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The liver is a highly metabolic organ and plays a crucial role in the transportation, storage, and/or detoxication of xenobiotics. Liver damage induced by xenobiotics (e.g., heavy metal, endocrine disrupting chemicals, Chinese herbal medicine, or nanoparticles) has become a pivotal reason for liver diseases, leading to great clinical challenge and much attention for the past decades. Given that endoplasmic reticulum (ER) is the prominent organelle involved in hepatic metabolism, ER dysfunction, namely, ER stress, is clearly observed in various liver diseases. In response to ER stress, a conserved adaptive signaling pathway known as unfolded protein response (UPR) is activated to restore ER homeostasis. However, the prolonged ER stress with UPR eventually leads to the death of hepatocytes, which is a pathogenic event in many hepatic diseases. Therefore, analyzing the perturbation in the activation or inhibition of ER stress and the UPR signaling pathway is likely an effective marker for investigating the molecular mechanisms behind the toxic effects of xenobiotics on the liver. We review the role of ER stress in hepatic diseases and xenobiotic-induced hepatotoxicity, which not only provides a theoretical basis for further understanding the pathogenesis of liver diseases and the mechanisms of hepatotoxicity induced by xenobiotics but also presents a potential target for the prevention and treatment of xenobiotic-related liver diseases.

The use of virtual reality (VR) for stroke rehabilitation has been implemented during the last decade. At present, most studies still focus on the effects of VR on upper limb rehabilitation, and few studies have explored VR games, VR system designs, and rehabilitation modes for upper limb rehabilitation. This study aims to (1) evaluate the rehabilitation effect of stroke patients using a game-based VR upper limb rehabilitation system in clinical settings; (2) investigate the impact of custom and commercial VR games on patients in clinical settings; and (3) review VR upper limb rehabilitation modes. The PubMed, ScienceDirect, Scopus, Web of Science, and IEEE Xplore databases were searched, and related literature published through December 2021 was included. A total of 4700 articles were retrieved according to the search strategy. We identified 24 studies, including 793 patients. We conducted a systematic search for randomized controlled trials with adult stroke patients to analyze the effect of game-based VR upper limb rehabilitation systems. A meta-analysis was conducted to compare the effects of upper limb function, hand dexterity, daily living ability, and cognitive function between the experimental group (EG, using VR for upper limb rehabilitation) and control group (CG, receiving conventional rehabilitation, including physical therapy and occupational therapy). We also conducted an analysis of both custom and commercial games. The results of the meta-analysis proved that game-based VR upper limb rehabilitation therapy for cerebral apoplexy is an effective method of rehabilitation in clinical settings and is more effective than traditional rehabilitation in improving patients' upper limb function and hand mobility. Custom games heal better than commercial games. This study only includes nonimmersive device rehabilitation modes due to research constraints and classified them into four categories. The mode of VR games combined with rehabilitation instruments may solve the problem that patients with severe upper limb dysfunction cannot operate games. Whether the use of immersive VR devices and the fun of games will affect patients' rehabilitation motivation and effect is the direction of future research.

Background The impact of asymptomatic superior mesenteric vein (SMV) thrombosis on the outcomes of cirrhotic patients remains uncertain. Methods Nonmalignant cirrhotic patients who were consecutively admitted between December 2014 and September 2021 and underwent contrast-enhanced computed tomography/magnetic resonance imaging scans were screened. Portal venous system thrombosis (PVST) was identified. Death and hepatic decompensation were the outcomes of interest. Nelson–Aalen cumulative risk curve analysis and competing risk regression analysis were performed to evaluate the impact of asymptomatic SMV thrombosis and portal vein thrombosis (PVT) on the outcomes. Results Overall, 475 patients were included, of whom 67 (14.1%) had asymptomatic SMV thrombosis, 95 (20%) had PVT, and 344 (72.4%) did not have any PVST. Nelson–Aalen cumulative risk curve analyses showed that the cumulative incidences of death (p = 0.653) and hepatic decompensation (p = 0.630) were not significantly different between patients with asymptomatic SMV thrombosis and those without PVST, but the cumulative incidences of death (p = 0.021) and hepatic decompensation (p = 0.004) were significantly higher in patients with PVT than those without PVST. Competing risk regression analyses demonstrated that asymptomatic SMV thrombosis was not a significant risk factor for death (subdistribution hazard ratio [sHR] = 0.89, p = 0.65) or hepatic decompensation (sHR = 1.09, p = 0.63), but PVT was a significant risk factor for death (sHR = 1.56, p = 0.02) and hepatic decompensation (sHR = 1.50, p = 0.006). These statistical results remained in competing risk regression analyses after adjusting for age, sex, and Child–Pugh score. Conclusion Asymptomatic SMV thrombosis may not influence the outcomes of cirrhotic patients. The timing of intervention for asymptomatic SMV thrombosis in liver cirrhosis should be further explored.

Human albumin infusion is effective for controlling systemic inflammation, thereby probably managing some liver cirrhosis-related complications, such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and hepatorenal syndrome. However, its clinical benefits remain controversial.EMBASE, PubMed, and Cochrane Library databases were searched. Randomized controlled trials (RCTs) regarding use of human albumin infusion in cirrhotic patients were eligible. Mortality and incidence of liver cirrhosis-related complications were pooled. Effect of human albumin infusion on mortality was also evaluated by subgroup analyses primarily according to target population and duration of human albumin infusion treatment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.Forty-two RCTs were finally included. Meta-analysis showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients (OR = 0.81, 95% CI = 0.67-0.98, p = 0.03). Subgroup analyses showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients with SBP (OR = 0.36, 95% CI = 0.20-0.64, p = 0.0005) and HE (OR = 0.43, 95% CI = 0.22-0.85, p = 0.02), but not those with ascites or non-SBP infections or undergoing large-volume paracentesis. Short-term human albumin infusion treatment could significantly decrease short-term mortality (OR = 0.67, 95% CI = 0.50-0.89, p = 0.005), but not long-term mortality. Long-term human albumin infusion treatment could not significantly decrease long-term mortality (OR = 0.72, 95% CI = 0.48-1.08, p = 0.11). In addition, human albumin infusion could significantly decrease the incidence of renal impairment (OR = 0.63, 95% CI = 0.45-0.88, p = 0.007) and ascites (OR = 0.45, 95% CI = 0.25-0.81, p = 0.007), but not infections or gastrointestinal bleeding.Human albumin infusion may improve the outcomes of cirrhotic patients. However, its indications for different complications and infusion strategy in liver cirrhosis should be further explored.

Background Current polymyxin B dosing in children relies on scant data. Objectives To build a population pharmacokinetic (PK) model for polymyxin B in paediatric patients and assess the likely appropriateness of different dosages. Methods A total of 19 paediatric patients were enrolled to receive intravenous polymyxin B (1.33–2.53 mg/kg/day), and the median age was 12.5 (range 3.2–17.8) years. Serial plasma samples were collected at steady-state and modelled by population PK analysis. Clinical efficacy and nephrotoxicity of polymyxin B treatment were also assessed. Results PK data were adequately described by a two-compartment model with first-order elimination, and weight was a significant covariate of polymyxin B clearance. Clinical success occurred in 14 of 19 patients (73.7%) and only one patient developed acute kidney injury. The 28 day mortality was 10.5% (2/19). The steady-state polymyxin B exposure was 36.97 ± 9.84 mg·h/L, lower than the therapeutic exposure of 50–100 mg·h/L. With the AUC24h/MIC target of 50, the dosage of 1.5–3.0 mg/kg/day had a probability of target attainments over 90% when MICs were Conclusions Dose adjustment of polymyxin B needs to consider the MIC of infecting pathogens. Current polymyxin B dosing for paediatric patients may be acceptable when MICs are

Type 2 diabetes mellitus (DM) accounts for more and more individuals worldwide. D-dimer has been demonstrated to be associated with cardiovascular diseases. The aim is to study the potential impact of D-dimer on the long-term prognosis of acute coronary syndrome (ACS) in the special population with type 2 DM.A total of 2265 consecutive patients with DM and ACS were eligible in the study. Patients were divided into four groups according to quartiles of D-dimer concentration. Univariate and multivariate Cox regression analysis were conducted to explore the prognostic value of D-dimer for future outcomes. Patients with higher level of D-dimer presented with higher percentage of major adverse cardiovascular events (MACEs) (23.7%), all-cause death (18.3%) and cardiovascular (CV) death (9.4%) in Quartile 4. In multivariate Cox regression analysis, D-dimer was demonstrated to be independently associated with MACEs, all-cause death and CV death. The prognostic value of D-dimer is still significant in subgroups of HbA1C7% and ≥7%. In Kaplan-Meier analysis, higher D-dimer showed poorer prognosis in MACEs, all-cause death and CV death (all log rank p 0.001). The area under the curve (AUC) by receiver operating characteristic (ROC) curve analysis is 0.609 for MACEs, 0.708 for all-cause death, 0.747 for CV death (p 0.001).The present study demonstrated the independent predictive value of D-dimer for outcomes in DM patients with ACS. In addition, for the first time, we explored the prognostic value in different glucose control status.

