CB-1158), an ARG1 inhibitor, suppressed TGF-β2-induced anterior subcapsular cataract (ASC) by reducing the proliferation of lens epithelial cells (LECs) and decreasing fibronectin, α-SMA, collagen 1A1, and vimentin expression. Compared with that in nonanterior subcapsular cataract (non-ASC) patients, the expression of ARG1, collagen 1A1, vimentin, fibronectin, and Ki67 was markedly increased in ASC patients. Conclusions ARG1 can regulate EMT in EMT-associated cataracts. Based on the pathogenesis of ASC, these findings are expected to provide new therapeutic strategies for patients. Graphical abstract

Abstract Schizophrenia is a chronic neuropsychiatric disorder that causes distinct structural alterations within the brain. We hypothesize that deep learning applied to a structural neuroimaging dataset could detect disease-related alteration and improve classification and diagnostic accuracy. We tested this hypothesis using a single, widely available, and conventional T1-weighted MRI scan, from which we extracted the 3D whole-brain structure using standard post-processing methods. A deep learning model was then developed, optimized, and evaluated on three open datasets with T1-weighted MRI scans of patients with schizophrenia. Our proposed model outperformed the benchmark model, which was also trained with structural MR images using a 3D CNN architecture. Our model is capable of almost perfectly (area under the ROC curve = 0.987) distinguishing schizophrenia patients from healthy controls on unseen structural MRI scans. Regional analysis localized subcortical regions and ventricles as the most predictive brain regions. Subcortical structures serve a pivotal role in cognitive, affective, and social functions in humans, and structural abnormalities of these regions have been associated with schizophrenia. Our finding corroborates that schizophrenia is associated with widespread alterations in subcortical brain structure and the subcortical structural information provides prominent features in diagnostic classification. Together, these results further demonstrate the potential of deep learning to improve schizophrenia diagnosis and identify its structural neuroimaging signatures from a single, standard T1-weighted brain MRI.

Objectives Radiofrequency catheter ablation is the first-line treatment for idiopathic premature ventricular complexes (PVCs) and ventricular tachycardias (VTs). However, the outcomes were less compared among the categories. The study aims to assess the effectiveness and safety of catheter ablation for idiopathic PVC/VTs in a single high-volume centre, using the right ventricular outflow tract (RVOT) as a reference.Design Retrospective cohort study.Setting Patient data were collected from a tertiary hospital in Guizhou, China.Participants Between September 2013 and September 2022, 1028 patients (male: 41.3%; age: 46.5±15.6 years) who underwent the first catheter ablation for idiopathic monomorphic PVC/VTs were enrolled.Outcome measures Acute success, procedure-related complications, and long-term recurrence were assessed. Antiarrhythmic drugs (AADs) were not administrated after procedures unless recurrence was identified.Results The overall acute success rate was 90.3%, with 368 patients (35.8%) experiencing left ventricular PVC/VTs. No cases of third-degree atrioventricular block or death were reported. Complications were more common in patients with left ventricular PVC/VTs than those with right-sided ones (4.6% vs 0.1%, p

IntroductionEarly postoperative seizures has been the most common clinical expression in gliomas; however, the incidence and risk factors for early postoperative seizures in gliomas are more controversial. This protocol describes a systematic review and meta-analysis to clarify the prevalence and risk factors of early postoperative seizures in patients with glioma.Methods and analysisSearches will be conducted on CNKI, WanFang, VIP, PubMed, Embase, Cochrane Library databases and Web of Science for the period from database inception to December 31st, 2023. Case-control and cohort studies of the incidence and risk factors for early postoperative seizures in all gliomas will be included. The primary outcome will be incidence, risk factors. Newcastle-Ottawa Scale was used for quality evaluation. Review of article screening, extracting data and risk of bias assessment will be repeated by two independent reviewers.ResultThis study will provide evidence for the risk factors and incidence of early postoperative seizures in patients with glioma.ConclusionOur study will provide evidence for the prevention of early postoperative seizures in glioma patients.Trail registrationThis protocol was registered in PROSPERO and registration number is CRD42023415658.

Objective Cardiac CT (CCT) is an emerging non-invasive modality for assessing left atrial appendage (LAA) thrombus, but the results were conflicting. Our study aims to evaluate the accuracy of CCT for detecting LAA thrombus in patients undergoing catheter ablation of atrial fibrillation, using trans-oesophageal echocardiography (TEE) as the reference standard.Design Case-control study.Setting Patient data were collected from a tertiary hospital in China between 2017 and 2022.Participants The study enrolled 726 patients (male: 60.2%, age: 61±11 years) who had both TEE and CCT before catheter ablation of atrial fibrillation.Measures The CCT protocol consisted of one angiographic phase and one delayed scan 30 s later. LAA thrombi were defined as solid masses on TEE or persistent defects on CCT. The thrombus dimension and location, the LAA filling and emptying flow velocity were assessed by TEE.Results Of the 57 (7.9%) patients with LAA thrombi identified by TEE, 29 (50.9%) were located at the LAA ostium, and 28 (49.1%) were in the LAA. The former showed higher motility following blood flow and heartbeats than the latter. The CCT detected 14 (48.3%) of the LAA-ostium thrombi but 25 (89.3%) of those in the LAA (p=0.001). The LAA-ostium thrombi with the LAA mean flow velocity >0.35 m/s and maximum diameters

