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Pouchitis is the most common complication following restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Fecal calprotectin (FC) is a noninvasive indicator of the intestinal inflammatory status. This study was conducted to evaluate the clinical value of the FC concentration for the diagnosis and risk assessment of pouchitis.This retrospective study involved patients who underwent IPAA for UC at Tianjin Medical University General Hospital from January 2015 to January 2019. The patients were categorized into pouchitis and non-pouchitis groups based on their Pouchitis Disease Activity Index (PDAI) score. Laboratory indicators, including the FC concentration, were collected from both groups.Sixty-six patients with UC after IPAA were included in the study and divided into the non-pouchitis group (FC is a useful biomarker in patients with pouchitis. Patients are advised to regularly undergo FC measurement to monitor for pouchitis. An FC concentration in the range of 143.25-579.60 μg/g is predictive of a high risk for pouchitis, and further examination and preventive treatment are necessary in such patients.KEY MESSAGESFecal calprotectin can be used to quantify pouch inflammation.Fecal calprotectin can be used to predict a high risk of pouchitis.

Capecitabine is a widely-used antineoplastic drug, a prodrug to 5-fluorouracil which commonly induces gastrointestinal toxicity. Enterocolitis, as a rarely recognized gastrointestinal adverse effect (AE) of capecitabine, is potentially severe and usually results in antitumor treatment withdrawal. For the better management of severe AEs, pharmacogenetics is one promising field. Herein, we describe a case of capecitabine-induced enterocolitis presenting with severe diarrhea in order to improve recognition by clinicians. Moreover, we conduct a pharmacogenetic profile of the patient and review the current studies of gene polymorphisms of 5-fluorouracil-related diarrhea, hoping to offer a reference for further clinical pharmacogenetic practice in predicting capecitabine AEs showing diarrhea as the main symptom.

Circular RNAs (circRNAs) act as crucial regulators in tumorigenesis. In this study, the working mechanism of circ_0091579 in hepatocellular carcinoma (HCC) progression was investigated.The expression of RNA and protein was measured via RT-qPCR and Western blot assay. Cell proliferation ability was analyzed via CCK8, EdU and colony formation assays. Cell migration and invasion abilities were detected via transwell assays. Flow cytometry was applied to assess cell cycle and apoptosis. The target relation between miR-136-5p and circ_0091579 or tripartite motif containing 27 (TRIM27) was certified using dual-luciferase reporter assay. Xenograft tumor model was utilized to assess the role of circ_0091579 in tumor growth in vivo. The protein level of Ki67 in tumor tissues was analyzed by immunohistochemistry (IHC) assay.Circ_0091579 expression was elevated in HCC tissues and cell lines. HCC patients with high circ_0091579 expression displayed low survival rate. Circ_0091579 knockdown suppressed the proliferation, migration, invasion, cell cycle progression and epithelial-mesenchymal transition (EMT) and induced apoptosis of HCC cells. Circ_0091579 acted as a molecular sponge for miR-136-5p, and circ_0091579 silencing-mediated effects were largely overturned by the knockdown of miR-136-5p in HCC cells. MiR-136-5p interacted with the 3' untranslated region (3'UTR) of TRIM27, and TRIM27 overexpression largely counteracted miR-136-5p overexpression-induced influences in HCC cells. Circ_0091579 sponged miR-136-5p to up-regulate TRIM27 expression in HCC cells. Circ_0091579 silencing suppressed xenograft tumor growth in vivo.Circ_0091579 exhibited an oncogenic role to enhance the malignant potential of HCC cells through mediating miR-136-5p/TRIM27 axis in vitro and in vivo.

Interleukin-24 (IL-24) has specific inhibitory effects on the proliferation of various tumor cells with almost no toxicity to normal cells. The antitumor activity of recombinant human IL-24 protein produced in mammalian cells is much higher than that of bacteria, but its expression level is extremely low. Sodium butyrate (NaBu) was utilized as a media additive to increase protein expression in Chinese hamster ovary cells. The site-specific integrated engineered cells FCHO/IL-24 were treated with NaBu under different culture conditions (10% and 0.5% serum adherent culture, 0.5% serum suspension culture). First, 3 days of 1 mmol/L NaBu treatment significantly increased rhIL-24 expression level in FCHO/IL-24 cells by 119.94 ± 1.5% (**p p p p p p p

Frequent intermittent bleeding control and suction are often necessary during microneurosurgical procedures. We compared the visual searching strategy that guides these types of gross hand movements between expert surgeons and neurosurgical residents.A total of 70 trials of a microsurgical task consisting of moving a cotton ball with bipolar forceps and a suction instrument under the microscope were recorded. Based on surgical videos, we extracted total task time, boarding time, gaze-tool time gap, number of fixations during the boarding time, and target-locked fixation duration. A comparison of these measures between experts and resident surgeons were performed.No significant difference was found for total task time, boarding time, and number of fixations during the boarding time between the 2 groups of surgeons. However, we found significant differences in the measure of gaze-tool time gap (P0.001, partial ηTask time analysis for this basic microsurgical task is not sufficient to evaluate participants' level of expertise. Gaze behavior analysis helps to reveal hidden differences between experts and residents. This research provides more evidence that supports the use of gaze analysis for assessing surgeons' skills in microsurgery.

ContextThere is little evidence regarding the association between serum vitamin B6 status and catabolism and all-cause mortality in patients with type-2 diabetes mellitus (T2DM).ObjectiveWe aimed to ascertain if the serum level of vitamin B6 and catabolism, including pyridoxal 5′-phosphate (PLP) and 4-pyridoxic acid (4-PA), were associated with risk of all-cause mortality in T2DM patients.MethodsThis prospective cohort study involved 2574 patients with T2DM who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The serum concentrations of PLP and 4-PA were used to assess the serum level of vitamin B6. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015.ResultsOver a median follow-up of 85 months, there were 588 deaths. The fully adjusted Cox model indicated that the highest serum PLP concentrations (> 63.6 nmol/L) were associated with a decrease in all-cause mortality (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99, P trend = .035). The risk for all-cause mortality was 59% higher for participants with the highest quartile of 4-PA level compared with the lowest quartile (HR, 1.62; 95% CI, 1.12-2.35; P trend = .003). The sensitivity and specificity of the combination of PLP and 4-PA levels for the prediction of all-cause mortality were 59.5% and 60.9%, respectively (area under the receiver operating characteristic curve = 0.632). The Kaplan-Meier method was used to estimate overall survival for patients based on different combinations of PLP level and 4-PA level. Patients with PLP less than 24.3 nmol/L and 4-PA greater than or equal to 25.4 nmol/L had the worst outcomes (log-rank P ConclusionOverall, our data suggest that a low serum level of PLP and high serum level of 4-PA, which represent the serum level of vitamin B6, increases the risk of all-cause mortality significantly in patients with T2DM.

At-risk alcohol consumption is the established most important risk factor for cirrhosis in people without HBV/HCV infection. We aimed to develop and validate a simple and non-invasive tool for triaging cirrhosis risk in at-risk alcohol drinkers without HBV/HCV infection. A large-sample size, cross-sectional study within the framework of a population-based Cancer Screening Program in Urban China (CanSPUC) was conducted. Data on the liver cancer screening in Henan province, China were used. At-risk alcohol drinkers were those who currently drink one or more alcohol units per week for at least six months. A total of 6,581 eligible participants enrolled from October 1, 2013 to December 31, 2016 were included into the derivation dataset, and 2,096 eligible participants enrolled from January 1, 2017 to October 31, 2018 were included into the external validation dataset, respectively. Using the derivation dataset, a 20-point scale risk score model was developed, based on sex, education background, dietary intake of vegetables, dietary intake of roughage, smoking index, length of secondhand smoke exposure, history of fatty liver, history of diabetes, and first-degree family history of liver cancer. The model showed excellent discrimination (AUC = 0.787; 95% CI, 0.7603–0.812) and calibration (Hosmer–Lemeshow test: P = 0.123) in the derivation dataset and an optimal cut-off value of 12 yield sensitivity of 61.3%, specificity of 82.7%. The model also had achieved similar performance in the external validation dataset. In conclusion, this model can be a practical tool to identify and triage population at high risk of cirrhosis in at-risk alcohol drinkers without HBV/HCV infection. Prevention Relevance: The risk model we developed will not only be used as a practical tool to triage high risk groups for liver cirrhosis, but also have implications for public health measures, such as guidelines for the prevention of liver cancer, in at-risk alcohol drinkers without HBV/HCV infection.

