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Adenosine deaminases acting on RNA 1 (ADAR1), an RNA editing enzyme, holds a role in cancer, inflammation, and immunity. However, its specific function in the nephropathy and high-glucose-induced human renal tubular epithelial cells (HK-2) injury in diabetic db/db mice is not clear.

Abstract The deterioration and deformation of brittle rock generally appear in railway tunnels with the operation of large buried deep tunnel. To investigate the macro-micro fracture and acoustic emission evolution characteristics of brittle rock, this paper conducted the uniaxial compression, scanning electron microscope (SEM), and acoustic emission (AE) signal monitoring under different loading rates. The results showed that the loading rate has an obvious enhancement effect on mechanical parameters. The increased loading rate extends the elastic deformation and improves the bearing strength, elastic modulus and deformation modulus. The fracture patterns include shear fracture, composite fracture, and tension fracture. The oblique shear fracture is transformed into composite fracture and tension fracture with the loading rate increasing. The microscopic fracture shows that increasing loading rate inhibits the evolution of oblique shear fractures and promotes the expansion of tensile fractures. The roughness level of tensile fractures is significantly lower than that of oblique shear fracture and composite fracture. The AE parameters and deformation behavior are characterized by simultaneous evolution. The AE amplitude changes from low-level and low-density distribution to high-level and high-density distribution as the loading rate increases. The AE activity intensity of tensile fracture is significantly greater than that of oblique shear fracture and composite fracture. The warning timeliness of cumulative AE events and cumulative AE energy is generally earlier than the AE b-value under the same loading rate, and the early warning timeliness of cumulative AE events is similar to that of cumulative AE energy.

Abstract. Background:. Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening. Methods:. We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial. Results:. This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios. Conclusion:. This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Abstract The combination of anti-angiogenic treatment and immunotherapy presents a promising strategy against colon cancer. Interleukin-17F (IL-17F) emerges as a critical immune cell cytokine expressed in colonic epithelial cells, demonstrating potential in inhibiting angiogenesis. In order to clarify the roles of IL-17F in the colon cancer microenvironment and elucidate its mechanism, we established a mouse colon carcinoma cell line CT26 overexpressing IL-17F and transplanted it subcutaneously into syngeneic BALB/c mice. We also analyzed induced colon tumor in IL-17F knockout and wild type mice. Our results demonstrated that IL-17F could suppress colon tumor growth in vivo with inhibited angiogenesis and enhanced recruitment of cysteine-cysteine motif chemokine receptor 6 (CCR6) positive immune cells. Additionally, IL-17F suppressed the tube formation, cell growth and migration of endothelial cells EOMA in vitro. Comprehensive bioinformatics analysis of transcriptome profiles between EOMA cells and those treated with three different concentrations of IL-17F identified 109 differentially expressed genes. Notably, a potential new target, Caspase 4, showed increased expressions after IL-17F treatment in endothelial cells. Further molecular validation revealed a novel downstream signaling for IL-17F: IL-17F enhanced Caspase 4/GSDMD signaling of endothelial cells, CT26 cells and CT26 transplanted tumors, while IL-17F knockout colon tumors exhibited decreased Caspase 4/GSDMD signaling. The heightened expression of the GSDMD N-terminus, coupled with increased cellular propidium iodide (PI) uptake and lactate dehydrogenase (LDH) release, revealed that IL-17F promoted pyroptosis of endothelial cells. Altogether, IL-17F could modulate the colon tumor microenvironment with inhibited angiogenesis, underscoring its potential as a therapeutic target for colon cancer.

Abstract This study retrospectively evaluated the outcomes of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using novel electrocautery-enhanced lumen-apposing metal stents (LAMS) in high-risk patients with acute cholecystitis (AC). Between January 1, 2021, and November 30, 2022, 58 high-risk surgical patients with AC underwent EUS-GBD with the novel electrocautery-enhanced LAMS. The technical success rate was 94.8% (55/58), with one case of duodenal perforation requiring surgery with complete stent migration and two of partial stent migration into the gallbladder. However, the clinical success rate was 100% (55/55). Recurrent AC occurred in 3.6% of the cases (2/55), managed with double pigtail plastic stents through the LAMS. Early AEs observed in 1.8% (1/55) due to stent obstruction. Late AEs occurred in 5.4% (3/55), including two cases of cholangitis and one of stent obstruction. For 33 patients followed over 6 months, LAMS maintenance was sustained in 30 cases. Two patients underwent double-pigtail plastic stent replacement after LAMS removal, and one underwent LAMS removal during surgery following tumor stage regression after chemotherapy for cholangiocarcinoma. The novel electrocautery-enhanced LAMS demonstrated high technical and clinical success rates in high-risk surgical patients with AC, maintaining effective gallbladder drainage with minimal AEs during long-term follow-up, thus highlighting its efficacy and safety in challenging patients.

AbstractPurpose It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs).Methods MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs.Results A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37–0.84, p = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m2, 95% CI 0.31–1.48, p = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = −0.21, 95% CI −0.41 to −0.01, p = 0.042).Conclusion Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout.Systematic review registration: PROSPERO CRD42021272591

Abstract Background As a dual-function metabolite, succinate has emerged in cell function and plays a key signaling role in linking mitochondrial function to other cellular functions. Succinate accumulation in the cytoplasm is commonly associated with hypoxia in the microenvironment and immune cell activation. Extracellular succinate released into the microenvironment is considered an inflammatory alarm that can be sensed by its membrane receptor SUCNR1, which boosts proinflammatory responses and acts akin to classical hormones and cytokines. Succinate plays an important role in the development of inflammatory diseases. Whether succinate facilitates the progression of endometriosis (EMs), characterized by chronic inflammation and peritoneal adhesion, is worth exploring. Objective We mimicked the ectopic milieu in vitro and in vivo to evaluate the main source and potential role of succinate in endometriosis. We assessed the molecular and functional effects of succinate on macrophages and peritoneal mesothelial cells in peritoneal cavity. The effect of succinate/SUCNR1 signaling on ectopic endometrial stromal cells (ESCs) was further explored in this study. Methods In this study, we used targeted organic acid metabolomics analysis and in vitro assays to assess the potential accumulation of succinate in the peritoneal fluid of EMs patients. We examined its correlation with disease severity, Visual Analogue Scale, and the Endometriosis Fertility Index. Flow cytometry, enzyme linked immunosorbent assay, western blot assay, quantitative real-time PCR, and other molecular biology techniques were used to explore the potential mechanisms. Results By mimicking the ectopic milieu, we constructed an in vitro co-culture system and found that M1 polarized macrophages and that the peritoneal mesothelial cell line (HMrSV5) mainly released succinate into their microenvironment and activated the succinate receptor (SUCNR1) signal, which further polarized the macrophages and significantly enhanced the invasive survival of ESCs, and the adhesion to the peritoneum. We further investigated the pathological effects of extracellular succinate in vivo using a xenograft mouse models of endometriosis. Conclusions Succinate-SUCNR1 signaling facilitates the creation of inflammatory cells and plays a vital role in EMs progression and peritoneal adhesion. Our work on the molecular mechanisms underlying succinate accumulation and function will help elucidate the phenotypic mysteries of pain and infertility in EMs. Video Abstract