Abstract Background A workplace-based primary prevention intervention be an effective approach to reducing the incidence of hypertension (HTN). However, few studies to date have addressed the effect among the Chinese working population. We assessed the effect of a workplace-based multicomponent prevention interventions program for cardiovascular disease on reducing the occurrence of HTN through encouraging employees to adopt a healthy lifestyle. Methods In this post hoc analysis of cluster randomized controlled study, 60 workplaces across 20 urban regions in China were randomized to either the intervention group (n = 40) or control group (n = 20). All employees in each workplace were asked to complete a baseline survey after randomization for obtaining sociodemographic information, health status, lifestyle, etc. Employees in the intervention group were given a 2-year workplace-based primary prevention intervention program for improving their cardiovascular health, including (1) cardiovascular health education, (2) a reasonable diet, (3) tobacco cessation, (4) physical environment promotion, (5) physical activity, (6) stress management, and (7) health screening. The primary outcome was the incidence of HTN, and the secondary outcomes were improvements of blood pressure (BP) levels and lifestyle factors from baseline to 24 months. A mix effect model was used to assess the intervention effect at the end of the intervention in the two groups. Results Overall, 24,396 participants (18,170 in the intervention group and 6,226 in the control group) were included (mean [standard deviation] age, 39.3 [9.1] years; 14,727 men [60.4%]). After 24 months of the intervention, the incidence of HTN was 8.0% in the intervention groups and 9.6% in the control groups [relative risk (RR) = 0.66, 95% CI, 0.58 ~ 0.76, P

Abstract To screen potential pivotal targets in sepsis through peripheral blood. Septic patients (n = 23) and healthy volunteers (n = 10) were enrolled according to SEPSIS 3.0. Peripheral blood was collected within 24 h of enrollment, RNA-seq was performed on the peripheral blood. The sequencing data was screened for DEGs (p

Abstract FK506 binding proteins (FKBPs) are a highly-conserved group of proteins known to bind to FK506, an immunosuppressive drug. They play different physiological roles, including transcription regulation, protein folding, signal transduction and immunosuppression. A number of FKBP genes have been identified in eukaryotes; however, very little information about these genes has been reported in Locusta migratoria. Here, we identified and characterized 10 FKBP genes from L. migratoria. Phylogenetic analysis and comparison of domain architectures indicated that the LmFKBP family can be divided into two subfamilies and five subclasses. Developmental and tissue expression pattern analysis revealed that all LmFKBPs transcripts, including LmFKBP46, LmFKBP12, LmFKBP47, LmFKBP79, LmFKBP16, LmFKBP24, LmFKBP44b, LmFKBP53, were periodically expressed during different developmental stages and mainly expressed in the fat body, hemolymph, testis, and ovary. In brief, our work depicts a outline but panoramic picture of LmFKBP family in L. migratoria, and provides a solid foundation to further investigate the molecular functions of LmFKBPs.

Trace elements play a crucial role in the growth and bioactive substance content of medicinal plants, but their utilization efficiency in soil is often low. In this study, soil and Aconitum carmichaelii samples were collected and measured from 22 different locations, followed by an analysis of the relationship between trace elements and the yield and alkaloid content of the plants. The results indicated a significant positive correlation between zinc, trace elements in the soil, and the yield and alkaloid content of A. carmichaelii. Subsequent treatment of A. carmichaelii with both bulk zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO NPs) demonstrated that the use of ZnO NPs significantly enhanced plant growth and monoester-type alkaloid content. To elucidate the underlying mechanisms responsible for these effects, metabolomic analysis was performed, resulting in the identification of 38 differentially expressed metabolites in eight metabolic pathways between the two treatments. Additionally, significant differences were observed in the rhizosphere bacterial communities, with Bacteroidota and Actinobacteriota identified as valuable biomarkers for ZnO NP treatment. Covariation analysis further revealed significant correlations between specific microbial communities and metabolite expression levels. These findings provide compelling evidence that nanoscale zinc exhibits much higher utilization efficiency compared to traditional zinc fertilizer.

Objectives Ovarian serous carcinoma (OSC) is a major cause of gynaecological cancer death, yet there is a lack of reliable prognostic models. To address this, we developed and validated a nomogram based on conventional clinical characteristics and log odds of positive lymph nodes (LODDS) to predict the prognosis of OSC patients.Setting A Real-World Retrospective Cohort Study from the Surveillance, Epidemiology and End Results programme.Participants We obtained data on 4192 patients diagnosed with OSC between 2010 and 2015. Eligibility criteria included specific diagnostic codes, OSC being the primary malignant tumour and age at diagnosis over 18 years. Exclusion criteria were missing information on various factors and unknown cause of death or survival time.Primary and secondary outcome measures The primary outcome were overall survival (OS) and ovarian cancer-specific survival (OCSS).Results For OS and OCSS outcomes, we selected 7 and 5 variables, respectively, to establish the nomogram. In the training and validation cohorts, the C index for OS or OCSS was 0.716 or 0.718 and 0.731 or 0.733, respectively, with a 3-year time-dependent area under the curve (AUC) of 0.745 or 0.751 and a 5-year time-dependent AUC of 0.742 or 0.751. Calibration curves demonstrated excellent consistency between predicted and observed outcomes. The Net Reclassification Index, integrated discrimination improvement and decision curve analysis curves indicated that our nomogram performed better than the International Federation of Gynaecology and Obstetrics (FIGO) staging system in predicting OS and OCSS for OSC patients in both the training and validation cohorts.Conclusion Our nomogram, which includes LODDS, offers higher accuracy and reliability than the FIGO staging system and can predict overall and OCSS in OSC patients.

Abstract Objective In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. Methods We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. Results Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09–1.26, P = 2.51E−05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48–0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36–0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001–1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. Conclusion This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

Highlights Sex differences exist in the prevalence, tumor invasiveness, treatment responses, and clinical outcomes of pan-cancer, suggesting that, while not yet incorporated, sex will probably be considered in future practice guidelines. Inherent genetic differences, overlapping epigenetic alterations, and sex hormone influences underpin everything. Androgen receptors influence the sexual differences in TME by regulating epigenetic and transcriptional differentiation programs. It highlights a sex-based therapeutic target for cancer immunotherapy. Proper consideration of sex, age, sex hormones/menopause status, and socio-cultural gender differences in clinical investigation and gene association studies of cancer are needed to fill current gaps and implement precision medicine for patients with cancer.