Objective: To investigate the potential correlation of transforming growth factor-β (TGF-β), matrix metalloprotein 9 (MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), Interleukin 1 (IL-1), IL-4, IL-6, IL-17, and tumor necrosis factor alpha (TNF-α) in refractory chronic rhinosinusitis. Methods: A total of 150 participants were retrospectively included in this study from August 2018 to February 2020. The people enrolled were equally allocated into refractory group (patients with refractory chronic rhinosinusitis), chronic group (patients with chronic rhinosinusitis), and control group (normal people). The level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α were recorded. The unconditional multivariate binary logistic regression was used to analyze the factors affecting refractory chronic rhinosinusitis. Results: The Davos score, T&T olfactometer threshold test, and Lund-Mackay CT scores in refractory group were significantly higher than the chronic group (P

Background: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking.Methods: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, Results: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups.Conclusions: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.). Background The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. Methods In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age

Purpose. This research is aimed at systematically assessing the safety and effectiveness of intravenous thrombolysis (IVT) with rt-PA plus human urinary kallidinogenase (HUK) for acute ischemic stroke (AIS). Methods. The data were obtained through rigorous searching of both domestic and foreign databases from inception to 2021.7.1. Randomized controlled trials (RCTs) were included for the comparison of the efficacy of IVT plus HUK. The Cochrane risk of bias (RoB) tool and Review Manager software 5.3 were responsible for RoB assessment and statistical analyses, respectively. Results. A total of 18 articles were retrieved, including 2676 AIS patients treated with IVT within the time window. The control group used standardized rt-PA IVT, and the test group added HUK. After 14 days of combined application of HUK, the National Institute of Health Stroke Scale (NIHSS) score was significantly better in moderate stroke patients using the combination treatment versus those with IVT alone ( mean difference MD = − 3.13 ; 95% confidence intervals (CI): -3.40,-2.86; P < 0.00001 ); the NIHSS score was also statistically in severe stroke patients with combined treatment than in those with IVT alone, but the degree of recovery of patients varied greatly. After 90 days of treatment, the NIHSS ( MD = − 1.93 ; 95% CI: -2.51,-1.34; P < 0.00001 ) and Barthel index (BI) scores ( MD = 22.23 ; 95% CI: 18.96, 25.49; P < 0.00001 ) of patients plus HUK were significantly better than those of patients with IVT alone, with fewer adverse events during treatment ( Relative Risk RR = 0.66 ; 95% CI: 0.47, 0.92; P = 0.02 ). Conclusions. For AIS patients with IVT within the time window, HUK plus rt-PA IVT could significantly improve the neurological function recovery after 14 days and the quality of life after 90 days and reduce the adverse reactions of IVT. This trial is registered with CRD42021226975.

Background and Objective. In view of the imperfection of the current public art evaluation system and practical utility detection system, this paper designs and invents a psychotherapy effect detector of public art based on ResNet network and EEG imaging. The detector includes sensor signal acquisition unit, signal storage and transmission unit, and human-computer interaction visualization unit. The detector is designed in order to test the psychotherapy effect of public art and quantify the public’s evaluation of public art to improve the public art evaluation system. Methods. The EEG emotion dataset seed is used for feature extraction with DE, and the emotion is recognized by ResNet. Adam optimizer is used to classify the extracted DE through ResNet50 model. Each batch is set as 5 groups of data and is trained for 50 rounds, then the model is optimized, and the accuracy rate is 76.47%, which output the probability of good emotion through the model. We put the model optimized by ResNet into the intelligent module and visualize it with numerical value. Results. The detector designed by EEG data and ResNet50 optimization model has high accuracy. The results show that the error between the detector data and the questionnaire interview data is small, the average error is 2.77, and the accuracy is 97%. The closer the subject’s emotion before the test is to neutral emotion, the closer the questionnaire result is to the test result of the tester, and the smaller the error is. The difference between the tester data and the survey questionnaire data is 0.2, which is in good agreement and has small error. It can be seen that the detector has high accuracy. Conclusion. Our proposed public art psychotherapy effect detector has good accuracy in detecting users’ emotions. It can detect the group psychotherapy effect of public art and can classify and screen a large number of public arts in the city by quantitative methods. It provides support for further summarizing the practical utility of public art and provides a new way for the optimal design and follow-up evaluation of public art design.

Lung cancer is the leading cause of cancer death worldwide. Data on the effectiveness of one-off low-dose CT (LDCT) in reducing lung cancer mortality and all-cause mortality are needed to inform screening programmes in countries with limited medical resources. We aimed to evaluate the effectiveness of one-off LDCT screening in the early detection of lung cancer in China.A multicentre, population-based, prospective cohort study was done in 12 cities of eight provinces across China, recruiting individuals aged 40-74 years who were asymptomatic for lung cancer with no lung cancer history. Participants were classified as at high risk or low risk of lung cancer using a sex-specific risk score that incorporated cigarette smoking, level of physical activity, occupational exposures, history of chronic respiratory diseases, family history of lung cancer, diet, and passive smoking (women only). Participants at high risk were invited for a one-off LDCT scan and were classified into screened and non-screened groups on the basis of whether or not they had the scan. Lung cancer incidence density, lung cancer mortality, and all-cause mortality were calculated for the screened and non-screened groups. The effectiveness of a one-off LDCT scan was evaluated by a comparison of the screened and non-screened groups in terms of lung cancer mortality and all-cause mortality in the period from cohort entry until administrative censoring (June 20, 2020). Inverse probability weighting was adopted to account for potential imbalanced factors between the two groups and Cox proportional hazards model was used to estimate the weighted associations between mortality and one-off LDCT scans.Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 individuals were assessed for eligibility. 1 016 740 participants were enrolled in the study, of whom 3581 had a lung cancer diagnosis after a median follow-up of 3·6 years (IQR 2·8-5·1). Among the 223 302 participants at high risk, 79 581 (35·6%) had an LDCT scan (screened group) and 143 721 (64·4%) did not (non-screened group). After inverse probability weighting, lung cancer incidence density was 47·0% higher (hazard ratio 1·47 [95% CI 1·27-1·70]; p0·0001), lung cancer mortality was 31·0% lower (0·69 [95% CI 0·53-0·92]; p=0·010) and all-cause mortality was 32·0% lower (0·68 [0·57-0·82]; p0·0001) for participants in the screened group compared with those in the non-screened group.One-off LDCT screening was associated with significantly lower lung cancer mortality and all-cause mortality in a large population in China. Our results point to the promise of one-off LDCT screening in countries with limited medical resources. Further studies are needed to explore interactions by subgroup-including sex, age, smoking status, and economic status-to develop population-specific screening strategies.Ministry of Finance and National Health Commission of the People's Republic of China.For the Chinese translation of the abstract see Supplementary Materials section.

To explore the synergistic effect of vitamin D deficiency and sarcopenia on vertebral osteoporostic fracture (VF) in patients with rheumatoid arthritis (RA).A total of 188 patients with RA and 158 control subjects were enrolled. Bone mineral density (BMD) at the total hip, neck of femur, lumbar vertebra 1-4, and skeletal muscle mass was measured by dual energy X-ray absorptiometry (DXA) and biological electrical impedance, respectively. Serum 25(OH)D was tested by electrochemiluminescence. The prevalence of VF and osteoporosis (OP) were compared between RA and controls. The synergism of sarcopenia and vitamin D deficiency on VF in patients with RA was tested by χThe prevalence of OP at all measured sites and VF in RA patients were all higher than those in controls (P 0.0001). The incidence of VF in RA either with sarcopenia or with vitamin D deficiency was higher than for those without sarcopenia or without vitamin D deficiency (χVF, sarcopenia, and vitamin D deficiency are common in patients with RA. Sarcopenia and vitamin D deficiency may be risk factors for the incidence of VF in RA patients.• RA patients had a higher incidence of OP and VF, also a high prevalence of sarcopenia and vitamin D deficiency. • Vitamin D deficiency and sarcopenia may might have a synergistic effect on VF in RA. • Aging and sarcopenia are risk factors for VF in RA patients, and sarcopenia were associated with disease activity and structural damage.