Abstract This study aimed to evaluate the efficacy and safety of induction immunochemotherapy followed by definitive chemoradiotherapy (CRT) for unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC). We identified unresectable stage III NSCLC patients who received induction immunochemotherapy. Overall survival (OS) and progression‐free survival (PFS) were the primary endpoints. From February 2019 to August 2022, 158 patients were enrolled. Following the completion of induction immunochemotherapy, the objective response rate (ORR) and disease control rate (DCR) were 52.5% and 83.5%, respectively. The ORR of CRT was 73.5%, representing 68.4% of the total cohort. The median PFS was 17.8 months, and the median OS was 41.9 months, significantly higher than in patients who received CRT alone (p

Abstract Background Several kinds of physical activities have been applied to improve the prognosis of patients with hemodialysis (HD). However, the comparative efficacy of physical activities on the outcomes in HD patients is still unknown. This study explored the effectiveness and safety of all exercise types in HD patients. Methods We searched randomized clinical trials from the PubMed, EMBASE, and Cochrane Library databases. Physical exercises interventions included resistance exercise (RE), aerobic exercise (AE), electrical muscle stimulation (EMS), range of motion (ROM), resistance exercise + aerobic exercise (RE + AE), stretching exercise (STE), respiratory muscle training (RMT), peripheral muscle training (PMT), walking exercise (WE), or usual care/sham exercise (UC/SE). Primary outcomes were six-minute walk test (6-mwt) and quality of life (QOL). Secondary outcomes were Kt/V, VO2max, hemoglobin (Hb), C-reactive protein (CRP), interleukin-6 (IL-6), and systolic and diastolic blood pressure (sbp and dbp). Frequentist network meta-analysis with multivariate random effects models provided mean with 95% confidence intervals (95%CI). Results A total of 58 eligible studies were included. AE, RMT, and RE + AE significantly improved 6-mwt compared with UC/SE. SE was the worst intervention and reduced QOL much more than the UC/SE and other exercise types. AE and RE + AE were associated with higher VO2max, while ROM and RE + AE induced higher Hb levels. All physical activities did not elevate blood pressure, CRP and IL-6. Only ROM decreased sbp/dbp. CRP is significantly lower in RE. Conclusion Physical activities play a crucial role in the different outcomes of HD patients. They can be applied to specific area for their specific efficacy.

Objective To observe the primary tumor of tree shrews and to provide a basis for studying the pathogenesis and prevention of trichoepithelioma.Methods A tumor was discovered in the chest and abdomen of a tree shrew during natural cultivation. The tree shrew was anesthetized, and the tumor was surgically removed. Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed on the tumor tissue after paraffin section, and the tumor cells were isolated and cultured by passage. The isolated tumor cells were subcutaneously injected into healthy tree shrews and nude mice. The tumorigenesis of tumor cells in vivo was observed once a day, with nude mice continuously observed for 2 months and tree shrews observed for more than 6 months.Results HE staining showed that the basal cells in the dermis were arranged as a whole, like a string of petals, forming nests and stripe-like structures with clear boundaries. The observation results after magnification revealed that the tumor cells were arranged in a pallisade-like and basal pattern, with deep nuclear staining and minimal cytoplasmic. Immunohistochemical staining showed the high expression of CK protein and low proportion expression of ki-67 protein in tumor cells, as well as the high expression of vimentin and low expressions of Bcl2 and CD10 in tumor cell mesenchyme. The isolated tumor cells grew well in DMEM medium containing 10% fetal bovine serum and could be cultured by passage, but no tumor formation was observed in healthy tree shrews and nude mice inoculated with tumor cells.Conclusion Combined with the location of the tumor, overall morphology, HE staining, and immunohistochemical results, the thoracoabdominal mass of the tree shrew was diagnosed as a trichoepithelioma.

Abstract Background Hematotoxicity, including severe myelosuppression, is a common adverse drug reaction (ADR) during platinum‐based treatment for oesophageal cancer (EC). Purpose The aim of this study was to identify single‐nucleotide polymorphisms (SNPs) associated with platinum‐induced hematotoxicity in patients with EC, as the relationship between SNPs and this ADR is incompletely demonstrated. Methods A total of 262 patients receiving platinum‐based chemotherapy (cisplatin, nedaplatin, carboplatin and oxaliplatin) were enrolled in this study. Ten SNPs in eight genes were genotyped via multiplex polymerase chain reaction and sequenced to evaluate their relationship with severe myelosuppression and its subset of leukopenia and neutropenia. Results Multivariate logistic analysis of cisplatin cohort in severe leukopenia group showed an odds ratio (OR) of GG + GA versus AA in ABCB1 rs1045642 was 5.83 (95% confidence interval (CI) 1.63–20.83, p = 0.007, false discovery rate (FDR) = 0.028), while the OR of AA versus AG + GG in rs1128503 was 0.34 (95% CI 0.14–0.86, p = 0.022, FDR = 0.044). In nedaplatin cohort of neutropenia group, the OR of AA versus GG, AA + AG versus GG in GSTP1 rs1695 was 10.34 (95% CI 1.71–62.40, p = 0.011, FDR = 0.040) and 7.48 (95% CI 1.37–40.81, p = 0.020, FDR = 0.040) respectively. XRCC1 rs1799782 GG genotype in nedaplatin cohort of myelosuppression group and CYP3A5 rs776746 CT genotype in nedaplatin cohort of severe leukopenia group and platinum cohorts of all groups appeared to be risk factors with the p values less than 0.05, but FDR values were all greater than 0.05. Conclusion This study identified SNPs of XRCC1, ABCB1, CYP3A5 and GSTP1 related to hematotoxicity of platinum‐based drugs, thereby providing a novel theoretical basis for the prediction and prevention of ADRs in platinum‐based chemotherapy.

Geotextiles are excellent anti-filtration materials commonly used in the field of water conservancy engineering; however, the factors affecting the water permeability performance of geotextiles under stressed states during operation have not been fully identified. To investigate the effect of unidirectional stretching on the water permeability of geotextiles, a unidirectional rheological head infiltration test was conducted on the geotextiles using a self-developed test apparatus. In addition, the water permeability of geotextiles with different thicknesses and tensile states was calculated using a set of water permeability calculation methods based on the nonlaminar flow state of geotextiles. The results showed that the water permeability of the W120 geotextile samples initially decreased and then increased under warp stretching and gradually increased under weft stretching. However, the water permeability of the W200 geotextile samples initially decreased and then increased under both warp and weft stretching. Therefore, the thickness of the geotextile affected its permeability properties.

BackgroundNeonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB.MethodsA retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity.ResultsContact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors.ConclusionAge at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

Abstract Intelligent reflective surface (IRS) and unmanned aerial vehicle (UAV) communication are two key technologies in the sixth generation of mobile communication (6G). In this paper, IRS is equipped on UAV to form aerial IRS, which can achieve 360° panoramic full-angle reflection and flexible deployment of IRS. In order to achieve high-quality and ubiquitous network coverage under data privacy and low latency requirements, we propose an Federated learning (FL) network via Over-the-Air computation (AirComp) in IRS-assisted UAV communications. Our goal is to minimize the worst-case mean square error (MSE) by jointly optimizing the IRS phase shift, denoising factor for noise suppression, the user’s transmission power, and UAV trajectory. Optimizing and quickly adjusting the UAV position and IRS phase shift, it flexibly assists the signal transmission between users and base stations (BS). In order to solve this complex non-convex problem, we propose a low-complexity iterative algorithm, which divides the original problem into four sub-problems, respectively using the semi-definite programming (SDP) method, slack variable introduction method, successive convex approximation (SCA) method to solve each sub-problem. Through the analysis of simulation results, our proposed design scheme is obviously better than other benchmark schemes.

Ovarian aging is a significant challenge in gynecology, and there is currently no effective treatment for it. However, the medicinal agent Qingxin Zishen decoction (QZD) has shown potential in the treatment of ovarian dysfunction. The present study aimed to evaluate the mitochondrial apoptotic mechanism of delayed ovarian aging in QZD in aging rats. The healthy female Sprague-Dawley (SD) rats (n = 40, 350 ± 20 g) were randomly assigned to different dosage groups and 4-month-old SD rats (n = 10) were assigned to the control group. QZD groups were treated with QZD for four weeks, and ovarian tissues were extracted for mRNA and protein assays to examine the role of the apoptotic pathway in QZD. The results showed that QZD treatment for four weeks significantly increased the mRNA and protein expressions of the anti-apoptotic gene B-cell lymphoma 2 (Bcl-2) and Bcl-2/Bax ratio, as well as downregulated the pro-apoptotic genes Bax, caspase-3, and caspase-9. Moreover, QZD treatment effectively reduced the expression of cytochrome C (cyto-C) and apoptotic protease-activating factor 1 (Apaf-1), both of which are components of the intrinsic apoptotic pathway. These changes exhibited a dose-response manner. The findings suggest that QZD might have therapeutic potential in delaying ovarian mitochondrial function decline and in preventing and treating ovarian aging-related diseases by downregulating and upregulating the pro-apoptotic (Bax, caspase-3, caspase-9, cyto-C, Apaf-1) and anti-apoptotic (Bcl-2 and Bcl-2/Bax ratio) genes, respectively.

Introduction Little is known about activity behaviours and quality of life (QoL) of patients with parapneumonic pleural effusions (PPE) after hospital discharge. This study is a secondary analysis of a randomised trial (dexamethasone versus placebo) for hospitalised patients with PPE. We: 1) described the patients’ activity behaviour patterns and QoL measured at discharge and at 30 days post-discharge; and 2) examined the association between activity behaviours and QoL scores. Methods Activity behaviour (7-day accelerometry; Actigraph GT3X+) and QoL (Medical Outcomes Study Short-Form 36) were assessed. Repeated measures analysis of covariance controlling for baseline values and a series of linear regression models were undertaken. Results 36 out of 53 eligible participants completed accelerometry assessments. Despite modest increases in light physical activity (+7.5%) and some domains of QoL (>2 points) from discharge to 30 days post-discharge, patients had persistently high levels of sedentary behaviour (>65% of waking wear time) and poor QoL (≤50 out of 100 points) irrespective of treatment group (p=0.135–0.903). Increasing moderate-to-vigorous physical activity was associated with higher scores on most QoL domains (p=0.006–0.037). Linear regression indicates that a clinically important difference of 5 points in physical composite QoL score can be achieved by reallocating 16.1 min·day−1 of sedentary time to moderate-to-vigorous physical activity. Conclusion Patients with PPE had low levels of physical activity and QoL at discharge and 30 days post-discharge irrespective of treatment. Moderate-to-vigorous physical activity participation was associated with higher QoL scores. Increasing moderate-to-vigorous physical activity following discharge from the hospital may be associated with improvements in QoL.

Abstract Prior studies have suggested a strong link between obesity and autoimmune diseases. This study aimed to evaluate the effects of high fat diet (HFD)-induced obesity on the disease pathogenesis, immune cell infiltration, and therapeutic efficacy in systemic lupus erythematosus (SLE). Treatment with methylprednisolone significantly increased the survival in the control diet group, but not in the HFD group. An HFD significantly increased the incidence of severe proteinuria and glucose intolerance. Regardless of the diet, treatment with methylprednisolone significantly decreased the serum levels of anti-dsDNA antibodies, IL-2, IL-10, and interferon γ-induced protein 10 (IP-10), and improved the renal pathology scores. Treatment with methylprednisolone significantly lowered the serum levels of IL-6, MCP-1, and TNF-α in the control diet group, but not in the HFD group. HFD significantly increased the proportions of CD45+ and M1 cells and significantly decreased the proportion of M2 cells in white adipose tissue; methylprednisolone treatment significantly rescued this effect. In the HFD group, methylprednisolone treatment significantly decreased the M1:M2 and increased the Foxp3+:RORγt+ cell in the spleen compared with the untreated group. These data improve our understanding of the effect of HFD on the therapeutic efficacy of corticosteroids in SLE treatment, which could have clinical implications.

Smart health technologies have been increasingly used in chronic disease management, and become an important way foroptimizing the health management behaviors in patients with chronic diseases. Based on a review of studies about healthcare-seeking behaviors in Chinese patients with chronic diseases and the framework of the Andersen's Behavioral Model of Healthcare Utilization, we summarized that healthcare-seeking behaviors in these patients are associated with predisposing, enabling, and need factors, with enabling factors (economic status and education level) being the key determinant. Therefore, it is necessary to utilize the advantages of care delivery modes using smart health technologies to integrate media resources for health knowledge education, strengthen the social support for vulnerable groups and optimize the cooperation between multiple care delivery groups. The implementation of these strategies will contribute to the empowerment of people with chronic diseases, optimizing their healthcare-seeking behaviors, and making effective use of health service resources.

Skin aging is a complex process involving intricate genetic and environmental factors. In this study, we performed a comprehensive analysis of the transcriptional regulatory landscape of skin aging in canines. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify aging-related gene modules. We subsequently validated the expression changes of these module genes in single-cell RNA sequencing (scRNA-seq) data of human aging skin. Notably, basal cell (BC), spinous cell (SC), mitotic cell (MC), and fibroblast (FB) were identified as the cell types with the most significant gene expression changes during aging. By integrating GENIE3 and RcisTarget, we constructed gene regulation networks (GRNs) for aging-related modules and identified core transcription factors (TFs) by intersecting significantly enriched TFs within the GRNs with hub TFs from WGCNA analysis, revealing key regulators of skin aging. Furthermore, we demonstrated the conserved role of CTCF and RAD21 in skin aging using an H2O2-stimulated cell aging model in HaCaT cells. Our findings provide new insights into the transcriptional regulatory landscape of skin aging and unveil potential targets for future intervention strategies against age-related skin disorders in both canines and humans.