Abstract. Background:. The increasing burden of non-alcoholic fatty liver disease (NAFLD) worldwide imposes an emerging public health issue. We perform the current study to estimate the global prevalence, incidence, disease progression, and clinical outcomes of NAFLD. Methods:. A systematic search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021. NAFLD prevalence, incidence, rate of disease progression, and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation. Results:. Our search identified 59,156 records, of which 578 studies fulfilled our inclusion criteria. The overall prevalence of NAFLD was 29.38% (95% confidence interval [CI] 28.09–30.69) regardless of the diagnostic techniques. Looking at the group in which the diagnosis was made by ultrasound exclusively, the pooled prevalence was 30.49% (95% CI 29.55–31.43). NAFLD has become more prevalent during the year 2011–2021 (31.63%, 95% CI 30.23–33.04) compared with year 2000–2010 (27.94%, 95% CI 26.23–29.69). The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26% (95% CI 1.13–21.01), 46.49% (95% CI 35.93–57.20), and 46.72% (95% CI 37.57–55.98) in general population, NAFLD patients, and severe/morbidly obese patients, respectively. Based on a total of 110,142 newly developed NAFLD patients, the pooled incident rate was estimated as 46.24 cases per 1000 person-years (95% CI 43.21–49.30). In patients with NAFLD, the incident rate of hepatocellular carcinoma was 1.46 (95% CI 0.90–2.03) cases per 1000 person-years. The overall pooled estimate of NAFLD related mortality was 23.91 (95% CI 13.55–37.18) death per 1000 person-years. Conclusions:. The prevalence of NAFLD is increasing globally. It is contributing to poor clinical outcomes including hepatocellular carcinoma and death. Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe. Registration:. PROSPERO, No. CRD42020171104.

Abstract Background Currently, there are relatively few studies on the effects of changes in oestrogen and androgen levels on prostatic microvessel density (MVD). This article aimed to study the changes in prostatic MVD in Sprague-Dawley (SD) rats after castration under the effect of oestrogen/androgen at different concentrations. Methods Male SD rats aged 3–4 months were randomly divided into a control group, a castration group, and groups with different concentrations of oestrogen/androgen treatment after castration. Dihydrotestosterone (DHT) and oestradiol (E) were administered daily by subcutaneous injection for one month. All the rats were killed by cervical dislocation after one month, and the serum DHT and E concentrations of the rats in each group were measured by ELISA. Prostate tissue specimens were immunohistochemically stained with monoclonal antibodies against CD34 and factor VIII for MVD. Results Compared with the control group, the MVD decreased significantly in the castration group (P

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

Abstract Background Apoptosis signal-regulating kinase 1-interacting protein 1 (AIP1) participates in inflammatory neovascularization induction. NADPH oxidase 4 (NOX4) produces reactive oxygen species (ROS), leading to an imbalance in nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) and NLR family pyrin domain containing 6 (NLRP6) expression. The mechanisms of AIP1, NOX4, ROS and inflammasomes in corneal neovascularization were studied herein. Methods C57BL/6 and AIP1-knockout mice were used in this study. The alkali burn procedure was performed on the right eye. Adenovirus encoding AIP1 plus green fluorescence protein (GFP) (Ad-AIP1-GFP) or GFP alone was injected into the right anterior chamber, GLX351322 was applied as a NOX4 inhibitor, and then corneal neovascularization was scored. The expression of related genes was measured by quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining. 2′,7′-Dichlorofluorescin diacetate staining was used to determine the ROS levels. Results The expression of AIP1 was decreased, while that of cleaved interleukin-1β (clv-IL-1β) and vascular endothelial growth factor A (VEGFa) was increased after alkali burn injury. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. NLRP3/NLRP6 expression was imbalanced after alkali burns. GLX351322 reversed the imbalance in NLRP3/NLRP6 by reducing the ROS levels. This treatment also reduced the expression of clv-IL-1β and VEGFa, suppressing neovascularization. Conclusions AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burn injury. Based on the pathogenesis of corneal neovascularization, these findings are expected to provide new therapeutic strategies for patients. Plain English summary Corneal alkali burn injury is a common type of ocular injury that is difficult to treat in the clinic. The cornea is a clear and avascular tissue. Corneal neovascularization after alkali burn injury is a serious complication; it not only seriously affects the patient’s vision but also is the main reason for failed corneal transplantation. Corneal neovascularization affects approximately 1.4 million patients a year. We show for the first time that AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burns. The expression of AIP1 was decreased, while that of clv-IL-1β and VEGFa was increased after alkali burns. We tried to elucidate the specific molecular mechanisms by which AIP1 regulates corneal neovascularization. NOX4 activation was due to decreased AIP1 expression in murine corneas with alkali burns. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. Additionally, NLRP3/NLRP6 expression was unbalanced, with NLRP3 activation and NLRP6 suppression in the corneal alkali burn murine model. Eye drops containing GLX351322, a NOX4 inhibitor, reversed the imbalance in NLRP3/NLRP6 by reducing ROS expression. This treatment also reduced the expression of clv-IL-1β and VEGFa, reducing neovascularization. Therefore, we provide new gene therapeutic strategies for patients. With the development of neovascularization therapy, we believe that in addition to corneal transplantation, new drug or gene therapies can achieve better results. Video Abstract

Polyvinyl alcohol (PVA) embolization particles, currently used in clinical practice, have good expansibility and are capable of permanent embolization. However, the lack of adhesion of embolization particles contributes to facilitated recanalization after embolization, while the lack of visualization facilitates misembolization. At present, embolization materials with good expansion, adhesion, and visualization potential are urgently required in clinical practice. Here, we report the development of PVA/gelatin/iohexol (I) fiber blocks as a novel embolization material for liver embolization in rats. In our work, electrospun PVA/gelatin/I nanofibrous mats were first prepared, homogenized, centrifuged in a gradient manner, and freeze-dried to obtain fiber blocks (fiber diameter ​= ​296.2 ​± ​74.23 ​nm, length 99.6 ​± ​17.0 ​μm ​× ​width 46.9 ​± ​13.3 ​μm). The fiber blocks exhibited excellent cytocompatibility and hemocompatibility. Fiber blocks with a PVA/gelatin/I mass ratio of 8:2:10 were selected due to their excellent expansibility and adhesive properties. The PVA/gelatin/I fiber blocks display excellent liver embolic effects and computed tomography (CT) imaging potential due to a combination of the following characteristics: expansibility of PVA and gelatin, adhesive property of gelatin, and CT imaging potential of I. The developed fiber block material is an embolic material that may potentially be used in interventional medicine.