In this systematic review and meta-analysis, we aimed to investigate the effect of oral simethicone (SIM), an antifoaming agent, on the quality of colonoscopy in terms of bowel preparation quality, adenoma or polyp detection rate (ADR/PDR) and cecal intubation rate (CIR).All randomized controlled trials (RCTs) on the use of SIM during bowel preparation for colonoscopy published up to 17 March 2021 were identified from the PubMed, EMBASE and Cochrane Library databases. Bowel preparation quality, ADR/PDR/CIR, cecal intubation time (CIT), withdrawal time (WT), patients' tolerability, acceptability and volume of foam and bubbles were compared between the SIM and non-SIM groups.Thirty-eight RCTs with 10 505 patients were included. Oral SIM significantly increased the rate of total Boston bowel preparation scale (BBPS) score ≥6 (risk ratio [RR] 1.13, P 0.0001), acceptability (RR 1.15, P = 0.01) and the rate of no or minimal foam and bubbles (RR 1.28, P 0.00001) and decreased abdominal distension (RR 0.64, P 0.0001). However, it had no significant impact on overall ADR, overall PDR, CIR, CIT or WT. The rate of total BBPS score ≥6 remained significantly higher in the SIM group when a single-dose laxative regimen or a SIM dosage of ≥320 mg was employed; and ADR, PDR and CIR were significantly increased in the SIM group among colonoscopy clinicians who achieved an ADR31%, PDR45% and CIR96%, respectively.Oral SIM can improve bowel preparation quality, especially in patients receiving a SIM dosage of ≥320 mg or a single-dose laxative regimen. SIM may be preferred by junior colonoscopy physicians/trainees with a lower ADR/PDR or CIR.

Peripheral artery disease (PAD) has high morbidity and mortality rates. A metabolomics approach was employed to determine whether consumption of bean-rich diets for 8 weeks would impact the metabolomic profile of individuals with PAD. Serum and urine, collected from 54 participants with clinical PAD at baseline and after 8 weeks on 0.3 cups beans/day (n = 19), 0.6 cups beans/day (n = 20), or control (n = 23) diet, and the beans were extracted and analyzed using LC-QTOF-MS. As a result, PGE2 p-acetamidophenyl ester, PGF2α diethyl amide and 5-l-glutamyl-l-alanine were significantly changed in the serum or urine of bean groups compared with control. Significant changes (P < 0.05) in the profile and/or levels of 22 flavonoids present in bean extracts showed the potential importance of the mixture of beans used in this study. In a subset of participants taking metoprolol, after 8 weeks the bean-rich diets significantly elevated metoprolol in the serum while reducing it in urine compared with baseline. In addition, the diets significantly enhanced the urinary excretion of metformin. In conclusion, several biochemical pathways including prostaglandins and glutathione were affected by bean consumption. Significant changes in the metabolism of metoprolol and metformin with bean consumption suggested the presence of diet-drug interactions that may require adjustment of the prescribed dose. ClinicalTrials.gov Identifier: NCT01382056. Novelty: Bean consumption by people with PAD alters the levels of certain metabolites in serum and urine. Different bean types (black, red kidney, pinto, navy) have unique flavonoid profiles. Metabolomics revealed potential diet–drug interactions as serum and/or urinary levels of metoprolol and metformin are modified by bean consumption.

The best revascularization strategy for patients with ischaemic heart failure (IHF) remains unclear. Current evidence and guidelines mainly focus on patients with severe ischaemic heart failure (ejection fraction [EF] 35%). There are limited data comparing clinical outcomes of coronary artery bypass grafting (CABG) with implantation of drug-eluting stents (DESs) in patients with mild to moderate ischaemic heart failure (EF 35-50%). It is therefore unknown whether percutaneous coronary intervention (PCI) with DES implantation can provide comparable outcomes to CABG in these patients.From January 2016 to December 2017, we enrolled patients with mildly to moderately reduced EF (35-50%) who had undergone PCI with DESs or CABG. Patients with a history of CABG, presented with acute ST-elevation myocardial infarction (MI) or acute heart failure, and patients who had undergone CABG concomitant valvular or aortic surgery were excluded. Propensity score-matching analysis was performed between the two groups. Kaplan-Meier analysis and multivariate Cox proportional hazard regression were applied to assess all-cause mortality and individual end points. A total of 2050 patients (1330 PCIs and 720 CABGs) were included, and median follow-up was 45 months (interquartile range 40 to 54). There were significant differences in all-cause death between the two groups: 77 patients in the PCI group and 27 in the CABG group (DES vs. CABG: 5.8% vs. 3.8%, P = 0.045). After propensity score matching for the entire population, 601 matched pairs were obtained. The long-term cumulative rate of all-cause death was significantly different between the two groups (DES vs. CABG: 5.8% vs. 2.7%, P = 0.006). No differences were found in the rates of cardiac death (DES vs. CABG: 4.8% vs. 3.0%, P = 0.096), recurrent MI (DES vs. CABG: 4.0% vs. 2.8%, P = 0.234), and stroke (DES vs. CABG: 6.8% vs. 5.2%, P = 0.163). The rate of repeat coronary revascularization was significantly higher in the PCI group than in the CABG group (12.1% vs. 6.0%, P = 0.000).Considering the higher long-term survival rate and lower repeat-revascularization rate, CABG may be superior to DES implantation in patients with mildly to moderately reduced EF (35-50%) and significant CAD.

Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment

Urine is conventionally used as a specimen to document diazepam-related crimes; however, few reports have described the pharmacokinetics of diazepam and its metabolites in urine.This study aimed to investigate the pharmacokinetics of diazepam and its metabolites, including glucuronide compounds, in the urine of Chinese participants.A total of 28 volunteers were recruited and each participant ingested 5 mg of diazepam orally. Ten milliliters of urine were collected from each participant at post-consumption timepoints of prior (zero), 1, 2, 4, 8, 12, and 24 h and 2, 3, 6, 12, and 15 days. All samples were extracted by solid-phase extraction and analyzed using high-performance liquid chromatography-tandem mass spectrometry. Diazepam and its main metabolites, except for temazepam, were detected in the urine of volunteers. Pharmacokinetic parameters were analyzed using the pharmacokinetic software DAS according to the non-compartment model.Urinary diazepam peaked at 2.38 ng/mL (CThe results regarding diazepam pharmacokinetics in urine would be of great help in forensic science and drug screening.

We report aminophenol-modified gold nanoparticles (AGNPs) that have a potent antibacterial activity and low ototoxicity. The AGNPs are promising as novel antibiotics to replace aminoglycosides.

Oridonin, a bioactive diterpenoid isolated from

Increasing evidence suggests the significant contribution of high levels of thioredoxin reductase (TrxR) in various stages of tumorigenesis and resistance to tumor chemotherapy. Thus, inhibition of TrxR with small molecules is an attractive strategy for cancer therapy. Eriocalyxin B (EriB), a naturally occurring diterpenoid extracted from Isodon eriocalyx, has reflected potential anticancer activities through numerous pathways. Here, we describe that EriB covalently modifies GSH and selectively inhibits TrxR activity by targeting the Sec residue of the enzyme. Pharmacological inhibition of TrxR by EriB results in elevated ROS levels, reduced total GSH and thiols content, which ultimately induced potent RKO cell apoptosis mediated by oxidative stress. Importantly, EriB indicates potent synthetic lethality with GSH inhibitors, BSO, in RKO cells. In summary, our results highlight that targeting TrxR by EriB explores a novel mechanism for the biological action of EriB. This opened up a new therapeutic indication for using EriB to combat cancers.