Widespread white matter (WM) injury is a hallmark feature of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, controversies about the mechanism of WM tract injury exist persistently. Excessive iron accumulation, frequently reported in CADASIL patients, might cause WM tract injury.To test the association between iron accumulation and WM tract injury in CADASIL patients.Retrospective.A total of 35 CADASIL patients (age = 50.4 ± 6.4, 62.9% female) and 48 healthy controls (age = 55.7 ± 8.0, 68.8% female).Diffusion-weighted spin-echo echo-planar sequence; enhanced susceptibility-weighted angiography (ESWAN) gradient echo sequence on a 3 T scanner.The phase images acquired by ESWAN were used to calculate quantitative susceptibility mapping (QSM). Iron accumulation was evaluated in deep gray matters using QSM. WM tract injury was quantified by diffusion metrics based on WM major tracts skeleton. We compared iron deposition between groups and analyzed the correlation between WM tract injury and iron deposition in regions showing significant differences from healthy controls. Exploratory analysis was carried out to investigate whether WM tract injury mediated the relationship between iron deposition and cognitive impairment evaluated by Mini-Mental State Examination (MMSE).General linear model (GLM), partial correlation, stepwise linear regression and mediation analysis were used. The threshold of statistical significance was set as p 0.05.Compared with healthy controls, CADASIL patients had significantly increased iron deposition in the caudate and putamen. Aberrant iron deposition in these two regions was significantly associated with decreased WM fractional anisotropy (FA) (caudate, r = -0.373； putamen, r = - 0.421), and increased radial diffusivity (RD) (caudate, r = 0.372; putamen, r = 0.386). Furthermore, WM tract injury mediated the relationship between iron deposition and cognitive impairment.Patients with CADASIL show increased iron deposition in the caudate and putamen that is correlated to WM tract injury, which may in turn mediate the association with cognitive impairment.2 TECHNICAL EFFICACY: Stage 2.

To develop and implement of a group-based acceptance and commitment therapy programme in helping clinical nurses with mental health problems during the sporadic COVID-19 outbreak period.In the face of the continuing COVID-19 pandemic, clinical nurses have a high risk of mental health issues.A quasi-experimental design was used. Two hundred twenty-six nurses were recruited from four general hospitals to receive 10 sessions of acceptance and commitment therapy programme. The Symptom Checklist-90, Perceived Stress Scale and Connor-Davidson Resilience Scale were used to assess nurses' mental health symptom, perceived stress and psychological resilience at pre-intervention and 4-week post-intervention.The mean attendance sessions was 5.78. The Symptom Checklist-90 score was significantly lower at post-intervention than pre-intervention (P 0.01), and there were no significant changes of perceived stress and psychological resilience. There were significant correlations among the changed rates of mental health, perceived stress and psychological resilience (P 0.01).The acceptance and commitment therapy programme was effective in relieving mental health symptoms for clinical nurses and could protect clinical nurses' perceived stress and psychological resilience. However, a randomized controlled trial is needed to confirm the findings.To facilitate clinical nurses' psychological health in crisis situation, nursing management team should provide and allocated appropriate resources to support the healthcare providers.

The pathogenesis of liver in patients with hepatitis B virus-associated acute chronic liver failure (HBV-ACLF) remains largely unknown. We aimed to elucidate the molecular mechanism underlying the pathogenesis of liver in HBV-ACLF patients by using multiple approaches including transcriptome analysis. We performed transcriptomic sequencing analysis on the liver of HBV-ACLF patients (n = 6), chronic hepatitis B (n = 6), liver cirrhosis (n = 6) and normal control (n = 5), then explored the potential pathogenesis mechanism in liver specimen from another 48 subjects and further validated the molecular and cellular mechanisms using THP-1 cells. RNA-sequencing data analysis indicated that, among the genes up-regulated in HBV-ACLF, genes related to inflammatory response and chemotaxis accounted for a large proportion of the total DEGs. A number of key chemokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8) and NF-ĸB pathway were identified to be robust in the liver samples from HBV-ACLF patients. Interestingly, cylindromatosis (CYLD) was found to be downregulated in the liver of HBV-ACLF patients, in line with the well-established role of CYLD in regulating most of the chemokines and pro-inflammatory cytokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8, IL-6, IL-1β) via inhibition of NF-ĸB. Indeed, the knockdown of CYLD resulted in sustained activation of NF-ĸB in macrophages and enhanced chemokines and inflammatory cytokines production, which in turn enhanced chemotactic migration of neutrophil, monocyte, T lymphocytes, and NK cell. In conclusions, down-regulated CYLD aggravated inflammatory cell chemotaxis through enhancing NF-κB activation in HBV-ACLF patients, thereby participating in the pathogenesis of HBV-ACLF injury.

A variant in signal transducer and activator of transcription 4 (STAT4) was reported to correlate with the response of interferon-α (IFN-α) in a retrospective study in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (CHB) patients. Here, we conducted a prospective study to analyze the effect of STAT4 genetic polymorphism on the response of pegylated interferon-α-2a (PegIFN-α-2a) in HBeAg-positive patients. A prospective, multicenter, open-label, parallel cohort study was performed. One hundred and fifty treatment-naïve and 156 nucleos(t)ide analog (NA)-experienced HBeAg-positive CHB patients were enrolled, respectively. All patients received PegIFN-α-2a treatment for 48 weeks and 24-week follow-up post PegIFN-α-2a treatment. Before treatment, STAT4 genetic polymorphism was determined by PCR and DNA sequencing. Serological markers, serum HBV DNA levels, and adverse events were collected at each visit. We observed a larger reduction of HBV DNA load and a significantly higher HBeAg seroconversion rate in the GT/TT group than in the GG group at week 72 (p = 0.002 and p = 0.023) in treatment-naïve patients. In NA-experienced patients, the HBeAg seroconversion rate in the GT/TT group was higher than that in the GG group at week 72 (p = 0.005). STAT4 rs7574865 gene polymorphism was the strongest independent predictor of HBeAg seroconversion in both paralleled cohorts. Also, patients in the GT/TT group had a higher hepatitis B surface antigen loss rate than in the GG group in the study. There was no significant difference in adverse events between GG and GT/TT groups. This prospective cohort study confirmed that STAT4 rs7574865 gene polymorphism is associated with HBeAg seroconversion and HBsAg loss irrespective of naïve and NA-experienced HBeAg-positive CHB patients treated with PegIFN-α-2a.

Oral squamous cell carcinoma (OSCC) is a malignant disease in the world which has a profound effect on human health and life quality. According to tumor stage and pathological diagnosis, OSCC is mainly treated by combinations of surgery, radiotherapy and chemotherapy. However, traditional treatment methods suffer from some limitations, such as systemic toxicity, limited therapeutic effect and drug resistance. With the rapid development of nanotechnology, nanodrug delivery systems (DDSs) and intelligent DDSs have been widely used in targeted therapy for OSCC. Meanwhile, the newly developed therapeutic techniques such as immunotherapy, gene therapy and bionic technology provide the possibility to realize the active targeted therapy. Here, the latest advances of target therapy for OSCC are reviewed, and their therapeutic remarks, current limits and future prospects are also systematically interpreted. It is believed that active and passive targeted therapies have great potentials for clinical transformation and application of OSCC, which will greatly improve human quality of life.