IntroductionRopivacaine oil delivery depot (RODD) can slowly release ropivacaine and block nerves for a long timejavascript:;. The aim of the present work was to investigate the safety, pharmacokinetics, and preliminary pharmacodynamics of RODD in subcutaneous injection among healthy subjects.MethodsThe abdomens of 3 subjects were subcutaneously administered with a single-needle RODD containing 12~30 mg of ropivacaine. The irritation, nerve blocking range and optimum dose were investigated. Forty-one subjects were divided into RODD groups containing 150, 230, 300, 350 and 400 mg of ropivacaine and a ropivacaine hydrochloride injection (RHI) 150 mg group. Multineedle subcutaneous injection of RODD or RHI was performed in the abdomens of the subjects. The primary endpoint was a safe dose or a maximum dose of ropivacaine (400 mg). Subjects' vital signs were observed; their blood was analyzed; their cardiovascular system and nervous systems were monitored, and their dermatological reactions were observed and scored. Second, the ropivacaine concentrations in plasma were determined, pharmacokinetic parameters were calculated, and the anesthetic effects of RODD were studied, including RODD onset time, duration and intensity of nerve block.ResultsSingle-needle injection of RODD 24 mg was optimal for 3 subjects, and the range of nerve block was 42.5±20.8 mm. Multineedle subcutaneous injection of RODD in the abdomens of subjects was safe, and all adverse events were no more severe than grade II. The incidence rate of grade II adverse events, such as pain, and abnormal ST and ST-T segment changes on electrocardiography, was approximately 1%. The incidence rate of grade I adverse events, including erythema, papules, hypertriglyceridemia, and hypotension was greater than 10%. Erythema and papules were relieved after 24 h and disappeared after 72 h. Other adverse reactions disappeared after 7 days. The curve of ropivacaine concentration-time in plasma presented a bimodal profile. The results showed that ropivacaine was slowly released from the RODD. Compared with the 150 mg RHI group, Tmax was longer in the RODD groups. In particular, Tmax in the 400 mg RODD group was longer than that in the RHI group (11.8±4.6 h vs. 0.77±0.06 h). The Cmax in the 150 mg RODD group was lower than that in the 150 mg RHI group (0.35±0.09 vs. 0.58±0.13 μg·mL-1). In particular, the Cmax increased by 48% when the dose was increased by 2.6 times in the 400 mg group. Cmax, the AUC value and the intensity of the nerve block increased with increasing doses of RODD. Among them, the 400 mg RODD group presented the strongest nerve block (the percentage of level 2 and 3, 42.9%). The corresponding median onset time was 0.42 h, and the duration median was 35.7⁓47.7 h.ConclusionsRODD has a sustained release effect. Compared with the RHI group, Tmax was delayed in the RODD groups, and the duration of nerve block was long. No abnormal reaction was found in the RODD group containing 400 mg of ropivacaine after subcutaneous injection among healthy subjects, suggesting that RODD was adequately safe.Trial registrationChictr.org: CTR2200058122; Chinadrugtrials.org: CTR20192280.

Background Radiotherapy (RT) combined with chemotherapy is the standard treatment for T1-2N1M0 nasopharyngeal carcinoma (NPC) based on conventional radiotherapy. However, intensity-modulated radiotherapy (IMRT) has narrowed the treatment gap between RT and chemoradiotherapy. Thus, this retrospective study aimed to compare the efficacy of RT and chemoradiotherapy (RT-chemo) in treating T1-2N1M0 NPC in the IMRT era. Materials and methods From January 2008 to December 2016, 343 consecutive patients with T1-2N1M0 NPC in two cancer centers were included. All patients received RT or RT-chemo, chemotherapy including induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT), CCRT, or CCRT + adjuvant chemotherapy (AC). The number of patients who received RT, CCRT, IC + CCRT, and CCRT + AC was 114, 101, 89, and 39. The survival rates were analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariable analysis was performed to identify valuable prognostic factors. Results The median follow-up time for survivors was 93 (range: 55–144) months. The 5-year overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) for the RT-chemo and RT groups were 93.7%, 88.5%, 93.8%, 93.8% and 93.0%, 87.7%, 91.9%, 91.2%, respectively (P>0.05 for all outcomes). No significant survival differences were found between the two groups. The T1N1M0 or T2N1M0 subgroup analysis showed that treatment outcomes had no significant differences between the RT and RT-chemo groups. After adjusting for various factors, treatment mode was not identified as an independent prognostic factor for all survival rates. Conclusions In this study, outcomes of T1-2N1M0 NPC patients treated by IMRT alone were comparable to chemoradiotherapy, supporting the omission or postponement of chemotherapy.