BACKGROUND Data on the association of subclinical hypothyroidism (SCH) with the severity of coronary artery disease and major adverse cardiovascular and cerebral events (MACCE) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) are limited and conflicting. OBJECTIVE We established the baseline rate of SCH and followed the trajectory of thyroid-stimulating hormone (TSH) values during and after hospitalisation for PCI for up to six months and determined whether persistent SCH was associated with the severity of coronary artery disease and MACCE in patients with NSTE-ACS after PCI. DESIGN Population-based prospective cohort study. PATIENTS We included patients with NSTE-ACS who underwent PCI with simple balloon angioplasty or stent implantation for coronary heart disease. MEASUREMENTS Thyroid function tests of patients before PCI and 1 day, 1 week, 1 and 6 months after PCI were performed. Cases showing transient SCH were excluded. Patients were divided into two groups based on the results of four TSH tests: 0.27-4.2 mIU/L (n = 1472, 89.7%) and >4.2 mIU/L (n = 170, 10.4%). The risk factors for the severity of coronary artery lesions were estimated using multinomial logistic regression analysis. Univariate and multivariate Cox regression analyses were used to study the relationship between TSH and MACCE. RESULTS Among 1642 patients, there were 1070 males (65.2%) and 572 females (34.8%), with an average age of 62.5 ± 9.6 years. SCH patients had a wider range of diseased vessels and a higher number of diseased vessels (p

Necrotizing enterocolitis, a devastating gastrointestinal disease with high mortality, poses great threats to global health. Therefore, we conducted this study to explore the role of ANGPT2, as well as the potential mechanism, in necrotizing enterocolitis. IEC-6 cells were stimulated with lipopolysaccharide (LPS) to induce necrotizing enterocolitis model in vitro. The expression of ANGPT2 was measured by RT-qPCR. The cell viability was detected using CCK-8. Besides, the expressions of endoplasmic reticulum (ER) stress-related proteins, Notch signaling pathway-related proteins and tight junction proteins were checked by western blot. The apoptosis and inflammatory response were detected by TUNEL and ELISA, respectively. Moreover, with the adoption of TEER, the cell monolayer permeability was detected. The results showed that ANGPT2 expression was greatly increased after LPS induction. In addition, ANGPT2 knockdown significantly decreased the apoptosis, inflammatory response, barrier dysfunction and endoplasmic reticulum stress of LPS-induced IEC-6 cells. What is more, ANGPT2 knockdown could block Notch signaling pathway. Additionally, with the treatment of Jagged-1, the protective effect of ANGPT2 knockdown on LPS-induced intestinal injury was partly abolished. To sum up, silencing ANGPT2 could improve LPS-induced inflammation, barrier dysfunction and ER stress of intestinal epithelial cells via blocking Notch signaling pathway.

BackgroundThe changing trends and risk-attributed burdens of kidney cancer in China are unknown. Therefore, this study aimed to describe the latest status and trends of kidney cancer burden in China and its associated risk factors.MethodsThe absolute numbers and rates of the incidence, deaths, and disability-adjusted life-years (DALYs) of kidney cancer in China were extracted from the Global Burden of Disease 2019 platform. Overall burden and burden attributed to smoking and high body mass index (BMI) were described. Average annual percent change (AAPC) was calculated to describe trend analyses from 1990 to 2019 using the Joinpoint regression program.ResultsIn 2019, 59,827 new cases, 23,954 deaths, and 642,799 DALYs of kidney cancer occurred in China, of which men accounted for 71.1, 70.5, and 72.0%, and the population aged ≥55 years accounted for 58.9, 77.9, and 60.1%, of new cases, deaths, and DALYs, respectively. From 1990 to 2019, the age-standardized incidence rate (per 100,000 person-years) increased from 1.16 in 1990 to 3.21 in 2019, with an AAPC of 3.4% (95% confidence interval [CI]: 3.1–3.8%, p < 0.05); the mortality rate increased from 0.70 to 1.27, with an AAPC of 2.1% (1.5–2.3%, p < 0.05); and the DALY rate increased from 0.70 to 1.27, with an AAPC of 2.1% (1.5–2.3%, p < 0.05). In 2019, the proportions of DALYs attributed to smoking and high BMI were 18.0% and 11.1%, respectively, and the DALY rates attributed to both smoking and high BMI increased from 1990 to 2019, with AAPC of 2.9% (2.6–3.3%, p < 0.05) and 4.8% (4.2–5.4%, p < 0.05), respectively.ConclusionThe kidney cancer burden in China has continued to grow over the recent three decades, with a severe burden among older adults and men. Therefore, timely preventive interventions for modifiable risk factors are required.

Tumor heterogeneity makes the diagnosis and treatment of endometrial cancer difficult. As an important modulator of gene expression, DNA methylation can affect tumor heterogeneity and, therefore, provide effective information for clinical treatment. In this study, we explored specific prognostic clusters based on 482 examples of endometrial cancer methylation data in the TCGA database. By analyzing 4870 CpG clusters, we distinguished three clusters with different prognostics. Differences in DNA methylation levels are associated with differences in age, grade, clinical pathological staging, and prognosis. Subsequently, we screened out 264 specific hypermethylation and hypomethylation sites and constructed a prognostic model for Bayesian network classification, which corresponded to the classification of the test set to the classification results of the train set. Since the tumor microenvironment plays a key role in determining immunotherapy responses, we conducted relevant analyses based on clusters separated from DNA methylation data to determine the immune function of each cluster. We also predicted their sensitivity to chemotherapy drugs. Specific classifications of DNA methylation may help to address the heterogeneity of previously existing molecular clusters of endometrial cancer, as well as to develop more effective, individualized treatments.

Background Protein phosphatase magnesium-dependent 1 delta (PPM1D), also referred to as wild-type p53-induced phosphatase 1 (Wip1) or protein phosphatase 2C delta (PP2Cδ), is an oncogenic nuclear serine/threonine phosphatase belonging to the PP2C family. However, the knowledge regarding PPM1D mRNA expression, tumor immunity, and the prognosis in hepatocellular carcinoma (HCC) is scanty. Methods We analyzed PPM1D, including its expression in both the normal and tumor tissue using the Sangerbox database and Tumor Immune Estimation Resource (TIMER). We evaluated its correlation with prognosis in different tumor types by the Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between PPM1D and the cancer immune infiltrates were determined using TIMER. The correlations between PPM1D expression and gene marker sets of the immune infiltrates were established by both the TIMER and GEPIA. Immunohistochemistry was performed to detect the expression of Wip1 protein encoded by PPM1D in HCC, and the relationship between Wip1 expression and the prognosis of HCC were analyzed. Results We found out that PPM1D mRNA expression was significantly higher in several human cancers, including HCC, than in the corresponding normal human tissues. The PPM1D mRNA high expression in HCC was significantly correlated with poor prognosis. The expression was associated with progression-free survival (PFS) in multiple HCC patients' cohorts (PFS HR = 1.5, P = 0.0066). This was especially in early stage (stage 1) and AJCC_T 1 of HCC. Besides, PPM1D mRNA expression indicated a positive correlation with tumor-infiltrating Monocytes, tumor-associated macrophages (TAMs), M1 Macrophage, M2 Macrophage, dendritic cells (DCs), T-helper (Th) and Treg. Wip1 was higher in HCC than paracancerous tissue. High expression of Wip1 was associated with poor prognosis of HCC. Conclusion Our findings suggested that PPM1D mRNA is critical in activating tumor immunity. Besides, they implied that PPM1D could be a potential prognostic biomarker for cancer progression. Moreover, it correlated with tumor immune cell infiltration in HCC.

Background and purpose To commission and implement an Autoencoder based Classification-Regression (ACLR) model for VMAT patient-specific quality assurance (PSQA) in a multi-institution scenario. Materials and methods 1835 VMAT plans from seven institutions were collected for the ACLR model commissioning and multi-institutional validation. We established three scenarios to validate the gamma passing rates (GPRs) prediction and classification accuracy with the ACLR model for different delivery equipment, QA devices, and treatment planning systems (TPS). The prediction performance of the ACLR model was evaluated using mean absolute error (MAE) and root mean square error (RMSE). The classification performance was evaluated using sensitivity and specificity. An independent end-to-end test (E2E) and routine QA of the ACLR model were performed to validate the clinical use of the model. Results For multi-institution validations, the MAEs were 1.30–2.80% and 2.42–4.60% at 3%/3 mm and 3%/2 mm, respectively, and RMSEs were 1.55–2.98% and 2.83–4.95% at 3%/3 mm and 3%/2 mm, respectively, with different delivery equipment, QA devices, and TPS, while the sensitivity was 90% and specificity was 70.1% at 3%/2 mm. For the E2E, the deviations between the predicted and measured results were within 3%, and the model passed the consistency check for clinical implementation. The predicted results of the model were the same in daily QA, while the deviations between the repeated monthly measured GPRs were all within 2%. Conclusions The performance of the ACLR model in multi-institution scenarios was validated on a large scale. Routine QA of the ACLR model was established and the model could be used for VMAT PSQA clinically.