Abstract Background Gastrointestinal stromal tumor (GIST) is a rare type of cancer that occurs in the gastrointestinal tract. The majority of GIST cases carry oncogenic forms of KIT, the receptor for stem cell factor (SCF). Small molecule kinase inhibitor imatinib is effective in prolonging the survival of GIST patients by targeting KIT. However, drug resistance often develops during the therapeutic treatment. Here, we produced a SCF-emtansine drug conjugate (SCF-DM1) with favorable drug efficacy towards GIST cells. Methods Recombinant human SCF (rhSCF) was expressed in E. coli cells and further purified with Ni–NTA Sepharose and Phenyl Sepharose. It was then conjugated with DM1, and the conjugated product SCF-DM1 was evaluated using in vitro cell-based assays and in vivo xenograft mouse model. Results SCF-DM1 was effective in inhibiting imatinib-sensitive and -resistant GIST cell lines and primary tumor cells, with IC50 values of

Background The clinical impact of phenotyping empyema is poorly described. This study was designed to evaluate clinical characteristics and outcomes based on the two readily available parameters, pleural fluid culture status and macroscopic fluid appearance. Methods A retrospective study was conducted on patients with empyema hospitalised between 2013 and 2020. Empyema was classified into culture-positive empyema (CPE) or culture-negative empyema (CNE) and pus-appearing empyema (PAE) or non-pus-appearing empyema (non-PAE) based on the pleural fluid culture status and macroscopic fluid appearance, respectively. Results Altogether, 212 patients had confirmed empyema (CPE: n=188, CNE: n=24; PAE: n=118, non-PAE: n=94). The cohort was predominantly male (n=163, 76.9%) with a mean age of 65.0±13.6 years. Most patients (n=180, 84.9%) had at least one comorbidity. Patients with CPE had higher rates of in-hospital mortality (19.1% versus 0.0%, p=0.017) and 90-day mortality (18.6% versus 0.0%, p=0.017) and more extrapulmonary sources of infection (29.8% versus 8.3%, p=0.026) when compared with patients with CNE. No significant difference in mortality rate was found between PAE and non-PAE during the in-hospital stay and at 30 days and 90 days. Patients with PAE had less extrapulmonary sources of infection (20.3% versus 36.2%, p=0.010) and more anaerobic infection (40.9% versus 24.5%, p=0.017) than those with non-PAE. The median RAPID (renal, age, purulence, infection source, and dietary factors) scores were higher in the CPE and non-PAE groups. After adjusting for covariates, culture positivity was not independently associated with mortality on multivariable analysis. Conclusion Empyema is a heterogeneous disease with different clinical characteristics. Phenotyping empyema into different subclasses based on pleural fluid microbiological results and macroscopic fluid appearance provides insight into the underlying bacteriology, source of infection and subsequent clinical outcomes.

Abstract Osteogenesis and osteoclastogenesis are closely associated during the bone regeneration process. The development of multifunctional bone repair scaffolds with dual therapeutic actions (pro-osteogenesis and anti-osteoclastogenesis) is still a challenging task for bone tissue engineering applications. Herein, through a facile surface coating process, mussel-inspired polydopamine (PDA) is adhered to the surface of a biocompatible porous scaffold followed by the immobilization of a small-molecule activator (LYN-1604 (LYN)) and the subsequent in situ coprecipitation of hydroxyapatite (HA) nanocrystals. PDA, acting as an intermediate bridge, can provide strong LYN immobilization and biomineralization ability, while LYN targets osteoclast precursor cells to inhibit osteoclastic differentiation and functional activity, which endows LYN/HA-coated hybrid scaffolds with robust anti-osteoclastogenesis ability. Due to the synergistic effects of the LYN and HA components, the obtained three-dimensional hybrid scaffolds exhibited the dual effects of osteoclastic inhibition and osteogenic stimulation, thereby promoting bone tissue repair. Systematic characterization experiments confirmed the successful fabrication of LYN/HA-coated hybrid scaffolds, which exhibited an interconnected porous structure with nanoroughened surface topography, favorable hydrophilicity, and improved mechanical properties, as well as the sustained sequential release of LYN and Ca ions. In vitro experiments demonstrated that LYN/HA-coated hybrid scaffolds possessed satisfactory cytocompatibility, effectively promoting cell adhesion, spreading, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene and protein secretion, as well as stimulating angiogenic differentiation of endothelial cells. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity, F-actin ring staining, and osteoclastogenesis-related gene and protein secretion. More importantly, in a rat calvarial defect model, the newly developed hybrid scaffolds significantly promoted bone repair and regeneration. Microcomputed tomography, histological, and immunohistochemical analyses all revealed that the LYN/HA-coated hybrid scaffolds possessed not only reliable biosafety but also excellent osteogenesis-inducing and osteoclastogenesis-inhibiting effects, resulting in faster and higher-quality bone tissue regeneration. Taken together, this study offers a powerful and promising strategy to construct multifunctional nanocomposite scaffolds by promoting osteo/angiogenesis and suppressing osteoclastogenesis to accelerate bone regeneration.

Abstract B cells secreting IL-10 functionally are recognized as functional regulatory B (Breg) cells; however, direct evidence concerning the phenotype, regulation, and functional and clinical relevance of IL-10-secreting Breg cells in humans is still lacking. Here, we demonstrate that, although IL-10 itself is anti-inflammatory, IL-10+ functional Breg cells in patients with systemic lupus erythematosus (SLE) display aggressive inflammatory features; these features shift their functions away from inducing CD8+ T cell tolerance and cause them to induce a pathogenic CD4+ T cell response. Functional Breg cells polarized by environmental factors (e.g., CPG-DNA) or directly isolated from patients with SLE mainly exhibit a CD24intCD27−CD38−CD69+/hi phenotype that is different from that of their precursors. Mechanistically, MAPK/ERK/P38-elicited sequential oncogenic c-Myc upregulation and enhanced glycolysis are necessary for the generation and functional maintenance of functional Breg cells. Consistently, strategies that abrogate the activity of ERK, P38, c-Myc, and/or cell glycolysis can efficiently eliminate the pathogenic effects triggered by functional Breg cells.