BackgroundSepsis associated encephalopathy (SAE) is a common but poorly understood complication during sepsis. Currently, there are no preventive or therapeutic agents available for this neurological disorder. The present study was designed to determine the potential protective effects of β-patchoulene (β-PAE) in a mouse model of SAE and explore the putative mechanisms underpinning the beneficial effects.Materials and methodsSAE was induced in C57BL/6 mice by cecal ligation and puncture(CLP). Mice were administrated with β-PAE or saline by intra-cerebral ventricle(i.c.v) injection immediately after CLP surgery. The inhibitory avoidance tests and open field tests were performed at 24h, 48h and 7days after procedures. Cytokines expression, oxidative parameters, microglia polarization and apoptosis in the brain tissue were assessed. Sirt1, Nrf2, HO-1and cleaved-caspase3 expression in hippocampus was determined by western-blotting. Further, serum cytokines expression and spleen lymphocytes apoptosis were evaluated, and survival study was performed.ResultsSeptic mice suffered severe cognitive decline following CLP as evidenced by decreased memory latency time and lower frequency of line crossing in the behavioral tests. A high dose of β-PAE(1mg/kg) improved the cognitive impairment in SAE mice, which was accompanied by reduced cytokines expression and oxidative stress. Immunofluorescence assay showed that β-PAE inhibited the expression of Iba-1 and iNOS in microglia. The mechanistic study indicated that β-PAE could promote the nuclear expression of Sirt1/Nrf2 and enhance cytoplasmic HO-1 expression. Furthermore, i.c.v administration of β-PAE decreased the expression of serum cytokines and apoptosis in the spleen, thus leading to an improved 7-day survival of septic mice. Finally, blockade of Nrf2 activation with ML385 largely mitigated the protective effects of β-PAE on the cognitive function, neuroinflammation and survival in SAE mice.ConclusionIn this study, we found that β-PAE significantly altered sepsis induced neuroinflammation and microglia activation, thus reversed the cognitive decline and improved the peripheral immune function. The neuroprotective effects were possibly mediated by the activation of Sirt1/Nrf2/HO-1 pathway. β-PAE might serve as a promising therapeutic agent for SAE prevention and treatment.

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is essential life support in patients with severe acute hypoxaemic respiratory failure. However, biopsies should be considered for some patients with unknown aetiology. This study aims to evaluate the feasibility of transbronchial lung cryobiopsy (TBLC) in such patients. Methods All patients with acute hypoxaemic respiratory failure of unknown aetiology who underwent TBLC with VV-ECMO support were retrospectively reviewed. Patients’ characteristics, ventilation settings, procedure parameters, complications, pathological diagnosis and survival were summarised and analysed. Results Eight female and five male patients with VV-ECMO support underwent TBLC. The median age was 58 (interquartile range (IQR) 38–67) years old. Concurrent diseases were present in 10 of the 13 patients, seven of which were immunosuppressed. The median time between biopsy and VV-ECMO establishment was 2.0 (IQR 0.5–6.5) days. No patient died from the procedure. Neither pneumothorax nor severe bleeding occurred in any of the patients. Five of the 13 patients experienced moderate bleeding, and all bleeding events were successfully controlled with prophylactic balloon blockers. Pathological diagnosis by TBLC was obtained in all patients, and the diagnosis of diffuse alveolar damage was made in nine of them. Conclusions In patients with VV-ECMO support, the TBLC procedure is generally safe when standardised bleeding prophylaxis is in place. TBLC contributes to identifying underlying aetiologies in patients with acute hypoxaemic respiratory failure of unknown aetiology.

De novo and acquired resistance are major impediments to the efficacy of conventional and targeted cancer therapy. In unselected gastric cancer (GC) patients with advanced disease, trials combining chemotherapy and an anti-EGFR monoclonal antibody have been largely unsuccessful. In an effort to identify biomarkers of resistance so as to better select patients for such trials, we screened the secretome of chemotherapy-treated human GC cell lines. We found that levels of CGA, the α-subunit of glycoprotein hormones, were markedly increased in the conditioned media of chemoresistant GC cells, and CGA immunoreactivity was enhanced in GC tissues that progressed on chemotherapy. CGA levels in plasma increased in GC patients who received chemotherapy, and this increase was correlated with reduced responsiveness to chemotherapy and poor survival. Mechanistically, secreted CGA was found to bind to EGFR and activate EGFR signaling, thereby conferring a survival advantage to GC cells. N-glycosylation of CGA at Asn52 and Asn78 is required for its stability, secretion, and interaction with EGFR. GATA2 was found to activate CGA transcription, whose increase, in turn, induced the expression and phosphorylation of GATA2 in an EGFR-dependent manner, forming a positive feedback circuit that was initiated by GATA2 autoregulation upon sublethal exposure to chemotherapy. Based on this circuit, combination strategies involving anti-EGFR therapies or targeting CGA with microRNAs (miR-708-3p and miR-761) restored chemotherapy sensitivity. These findings identify a clinically actionable CGA/EGFR/GATA2 circuit and highlight CGA as a predictive biomarker and therapeutic target in chemoresistant GC.

Abstract For the purpose of assessing the radiation dose of the victims involved in the nuclear emergency or radiation accident, a new type of X-band EPR resonant cavity for in vivo fingernail EPR dosimetry was designed and a homemade EPR spectrometer for in vivo fingernail detection was constructed. The microwave resonant mode of the cavity was rectangular TE101, and there was a narrow aperture for fingernail detection opened on the cavity’s wall at the position of high detection sensitivity. The DPPH dot sample and the fingernail samples were measured based on the in vivo fingernail EPR spectrometer. The measurements of the DPPH dot sample verified the preliminary functional applicable of the EPR spectrometer and illustrated the microwave power and modulation response features. The fingernails after irradiation by gamma-ray were measured and the radiation-induced signal was acquired. The results indicated that the cavity and the in vivo EPR dosimeter instrument was able to detect the radiation-induced signal in irradiated fingernail, and preliminarily verified the basic function of the instrument and its potential for emergency dose estimate after a radiation accident.