Backgrounds:. Cancer is one of the main causes of death worldwide, seriously threatening human health and life expectancy. We aimed to analyze the cancer incidence and mortality rates during 2016 in Zhejiang Province, Southeast China. Methods:. Data were collected from 14 population-based cancer registries across Zhejiang Province of China. Cancer incidence and mortality rates stratified by sex and region were analyzed. The crude rate, age-standardized rate, age-specific and region-specific rate, and cumulative rate were calculated. The proportions of 10 common cancers in different groups and the incidence and mortality rates of the top five cancers in different age groups were also calculated. The Chinese national census of 2000 and the world Segi population was used for calculating the age-standardized incidence and mortality rates. Results:. The 14 cancer registries covered a population of 14,250,844 individuals, accounting for 29.13% of the population of Zhejiang Province. The total reported cancer cases and deaths were 55,835 and 27,013, respectively. The proportion of morphological verification (MV%) was 78.95% of the population, and percentage of incident cases identified through death certificates only (DCO%) was 1.23% with a mortality-to-incidence ratio (M/I ratio) of 0.48. The crude incidence rate in Zhejiang cancer registration areas was 391.80/105; the age-standardized incidence rate of the Chinese standard population (ASIRC) and the age-standardized incidence rate of the world standard population (ASIRW) were 229.76/105 and 220.96/105, respectively. The incidence rate in men was higher than that in women. The incidence rate increased rapidly after 45 years of age and peaked in individuals aged 80 to 84 years. The top 10 incidence rates of cancers were lung cancer, female breast cancer, thyroid cancer, colorectal cancer, stomach cancer, liver cancer, prostate cancer, cervical cancer, esophageal cancer, and pancreatic cancer (from highest to lowest). The crude mortality rate in Zhejiang cancer registration areas was 189.55/105; the age-standardized mortality rate of the Chinese standard population (ASMRC) and the age-standardized mortality rate of the world standard population (ASMRW) were 94.46/105 and 93.42/105, respectively. The mortality rate in men was higher than that in women, and the male population in rural areas was higher than that in urban areas. The cancer mortality rate increased rapidly after 50 years of age and peaked in individuals aged 85+ years. The top 10 mortality rates of cancers were lung cancer, liver cancer, stomach cancer, colorectal cancer, pancreatic cancer, esophageal cancer, female breast cancer, prostate cancer, lymphoma, and leukemia (from highest to lowest). Conclusions:. Lung cancer, female breast cancer, thyroid cancer, colorectal cancer, prostate cancer, liver cancer, and stomach cancer were the most common cancers in Zhejiang Province. Effective prevention and control measures should be established after considering the different characteristics of cancers in urban and rural areas.

ObjectivesOver the past decade, the incidence and global burden of coronary heart disease (CHD) have increased in the young population. We aimed to identify patient characteristics and risk factors for premature CHD, including single-vessel disease (SVD) and multivessel disease (MVD).DesignRetrospective, cross-sectional study.SettingDemographic and clinical data of patients with CHD were collected from the patient medical records of a tertiary hospital in Tianjin, China, between 2014 and 2017.ParticipantsA total of 2846 patients were enrolled in the study.Primary and secondary outcome measuresPremature CHD, which is the primary outcome, was defined as menResultsMost of the characteristics between patients with premature and mature CHD were not statistically significant. A significantly higher dyslipidaemia prevalence was found in female patients with premature CHD (OR=1.412, 95% CI: 1.029 to 1.936). In the crude model, instead of premature SVD, premature (OR=2.065, 95% CI: 1.426 to 2.991) or mature (OR=1.837, 95% CI: 1.104 to 3.056) MVD was more common in female patients with the highest triglyceride–glucose (TyG) index quartile than those with the lowest TyG index quartile. In male patients, the same trend was observed for mature MVD (OR=2.272, 95% CI: 1.312 to 3.937). The significance of the TyG index was not revealed in multivariate analyses; however, hypertension, diabetes, obesity, smoking, old myocardial infarction and lipoprotein (a) showed a positive association with MVD.ConclusionsDyslipidaemia should be considered as an effective factor for the prediction and prevention of premature CHD in women. The TyG index can be a simple auxiliary indicator that can be used in population-based cardiovascular disease screening for the early identification of vascular disease severity.

Automatic seizure detection algorithms are necessary for patients with refractory epilepsy. Many excellent algorithms have achieved good results in seizure detection. Still, most of them are based on discontinuous intracranial electroencephalogram (iEEG) and ignore the impact of different channels on detection. This study aimed to evaluate the proposed algorithm using continuous, long-term iEEG to show its applicability in clinical routine. In this study, we introduced the ability of the transformer network to calculate the attention between the channels of input signals into seizure detection. We proposed an end-to-end model that included convolution and transformer layers. The model did not need feature engineering or format transformation of the original multi-channel time series. Through evaluation on two datasets, we demonstrated experimentally that the transformer layer could improve the performance of the seizure detection algorithm. For the SWEC-ETHZ iEEG dataset, we achieved 97.5% event-based sensitivity, 0.06/h FDR, and 13.7 s latency. For the TJU-HH iEEG dataset, we achieved 98.1% event-based sensitivity, 0.22/h FDR, and 9.9 s latency. In addition, statistics showed that the model allocated more attention to the channels close to the seizure onset zone within 20 s after the seizure onset, which improved the explainability of the model. This paper provides a new method to improve the performance and explainability of automatic seizure detection.

BackgroundHypothyroidism could cause obstructive sleep apnea (OSA), however, the specific association of them remained unclear. This cross-sectional study aimed to determine the prevalence of hypothyroidism among patients with OSA, and the characteristics and predictors of hypothyroidism associated with OSA.MethodsA total of 573 patients with OSA were included in the study. Serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were measured in all participants. Univariate and binary logistic regression analysis were performed to assess the association of OSA with hypothyroidism while controlling for potential confounders. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the OSA effect in the distinction between euthyroid and hypothyroidism.ResultsThe prevalence of hypothyroidism was 6.75%、5.12%、10.38% in the total, men, and women cohort, respectively, and the prevalence rate in women OSA patients was significantly higher than that in men OSA patients (P=0.018). The men OSA patients with hypothyroidism had a higher Epworth sleepiness scale (ESS) than women OSA patients with hypothyroidism (P=0.022). Additionally, the ESS was significantly higher in men OSA patients with hypothyroidism than those with euthyroid (P=0.042), while women OSA patients had no such difference (P=0.822). In men patients with OSA, ROC curve analyses revealed that the risk of hypothyroidism increased in accordance with increasing ESS after adjustment for potential confounders, and the optimal cutoff value was 10 score. Higher ESS category was significantly associated with a higher risk of prevalent hypothyroidism in men patients with OSA [odds ratio (OR) = 4.898 for ESS≥10 relative to ESS ConclusionsThe prevalence of hypothyroidism in OSA patients was relatively higher, especially in women OSA patients. ESS was significantly and positively associated with hypothyroidism in men patients with OSA, suggesting that ESS may have a potential role in identification and diagnosis of men OSA patients complicated with hypothyroidism.