A two- to three-fold increased risk of venous thrombotic events (VTE) has been demonstrated in patients with inflammatory bowel disease (IBD) compared to the general population, but less is known about the risk of VTE in child- and pediatric-onset IBD. In recent years, several studies have reported the rising incidence rate of VTE in juvenile patients with IBD, and the related risk factors have been explored.To evaluate the risk of VTE in children and adolescents with IBD.Articles published up to April 2021 were retrieved from PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, and WANFANG. Data from observational studies and clinical work were extracted. The outcome was the occurrence of VTE according to the type of IBD. The available odds ratio (OR) and the corresponding 95% confidence interval (CI) were extracted to compare the outcomes. Effect size (P), odds ratio (OR), and 95%CI were used to assess the association between VTE risk and IBD disease. Subgroup analyses stratified by subtypes of VTE and IBD were performed.Twelve studies (7450272 IBD patients) were included in the meta-analysis. Child and adolescent IBD patients showed increased VTE risk (The current meta-analysis showed that the incidence and risk of VTE are significantly increased in pediatric and adolescent IBD patients. Thus, IBD might be a risk factor for VTE in children and young adults. High-quality prospective cohort studies are necessary to confirm these findings.

We aimed to determine participation in low-dose computed tomography (LDCT) of individuals with a family history of common cancers in a population-based screening program to provide timely evidence in high-risk populations in China. The analysis was conducted using data from the Cancer Screening Program in Urban China (CanSPUC), which recruited 282 377 participants aged 40 to 74 years from eight cities in the Henan province. Using the CanSPUC risk score system, 55 428 participants were evaluated to have high risk for lung cancer and were recommended for LDCT. We calculated the overall and group-specific participation rates using family history of common cancers and compared differences in participation rates between different groups. Odds ratios (ORs) and 95% confidence intervals were derived by multivariable logistic regression. Of the 55 428 participants, 22 260 underwent LDCT (participation rate, 40.16%). Family history of lung, esophageal, stomach, liver and colorectal cancer was associated with increased participation in LDCT screening. The odds of participants with a family history of one, two, three and four or more cancer cases undergoing LDCT screening were 1.9, 2.7, 2.8 and 3.5 times, respectively, than those without a family history of cancer. Compared to those without a history of cancer, participation in LDCT gradually increased as the number of cancer cases in the family increased (P .001). Our findings suggest that there is room for improvement in lung cancer screening given the relatively low participation rate. Lung cancer screening in populations with a family history of cancer may improve efficiency and cost-effectiveness; however, this requires further verification.

Objectives To explore efficacy, risk factors, safety, and persistence of teriflunomide in relapsing–remitting multiple sclerosis (RRMS) cohort. Methods This prospective, observational cohort study included 217 consecutive teriflunomide treated RRMS patients, 192 of which with at least 3-month persistence on teriflunomide were included in effectiveness and risk factor analyses. Multivariate Cox proportional regression analysis was performed to identify factors associated with failure of no evidence of disease activity (NEDA) 3. Results At baseline 82% patients were treatment naïve while 18.0% interferon-β1b treated patients had stopped treatments for more than 1 year. After treatment, 79.0% patients achieved NEDA 3 at 12-month, mean annualized relapse rate (ARR) reduced significantly (0.79 ± 0.80 vs 0.16 ± 0.70; P P > 0.05). Male sex (hazard ratio [HR] 1.856; 95% confidence interval [CI] 1.118–3.082, P P P Conclusions Our results support efficacy and tolerability of teriflunomide for treatment-naïve RRMS patients in real-world practice. Female patients, patients with less relapses and less disability before treatment are most likely to benefit from teriflunomide treatment.

AimsHeart failure (HF) remains a major public health problem with increasing prevalence in China. This study evaluated the clinical performance and quality measures for HF management to identify gaps in the standardization of care for patients hospitalized for HF in China.Methods and resultsFollowing the results of China-HF stage I (2012-2015), the second stage of the China-HF was launched in 2017. Among 113 hospitals with ≥100 cases, the China-HF Stage II assessed the quality of care measures for HF and compared results with previous data in China and the US-based Get with The Guidelines-Heart Failure (GWTG-HF) registries. In total, 34938 patients hospitalized with HF were enrolled from January 2017 to October 2020. Echocardiographic left ventricular function and natriuretic peptide test were performed in 93.7% and 93.0% of the cases, respectively. Adherence to standardized guidelines in China-HF stage II was higher than that in the China-HF stage I, but generally lower than GWTG-HF registry with 78.2% of eligible patients was prescribed oral diuretics, 78.7% renin-angiotensin-system inhibitors, and 82.2% beta-blockers. Implantable cardioverter-defibrillators and cardiac resynchronization devices were implanted in 3.9% and 14.6%, respectively. In contrast, the proportion of eligible patients discharged with spironolactone (87.8%) was higher than GWTG-HF. The median length of hospitalization was 9 (6, 12) days, and 938 (2.8%) patients died or withdrew from treatment during hospitalization.ConclusionsDespite significant improvements in the use of guideline-recommended testing and therapy, there remain major gaps in quality of care for patients hospitalized for HF in China that are generally larger than gaps observed in the United States.

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

As the coronavirus disease 2019 (COVID-19) pandemic is still ongoing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are circulating worldwide, an increasing number of breakthrough infections are being detected despite the good efficacy of COVID-19 vaccines. Data on 88 COVID-19 breakthrough cases (breakthrough infections group) and 41 unvaccinated cases (unvaccinated group) from June 1 to August 22, 2021, were extracted from a cloud database established at Beijing Ditan Hospital to evaluate the clinical, immunological, and genomic characteristics of COVID-19 breakthrough infections. Among these 129 COVID-19 cases, 33 whole genomes were successfully sequenced, of which 23 were Delta variants, including 15 from the breakthrough infections group. Asymptomatic and mild cases predominated in both groups, but two patients developed severe disease in the unvaccinated group. The median time of viral shedding in the breakthrough infections group was significantly lower than that in the unvaccinated group (p = 0.003). In the breakthrough infections group, the IgG titers showed a significantly increasing trend (p = 0.007), and the CD4 + T lymphocyte count was significantly elevated (p = 0.018). For people infected with the Delta variant in the two groups, no significant difference was observed in either the quantitative reverse-transcription polymerase chain reaction results or viral shedding time. In conclusion, among vaccinated patients, the cases of COVID-19 vaccine breakthrough infections were mainly asymptomatic and mild, IgG titers were significantly increased and rose rapidly, and the viral shedding time was shorter.

Hypoxia-inducible factor 2α (HIF2α) plays a pivotal role in breast tumor growth and metastasis. However, the regulatory mechanisms of HIF2α protein stability remain poorly understood. The precise role of the deubiquitinase (DUB) ubiquitin-specific peptidase 5 (USP5) in breast cancer and the underlying mechanism remains largely unknown. Here, we identified USP5 as a novel DUB for HIF2α. Physically, USP5 interacts with HIF2α and protects HIF2α from ubiquitin-proteasome degradation, thereby promoting the transcription of HIF2α target genes, such as SLC2A1, PLOD2, P4HA1, and VEGFA. USP5 ablation impairs breast cancer cells proliferation, colony formation, migration, and invasion. Moreover, USP5 is highly expressed in breast cancer, and the protein levels of USP5 are positively correlated with HIF2α protein levels in human breast cancer tissues. Importantly, high levels of USP5 leads to poor clinical outcome in patients with breast cancer. Collectively, USP5 stabilizes HIF2α through its DUB activity and provides a potential therapeutic target for breast cancer.

The objective of this study is to describe the typical and atypical clinical and neuroimaging features of ALD in Chinese patients, which will help early diagnosis and intervention to improve prognosis of ALD.Forty-one patients in the Leukoencephalopathy Clinic of Neurology Department, Peking Union Medical College Hospital were enrolled. Detailed clinical manifestations and MRI features were analyzed. The relationship between phenotype and genotype as well as biochemical analysis was observed.The patients were classified according to phenotype and onset age, including 14 childhood cerebral ALD (CCALD), 8 adolescent cerebral ALD (adoCALD), 3 adult cerebral ALD (ACALD), 14 adrenomyeloneuropathy (AMN), and 2 ALD in women. AMN was the main presentation in adults. Visual impairment was usual onset symptom in CCALD and cognitive decline and psychiatric symptoms were found in adoCALD and ACALD. Typical MRI feature of CALD was symmetrical peri-ventricular "butterfly wings" like lesions in frontal and/or occipital lobe with peripheral DWI hyperintensities and Gd enhancement. Corpus callosum and internal capsule were always involved. Unilateral lesions were also possible. Cerebral AMN presented with centrum semiovale diffuse involvement. Spinocerebellar variant was a special subtype of AMN with obvious cerebellar and brainstem lesions. No relationships between phenotype and genotype as well as biochemical VLCFAs analysis were found.We emphasize that corpus callosum and internal capsule are always involved in ALD. A unilateral lesion is also possible. Neuroimaging of cerebral AMN is different from typical CALD with more centrum semiovale involvement. We support spinocerebellar variant was a rare subtype of AMN.