Importance: The protective efficacy of COVID-19 vaccinations has declined over time such that booster doses are required. Objective: To evaluate the efficacy and adverse events of booster doses of two inactivated COVID-19 vaccines. Design: This is a double-blind, randomized, placebo-controlled phase 3 trial aiming to evaluate the protective efficacy, safety, and immunogenicity of inactivated SARS-CoV-2 vaccine (Vero cells) after inoculation with booster doses of inactivated COVID-19 vaccine. Setting: Healthy volunteers were recruited in an earlier phase 3 trial of two doses of inactivated vaccine. The participants in Abu Dhabi maintained the blind state of the trial and received a booster dose of vaccine or placebo at least six months after the primary immunization. Participants: Adults aged 18 and older with no history of SARS-CoV, SARS-CoV-2, or Middle East respiratory syndrome infection (via onsite inquiry) were screened for eligibility. Interventions: A total of 9370 volunteers were screened and randomly allocated, of which 61 voluntarily withdrew from the screening stage without booster inoculation; 9309 received the booster vaccination, with 3083 in the WIV04 group, 3150 in the HB02 group, and 3076 in the alum-only group. Further, 5μg and 4μg of inactivated SARS-CoV-2 virion was adsorbed into aluminum hydroxide in a 0.5 mL aqueous suspension for WIV04 and HB02 vaccines. Main Outcomes and Measures: The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 from 14 days after the booster vaccine in the per-protocol population. A safety analysis was performed in the intention-to-treat population. Results: Symptomatic COVID-19 was identified in 36 participants in the WIV04 group (9.9 [95% CI, 7.2–13.8] per 1000 person-years), 28 in the HB02 group (7.6 [95% CI, 5.2–11.0] per 1000 person-years), and 193 in the alum-only group (55.2 [95% CI, 47.9–63.5] per 1000 person-years), resulting in a vaccine efficacy of 82.0% (95% CI, 74.2–87.8%) for WIV04 and 86.3% (95% CI, 79.6–91.1%) for HB02. One severe case of COVID-19 occurred in the alum-only group, and none occurred in the vaccine groups. Adverse reactions within seven days after vaccination occurred in 29.4% to 34.3% of participants in the three groups. Serious adverse events were rare and not related to vaccines (WIV04: 17 [0.5%]; HB02: 11 [0.4%]; alum only: 40 [1.3%]). Conclusions and Relevance: This study evaluated the safety of the booster dose, which was well tolerated by participants. Booster doses given over six months after the completion of primary immunization can help to provide more-effective protection against COVID-19 in healthy people 18 years of age or older. At the same time, the anti-SARS-CoV-2 antibodies produced by the two groups of experimental vaccines exhibited extensive cross-neutralization against representative SARS-CoV-2 variants. Trial Registration: This study is registered on ClinicalTrials.gov (NCT04510207).

BackgroundThe rupture of vulnerable atherosclerotic plaque is the main cause of acute ischemic vascular events, and is characterized by pathological degradation of matrix collagen in the fibrous cap. In a previous study, we reported that 5-aminolevulinic acid-mediated sonodynamic therapy suppressed collagen degradation in rabbit plaque. However, the underlying molecular mechanism has yet to be fully elucidated.MethodsWe applied sinoporphyrin sodium-mediated sonodynamic therapy (DVDMS-SDT) to balloon-denuded rabbit and apolipoprotein E-deficient (ApoE-/-) mouse models to observe collagen content in plaque. Cultured human THP-1 and mouse peritoneal macrophage-derived foam cells were used for in vitro mechanistic studies.ResultsWe observed that DVDMS-SDT decreased plaque area and increased the percentages of collagen and smooth muscle cells and reduced the percentage of macrophages in rabbit and ApoE-/- mouse advanced plaques. In vitro, DVDMS-SDT modulated the caspase 3-pigment epithelium-derived factor/hypoxia-inducible factor-1α (PEDF/HIF-1α)-matrix metalloprotease-2/9 (MMP-2/MMP-9) signaling in macrophage foam cells.ConclusionsOur findings show that DVDMS-SDT effectively inhibits matrix collagen degradation in advanced atherosclerotic plaque by modulating caspase 3-PEDF/HIF-1α-MMP-2/MMP-9 signaling in macrophage foam cells and therefore represents a suitable and promising clinical regimen to stabilize vulnerable plaques.

Abstract The ischaemia-reperfusion (I/R) model is a widely used model of acute kidney injury (AKI) and renal fibrosis. However, the ischaemia duration that is long enough to cause broad fibrosis shows that a high mortality rate and a short ischaemia duration does not cause fibrosis, resulting in a large variation in fibrosis progression in this experimental model. Inter-operator variation occurs for I/R injury severity because the I/R procedure is complex, which results in poor reproducibility of subsequent fibrosis in the model. In the present study, we developed a renal fibrosis model in which the fibrosis progression for 8 weeks is predictable within 8 days. Three operators independently performed I/R followed by uninephrectomy at day 7 in mice. The aim was to create a model that would show a blood urea nitrogen (BUN) level >100 mg/dL at day 8 after I/R (day 1 after uninephrectomy). Although the ischaemia duration to satisfy this BUN criterion differed among operators, the mice developed anaemia, polyuria, and fibrosis in a similar manner under the same BUN criterion with a low mortality rate. Interstitial fibrosis had developed at week 8, which was strongly correlated with the BUN at day 8. This protocol allows operators to adjust the ischaemia duration based on the BUN criterion and to separate mice into the desired number of groups based on the BUN to study interventions against renal fibrosis.

Abstract Background Acetaminophen (APAP) overdose-induced acute liver failure (ALF) is mainly resulted from uncontrolled oxidative stress. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a key antioxidant transcription factor, is essential for alleviating APAP-induced hepatotoxicity. Corilagin (Cori) is a natural polyphenol compound that possesses effective antioxidant activity; however, the protective effect of Cori on APAP-induced hepatotoxicity is still unknown. The current study aimed to explore whether Cori could mitigate hepatotoxicity caused by APAP and the underlying molecular mechanisms of action. Methods Cell counting kit-8 (CCK-8) assays, Western blotting analysis, dual-luciferase reporter assays, a mouse model, CRISPR/Cas9 knockout technology, and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which Cori exerts a protective effect on hepatotoxicity in HepG2 cells and in a mouse model. Results Our findings suggested that Cori efficiently decreased APAP-triggered the generation of reactive oxygen species (ROS) and cell death in HepG2 cells. Additionally, Cori significantly induced the expression of several antioxidant enzymes, and this induced expression was closely linked to the upregulation of Nrf2, inhibition of Keap1 protein expression, and promotion of antioxidant response element (ARE) activity in HepG2 cells. Moreover, Cori clearly induced the phosphorylation of AMP-activated protein kinase (AMPK), glycogen synthase kinase-3β (GSK3β), liver kinase B1 (LKB1) and acetyl-CoA carboxylase (ACC). Furthermore, Cori-mediated GSK3β inactivation, Nrf2 upregulation and cytoprotection were abolished by an AMPK inhibitor (Compound C) in HepG2 cells. Lastly, we found that Cori inhibited APAP-induced hepatotoxicity and mediated the expression of many antioxidant enzymes; these results were reversed in Nrf2 −/− HepG2 cells. In vivo, Cori significantly protected against APAP-induced ALF by reducing mortality and alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, attenuating histopathological liver changes, inhibiting myeloperoxidase (MPO) and malondialdehyde (MDA) levels, and increasing the superoxide dismutase (SOD) content and GSH-to-GSSG ratio as well as suppressing c-jun N-terminal kinase (JNK) phosphorylation. However, Cori-induced reductions in mortality, AST and ALT levels, and histopathological liver changes induced by APAP were clearly abrogated in Nrf2-deficienct mice. Conclusions These findings principally indicated that Cori effectively protects against APAP-induced ALF via the upregulation of the AMPK/GSK3β-Nrf2 signaling pathway.