Cardiovascular diseases are the most common cause of death globally. Accurately modeling cardiac homeostasis, dysfunction, and drug response lies at the heart of cardiac research. Adult human primary cardiomyocytes (hPCMs) are a promising cellular model, but unstable isolation efficiency and quality, rapid cell death in culture, and unknown response to cryopreservation prevent them from becoming a reliable and flexible in vitro cardiac model. Combing the use of a reversible inhibitor of myosin II ATPase, (-)-blebbistatin (Bleb), and multiple optimization steps of the isolation procedure, we achieved a 2.74-fold increase in cell viability over traditional methods, accompanied by better cellular morphology, minimally perturbed gene expression, intact electrophysiology, and normal neurohormonal signaling. Further optimization of culture conditions established a method that was capable of maintaining optimal cell viability, morphology, and mitochondrial respiration for at least 7 days. Most importantly, we successfully cryopreserved hPCMs, which were structurally, molecularly, and functionally intact after undergoing the freeze-thaw cycle. hPCMs demonstrated greater sensitivity towards a set of cardiotoxic drugs, compared to human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Further dissection of cardiomyocyte drug response at both the population and single-cell transcriptomic level revealed that hPCM responses were more pronouncedly enriched in cardiac function, whereas hiPSC-CMs responses reflected cardiac development. Together, we established a full set of methodologies for the efficient isolation and prolonged maintenance of functional primary adult human cardiomyocytes in vitro, unlocking their potential as a cellular model for cardiovascular research, drug discovery, and safety pharmacology.

Fluorescence quenching occurs in most nitroaromatic compounds due to photoinduced electron transfer (PET) effects, limiting their use as image-guided photosensitizers for anticancer photodynamic therapy (PDT) or as probes for nitroreductase in hypoxic cells. Herein, we developed a tumor-targeting aggregation-induced emission photosensitizer (AIE-PS), Biotin-TTVBA, by binding TTVBA (a nitrobenzoic acid-based AIE-PS with a free carboxylic acid group) to biotin. Biotin-TTVBA has near-infrared emission characteristics in DMSO containing 99% toluene, a large Stoke's shift (210 nm), high photostability, wash-free cell staining ability and type I/II photosensitivity. Compared with TTVBA, Biotin-TTVBA significantly increased cellular uptake (a 60-fold increase) and selective uptake of tumor cells (a 250% increase in the ratio of tumor cells to normal cells), resulting in enhanced antitumor activity against tumor cells (HeLa and MCF-7) and a decreased IC

The metastasis of tumor cells is a challenge for the clinical treatment of glioma. Epithelial-mesenchymal transition (EMT) contributes to glioma cell invasiveness. Our previous study confirmed that the expression of miRNA-451, which inhibits the PI3K/Akt signaling pathway by directly targeting CAB39 and plays a repressive role in glioma, is downregulated in glioma. However, the specific mechanism of miRNA-451 regulation in glioma is unclear. In this study, we investigated whether miRNA-451 blocks the processes of EMT and metastasis in glioma cells in vivo and in vitro. By targeting CAB39, miRNA-451 likely triggers the PI3K/Akt/Snail signaling pathway to reduce glioma proliferation, invasion, migration and EMT. We used Western blotting experiments to demonstrate that overexpression of miRNA-451 significantly reduced p-AKT(Ser473), N-cadherin, Vimentin, Twist, Snail and Cyclin D1 expression and increased E-cadherin expression. We demonstrated that overexpression of miR-451 suppressed glioma cell proliferation, invasion, migration and EMT by MTT and colony formation assays, Transwell assays, wound healing assays and animal experiments. Taken together, these results suggest that miRNA-451 can reduce EMT and metastasis in glioma cells through the suppression of the PI3K/Akt/Snail signaling pathway by targeting CAB39 in vitro and in vivo. miR-451 may be a new target for glioma treatment.

Schizophrenia (SZ) is characterized by a series of cognitive impairments, including automatic processing impairment of basic auditory information, indexed by mismatch negativity (MMN). Existing studies mainly focus on MMN induced by deviant of single acoustic features, and relatively few studies have focused on complex acoustic stimuli, especially speech-induced MMN. Many cognitive impairments in SZ are related to speech function. Thus, the present study aimed to examine the reduction of phonetic MMN in SZ as a potential biomarker and its relationship with illness course and functional outcomes. Electroencephalogram (EEG) signals were recorded from 32 SZ and 32 healthy controls (HC) in a double oddball paradigm, with /da/ as the standard stimulus and /ba/ and /du/ as the deviant stimuli. MMN was computed for vowel and consonant deviants separately. Clinical symptoms were assessed using the Positive and Negative Symptom Rating Scale (PANSS). Illness duration and illness relapse were acquired by combining clinical interviews and electronic medical records. Functional outcomes were assessed using the Global Assessment of Functioning scale (GAF). Compared with HC, SZ showed lower amplitudes of phonetic MMN, especially for vowel deviants. In addition, the MMN amplitude of the vowel deviant was significantly correlated with illness duration, illness relapse, and functional outcomes among patients with SZ. These findings indicate that the pre-attentive automatic phonetic processing of SZ was impaired for both consonants and vowels, while the vowel processing deficit may be the key speech processing deficit in SZ, which could depict the illness course and predict the functional outcomes.

Background To compare the efficacy and safety of microwave ablation (MWA) and radiofrequency ablation (RFA) as first-line treatments for perivascular HCC. Methods This multicentre study enrolled 170 patients with perivascular HCC who underwent MWA or RFA. The ablation response, progression-free survival (PFS), overall survival (OS), and complications between the treatment groups for the total and propensity score-matched (PSM) cohorts were compared. Results The disease control rates for MWA and RFA were similar in total (94% vs. 91%, p = 0.492) and PSM (93% vs. 93%, p = 1.00) cohorts. The PFS rates at 1, 3, and 5 years were 71%, 55% and 52% in MWA group and 61%, 33% and 28% in RFA group (p = 0.017). The OS rates were comparable between two groups in total (p = 0.249) and PSM cohorts (p = 0.345). In subgroup analyses, the PFS of patients with periportal HCC (45 vs. 36 months, p = 0.048) and a single HCC nodule (51 vs. 42 months, p = 0.014) were significantly better in MWA group than RFA. Major complications were more frequent in the MWA group than in RFA (27% vs. 7%, p Conclusion Compared with RFA, MWA provides better control of tumour progression especially in periportal HCC or single-nodule perivascular HCC patients.

Background Numerous predictive formulas based on different ethnics have been developed to determine continuous positive airway pressure (CPAP) for patients with obstructive sleep apnea (OSA) without laboratory-based manual titrations. However, few studies have focused on patients with OSA in China. Therefore, this study aimed to develop a predictive equation for determining the optimal value of CPAP for patients with OSA in China. Methods 526 pure moderate to severe OSA patients with attended CPAP titrations during overnight polysomnogram were spited into either formula derivation (419 patients) or validation (107 patients) group according to the treatment time. Predictive model was created in the derivation group, and the accuracy of the model was tested in the validation group. Results Apnea hypopnea index (AHI), body mass index (BMI), longest apnea time (LAT), and minimum percutaneous oxygen saturation (minSpO2) were considered as independent predictors of optimal CPAP through correlation analysis and multiple stepwise regression analysis. The best equation to predict the optimal value of CPAP was: CPAPpred = 7.581 + 0.020*AHI + 0.101*BMI + 0.015*LAT-0.028*minSpO2 (R2 = 27.2%, p 2O vs. 11 ± 3 cmH2O, p = 0.766). Conclusions The predictive formula based on AHI, BMI, LAT, and minSpO2 is useful in calculating the effective CPAP for patients with pure moderate to severe OSA in China to some extent.

To explore how family functioning and family resilience mediate the relationship between disability severity and quality of home-based care among families with disabled older adults.A cross-sectional survey was conducted with 431 families with Uygur and Kazakh disabled older adults in Xinjiang, China, in 2020. The data were collected using the Katz Activity of Daily Living Scale; Mini-Mental State Examination; Family Adaptation, Partnership, Growth, Affection and Resolve Index Scale; Family Resilience Assessment Scale; and Family Caregiving Consequences Inventory Scale. All mediation effects were estimated in SPSS26.0.Disability severity, family functioning and family resilience were all significantly correlated with home-based care quality. Disability severity had a 46.16% direct effect on home-based care quality and a 53.84% indirect effect on home-based care quality independently and in series through family functioning and family resilience.Disability severity directly affected home-based care quality and had an indirect influence via family functioning and family resilience. Multidisciplinary care teams should focus on families with disabled older adults and help them improve family functioning and family resilience by implementing targeted interventions, so as to improve home-based care quality.