During the development of COVID-19 caused by SARS-CoV-2 infection from mild disease to severe disease, it can trigger a series of complications and stimulate a strong cellular and humoral immune response. However, the precise identification of blood immune cell response dynamics and the relevance to disease progression in COVID-19 patients remains unclear. We propose for the first time to use changes in cell numbers to establish new subgroups, which were divided into four groups: first from high to low cell number (H_L_Group), first from low to high (L_H_Group), continuously high (H_Group), and continuously low (L_Group). It was found that in the course of disease development. In the T cell subgroup, the immune response is mainly concentrated in the H_L_Group cell type, and the complications are mainly in the L_H_Group cell type. In the NK cell subgroup, the moderate patients are mainly related to cellular immunity, and the severe patients are mainly caused by the disease, while severe patients are mainly related to complications caused by diseases. Our study provides a dynamic response of immune cells in human blood during SARS-CoV-2 infection and the first subgroup analysis using dynamic changes in cell numbers, providing a new reference for clinical treatment of COVID-19.

The molecularly imprinted polymers coated on the Fe3O4 nanoparticles not only contribute to forming an albumin-rich corona on the surface of Fe3O4 nanoparticles, but also enhance the photothermal conversion of Fe3O4 nanoparticles.

Two large randomized controlled trials (RCTs) have demonstrated that low dose computed tomography (LDCT) screening reduces lung cancer mortality. Risk-prediction models have been proved to select individuals for lung cancer screening effectively. With the focus on established risk factors for lung cancer routinely available in general cancer screening settings, we aimed to develop and internally validated a risk prediction model for lung cancer.Using data from the Cancer Screening Program in Urban China (CanSPUC) in Henan province, China between 2013 and 2019, we conducted a prospective cohort study consisting of 282,254 participants including 126,445 males and 155,809 females. Detailed questionnaire, physical assessment and follow-up were completed for all participants. Using Cox proportional risk regression analysis, we developed the Henan Lung Cancer Risk Models based on simplified questionnaire. Model discrimination was evaluated by concordance statistics (C-statistics), and model calibration was evaluated by the bootstrap sampling, respectively.By 2020, a total of 589 lung cancer cases occurred in the follow-up yielding an incident density of 64.91/100,000 person-years (pyrs). Age, gender, smoking, history of tuberculosis and history of emphysema were included into the model. The C-index of the model for 1-year lung cancer risk was 0.766 and 0.741 in the training set and validation set, respectively. In stratified analysis, the model showed better predictive power in males, younger participants, and former or current smoking participants. The model calibrated well across the deciles of predicted risk in both the overall population and all subgroups.We developed and internally validated a simple risk prediction model for lung cancer, which may be useful to identify high-risk individuals for more intensive screening for cancer prevention.

Specific patterns of lung ultrasound (LUS) images are used to assess the severity of coronavirus disease 2019 (COVID-19) pneumonia, while such assessment is mainly based on clinicians' qualitative and subjective observations. In this study, we quantitatively analyze the LUS images to assess the severity of COVID-19 pneumonia by characterizing the patterns related to the pleural line (PL) and B-lines (BLs). Twenty-seven patients with COVID-19 pneumonia, including 13 moderate cases, seven severe cases, and seven critical cases, are enrolled. Features related to the PL, including the thickness (TPL) and roughness of the PL (RPL), and the mean (MPLI) and standard deviation (SDPLI) of the PL intensities are extracted from the LUS images. Features related to the BLs, including the number (NBL), accumulated width (AWBL), attenuation coefficient (ACBL), and accumulated intensity (AIBL) of BLs, are also extracted. The correlations of these features with the disease severity are evaluated. The performances of the binary severe/non-severe classification are assessed for each feature and support vector machine (SVM) classifiers with various combinations of features as input. Several features, including the RPL, NBL, AWBL, and AIBL, show significant correlations with disease severity (all ). The classification performance is optimal using the SVM classifier using all the features as input (area under the receiver operating characteristic (ROC) curve = 0.96, sensitivity = 0.93, and specificity = 1). These findings demonstrate that the proposed method may be a promising tool for automatic grading diagnosis and follow-up of patients with COVID-19 pneumonia.

Remifentanil (RFT), extensively used for general anesthesia, is a synthetic ultra-short-acting opioid used as an anti-inflammatory oxidant to alleviate a plethora of diseases. This study was designed to determine whether RFT would provide protective effects on sepsis-induced intestinal injury.RFT was used to incubate the lipopolysaccharide (LPS)-treated IEC-6 cells for determining the role of RFT in sepsis-induced intestinal injury and the underlying mechanism. The determination of cell viability and inflammation of LPS-treated IEC-6 cells influenced by RFT was conducted by Cell counting Kit-8 (CCK-8), RT-qPCR, and western blot, while the detection of LDH, diamine oxidase (DAO), and intestinal-type fatty acid binding proteins (I-FABP) was conducted for determining the intestinal cytotoxicity in these cells. The apoptosis of these cells was detected by TUNEL, with autophagy-related protein expression measured by western blot to confirm whether autophagy was activated. Finally, the aforementioned assays were conducted again after 3-Methyladenine (3-MA), an autophagy inhibitor, was used on these cells to investigate whether RFT exerted its effects on LPS-treated IEC-6 cells via modulation of autophagy.RFT alleviates LPS-induced IEC-6 cell inflammation, cytotoxicity and apoptosis, and autophagy-related proteins were expressed at higher levels when RFT was used on these cells. Nevertheless, further treatment of 3-MA weakened the restorative impacts of RFT on the inflammation, cytotoxicity and apoptosis of these cells.To conclude, this paper is the first to present evidence that RFT attenuates sepsis-induced intestinal injury by inducing autophagy, which will provide instructions for the future investigations into the use of RFT in treatment of intestinal injury.

Background:. The scale assessment was helpful in predicting the presence of antibodies to autoimmune encephalitis. This study aimed to evaluate the application of antibody prevalence in Chinese patients with epilepsy and encephalopathy (APE2-CHN) and response to immunotherapy in Chinese patients with epilepsy and encephalopathy (RITE2-CHN) for patients with different neuronal surface antibodies. Methods:. A total of 1365 patients with epileptic seizures as the prominent feature in Xuanwu Hospital, Capital Medical University, from June 2016 to June 2020 were enrolled in our study. Of these, 915 patients with epilepsy of unknown etiology whose serum and/or cerebrospinal fluid samples were examined for autoimmune antibodies were selected. All patients were scored with antibody prevalence in patients with epilepsy and encephalopathy (APE2), response to immunotherapy with epilepsy and encephalopathy (RITE2), APE2-CHN, and RITE2-CHN scores. Results:. Of the 915 patients, 191 patients were positive for neural-surface specific antibodies (115 N-methyl-D-aspartate receptor (NMDAR) Ab, 47 leucine-rich glioma-inactivated protein 1 (LGI1) Ab, 8 contactin-associated protein 2 (CASPR2) Ab, 4 AMPA2R-Ab, and 11 GABAR-B-Ab; 3 CASPR2-Ab and LGI1-Ab, 2 NMDAR-Ab and CASPR2-Ab, and 1 NMDAR-Ab and myelin-oligodendrocyte glycoprotein [MOG] Ab). The sensitivity and specificity of APE2 ≥4 in predicting the presence of neural-surface specific antibodies in our study were 74.35% and 81.77%, respectively, and the sensitivity and specificity of APE2-CHN ≥4 were 75.92% and 84.53%, respectively. Eight cases had an APE2 score

Artificial intelligence (AI) is a new technical discipline that uses computer technology to research and develop the theory, method, technique, and application system for the simulation, extension, and expansion of human intelligence. With the assistance of new AI technology, the traditional medical environment has changed a lot. For example, a patient’s diagnosis based on radiological, pathological, endoscopic, ultrasonographic, and biochemical examinations has been effectively promoted with a higher accuracy and a lower human workload. The medical treatments during the perioperative period, including the preoperative preparation, surgical period, and postoperative recovery period, have been significantly enhanced with better surgical effects. In addition, AI technology has also played a crucial role in medical drug production, medical management, and medical education, taking them into a new direction. The purpose of this review is to introduce the application of AI in medicine and to provide an outlook of future trends.