ABSTRACT: Objective This study was conducted to elucidate the potential key candidate genes and pathways in role of astrocyte involved in glaucoma with ocular hypertension.Methods Expression profiles GSE2378 and GSE758 including 27 reactive optic nerve head astrocytes (ONHAs) by hypertensions and 26 normal controls, were integrated and deeply analyzed. Differentially expressed genes (DEGs) were sorted and candidate genes and pathways enrichment were analyzed. DEGs-associated protein-protein interaction network (PPI) was performed.Results A total of 119 consistently expressed genes were identified from 281 commonly changed DEGs, including 68 up-regulated genes and 51 down-regulated genes. PPI network complex filtered 75 DEGs (43 up-regulated and 32 down-regulated genes) of the 119 consistently altered DEGs and developed 117 edges, and 10 hub genes were identified. The most significant 3 modules were filtered from PPI, pathway enrichment analysis showed that module 1 was associated with extracellular exosome. Module 2 was mainly associated with antibody-dependent cellular cytotoxicity (ADCC) and module 3 was mainly associated with Hippo signaling pathway.Conclusion Taken above, using integrated bioinformatical analysis, we have identified DEGs candidate genes and pathways in role of astrocyte involved in glaucoma with ocular hypertension, which could improve our understanding of the cause and underlying molecular events, and these candidate genes and pathways could be therapeutic targets for glaucoma. Keywords: Glaucoma, Ocular hypertension, Reactive optic nerve head astrocytes, Hub gene, Pathway enrichment

Abstract Background Epigenetic modification has an effect on gene expression under the environmental alteration, but it does not change corresponding genome sequence. DNA methylation (DNAm) is one of the important epigenetic mechanisms. DNAm variations could be used as epigenetic markers to predict and account for the change of many human phenotypic traits, such as cancer, diabetes, and high blood pressure. In this study, we built deep neural network (DNN) regression models to account for interindividual variation in triglyceride concentrations measured at different visits of peripheral blood samples using epigenome-wide DNAm profiles. Results We used epigenome-wide DNAm profiles of before and after medication interventions (called pretreatment and posttreatment, respectively) to predict triglyceride concentrations for peripheral blood draws at visit 2 (using pretreatment data) and at visit 4 (using both pretreatment and posttreatment data). Our experimental results showed that DNN models can predict triglyceride concentrations for blood draws at visit 4 using pretreatment and posttreatment DNAm data more accurately than for blood draws at visit 2 using pretreatment DNAm data. Furthermore, we got the best prediction results when we used pretreatment DNAm data to predict triglyceride concentrations for blood draws at visit 4, which suggests a long-term epigenetic effect on phenotypic traits. We compared the prediction performances of our proposed DNN models with that of support vector machine (SVM). This comparison showed that our DNN models achieved better prediction performance than did SVM. Conclusions We demonstrated the superiority of our proposed DNN models over the SVM model for predicting triglyceride concentrations. This study also suggests that the DNN approach has advantages over other traditional machine-learning methods to model high-dimensional epigenome-wide DNAm data and other genomic data.

Tissue resident mesenchymal stem/stromal cells (MSCs) occupy perivascular spaces. Profiling human adipose perivascular mesenchyme with antibody arrays identified 16 novel surface antigens, including endolysosomal protein CD107a. Surface CD107a expression segregates MSCs into functionally distinct subsets. In culture, CD107alow cells demonstrate high colony formation, osteoprogenitor cell frequency, and osteogenic potential. Conversely, CD107ahigh cells include almost exclusively adipocyte progenitor cells. Accordingly, human CD107alow cells drove dramatic bone formation after intramuscular transplantation in mice, and induced spine fusion in rats, whereas CD107ahigh cells did not. CD107a protein trafficking to the cell surface is associated with exocytosis during early adipogenic differentiation. RNA sequencing also suggested that CD107alow cells are precursors of CD107ahigh cells. These results document the molecular and functional diversity of perivascular regenerative cells, and show that relocation to cell surface of a lysosomal protein marks the transition from osteo- to adipogenic potential in native human MSCs, a population of substantial therapeutic interest.

Background: Intracavernous injection (ICI) of adipose-derived stem cells (ADSCs) has been demonstrated promising for neurogenic erectile dysfunction (ED). However, due to the sponge-like structure of corpus cavernosum (CC) with abundant vessels, ICI was indeed like intravenous injection. Thus, the cell escaping may be a concern of safety and limited therapy, but the issue has not been clearly demonstrated yet. Methods: Suspensions of free ADSCs (FAs) and ADSCs-based spheroids (ASs) with suitable size were intracavernously injected at doses of 0.5, 1, 2, or 4 million cells. The cell loss and safety after ICI, erectile function and histopathologic change, etc. were analyzed with multimodality of methods. Findings: Most FAs escaped from sponge-like CC after ICI due to their small size, weakening stem-cell therapeutic efficacy. Worse still, the escaped cells were shown to cause widespread pulmonary embolism (PE), and even death in some animals. Further, it was founded that the therapeutic effect of FAs may be ascribed to the larger cell clusters which spontaneously aggregated before ICI and were trapped within CC after ICI. In comparison, cell loss and PE were significantly avoided by transplanting ASs. Importantly, better therapeutic outcomes were detected after ICI of ASs when compared to FAs with the same cell number. Interpretation: Transplantation of size-specific ASs instead of single-cell suspension of FAs for neurogenic ED may be a wiser choice to achieve steady therapeutic outcome and to reduce risks for the future clinical application. Fund: This work was supported by the National Natural Science Foundation of China (81701432) (to Y. Xu). Youth Training Project for Medical science (16QNP129) and Beijing Nova Program of science and technology (Z171100001117115) (to Z. Liu). Keywords: Erectile dysfunction, Stem cells, Three-dimensional culture, Pulmonary embolism, Intracavernous injection