Multidrug-resistant (MDR) bacteria-infected wounds are challenging issues that threaten human health. Herein, L-thioproline (T) and Boc-capped L-thioproline (BT)-decorated gold nanoparticles (TBT-GNPs) with potent antibacterial activity against MDR bacteria are reported. The TBT-GNPs are composited with bacterial cellulose to form wound dressings which show excellent antimicrobial performance both in vitro and in vivo. Moreover, this dressing is both breathable and stretchable which is favorable for gas exchange to accelerate the wound healing. This work is insightful for developing multifunctional dressings to satisfy the clinical requirements.

The design of nanomedicine for cancer therapy, especially the treatment of tumor metastasis has received great attention. Proteasome inhibition is accepted as a new strategy for cancer therapy. Despite being a big breakthrough in multiple myeloma therapy, carfilzomib (CFZ), a second-in-class proteasome inhibitor is still unsatisfactory for solid tumor and metastasis therapy. In this study, hollow titanium nitride (TiN) nanoshells are synthesized as a drug carrier of CFZ. The TiN nanoshells have a high loading capacity of CFZ, and their intrinsic inhibitory effect on autophagy synergistically enhances the activity of CFZ. Due to an excellent photothermal conversion efficiency in the second near-infrared (NIR-II) region, TiN nanoshell-based photothermal therapy further induces a synergistic anticancer effect. In vivo study demonstrates that TiN nanoshells readily drain into the lymph nodes, which are responsible for tumor lymphatic metastasis. The CFZ-loaded TiN nanoshell-based chemo-photothermal therapy combined with surgery offers a remarkable therapeutic outcome in greatly inhibiting further metastatic spread of cancer cells. These findings suggest that TiN nanoshells act as an efficient carrier of CFZ for realizing enhanced outcomes for proteasome inhibitor-based cancer therapy, and this work also presents a "combined chemo-phototherapy assisted surgery" strategy, promising for future cancer treatment.

Currently, there are insufficient indicators for the reliable assessment of treatment response following neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal squamous cell carcinoma (ESCC). Considering the essential role of protein-coding and non-coding RNAs in gene regulation and cellular processes, we systematically explored the molecular features and clinical significance of mRNA and lncRNA in 249 pretreatment biopsies from four hospitals in three districts with a high incidence of ESCC patients in China.During the discovery phrase, 13 differentially expressed genes were identified and validated between samples with a complete pathological response (pCR) and those with an incomplete pathological response (pCR). Subsequently, we constructed a predictive mRNA and lncRNA signature (SERPINE1, LINC00592, and PRKAG2-AS1) using Fisher's linear discriminant analysis (FLDA) with stepwise variant-selection, followed by validation of its predictive ability in both internal and external cohorts.Our signature showed great value in predicting the response to nCRT among ESCC samples and acted as an independent predictive indicator, in addition to demonstrating great potential in estimating patient prognosis. Interestingly, we found that patients with a high signature score had lower PD-L1 and IDO1 expression levels but higher CD8The present study identified a promising three-gene-based predictive signature that has powerful clinical implications for the identification of pCR and a good prognosis among patients with ESCC. Further immune-related exploration may provide an opportunity for future therapeutic combination.

Emotion is an important factor affecting a person's physical and mental health, but there are few ways to detect a patient's emotions in daily life. Negative emotions not only affect recovery after treatment, but also cause poor health. Current emotion classification research based on EEG image recognition is highly accurate, making the development of an emotion detector feasible. Using emotion data from the SEED, this study trained a detection model using the residual neural network ResNet-50 with a SAM and SE-block double attention mechanism, and used quantitative parameters based on the Russell emotion cycle model to construct a human-computer interactive health detector for emotion recognition in EEG images induced by environmental stimuli.Images of 61 environmental scenes were collected and divided into three categories according to the visual characteristics of the environment. Eight volunteers were recruited to collect a total of 488 EEG image data. The trained ResNet-50 model was used to automatically analyze the characteristics of the collected EEG images and classify emotions. The model was compared the support vector machine (SVM), transfer component analysis (TCA), dynamic graph convolutional neural network (DGCNN), and DAN methods.The accuracy of the ResNet-50 model trained in this study is 85.11% and its variance is 7.91. Through the verification of EEG images induced by environmental stimuli, the results are improved by 2.01% and the variance is reduced by 0.04 compared with the model's training results. The model is more accurate in identifying negative and neutral emotions, indicating that the ResNet-50 architecture better recognizes motions in EEG images induced by environmental stimuli. Compared with other algorithm models, the proposed model has the lowest variance and highest stability. The comparison of various algorithms revealed that environmental scenes with different visual features induce different emotions.The proposed monitor can collect EEG images of patients induced by environmental stimuli in daily life in real time, automatically analyze and identify emotional characteristics, and provide quantitative parameters and visualization. It not only enables patients to conveniently monitor their emotional state and make timely adjustments, but also assists doctors in clinical diagnosis.

Pathogenesis-related (PR) proteins are active participants of plant defense against biotic and abiotic stresses. The PR-4 family features a Barwin domain at the C-terminus, which endows the host plant with disease resistance. However, comprehensive analysis of PR-4 genes is still lacking in Qingke (Hordeum vulgare L. var. nudum).Herein, a total of four PR-4 genes were identified from the genome of Qingke through HMM profiling. Devoid of the chitin-binding domain, these 4 proteins were grouped as class II PR-4s. Phylogenic analysis revealed that 127 PR-4s from 47 species were clustered into 3 major groups, among which the four Qingke PR-4s were claded into group I. Analysis of gene structure demonstrated that no intron was found in 3 out of the 4 Qingke PR-4s, and HOVUSG0928500 was the only gene contained one intron. An array of cis-acting motifs were detected in promoters of Qingke PR-4 genes, including elements associated with hormone response, light response, stress response, growth and development processes and binding sites of transcription factors, implying their diverse role. Expression profiling confirmed that Qingke PR-4s were involved in defense response against drought, cold and powdery mildews infection, and transcription of HOVUSG1974300 and HOVUSG5705400 was differentially regulated by MeJA and SA.Findings of the study provided insights into the genetic basis of the PR-4 family genes, and would promote further investigation on protein function and utilization.

Insufficient vascularization is a major challenge in the repair of critical-sized bone defects. Deferoxamine (DFO) has been reported to play a potential role in promoting the formation of H-type blood vessels, a specialized vascular subtype with coupled angiogenesis and osteogenesis. However, whether DFO promotes the expression of H-type vessels in critical femoral defects with complete periosteal damage remains unknown. Moreover, stable drug loading systems need to be designed owing to the short half-life and high-dose toxic effects of DFO. In this study, we developed an injectable DFO-gelatin microspheres (GMs) hydrogel complex as a stable drug loading system for the treatment of critical femoral defects in rats. Our results showed that sustained release of DFO in critical femoral defects stimulated the generation of functional H-type vessels. The DFO-GMs hydrogel complex effectively promoted proliferation, formation, and migration of human umbilical vein endothelial cells in vitro. In vivo, the application of the DFO-GMs hydrogel complex expanded the distribution range and prolonged the expression time of H-type vessels in the defect area and was positively correlated with the number of osterix+ cells and new bone tissue. Topical application of the HIF-1α inhibitor PX-478 partially blocked the stimulation of H-type vessels by DFO, whereas the osteogenic potential of the latter was also weakened. Our results extended the local application of DFO and provided a theoretical basis for targeting H-type vessels to treat large femoral defects. STATEMENT OF SIGNIFICANCE: Abundant functional blood vessels are essential for bone repair. The H-type blood vessel is a functional subtype with angiogenesis and osteogenesis coupling potential. A drug loading system with long-term controlled release was first used to investigate the formation of H-type blood vessels in critical femoral defects and promotion of bone repair. Our results showed that the application of DFO-GMs hydrogel complex expanded the distribution range and expression time of H-type vessels, and was positively correlated with the number of osteoblasts and volume of new bone tissue. These results expanded the local application approach of DFO and provide a theoretical basis for targeting H-type vessels to treat large femoral defects.