Declining autophagy and rising apoptosis are the main factors driving the development of steroid‐induced osteonecrosis of the femoral head (SONFH). Here, we showed that astragalus polysaccharide (APS) improved femoral head necrosis via regulation of cell autophagy and apoptosis through microRNA (miR)‐206/hypoxia inducible factor‐1 (HIF‐1α)/BCL2 interacting protein 3 (BNIP3) axis. The expression of miR‐206, HIF‐1α, and BNIP3 in SONFH specimens and cell model were measured using qPCR. SONFH cell model was treated with APS. Cell autophagy was evaluated using LC3‐immunofluorescence assays. Flow cytometry was conducted to assess cell apoptosis. Apoptosis‐related proteins and autophagy‐related proteins were determined using western blot. Besides, dual‐luciferase reporter assay was employed to investigate the relationship between miR‐206 and HIF‐1α. Here we showed that miR‐206 expression was upregulated in SONFH tissues and cell model. APS promoted autophagy and inhibited apoptosis in SONFH cell model via downregulating miR‐206. What is more, HIF‐1α was the target of miR‐206. Knockdown of HIF‐1α reversed the recovery effect of miR‐206 inhibitor on SONFH cell model. Furthermore, BNIP3 was the target of HIF‐1α. HIF‐1α overexpression promoted autophagy and inhibited apoptosis, and knockdown of BNIP3 abolished the recovery effect of HIF‐1α overexpression in SONFH cell model. These results provided evidence that APS reduced miR‐206 expression, and the downregulated miR‐206 increased BNIP3 expression by targeting HIF‐1α to promote autophagy and inhibit bone cell apoptosis. Our research proved that APS effectively improved SONFH by regulating cell autophagy and apoptosis.

Although members of the Mycobacterium tuberculosis complex (MTBC) exhibit high similarity, they are characterized by differences with respect to virulence, immune response, and transmissibility. To understand the virulence of these bacteria and identify potential novel therapeutic targets, we systemically investigated the total cell protein contents of virulent H37Rv, attenuated H37Ra, and avirulent M. bovis BCG vaccine strains at the log and stationary phases, based on tandem mass tag (TMT) quantitative proteomics. Data analysis revealed that we obtained deep-coverage protein identification and high quantification. Although 272 genetic variations were reported in H37Ra and H37Rv, they showed very little expression difference in log and stationary phase. Quantitative comparison revealed H37Ra and H37Rv had significantly dysregulation in log phase (227) compared with stationary phase (61). While BCG and H37Rv, and BCG and H37Ra showed notable differences in stationary phase (1171 and 1124) with respect to log phase (381 and 414). In the log phase, similar patterns of protein abundance were observed between H37Ra and BCG, whereas a more similar expression pattern was observed between H37Rv and H37Ra in the stationary phase. Bioinformatic analysis revealed that the upregulated proteins detected for H37Rv and H37Ra in log phase were virulence-related factors. In both log and stationary phases, the dysregulated proteins detected for BCG, which have also been identified as M. tuberculosis response proteins under dormancy conditions. We accordingly describe the proteomic profiles of H37Rv, H37Ra, and BCG, which we believe will potentially provide a better understanding of H37Rv pathogenesis, H37Ra attenuation, and BCG immuno protection.

China, with its growing population and economic development, faces increasing risks to health from climate change, but also opportunities to address these risks and protect health for generations to come. Without a timely and adequate response, climate change will impact lives and livelihoods at an accelerated rate. In 2020, the Lancet Countdown Regional Centre in Asia, led by Tsinghua University, built on the work of the global Lancet Countdown and began its assessment of the health profile of climate change in China with the aim of triggering rapid and health-responsive actions. This 2021 report is the first annual update, presenting 25 indicators within five domains: climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. The report represents the contributions of 88 experts from 25 leading institutions in, and outside of, China. From 2020 to 2021, five new indicators have been added and methods have been improved for many indicators. Where possible, the indicator results are presented at national and provincial levels to facilitate local understanding and policy making. In a year marked by COVID-19, this report also endeavours to reflect on China's pathway for a green recovery, ensuring it aligns with the carbon neutrality goal, for the health of the current and future generations.

The effects of ultrasound combined with glycation (UCG) on the allergenicity and human microbial community of β-Lg during in vitro digestion were studied by ELISA, cell experiments, and 16S rRNA high-throughput sequencing. UCG modification and subsequent digestion significantly reduced allergenicity. The decrease in the allergenicity of β-Lg depended not only on the low digestibility of glycated β-Lg, which led to the decrease of some peptides with complete immunogenicity, but also the masking effect of glycation on allergen epitopes of β-Lg. Meanwhile, UCG modification and subsequent digestion could alter the structures of intestinal microbiota and the community abundance at phylum, family, and genus levels, such as Bacteroidota, Fusobacteriota, Enterobacteriaceae, Bacteroidaceae, Ruminococcaceae, Bacteroides, and Faecalibacterium. These results show that simulated in vitro digestion of modified β-Lg reduces allergenicity and alters human intestinal microbiota, which could provide a theoretical basis for studying the relationship between intestinal dysbiosis and cow's milk allergy.

Identification of high-risk population among hepatitis B virus (HBV)/hepatitis C virus (HCV)-infected individuals with first-degree relatives (FDR) who have liver cancer is important to implement precise intervention. A cross-sectional study was conducted under the framework of a population-based Cancer Screening Program in Urban China (CanSPUC), aimed to develop and validate a simple noninvasive model that could assess and stratify cirrhosis risk, in HBV/HCV-infected individuals with FDRs who have liver cancer. People who participated in liver cancer screening in Henan province were enrolled. Using the data set consisting of participants admitted from October 1, 2013, to December 31, 2016, a 24-point scale risk score model was developed through logistic regression, based on educational background, dietary habit, smoking index, cooking oil fume exposure, history of severe trauma, HBV/HCV infection status, history of diabetes, history of hyperlipidemia, and parent history of liver cancer. The model showed excellent discrimination with area under the receiver operator characteristic curve (AUROC) of 0.875 [95% confidence interval (CI), 0.853–0.896] and fair calibration with a Hosmer–Lemeshow test P = 0.106. The prevalence rates in the medium- and high-risk groups were 2.87 (95% CI, 1.94–4.25) and 47.57 (95% CI, 31.59–71.63) times of low-risk group, respectively. After internal validation, bias-corrected AUROC was 0.874 (95% CI, 0.873–0.875). In the external validation data set consisting of participants admitted from January 1, 2017, to October 31, 2018, the model had achieved similar discrimination, calibration, and risk stratification ability. In conclusion, the risk score model we developed can be a practical tool for the screening and prevention of liver cirrhosis among HBV/HCV-infected individuals with FDRs who have liver cancer. Prevention Relevance: We created a simple and noninvasive cirrhosis risk model for individuals infected by HBV/HCV who have FDRs with liver cancer. This model is useful not only for the prognosis of HBV/HCV infection, but also for the prevention of hepatocellular carcinoma.