Online shopping behavior has the characteristics of rich granularity dimension and data sparsity and presents a challenging task in e-commerce. Previous studies on user behavior prediction did not seriously discuss feature selection and ensemble design, which are important to improving the performance of machine learning algorithms. In this paper, we proposed an SE-stacking model based on information fusion and ensemble learning for user purchase behavior prediction. After successfully using the ensemble feature selection method to screen purchase-related factors, we used the stacking algorithm for user purchase behavior prediction. In our efforts to avoid the deviation of the prediction results, we optimized the model by selecting ten different types of models as base learners and modifying the relevant parameters specifically for them. Experiments conducted on a publicly available dataset show that the SE-stacking model can achieve a 98.40% F1 score, approximately 0.09% higher than the optimal base models. The SE-stacking model not only has a good application in the prediction of user purchase behavior but also has practical value when combined with the actual e-commerce scene. At the same time, this model has important significance in academic research and the development of this field.

Green innovation is an important driving force to promote the sustainable development of urban society and economy. This paper constructs an evaluation index system containing social undesirable outputs, and uses the Super-SBM model and the Malmquist-Luenberger index to evaluate green innovation efficiency in 42 cities along the Yangtze River Economic Belt from 2013 to 2017. Additionally, spatial autocorrelation analysis is used to study the spatial correlation of green innovation efficiency. Finally, the coupling coordination degree model is used to study the coupling coordination degree between green innovation efficiency and high-tech industries. The following results were obtained. (1) The average value of green innovation efficiency increased from 1.0446 to 1.0987, and the annual average growth rate of total factor productivity of green innovation was 1.1%. (2) Green innovation efficiency of the Yangtze River Economic Belt had a significant spatial positive correlation, but the types of agglomeration among cities in different sections of the Yangtze River were quite different. (3) The coupling coordination degree between green innovation efficiency and the development level of high-tech industries in the cities of the Yangtze River Economic Belt was in the basic coordination stage. Based on the research results, we suggest that cities in this belt further enhance the interactive relationship between green innovation and economic development and promote the coordinated development of economy and society.

The present study aimed to adapt the Attitudes Toward Accompanied Driving Scale (ATADS) to a Chinese drivers sample and to examine its reliability and validity. Five hundred and seventy-two drivers aged 18 to 25 years old were asked to complete the ATADS and a validated Chinese version of the Multidimensional Driving Style Inventory. The factorial structure of the ATADS was examined using exploratory factor analysis (N = 259) and confirmatory factor analysis (N = 313). The validity of the scale was evaluated by examining the associations between the ATADS factors, demographic variables and driving styles. The results showed that both the findings of the EFA and CFA showed a five-factor structure of the ATADS, including tension, relatedness, avoidance, disapproval and anxiety. Second, significant gender differences were found in tension, relatedness, avoidance and anxiety. Third, tension, avoidance, disapproval and anxiety were moderately or weakly correlated with risky, anxious, angry and careful driving styles. Moreover, the number of traffic accidents after the accompanying phase was positively correlated with disapproval and avoidance. The findings supported the psychometric properties of the Chinese version of the ATADS and highlighted the adverse effects of young drivers' negative attitudes toward accompanied driving on their driving styles.

Heterogeneity broadly exists in various cell types both during development and at homeostasis. Investigating heterogeneity is crucial for comprehensively understanding the complexity of ontogeny, dynamics, and function of specific cell types. Traditional bulk-labeling techniques are incompetent to dissect heterogeneity within cell population, while the new single-cell lineage tracing methodologies invented in the last decade can hardly achieve high-fidelity single-cell labeling and long-term in-vivo observation simultaneously. In this work, we developed a high-precision infrared laser-evoked gene operator heat-shock system, which uses laser-induced CreERT2 combined with loxP-DsRedx-loxP-GFP reporter to achieve precise single-cell labeling and tracing. In vivo study indicated that this system can precisely label single cell in brain, muscle and hematopoietic system in zebrafish embryo. Using this system, we traced the hematopoietic potential of hemogenic endothelium (HE) in the posterior blood island (PBI) of zebrafish embryo and found that HEs in the PBI are heterogeneous, which contains at least myeloid unipotent and myeloid-lymphoid bipotent subtypes.

Abstract Irradiation on hippocampus would lead to neuro-cognitive dysfunction in locally advanced nasopharyneal carcinoma (LA-NPC) patients accepting radiotherapy. Our study here aimed to investigate if undergoing hippocampus sparing (HS) volume modulated arc therapy (VMAT) would influence the plan quality in LA NPC patients. We designed three kinds of radiotherapeutic plans for 11 LA NPC patients: conventional VMAT (C-VMAT), HS-VMAT and HS intensity modulated radiation therapy with dynamic multileaf collimator (HS-dMLC). And the dose distribution on targets and surrounding organs at risk (OAR) were carefully evaluated. We found out that the expected doses on hippocampus were significantly lowered in HS-VMAT (899 ± 378 cGy) and HS-dMLC (896 ± 321 cGy) as compared to C-VMAT (1518 ± 337 cGy, p 0.05). Moreover, lower radiation doses on brain stem were observed in HS-VMAT plan in comparison with C-VMAT plan (p