Droughts have severely affected Afghanistan over the last four decades, leading to critical food shortages where two-thirds of the country's population are in a food crisis. Long years of conflict have lowered the country's ability to deal with hazards such as drought which can rapidly escalate into disasters. Understanding the spatial and temporal distribution of droughts is needed to be able to respond effectively to disasters and plan for future occurrences. This study used Standardized Precipitation Evapotranspiration Index (SPEI) at monthly, seasonal and annual temporal scales to map the spatiotemporal change dynamics of drought characteristics (distribution, frequency, duration and severity) in Afghanistan. SPEI indices were mapped for river basins, disaggregated into 189 sub-catchments, using monthly precipitation and potential evapotranspiration derived from temperature station observations from 1980 to 2017. The results show these multi-dimensional drought characteristics vary along different years, change among sub-catchments, and differ across temporal scales. During the 38 years, the driest decade and period are 2000s and 1999-2022, respectively. The 2000-01 water year is the driest with the whole country experiencing 'severe' to 'extreme' drought, more than 53% (87 sub-catchments) suffering the worst drought in history, and about 58% (94 sub-catchments) having 'very frequent' drought (7 to 8 months) or 'extremely frequent' drought (9 to 10 months). The estimated seasonal duration and severity present significant variations across the study area and among the study period. The nation also suffers from recurring droughts with varying length and intensity in 2004, 2006, 2008 and most recently 2011. There is a trend towards increasing drought with longer duration and higher severity extending all over sub-catchments from southeast to north and central regions. These datasets and maps help to fill the knowledge gap on detailed sub-catchment scale meteorological drought characteristics in Afghanistan. The study findings improve our understanding of the influences of climate change on the drought dynamics and can guide catchment planning for reliable adaptation to and mitigation against future droughts.

Abstract Background Medication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC). Methods RS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation. Results Increased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients. Conclusions The current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.

Introduction Perfusion imaging according to the DEFUSE 3 or DAWN criteria has been applied to select patients with large vascular occlusive stroke undergo endovascular therapy (EVT) in the extended time window. Emerging studies have shown that collateral blood flow-based criteria may be as effective as DEFUSE 3 and DAWN criteria for the evaluation of EVT eligibility beyond 6 hours. We will conduct a meta-analysis to compare collateral status-based criteria with DEFUSE 3 or DAWN criteria.Methods and analysis We will conduct a search for the studies comparing collateral blood flow-based imaging with CT perfusion using the DEFUSE 3 or DAWN criteria in selecting patients with acute ischaemic stroke undergo EVT in the Web of Science, PubMed, EMBASE and the Cochrane Library databases between November 2017 and November 2021. We will also search the sources of grey literature, the reference lists of included studies and the newly published studies during the review period. Two investigators will independently screen the eligible studies and extract data. The study quality will be assessed by using the Newcastle-Ottawa Scale or the Cochrane risk bias tool. Stata V.17 will be used to conduct data analysis.Ethics and dissemination Patient informed consent and ethics approval are not necessary as this study uses only published studies. The finding of this meta-analysis will be propagated through committee conferences or peer-reviewed journals.PROSPERO registration number CRD42021281928.

Objective To describe changes in alcohol drinking behaviour, estimate the incidence rate of alcohol drinking and explore its risk factors in the Chinese community population.Design A community population prospective cohort study.Setting A total of 48 townships of 12 counties or districts in Guizhou province, China.Participants With the multistage proportional stratified cluster sampling method, a total of 7343 adult residents were enrolled into this study and eligible to be analysed.Primary and secondary outcome measures The incidence rate and its risk factor (adjusted HR (aHR) and 95% CIs) as well as the prevalence of alcohol drinking.Results There was a little increase trend in the overall prevalence of alcohol drinking among 7343 subjects over an average of 7.22-year follow-up, and the prevalence in women increased by 2.5% statistically (p=0.001). Among 5005 non-drinkers in 7343 subjects at baseline, 1107 incident drinkers were identified, and the incidence rate of alcohol drinking was estimated at 30.63/1000 person-years with significant sex difference (57.46 vs 17.99 per 1000 person-years for men and women, respectively, p

Abstract Background To investigate the genetic contribution of copy number variations (CNVs) in Wingless-type MMTV integration site family, member 4 (WNT4), in a Chinese population with Müllerian anomalies (MA), copy number analysis of WNT4 by Multiplex ligation‐dependent probe amplification (MLPA) was performed on 248 female patients. Some studies have shown that heterozygous missense mutation of WNT4 can lead to MA. However, few studies on the relationship between WNT4 CNVs and MA have been performed. Results Among the 248 Chinese women affected by MA in this study, heterozygous deletion of WNT4 was detected in a single patient. Conclusions MLPA identified one heterozygous deletion in WNT4 in a single female patient among 248 Chinese women affected by MA. This study firstly reports CNVs of WNT4 in a large sample of MA patients from the Chinese population, which suggests that CNVs of WNT4 cannot be excluded in the occurrence of MA. This provides a genetic basis for precise treatment in the future.

Introduction: Research suggests that pain assessment involves a complex interaction between patients and clinicians. We sought to assess the agreement between pain scores reported by the patients themselves and the clinician’s perception of a patient’s pain in the emergency department (ED). In addition, we attempted to identify patient and physician factors that lead to greater discrepancies in pain assessment. Methods: We conducted a prospective observational study in the ED of a tertiary academic medical center. Using a standard protocol, trained research personnel prospectively enrolled adult patients who presented to the ED. The entire triage process was recorded, and triage data were collected. Pain scores were obtained from patients on a numeric rating scale of 0 to 10. Five physician raters provided their perception of pain ratings after reviewing videos. Results: A total of 279 patients were enrolled. The mean age was 53 years. There were 141 (50.5%) female patients. The median self-reported pain score was 4 (interquartile range 0–6). There was a moderately positive correlation between self-reported pain scores and physician ratings of pain (correlation coefficient, 0.46; P

Background Intrapartum fever is a well-known risk factor for adverse perinatal outcomes. In this study, we evaluated the clinical features for intrapartum maternal fever and investigated the risk factors for neonatal early-onset sepsis (EOS) with intrapartum maternal fever. Methods This retrospective cohort study involved a total of 568 neonates born to mothers with intrapartum maternal fever (temperature peak ≥38 degree Celsius) in Hangzhou Women’s Hospital from January 1st to December 31st, 2019. Neonates were assigned to the EOS and non-sepsis groups based on the diagnostic criteria for early-onset neonatal sepsis,. Demographic data, clinical information and laboratory test results were evaluated to assess the risk factors for EOS. Results A total of 568 neonates were included in this study, 84 of whom were diagnosed with EOS. The EOS group was significantly different from the non-sepsis group in 11 items including the both white blood cell (WBC) count and C-reactive protein (CRP) level of the mother before delivery (p

The coronavirus disease 2019 (COVID-19) has infected more than 9.3 million people and has caused over 0.47 million deaths worldwide as of June 24, 2020. Chest imaging techniques including computed tomography and X-ray scans are indispensable tools in COVID-19 diagnosis and its management. The strong infectiousness of this disease brings a huge burden for radiologists. In order to overcome the difficulty and improve accuracy of the diagnosis, artificial intelligence (AI)-based imaging analysis methods are explored. This survey focuses on the development of chest imaging analysis methods based on AI for COVID-19 in the past few months. Specially, we first recall imaging analysis methods of two typical viral pneumonias, which can provide a reference for studying the disease on chest images. We further describe the development of AI-assisted diagnosis and assessment for the disease, and find that AI techniques have great advantage in this application.