This study aimed to introduce a novel loop neurorrhaphy technique using an innervated vascularized iliac bone flap (VIBF) with vascularized ilioinguinal nerve (IIN) to reconstruct the inferior alveolar nerve (IAN) and preserve lower lip sensation simultaneously with mandibular reconstruction.This study prospectively included patients who underwent mandibular reconstruction using VIBF from May 2018 to April 2020. Subjects were allocated into two groups: (1) Group I; innervated VIBF with loop neurorrhaphy (IIN doubly anastomosed with IAN and mental nerve), (2) Group II (control); conventional VIBF. Evaluation was done with operative time, intraoperative indocyanine green (ICG), lower lip sensory assessment (two-point discrimination [TPD] test and current perception threshold [CPT]), and drooling.Twelve patients were included; 6 in each group, (7 males and 5 females), age ranging from 18 to 57 years (average: 36.75 years). In all cases, intraoperative perfusion of IIN was confirmed by ICG. Group I showed a statistically significant more flap harvesting time compared with group II (mean difference, 5.67 min; P = 0.0091). There was a significant difference in sensory recovery favoring group I (P 0.05). The TPD results in group I showed an average of 9.8 ± 6.9 mm and 6.2 ± 5.7 mm on operated and non-operated sides, while Group II showed a poor sensory recovery, and the TPD showed an average of 24.6 ± 6.7 mm and 8.4 ± 2.3 mm on operated and non-operated sides. The CPT results showed a significant difference between both groups. In Group I, the extent of drooling was 3.16 ± 0.75, while in Group II, the score was 1.6 ± 0.81, revealing a significant difference favoring Group I.Concurrent mandibular reconstruction using VIBF and loop neurorrhaphy with vascularized IIN to reconstruct IAN successfully restore lower jaw form and preserve lip sensation.

Recent studies have suggested that exposure to ambient airborne pollutants is associated with inflammatory skin diseases, but the epidemiological evidence regarding the association between air pollution and acne vulgaris is limited. To address that, a hospital-based time-series analysis was conducted in Xi’an, a metropolitan in northwest China. A total of 71,625 outpatient visits for acne from 2010 to 2013 were identified. The mean daily concentrations of PM10, SO2, and NO2 were 142.6 μg/m3, 44.7 μg/m3, and 48.5 μg/m3, and all were higher than WHO air quality guidelines. A generalized additive model was used to analyze the relationship between short-term ambient air pollution exposure and outpatient visits for acne. The gender- and age-specific analyses were conducted as well. The results showed that the increase of SO2 and NO2 concentrations corresponded to a significant rise in the number of outpatient visits for acne at lag 0 in both single-lag and cumulative exposure models. Both SO2 and NO2 were positively associated with acne outpatient visits for both males and females. In age-specific analyses, the effect estimate of PM10 was only significant for adults over 30 years old; SO2 was significantly associated with acne visits in children and adolescents (

Background:. Histidine-tryptophan-ketoglutarate (HTK) is a solution commonly used for organ transplantation. However, there is no certified fixed regimen for on-pump heart surgery in neonates. We aimed to retrospectively evaluate the outcomes related to different HTK dosages and to analyze the safety of high-dosage perfusion. Methods:. A total of 146 neonates who underwent on-pump heart surgery with single-shot HTK perfusion were divided into two groups according to HTK dosages: a standard-dose (SD) group (n = 63, 40 mL/kg 60 mL/kg). Propensity score matching (PSM) was performed to control confounding bias. Results:. The SD group had a higher weight (3.7 ± 0.4 vs. 3.4 ± 0.4 kg, P 0.05). The incidences of post-operative complications were not significantly different between the two groups. There were no significant differences in ventilation time, intensive care unit stay, and post-operative hospital stay (P > 0.05). Follow-up echocardiography outcomes at 1 month, 3 to 6 months, and 1 year showed that left ventricular ejection fraction and end-diastolic dimension were comparable between the two groups. Conclusions:. In neonatal on-pump cardiac surgery patients, single-shot HD (>60 mL/kg) HTK perfusion had a comparable heart protection effect and short-term post-operative prognosis as standard dosage perfusion of 40 to 60 mL/kg. Thus, this study provides supporting evidence of the safety of HD HTK perfusion.

Background In COVID-19 patients, information regarding superinfection, antimicrobial assessment, and the value of metagenomic sequencing (MS) could help develop antimicrobial stewardship. Method This retrospective study analyzed 323 laboratory-confirmed COVID-19 patients for co-infection rate and antimicrobial usage in the Shanghai Public Health Clinical Center (SPHCC) from January 23rd to March 14th 2020. The microbiota composition was also investigated in patients with critically severe COVID-19. Results The total population co-infection rate was 17/323 (5.3%) and 0/229 (0), 4/78 (5.1%), and 13/16 (81.3%) for the mild, severe, and critically severe subgroups, respectively. Proven fungal infection was significantly associated with a higher mortality rate (p = 0.029). In critically severe patients, the rate of antimicrobials and carbapenem usage were 16/16 (100%) and 13/16 (81.3%), respectively, in which the preemptive and empiric antimicrobial days accounted for 51.6% and 30.1%, respectively. Targeted therapy only accounted for 18.3%. MS was implemented to detect non-COVID-19 virus co-existence and the semi-quantitative surveillance of bacteremia, with clear clinical benefit seen in cases with MS-based precision antimicrobial management. Airway microbiome analysis suggested that the microbiota compositions in critically severe COVID-19 patients were likely due to intubation and mechanical ventilation. Conclusions In the SPHCC cohort, we observed a non-negligible rate of super-infection, especially for the critically ill COVID-19 patients. Fungal co-infection requires intensive attention due to the high risk of mortality, and the clinical benefit of MS in guiding antimicrobial management warrants further investigation.

Proliferative diabetic retinopathy (PDR) is a world-wide leading cause of blindness among adults and may be associated with the influence of genetic factors. It is significant to search for genetic biomarkers of PDR. In our study, we collected genomic data about PDR from gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were carried out. The gene module with the highest gene significance (GS) was defined as the key module. Hub genes were identified by Venn diagram. Then we verified the expression of hub genes in validation data sets and built a diagnostic model by least absolute shrinkage and selection operator (LASSO) regression. Enrichment analysis, including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and construction of a protein-protein interaction (PPI) network were conducted. In GSE60436, we identified 466 DEGs. WGCNA established 14 gene modules, and the blue module (GS = 0.64), was the key module. Interferon (IFN)-induced protein 44-like (IFI44L) and complement C1q tumor necrosis factor-related protein 5 (C1QTNF5) were identified as hub genes. The expression of hub genes in GEO datasets was verified and a diagnostic model was constructed by LASSO as follows: index = IFI44L * 0.0432 + C1QTNF5 * 0.11246. IFI44L and C1QTNF5 might affect the disease progression of PDR by regulating metabolism-related and inflammatory pathways. IFI44L and C1QTNF5 may play important roles in the disease process of PDR, and a LASSO regression model suggested that the 2 genes could serve as promising biomarkers of PDR.

Avian pathogenic

Background RNA N6-methyladenosine (m6A) is involved in mammalian spermatogenesis. In both germ cells and Leydig cells, ALKBH5 regulates spermatogenesis and androgen synthesis in an m6A-dependent manner. However, it is unclear whether ALKBH5 plays a role in testicular Sertoli cells, which constitute the blood–testis barrier (BTB) through cell junctions between adjacent Sertoli cells. Methods ALKBH5 expression in the testes of humans and mice was detected by immunohistochemical staining and immunofluorescence staining. BTB integrity was evaluated by BTB assay. m6A-seq was performed to screen for BTB-related molecules regulated by ALKBH5. m6A immunoprecipitation–quantitative real-time polymerase chain reaction (qPCR), RNA immunoprecipitation–qPCR, western blot, coimmunoprecipitation, and polysome fractionation–qPCR analyses were performed to explore the mechanisms of ALKBH5 in BTB. Transmission electron microscopy was applied to observe the BTB ultrastructure. Results ALKBH5 in Sertoli cells is related to the integrity of the BTB. Subsequently, the m6A level on Cdh2 mRNA, encoding a structural protein N-cadherin in the BTB, was found to be regulated by ALKBH5. IGF2BP1/2/3 complexes and YTHDF1 promoted Cdh2 mRNA translation. In addition, we found that basal endoplasmic specialization, in which N-cadherin is a main structural protein, was severely disordered in the testes of Alkbh5-knockout mice. Conclusions Our study revealed that ALKBH5 regulates BTB integrity via basal endoplasmic specialization by affecting Cdh2 mRNA translation.