Nanomaterials usually kill bacteria via multiple mechanisms which are not explicit to the same degree as those of conventional antibiotics. This situation may hinder the development of novel nanoscale antibiotics. Here, we present aminophenol (AP) to modify gold nanoparticles (AP_Au NPs) which show a broad antibacterial spectrum and potent antibacterial effects against multidrug-resistant (MDR) bacteria with clear antibacterial mechanisms. AP_Au NPs can not only damage bacterial cell walls but also bind to the 16S rRNA to block bacterial protein synthesis. Moreover, AP_Au NPs show excellent performance in curing abdominal bacterial infections in an

The vast amount of reflectance information obtained from the hyperspectral imaging devices offers great opportunities for investigating the function and structure of human tissue. However, the captured hyperspectral data often contain various noises due to the intrinsic imperfection of associated electrical and optical imaging components. This work proposed an automatic total variation algorithm to suppress the noises while preserving the details of the spectral and spatial information. The variation of spectral images at neighboring bands was calculated for regulating the total variation of hyperspectral data so that the spectral-dependent noises can be treated differentially across all bands. Experimental results demonstrated that the proposed method could effectively remove the spectral noises, especially near the ends of those extreme bands. The noise suppressed hyperspectral data could then be used for the visualization enhancement on pathophysiological conditions of intraoperative observed anatomies such as the vessels of brain tissues.

Background Immune-related long non-coding RNAs (irlncRNAs) are known to hold great promise as superior biomarkers for cervical cancer-related immunotherapeutic response and the tumor immune microenvironment. Here, we constructed a prognostic signature based on irlncRNA pairs (IRLPs). Methods The samples were downloaded from The Cancer Genome Atlas and the Genotype-Tissue Expression databases. The least absolute shrinkage and selection operator Cox regression was performed to construct the prognostic model. Receiver operating characteristic (ROC) curve and nomogram were plotted to validate accuracy of the model. Next, we estimated the immune cell infiltration and the correlation between risk score and the expression of genes related to immune checkpoint. Finally, we calculated the score of the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the half maximal inhibitory concentration of the chemotherapeutic agent to evaluate the response to immunotherapy and chemotherapy. Results We constructed a prognostic signature that consisted of 11 irlncRNAs. The area under the curve values of the 1-, 3-, and 5-year ROC curves were 0.844, 0.891, and 0.871, respectively. The expression of CTLA-4, HAVCR2, IDO1, LAG3, and PDCD1 were negatively correlated with risk scores. The score of TIDE in the high-risk group was significantly higher than in the low-risk group ( P Conclusion Our study highlighted the value of the 11 IRLPs signatures to predict the prognosis and the response to immunotherapy and chemotherapeutics for patients with cervical cancer.

Background. Shrunken pore syndrome (SPS) represents selective impairment of kidney filtration of low-molecular-weight molecules between 1 and 30 kDa and has been related to outcomes including morbidity, mortality, and cardiovascular events. However, the prevalence and kidney outcomes of SPS have not been investigated in patients with IgA nephropathy (IgAN) and membranous nephropathy (MN). Methods. We retrospectively collected information of 536 patients including 414 with IgAN and 122 with MN. SPS was mainly defined by cystatin C-based eGFR < 70 % of creatinine-based eGFR using the CAPA-LM equation pairs, while CKD-EPI equations were also employed in sensitivity analyses. Prevalence rate of SPS and its association with end-stage renal disease (ESRD) or severe eGFR decline (≥50% eGFR reduction or doubling of baseline creatinine) were investigated. Results. 44% (8%) patients were identified as possessing SPS using the CAPA-LM definition. ESRD happened in 24 patients during the average follow-up period of 27.7 months. Despite dramatic increase of incidence rate of ESRD for SPS, significant hazard ratio (HR) only existed in IgAN patients after multivariable adjustment (HR: 8.35, 95% CI: 2.10~33.26), but lost significance in sensitivity analyses. 36 patients were determined as having experienced severe eGFR decline after excluding transient creatinine fluctuation. SPS was associated with severe eGFR decline by Kaplan-Meier survival analyses in the overall population as well as the IgAN, MN, male, and female subpopulations, which remained significant in multivariable adjustments in all groups except IgAN. However, only in female patients the association between SPS and eGFR decline remained significant in all the sensitivity analyses. Conclusions. SPS was independently associated with eGFR decline in female patients with IgAN and MN.

Splenectomy and splenic artery embolization are major treatment options for hypersplenism and portal hypertension in liver cirrhosis, but may lead to splanchnic vein thrombosis (SVT), which is potentially lethal. We conducted a systematic review and meta-analysis to explore the incidence of SVT in liver cirrhosis after splenectomy or splenic artery embolization and the risk factors for SVT. All relevant studies were searched through the PubMed, EMBASE, and Cochrane Library databases. The incidence of SVT in liver cirrhosis after splenectomy or splenic artery embolization was pooled. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sixty-six studies with 5632 patients with cirrhosis were included. The pooled incidence of SVT after splenectomy and splenic artery embolization was 24.6% (95% CI 20.2–29.3%) and 11.7% (95% CI 7.1–17.3%), respectively. A meta-analysis of three comparative studies demonstrated that the incidence of SVT after splenectomy was statistically similar to that after splenic artery embolization (OR 3.15, P = 0.290). Platelet count, mean platelet volume, preoperative splenic or portal vein diameter, preoperative or postoperative portal blood velocity, splenic volume and weight, and periesophagogastric devascularization were significant risk factors for SVT after splenectomy. Postoperative use of preventive antithrombotic therapy was a significant protective factor against SVT after splenectomy. SVT is common in liver cirrhosis after splenectomy and splenic artery embolization. Coagulation and hemostasis factors, anatomical factors, and surgery-related factors have been widely identified for the assessment of high risk of SVT after splenectomy. Prophylactic strategy after splenectomy, such as antithrombotic therapy, might be considered in such high-risk patients. This study was registered in PROSPERO with a registration number of CRD42019129673.

Background NKX6.1 is a transcription factor for insulin, as well as a marker for β cell maturity. Abnormal NKX6.1 expression in β cells, such as translocation from the nucleus to cytoplasm or lost expression, has been shown as a marker for β cell dedifferentiation. Methods We obtained pancreatic sections from organ donors and immunofluorescence staining with NKX6.1 and insulin was performed to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM). Results Our results showed that cells with insulin expression but no nucleic NKX6.1 expression (NKX6.1Nuc-Ins+), and cells with cytoplasmic NKX6.1 expression but no insulin expression (NKX6.1cytIns−) were significantly increased in T2DM subjects and positively correlated with glycated hemoglobin (HbA1c), indicating the elevated β cell dedifferentiation with NKX6.1 inactivation in T2DM. To investigate whether β cell dedifferentiation has initiated in subjects with higher risks for T2DM, we next analyzed the association between β-cell dedifferentiation level in ND subjects with different ages, body mass index, and HbA1c. The results showed the absolute number and percentage of dedifferentiated β cells with NKX6.1 inactivation did not significantly change in subjects with advanced aging, obesity, or modest hyperglycemia, indicating that the β cell dedifferentiation might mainly occur after T2DM was diagnosed. Conclusion Our results suggested that NKX6.1 expression in β cells was changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1Nuc-Ins+ and NKX6.1cytIns− cells. This abnormality did not occur more frequently in subjects with a higher risk for T2DM, suggesting that β cell dedifferentiation might be secondary to the pathological changes in T2DM.

Background Subclinical hypothyroidism (SCH) is reportedly associated with an increased risk of adverse events in patients undergoing percutaneous coronary intervention (PCI). The prognostic significance of SCH in the elderly was poorly defined. The purpose of this study was to evaluate the association between SCH and long-term outcomes in older patients undergoing PCI. Methods Three thousand one hundred sixty-eight patients aged 65 years or older who underwent PCI from January 2012 to October 2014 were included. Patients were divided into SCH group (n = 320) and euthyroidism (ET) group (n = 2848) based on thyroid function test. Cox proportional hazard regression analyses were used to estimate the relative risks (RRs) of all-cause death and cardiac death for patients with SCH during a 4-year follow-up period. Results There were 227 deaths during the follow-up period including 124 deaths caused by cardiac events. There was no significant difference in mortality rate between the SCH group and the ET group (p > 0.05). After adjustment for covariates, compared with patients with ET, the RRs of death from all-cause and cardiac in patients with SCH were 1.261 (95%CI: 0.802–1.982, p = 0.315) and 1.231 (95%CI: 0.650–2.334, p = 0.524), respectively. When SCH was stratified by age, gender, and degree of thyroid-stimulating hormone elevation, no significant associations were also found in any stratum. Conclusion Our investigation revealed that SCH was negatively associated with the outcome of PCI in older patients.