Objective We determined whether regional haemodynamics and perfusion index (PI) could be reliable indicators of a successful sciatic nerve block (SNB).Design Prospective observational trial.Setting A tertiary teaching hospital in China from April 2020 to August 2020.Participants We assessed 79 patients for eligibility to participate in this study. Nine patients were excluded for not meeting our inclusion criteria, and three patients were excluded due to missing measurements at all time points.Interventions The patients underwent SNB. Pulsed-wave Doppler and PI measurements were performed.Primary and secondary outcome measures The primary outcome measure was the diagnostic power of regional haemodynamic change and PI to predict successful SNB. The secondary outcome measure was the effect of SNB on the regional haemodynamics and PI in the lower extremity.Results We assessed 79 patients in this study and 67 patients available for the final analysis. The SNB was successful in 59 patients and failed in eight patients. There were no significant differences in demographic characteristics between the patients with successful and failed SNB. Starting from 10 min after SNB, the peak systolic velocity (PSV), end-diastolic velocity, time-averaged maximum velocity and time-averaged mean velocity of the anterior tibial artery and posterior tibial artery of patients in the successful SNB group were significantly higher than those in the failed SNB group (p

Typhoid toxin is an essential virulence factor for Salmonella Typhi, the cause of typhoid fever in humans. This toxin has an unusual biology in that it is produced by Salmonella Typhi only when located within host cells. Once synthesized, the toxin is secreted to the lumen of the Salmonella-containing vacuole from where it is transported to the extracellular space by vesicle carrier intermediates. Here, we report the identification of the typhoid toxin sorting receptor and components of the cellular machinery that packages the toxin into vesicle carriers, and exports it to the extracellular space. We found that the cation-independent mannose-6-phosphate receptor serves as typhoid toxin sorting receptor and that the coat protein COPII and the GTPase Sar1 mediate its packaging into vesicle carriers. Formation of the typhoid toxin carriers requires the specific environment of the Salmonella Typhi-containing vacuole, which is determined by the activities of specific effectors of its type III protein secretion systems. We also found that Rab11B and its interacting protein Rip11 control the intracellular transport of the typhoid toxin carriers, and the SNARE proteins VAMP7, SNAP23, and Syntaxin 4 their fusion to the plasma membrane. Typhoid toxin’s cooption of specific cellular machinery for its transport to the extracellular space illustrates the remarkable adaptation of an exotoxin to exert its function in the context of an intracellular pathogen.

Abstract Background The SARS-CoV-2 RNA was detected positive again after discharged from hospital in some COVID-19 patients, with or without clinical symptoms such as fever or dry cough. Methods 1008 severe COVID-19 patients, with SARS-CoV-2 RNA positive detected with the mixed specimen of nasopharyngeal swab and oropharyngeal swab by real-time fluorescence quantitative PCR (RT-qPCR), were selected to monitor SARS-CoV-2 RNA with the 12 types of specimens by RT-qPCR during hospitalization. All of 20 discharged cases with COVID-19 were selected to detect SARS-CoV-2 RNA in isolation period with 7 types of specimens by RT-qPCR before releasing the isolation period. Results Of the enrolled 1008 severe patients, the nasopharyngeal swab specimens showed the highest positive rate of SARS-CoV-2 RNA (71.06%), followed by alveolar lavage fluid (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), urine (16.30%), blood (12.5%), stool (12.21%), anal swab (11.22%) and corneal secretion (2.99%), and SARS-CoV-2 RNA couldn’t be detected in other types of specimen in this study. Of the 20 discharged cases during the isolation period, the positive rate of SARS-CoV-2 RNA was 30% (6/20): 2 cases were positive in sputum at the eighth and ninth day after discharge, respectively, 1 case was positive in nasopharynx swab at the sixth day after discharge, 1 case was positive in anal swab at the eighth day after discharge, and 1 case was positive in 3 specimens (nasopharynx swab, oropharynx swab and sputum) simultaneously at the fourth day after discharge, and no positive SARS-CoV-2 RNA was detected in other specimens including stool, urine and blood at the discharged patients. Conclusions SARS-CoV-2 RNA should be detected in multiple specimens, such as nasopharynx swab, oropharynx swab, sputum, and if necessary, stool and anal swab specimens should be performed simultaneously at discharge when the patients were considered for clinical cure and before releasing the isolation period.

Healthy ecosystems are the basis of social and economic development. It is of great significance to conduct ecological security assessments in rapidly urbanization areas. Based on the driving forces, pressure, state, impact, and response (DPSIR) model, five years (1995, 2000, 2005, 2010 and 2015) of remote sensing images, social and economic statistics, and field survey data were used to establish an ecological security assessment index system. The ecological security assessment of central Yunnan Province (CYP) urban agglomeration was conducted at the 1 km × 1 km pixel scale and at the county scale based on the multilevel weighted comprehensive index method. The results showed that: (1) With 2005 as the turning point, the ecological security situation in CYP first decreased and then increased. (2) The ecological security at the county scale was mainly categorized as unsafe. At the pixel scale, ecologically unsafe and relatively unsafe areas were mainly distributed in central, northern, and western CYP. (3) The ecological security deterioration and strengthened spatial distribution differences were caused by habitat fragmentation, different physical geographical conditions, and population agglomeration. These results can provide a basis for the coordination and sustainability of economic development and environmental protection in urban agglomerations with rapid urbanization.

ObjectivePolycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. Recently it has been implicated as a significant risk factor for endometrial cancer (EC). Our study aims to detect shared gene signatures and biological mechanism between PCOS and EC by bioinformatics analysis.MethodsBioinformatics analysis based on GEO database consisted of data integration, network construction and functional enrichment analysis was applied. In addition, the pharmacological methodology and molecular docking was also performed.ResultsTotally 10 hub common genes, MRPL16, MRPL22, MRPS11, RPL26L1, ESR1, JUN, UBE2I, MRPL17, RPL37A, GTF2H3, were considered as shared gene signatures for EC and PCOS. The GO and KEGG pathway analysis of these hub genes showed that "mitochondrial translational elongation", "ribosomal subunit", "structural constituent of ribosome" and "ribosome" were highly correlated. Besides, associated transcription factors (TFs) and miRNAs network were constructed. We identified candidate drug molecules including fenofibrate, cinnarizine, propanil, fenthion, clindamycin, chloramphenicol, demeclocycline, hydrochloride, azacitidine, chrysene and artenimol according to these hub genes. Molecular docking analysis verified a good binding interaction of fenofibrate against available targets (JUN, ESR1, UBE2I).ConclusionGene signatures and regulatory biological pathways were identified through bioinformatics analysis. Moreover, the molecular mechanisms of these signatures were explored and potential drug molecules associated with PCOS and EC were screened out.