PurposeNeoadjuvant chemoradiotherapy (nCRT) is a standard treatment option for patients with stage III oesophageal cancer. Approximately 30% of oesophageal cancer patients will have a pathological complete response (pCR) after nCRT. However, available clinical methods cannot accurately predict pCR for patients. We aimed to find more indicators that could be used to predict the pathological response to nCRT.MethodA total of 84 patients with stage III oesophageal squamous cell cancer were enrolled in this study. Ten patients failed to have surgery as a result of progressive disease (PD). Among the patients who underwent surgery, 32 patients had a pathologic complete response (pCR), whereas 42 patients showed no or partial response (npCR) after nCRT. Routine blood test results and lymphocyte subset assessments before and after nCRT were retrospectively analysed. Univariate and multivariate analyses were used to identify independent predictors of the clinical curative effect of nCRT. Eventually, nomograms were established for predicting the PD and pCR rates.ResultsThe numbers of lymphocytes, B lymphocytes, T lymphocytes, Th lymphocytes, Ts lymphocytes, and NK cells and the percentages of B lymphocytes and NK cells were decreased significantly after nCRT (P < 0.0001), whereas the percentages of T lymphocytes and Ts lymphocytes increased (P < 0.0001). Univariate analysis showed that age, the length of the lesion, the level of haemoglobin before nCRT, and the amount of change in haemoglobin were related to PD, and the percentage of NK cells after nCRT was related to pCR. Multivariate logistic analysis demonstrated that the length of the lesion, the neutrophil-to-lymphocyte ratio (NLR) before nCRT, and the amount of change in haemoglobin were independent predictors of PD, whereas the percentage of NK cells after nCRT was an independent predictor of pCR.ConclusionLymphocyte subsets changed dramatically during nCRT, and these changes together with baseline and posttreatment lymphocyte subsets have predictive value in determining the response to nCRT for oesophageal cancer.

Vaccinia virus (VACV) encodes scores of proteins that suppress host innate immunity and many of these target intracellular signalling pathways leading to activation of inflammation. The transcription factor NF-κB plays a critical role in the host response to infection and is targeted by many viruses, including VACV that encodes 12 NF-κB inhibitors that interfere at different stages in this signalling pathway. Here we report that VACV proteins C2 and F3 are additional inhibitors of this pathway. C2 and F3 are BTB-Kelch proteins that are expressed early during infection, are non-essential for virus replication, but affect the outcome of infection in vivo. Using reporter gene assays, RT-qPCR analyses of endogenous gene expression, and ELISA, these BTB-Kelch proteins are shown here to diminish NF-κB activation by reducing translocation of p65 into the nucleus. C2 and F3 are the 13th and 14th NF-κB inhibitors encoded by VACV. Remarkably, in every case tested, these individual proteins affect virulence in vivo and therefore have non-redundant functions. Lastly, immunisation with a VACV strain lacking C2 induced a stronger CD8+ T cell response and better protection against virus challenge.

Objective: To explore the effect of problematic mobile phone use on college students’ physical activity and their relationships. Methods: A cross-sectional study was conducted among 3980 college students from three universities in Jiangsu province by random cluster sampling. The International Physical Activity Questionnaire Short (IPAQ-SF) measured college students’ physical activity. The Mobile Phone Addiction Tendency Scale for College Students (MPATS) measured problematic mobile phone use tendencies. College students’ physical activity was measured by the International Physical Activity Questionnaire Short (IPAQ-SF), and the Mobile Phone Addiction Tendency Scale measured their mobile phone addiction tendency for College Students (MPATS). Results: (1) The proportions of the low-, medium-, and high-intensity physical activity were 83.5%, 10.7%, and 5.8%, respectively, with gender differences; The score of problematic mobile phone use tendency was 38.725 ± 15.139. (2) There were significant differences in problematic mobile phone use tendency among college students with different physical activity intensity (F = 11.839, p < 0.001, η2 = 0.007). (3) The level of physical activity was significantly correlated with the tendency of problematic mobile phone use (r = −0.173, p < 0.001). (4) Physical activity of college students could significantly predict the tendency of problematic mobile phone use (F (3,3605) = 11.296, p < 0.001). Conclusions: The physical activity of college students was mainly moderate to low intensity, while the tendency of problematic mobile phone use was high. College students’ physical activity level was one of the important constraints of problematic mobile phone use tendency.

Background Geothermal systems have contributed greatly to both our understanding of the functions of extreme life and the evolutionary history of life itself. Shallow-sea hydrothermal systems are ecological intermediates of deep-sea systems and terrestrial springs, harboring unique and complexed ecosystems, which are well-lit and present physicochemical gradients. The microbial communities of deep-sea and terrestrial geothermal systems have been well-studied at the population genome level, yet little is known about the communities inhabiting the shallow-sea hydrothermal systems and how they compare to those inhabiting other geothermal systems. Results Here, we used genome-resolved metagenomic and metaproteomic approaches to probe into the genetic potential and protein expression of microorganisms from the shallow-sea vent fluids off Kueishantao Island. The families Nautiliaceae and Campylobacteraceae within the Epsilonbacteraeota and the Thiomicrospiraceae within the Gammaproteobacteria were prevalent in vent fluids over a 3-year sampling period. We successfully reconstructed the in situ metabolic modules of the predominant populations within the Epsilonbacteraeota and Gammaproteobacteria by mapping the metaproteomic data back to metagenome-assembled genomes. Those active bacteria could use the reductive tricarboxylic acid cycle or Calvin-Benson-Bassham cycle for autotrophic carbon fixation, with the ability to use reduced sulfur species, hydrogen or formate as electron donors, and oxygen as a terminal electron acceptor via cytochrome bd oxidase or cytochrome bb3 oxidase. Comparative metagenomic and genomic analyses revealed dramatic differences between submarine and terrestrial geothermal systems, including microbial functional potentials for carbon fixation and energy conversion. Furthermore, shallow-sea hydrothermal systems shared many of the major microbial genera that were first isolated from deep-sea and terrestrial geothermal systems, while deep-sea and terrestrial geothermal systems shared few genera. Conclusions The metabolic machinery of the active populations within Epsilonbacteraeota and Gammaproteobacteria at shallow-sea vents can mirror those living at deep-sea vents. With respect to specific taxa and metabolic potentials, the microbial realm in the shallow-sea hydrothermal system presented ecological linkage to both deep-sea and terrestrial geothermal systems.

The latest research confirms that cytotoxic lymphocytes rely on pyroptosis to kill tumor cells, suggesting that pyroptosis plays a vital role in immune response. However, the influence of pyroptosis on tumor microenvironment (TME) remodeling and immunotherapy is still unclear. We analyzed the variations in the expression of 28 pyroptosis-related molecules in pan-cancer tissues and normal tissues and the influence of genome changes. We investigated 2,214 bladder cancer samples and determined that there are three pyroptosis phenotypes in bladder cancer, and there are significant differences in cell infiltration characteristics in different pyroptosis phenotypes. Phenotypes with high expression of pyroptosis-related molecules are "hot tumors" with better immune function. We used a principal component analysis to measure the level of pyroptosis in patients with PyroScore, and confirmed that the PyroScore can predict the prognosis of bladder cancer patients, the sensitivity of the immune phenotype to chemotherapy, and the response to immunotherapy. Patients with a high PyroScore are more sensitive to chemotherapeutics such as cisplatin and gemcitabine, and have a better prognosis (HR = 0.7; 95%CI = 0.51-0.97, P = 0.041). Our study suggests a significant correlation between the expression imbalance of pyroptosis-related molecules and genome variation in various cancers and suggests pyroptosis plays an important role in modeling the TME. Evaluating pyroptosis modification patterns contributes to enhancing our understanding of TME infiltration and can guide more effective immunotherapy strategies.