The impact of collusion during the bidding processes of Chinese government investment projects is a major concern in academic and policy circles, as collusion breeds corruption and destroys the credibility of governments. Furthermore, it negatively impacts successful project completion, leading to cost overruns and the illegitimate enrichment of colluding agents, regardless of the intended social benefits. Using data from 166 selected regional policy implementations as the research sample, this paper uses the fuzzy set qualitative comparative analysis method to conduct a group analysis of typical cases. The purpose of this study is to identify and better understand the cooperative regional policy implementation environments in China and to identify effective methods to improve the governance quality of collusion controls in construction investment project bidding processes. Five key control paths are identified, covering 94% of the cases. It is also found that in lower social collusion situations, reasonable market competition regulations can directly reduce collusive behavior. The research results will help the government to formulate more adaptive control policies and promote high-quality development of government investment projects.

Human papillomavirus (HPV) is a common infection principally spread through sexual activity. Most HPV infections are asymptomatic and resolve spontaneously. However, persistent infection may progress to cervical cancer. Highly efficacious HPV vaccines have been available since 2006, yet uptake into national programs has been slow in part due to cost. WHO guidelines call for a two-dose (0,6 month) schedule for girls 9-14 years of age. Post-hoc analyses of randomized trials have found high vaccine effectiveness following a single dose of vaccine. In order to provide additional data on the potential impact of single dose HPV vaccination in a real-world setting, we are conducting an effectiveness study among Thai schoolgirls. This is an observational study of a single dose (SD) or two doses (2D) of the bivalent HPV vaccine CERVARIX® (GlaxoSmithKline plc.) administered in a school-based program to 8-9,000 Grade 8 female students in two provinces of Thailand beginning in 2018; one province is assigned the SD, and the other the standard 2D regimen. The reduction in HPV vaccine-type prevalence will be assessed in each province two and four years after vaccination by comparing HPV prevalence in urine samples obtained through cross-sectional surveys of the immunized grade cohort as they age and compared to a historical "baseline" HPV prevalence of same age students.

Objective Polycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. Recently it has been implicated as a significant risk factor for endometrial cancer (EC). Our study aims to detect shared gene signatures and biological mechanism between PCOS and EC by bioinformatics analysis. Methods Bioinformatics analysis based on GEO database consisted of data integration, network construction and functional enrichment analysis was applied. In addition, the pharmacological methodology and molecular docking was also performed. Results Totally 10 hub common genes, MRPL16, MRPL22, MRPS11, RPL26L1, ESR1, JUN, UBE2I, MRPL17, RPL37A, GTF2H3, were considered as shared gene signatures for EC and PCOS. The GO and KEGG pathway analysis of these hub genes showed that “mitochondrial translational elongation”, “ribosomal subunit”, “structural constituent of ribosome” and “ribosome” were highly correlated. Besides, associated transcription factors (TFs) and miRNAs network were constructed. We identified candidate drug molecules including fenofibrate, cinnarizine, propanil, fenthion, clindamycin, chloramphenicol, demeclocycline, hydrochloride, azacitidine, chrysene and artenimol according to these hub genes. Molecular docking analysis verified a good binding interaction of fenofibrate against available targets (JUN, ESR1, UBE2I). Conclusion Gene signatures and regulatory biological pathways were identified through bioinformatics analysis. Moreover, the molecular mechanisms of these signatures were explored and potential drug molecules associated with PCOS and EC were screened out.

Purpose Soil salinization is one of the key problems of sustainable development of arid agricultural land. Exploring the use of shallow subsurface pipe drainage to improve soil salinization. Methods This study investigates the desalinization effect of shallow subsurface pipe drainage, in combination with drip irrigation under plastic mulch, in an arid region in China. Field data collection was conducted in 2010. Soil salinity at a range of soil depths, water EC and pH of subsurface pipe drainage and crop yield during crop growth stages in salinized farmlands were measured. Results and Conclusion The results show that soil salinity was reduced significantly on mildly (1–3 dS m−1) and moderately (3–6 dS m−1) salinized farmlands. The highest desalinization rate of mildly and moderately salinized soils was 51% and 91% respectively. The desalinization in upper soil layers, to a depth of 60 cm, was more significant than that in lower soil layers. Drainage water salinity was much higher than irrigation water salinity. Crop yield on mildly and moderately salinized land increased about 25% and 50%, respectively. This indicates that the combination of drip irrigation and shallow subsurface pipe drainage on farmlands is potential feasible to desalt farmlands and to improve crop yield. The study has led to a desalinization of 330 ha year−1 in Xinjiang.

BackgroundGroup-based formats typically used in low-resource substance use disorder (SUD) treatment settings result in little individual attention to help reinforce and guide skill use, which may contribute to poor posttreatment outcomes. Smartphone apps offer a convenient, user-friendly, and cost-effective tool that can extend the reach of effective SUD treatments. A smartphone app was developed and integrated into a group-based, brief behavioral activation (BA) treatment for SUD to increase engagement in treatment skills outside clinician-administered sessions. ObjectiveThis study aims to describe the features of the app and its use and integration into treatment, report the participants’ self-reported feasibility and acceptability of the app, and discuss challenges and provide recommendations for future smartphone app integration into behavioral treatments for SUD. MethodsA total of 56 individuals recruited from intensive outpatient SUD treatment received a smartphone-enhanced BA treatment, the Life Enhancement Treatment for Substance Use. Self-reported weekly app use and reasons for nonuse were assessed at posttreatment and at 1- and 3-month follow-ups. In addition, 2-tailed t tests and chi-square tests compared the self-reported use of each app component and overall app use over time. ResultsParticipant feedback suggested that the integration of the smartphone app into the Life Enhancement Treatment for Substance Use was feasible and well accepted, and participants found the app useful for planning value-based activities outside of sessions. Self-reported app engagement decreased over the follow-up period: 72% (39/54) of participants reported using the app at posttreatment, decreasing to 69% (37/54) at the 1-month follow-up and 37% (20/54) at the 3-month follow-up. Participants reported forgetting to use the app as a primary reason for nonuse. ConclusionsThis study provides support for the feasibility and acceptability of smartphone-enhanced BA treatment, offering promise for future research testing the integration of technology into SUD treatment. Design decisions may help streamline smartphone integration into treatment, for example, allowing participants to download the treatment app on their own phones or use a low-cost study smartphone (or offering both options). Long-term app engagement may be increased via built-in reminders, alerts, and in-app messages. Trial RegistrationClinicalTrials.gov NCT02707887; https://clinicaltrials.gov/ct2/show/study/NCT02707887

Abstract Background Triggering receptor expressed on myeloid cells-1 (TREM-1) is highly expressed on macrophages in inflamed intestines and reportedly promotes inflammatory bowel disease (IBD) by augmenting pro-inflammatory responses. To study the mechanism mediated by TREM-1 on macrophages, we generated an independent TREM-1 deficient mouse. Methods Acute colitis was induced in C57BL/6 and TREM-1-deficient mice by the administration of dextran sodium sulfate (DSS). Colonic lamina propria immune cell composition and cytokines were analyzed. An innate lymphoid cell (ILC) co-culture experiment with macrophages was used to analyze IL-22 levels. Exogenous IL-22 and TREM-1-expressing macrophages were supplied to TREM-1-deficient mice for examining their effects on intestinal barrier integrity. Results In inflamed colons, TREM-1 loss compromised the activation of ILC3 and their production of IL-22, which is required for intestinal barrier integrity. ILC3-mediated IL-22 production depends on IL-1β secreted by M1-polarized macrophages, and we found that TREM-1 deficiency results in a decreased number of IL-1β producing-M1 macrophages in colons exposed to DSS. Accordingly, DSS-mediated damage was ameliorated by supplying exogenous IL-22 and TREM-1-expressing macrophages to TREM-1-deficient mice. Conclusions TREM-1 plays a crucial role in regulating IL-22 production by ILC3 through modulating M1-macrophage polarization during DSS-induced acute colitis.