Background Recurrent hepatocellular carcinoma (HCC) shows strong resistance to sorafenib, and the tumor-repopulating cells (TRCs) with cancer stem cell-like properties are considered a driver for its high recurrent rate and drug resistance. Methods Suppression of TRCs may thus be an effective therapeutic strategy for treating this fatal disease. We evaluated the pharmacology and mechanism of sulfarotene, a new type of synthetic retinoid, on the cancer stem cell-like properties of HCC TRCs, and assessed its preclinical efficacy in models of HCC patient-derived xenografts (PDXs). Results Sulfarotene selectively inhibited the growth of HCC TRCs in vitro and significantly deterred TRC-mediated tumor formation and lung metastasis in vivo without apparent toxicity, with an IC50 superior to that of acyclic retinoid and sorafenib, to which the recurrent HCC exhibits significant resistance at advanced stage. Sulfarotene promoted the expression and activation of RARα, which down-regulated SOS2, a key signal mediator associated with RAS activation and signal transduction involved in multiple downstream pathways. Moreover, sulfarotene selectively inhibited tumorigenesis of HCC PDXs with high expression for SOS2. Conclusions Our study identified sulfarotene as a selective inhibitor for the TRCs of HCC, which targets a novel RARα-SOS2-RAS signal nexus, shedding light on a new, promising strategy of target therapy for advanced liver cancer.

Non‐small‐cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases. TBC1D23, a member of the TBC/RABGAP family, is widely expressed in human tissues; however, its role in NSCLC is currently unknown. Immunohistochemical analysis was conducted on 173 paraffin‐embedded lung tissue sections from patients with NSCLC from 2014 to 2018 at the First Affiliated Hospital of China Medical University. MTT, colony formation assay, cell cycle assay, scratch assay, transwell assay, Western blotting and real‐time PCR were employed on multiple NSCLC cell lines modified to knock down or overexpress TBC1D23/RAB11A. Immunoprecipitation, immunoprecipitation‐mass spectrometry, immunofluorescence and flow cytometry were performed to explore the interaction between TBC1D23 and RAB11A and TBC1D23 involvement in the interaction between RAB11A and β1 integrin in the para‐nucleus. TBC1D23 was correlated with tumour size, differentiation degree, metastasis, TNM stage and poor prognosis. TBC1D23 was involved in the interaction between RAB11A and β1 integrin in the para‐nucleus, thus activating the β1 integrin/FAK/ERK signalling pathway to promote NSCLC. Furthermore, TBC1D23 promoted NSCLC progression by inducing cell proliferation, migration and invasion. This study indicated the relationship between TBC1D23 expression and the adverse clinicopathological characteristics of patients with NSCLC, suggesting that TBC1D23 may be an important target for NSCLC treatment.

Background The causes of gestational diabetes mellitus (GDM) are still unclear. Recent studies have found that the imbalance of the gut microbiome could lead to disorders of human metabolism and immune system, resulting in GDM. This study aims to reveal the different gut compositions between GDM and normoglycemic pregnant women and find the relationship between gut microbiota and GDM. Methods Fecal microbiota profiles from women with GDM (n = 21) and normoglycemic women (n = 32) were assessed by 16S rRNA gene sequencing. Fasting metabolic hormone concentrations were measured using multiplex ELISA. Results Metabolic hormone levels, microbiome profiles, and inferred functional characteristics differed between women with GDM and healthy women. Additionally, four phyla and seven genera levels have different correlations with plasma glucose and insulin levels. Corynebacteriales (order), Nocardiaceae (family), Desulfovibrionaceae (family), Rhodococcus (genus), and Bacteroidetes (phylum) may be the taxonomic biomarkers of GDM. Microbial gene functions related to amino sugar and nucleotide sugar metabolism were found to be enriched in patients with GDM. Conclusion Our study indicated that dysbiosis of the gut microbiome exists in patients with GDM in the second trimester of pregnancy, and gut microbiota might be a potential diagnostic biomarker for the diagnosis, prevention, and treatment of GDM.

The survival rate of cancer has increased significantly during the past two decades for breast, prostate, testicular, and colon cancer, while the brain and pancreatic cancers have a much lower median survival rate that has not improved much over the last forty years. This has imposed the challenge of finding gene markers for early cancer detection and treatment strategies. Different methods including regression-based Cox-PH, artificial neural networks, and recently deep learning algorithms have been proposed to predict the survival rate for cancers. We established in this work a novel graph convolution neural network (GCNN) approach called Surv_GCNN to predict the survival rate for 13 different cancer types using the TCGA dataset. For each cancer type, 6 Surv_GCNN models with graphs generated by correlation analysis, GeneMania database, and correlation + GeneMania were trained with and without clinical data to predict the risk score (RS). The performance of the 6 Surv_GCNN models was compared with two other existing models, Cox-PH and Cox-nnet. The results showed that Cox-PH has the worst performance among 8 tested models across the 13 cancer types while Surv_GCNN models with clinical data reported the best overall performance, outperforming other competing models in 7 out of 13 cancer types including BLCA, BRCA, COAD, LUSC, SARC, STAD, and UCEC. A novel network-based interpretation of Surv_GCNN was also proposed to identify potential gene markers for breast cancer. The signatures learned by the nodes in the hidden layer of Surv_GCNN were identified and were linked to potential gene markers by network modularization. The identified gene markers for breast cancer have been compared to a total of 213 gene markers from three widely cited lists for breast cancer survival analysis. About 57% of gene markers obtained by Surv_GCNN with correlation + GeneMania graph either overlap or directly interact with the 213 genes, confirming the effectiveness of the identified markers by Surv_GCNN.

Background This study explored the relevance between rs1695 and susceptibility to the lung cancer in the Chinese Han population. Stratification analysis was conducted on the basis of age, gender, smoking status, tumor-related family history, and pathological type to observe relations between rs1695 and susceptibility to lung cancer in the subgroups. Methods A case-control study was performed with 974 lung cancer patients who were pathologically diagnosed and 1005 healthy cases based on physical examination to analyze the association between rs1695 and the risk of lung cancer. Results The frequencies of the AA, GA, and GG genotypes of rs1695 were 68.4%, 28.7%, and 2.9% in cases and 64.8%, 30.8%, and 4.2% in controls, respectively. After adjustment for age, gender, smoking status, and family history, it appears that the rs1695 G allele decreases the risk of lung cancer (OR = 0.811, 95% CI 0.684–0.961, P = 0.016). Moreover, compared with the AA genotype, the GA + GG genotype decreased lung cancer susceptibility (OR = 0.808, 95% CI 0.663–0.985, P = 0.035) and the GG genotype (OR = 0.591, 95% CI 0.347–0.988, P = 0.048). In a stratified analysis, the risk of lung cancer in the G allele carriers decreased among the males, patients without a tumor-related family history, and patients with lung adenocarcinoma, especially in smokers. Conclusion The polymorphism of locus rs1695 is related to the risk of lung cancer and is expected to be a target for the prediction of lung cancer.

Aim This study investigated the cost-effectiveness of a community-based colorectal cancer-screening program (C-CRCSP) in Shanghai, China, with a comparison of urban, suburban, and rural areas. Methods A Markov model was constructed to evaluate the cost-effectiveness of a 25-year-long annual C-CRCSP with 100,000 samples. Cost-effectiveness was determined by the incremental cost-effectiveness ratio (ICER) referring to either life-years gained, or quality-adjusted life-years (QALYs) gained. The threshold was gross domestic product per capita. Univariate and multivariate sensitivity analyses were performed to investigate the influence of compliance, prevalence, technological performance, price, and an annual cost discount rate (3.5%) on ICERs. A probabilistic sensitivity analysis evaluated the probability of cost-effectiveness of C-CRCSP at different maximum acceptable ceiling ratios. Results Compared with no screening, the C-CRCSP could result in total gains of 7840 QALYs and 2210 life-years, at a total cost of CNY 58.54 million; that is, the ICERs were CNY 7460/QALY and CNY 26,650/life-year. Stratifying by residency, the highest cumulative gains in QALYs and life-years were estimated for the rural population, followed by the suburban and urban. The cost for the urban population was 3- and 6-fold that of the suburban and rural populations. The ICERS for QALYs ranged from 2180 (rural) to 16,840 (urban). Conclusion The cost-effectiveness of a C-CRCSP in Shanghai was most favorable for the rural population, while the urban population would realize lesser benefit in terms of QALYs. ICERs could be enhanced by measures that increase compliance. This article is protected by copyright. All rights reserved.