Abstract. Background:. The precise pathophysiology of venous erectile dysfunction (VED) was still unclear. Dynamic infusion cavernosometry and cavernosography (DICC) was the gold standard approach for the diagnoses of VED. However, a standard operative procedure of DICC was needed and it was unclear whether DICC could show promise in accurate assessment and treatment of VED. The aim of this study was to establish an optimized operation process of DICC and evaluate the efficacy of DICC in the diagnoses and therapy of VED. Methods:. One hundred and forty-seven VED patients identified by the color doppler duplex ultrasonography (CDDU) were included. Then the method of DICC was adopted to assess the severity of VED and all patients were divided into 4 groups, including (1) non-VED; (2) mild VED; (3) moderate VED and (4) severe VED. All patients received the treatment of psychotherapy. Drug therapy, the intervention embolism of corpus cavernosum and the implantation of penile prosthesis were applied if psychotherapy was ineffective for patients. The international index of erectile function (IIEF-5) scores of patients were collected and compared before and after treatment. Results:. IIEF-5 score of non-VED group after psychotherapy (19.35 ± 3.59) and drug therapy (23.31 ± 0.75) was higher than that before psychotherapy (15.30 ± 2.72, t = −4.31, P 0.05). IIEF-5 score of severe VED group was increased under the treatment of implantation of penile prosthesis (23.25 ± 0.71) compared with that before treatment (8.00 ± 0.39, t = −53.25, P

Introduction Histone deacetylase inhibitors (HDACIs) inhibit human osteosarcoma growth and cause apoptosis. Previously, we reported that HDACIs induce autophagy via the FOXO1 pathway. Whether there is involvement of autophagy in anti-osteosarcoma activity of HDACIs is still unknown. Material and methods Confocal microscopy was performed to determine the formation of GFP-LC3 puncta. Western blotting was conducted to measure FOXO1, and autophagy-related protein levels. Small interference RNA (siRNA) specific for FOXO1 was transfected into U2OS cells to knock down FOXO1 expression level. Flow cytometry was performed to quantify cell death. Results In this study, we first observed that trichostatin A (TSA) induces autophagy in human osteosarcoma cells. Moreover, we found that TSA treatment inhibits the mammalian target of rapamycin (mTOR) signaling pathway and enhances forkhead box O1 (FOXO1) transcriptional activity, which is responsible for the increased autophagy level, while suppression of FOXO1 function by siRNA knockdown markedly decreases TSA-induced autophagy. Conclusions We found that inhibition of autophagy, either by autophagy inhibitors or ATG gene knockdown, markedly enhances TSA-caused cell death. Taken together, our studies reveal the function of autophagy in HDACI-caused osteosarcoma cell death and thus support the development of a novel therapeutic strategy by combining HDACIs and autophagy inhibitors in osteosarcoma treatment.

Objectives To develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data.Design A nationally representative retrospective study.Setting Representative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort.Participants Representative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort.Primary outcome measures In-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR).Results A total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as ‘reference model’, was 0.08% (10th and 90th percentiles: −1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.Conclusions The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.

Objectives Despite remarkable advances in the treatment of oesophageal cancer (OC), the role of antiepidermal growth factor receptor (anti-EGFR) agents in treating OC remains controversial. Herein, a systematic review and meta-analysis were conducted to elucidate the efficacy and safety of anti-EGFR agents in patients with OC.Design Meta-analysis of randomised controlled trials (RCTs) identified by searching the PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese Biology Medicine, China National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform databases from inception to December 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Setting RCTs from any country and healthcare setting.Participants Patients with OC.Interventions Combination therapy with anti-EGFR agents and conventional treatments versus conventional treatments alone in patients with OC.Primary and secondary outcome measures Overall survival (OS) and progression-free survival (PFS) were primary outcome measures, and objective response rate (ORR), disease control rate (DCR) and treatment toxicities were secondary outcome measures.Results In total, 25 RCTs comprising 3406 patients with OC were included. Overall, anti-EGFR treatment significantly improved the OS (HR: 0.81, 95% CI 0.74 to 0.89, p

Background: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes severely afflicting the patients, while there is yet no effective medication against this disease. As Kv2.1 channel functions potently in regulating neurological disorders, the present work was to investigate the regulation of Kv2.1 channel against DPN-like pathology of DPN model mice by using selective Kv2.1 inhibitor SP6616 (ethyl 5-(3-ethoxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxybenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate) as a probe. Methods: STZ-induced type 1 diabetic mice with DPN (STZ mice) were defined at 12 weeks of age (4 weeks after STZ injection) through behavioral tests, and db/db (BKS Cg-m+/+Leprdb/J) type 2 diabetic mice with DPN (db/db mice) were at 18 weeks of age. SP6616 was administered daily via intraperitoneal injection for 4 weeks. The mechanisms underlying the amelioration of SP6616 on DPN-like pathology were investigated by RT-PCR, western blot and immunohistochemistry technical approaches against diabetic mice, and verified against the STZ mice with Kv2.1 knockdown in dorsal root ganglion (DRG) tissue by injection of adeno associated virus AAV9-Kv2.1-RNAi. Amelioration of SP6616 on the pathological behaviors of diabetic mice was assessed against tactile allodynia, thermal sensitivity and motor nerve conduction velocity (MNCV). Findings: SP6616 treatment effectively ameliorated the threshold of mechanical stimuli, thermal sensitivity and MNCV of diabetic mice. Mechanism research results indicated that SP6616 suppressed Kv2.1 expression, increased the number of intraepidermal nerve fibers (IENFs), improved peripheral nerve structure and vascular function in DRG tissue. In addition, SP6616 improved mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC-1α pathway, repressed inflammatory response by inhibiting Kv2.1/NF-κB signaling and alleviated apoptosis of DRG neuron through Kv2.1-mediated regulation of Bcl-2 family proteins and Caspase-3 in diabetic mice. Interpretation: Our work has highly supported the beneficial of Kv2.1 inhibition in ameliorating DPN-like pathology and highlighted the potential of SP6616 in the treatment of DPN. Funding: Please see funding sources.