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Drug resistance in chemotherapy has been greatly challenging for cancer treatment. Research has revealed that extracellular vesicles (EVs) secreted by drug-resistant cells could induce chemoresistance in susceptible cells. However, there are few ways to give direct evidence of it. Herein, we have proposed a microchip-based system to study the drug resistance of a wild-type human lung adenocarcinoma cell line (A549/WT) induced by EVs derived from A549/DDP cells that are resistant to cisplatin (DDP) inherently. EVs derived from A549/DDP were proved to be the crucial factor that enhanced the resistance of A549/WT to DDP through live and dead cell staining, cell viability testing, and immunofluorescence of P-glycoprotein in the off-chip assay. Then, it was further validated that drug resistance of A549/WT cells to DDP significantly increased after being cocultured with A549/DDP cells within 96 h in the on-chip assay. These findings proved that the change of A549/WT drug resistance was caused by intercellular interaction, which was mainly mediated by EVs. In addition, we successfully reversed the EV-induced drug resistance of A549/WT cells by combining DDP and metformin, a hypoglycemic drug with low cytotoxicity when used alone. This microchip system provides a novel tool that has great potential for the investigation of cell interaction, drug resistance, and the tumor microenvironment in fundamental and clinical medicine.

BACKGROUND: Ultrasound-guided needle placement has revolutionized the thoracic paravertebral block technique and can be applied in thoracoscopic surgery. OBJECTIVE: This study investigated the median effective volume (EV50) of an ultrasound-guided single shot of 0.3% ropivacaine used as a thoracic paravertebral nerve block for the radical thoracoscopic resection of lung cancer. METHODS: A total of 27 patients who received a single shot of ultrasound-guided thoracic paravertebral nerve block and underwent radical thoracoscopic resection of lung cancer were enrolled in this study between February 10 and August 13, 2018. All patients were rated as ASA grades I or II. Using ultrasound as a guide, the block needle was gradually pushed through the lateral costotransverse ligaments to the thoracic paravertebral space by the in-plane technique. After confirming the absence of blood or cerebrospinal fluid, 1–2 ml of 0.3% ropivacaine hydrochloride was injected to confirm that the position of the needle was appropriate, and a pre-determined volume of 0.3% ropivacaine hydrochloride was then administered to the patients. Sensory testing by pinprick was performed every 5 minutes for 30 minutes following the thoracic paravertebral block injection to identify the time segments during which the loss of sensation to the pinprick and its blocking effect occurred. RESULTS: All patients completed the study and 14 (51.8%) had a successful block. CONCLUSION: The EV50 of 0.3% ropivacaine was 18.46 ml (95% CI 17.09–19.95 ml) and the EV95 was 20.89 ml.

Tuberculosis recurrence after an initial successful treatment episode can occur from either reinfection or relapse. In a population-based sample and whole genome sequencing in eastern China, we aimed to evaluate risk factors for tuberculosis recurrence and assess the proportion of recurrence because of either reinfection or relapse.Successfully treated pulmonary tuberculosis patients with sputum culture positive results were recruited from five cities in Jiangsu Province from 2013 to 2015 and followed for 2 years for tuberculosis recurrence. Among patients developing a second tuberculosis episode, whole genome sequencing was performed to distinguish relapse or reinfection through a distance threshold of 6-single-nucleotide polymorphisms. We analyzed risk factors for recurrence and epidemiological characteristics of different types of recurrent patients.Of 1897 successfully treated tuberculosis patients, 7.4% (141/1879) developed recurrent tuberculosis. Compared with nonrecurrent tuberculosis, patients were at higher risk of recurrence in older age (adjusted odds ratio, 1.02 for each additional year; 95% CI, 1.01 to 1.03, p = 0.003), patients previously treated for tuberculosis (adjusted odds ratio = 2.22; 95% CI, 1.52 to 3.26, p 0.001), or with bilateral cavities (adjusted odds ratio, 1.56; 95% CI, 1.05 to 2.32, p = 0.029). Among 27.0% (38/141) recurrent tuberculosis patients with successfully sequenced pairs, relapse was substantially more common than reinfection (71.1% vs 28.9%, p = 0.014).Endogenous relapse was significantly more common than exogenous reinfection in the first 2 years after treatment in eastern China. Prioritization of high-risk groups for recurrence, such as the elderly, with a previous tuberculosis diagnosis, or with bilateral cavities, may provide opportunities to reduce post-tuberculosis morbidity.

Background: Uneven body-surface thermal distribution is a manifestation of hypoperfusion and can be quantified by infrared thermography. Our aim was to investigate whether body-surface thermal inhomogeneity could accurately evaluate the severity of patients at risk of hypoperfusion. Methods: This was a prospective cohort study in which infrared thermography images were taken from unilateral legs of critically ill patients at high risk of hypoperfusion in a cardiac surgical intensive care unit. For each patient, five body-surface thermal inhomogeneity parameters, including standard deviation (SD), kurtosis, skewness, entropy, and low-temperature area rate (LTAR), were calculated. Demographic, clinical, and thermal characteristics of deceased and living patients were compared. The risk of mortality and capillary refill time (CRT) were chosen as the primary outcome and benchmarking parameter for hypoperfusion, respectively. The area under the receiver operating characteristic curve (AUROC) was used to evaluate predictive accuracy. Results: Three hundred seventy-three patients were included, and 55 (14.7%) died during hospital stay. Of inhomogeneity parameters, SD (0.738) and LTAR (0.768) had similar AUROC to CRT (0.757) for assessing mortality risk. Besides, there was a tendency for LTAR (1%-3%-7%) and SD (0.81°C-0.88°C-0.94°C) to increase in normotensive, hypotensive, and shock patients. These thermal parameters are associated with CRT, lactate, and blood pressure. The AUROC of a combined prediction incorporating three thermal inhomogeneity parameters (SD, kurtosis, and entropy) was considerably higher at 0.866. Conclusions: Body-surface thermal inhomogeneity provided a noninvasive and accurate assessment of the severity of critically ill patients at high risk of hypoperfusion.

Azathioprine (AZA) is commonly used for many autoimmune disorders; however, the limitation of its clinical use is due to potential toxicities, including severe leukopenia. Recent studies have identified genetic NUDT15 variants strongly associated with AZA-induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the NUDT15 variants to prevent AZA-induced leukopenia in Chinese patients. AZA-induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan/China between 2012 and 2017 to determine the strength of genetic association of NUDT15 or TPMT variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA-induced leukopenia with and without genetic screening. The WES result showed the genetic variants of NUDT15 R139C (rs116855232) (P = 3.7 × 10

Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM).In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/mm 2 .Abnormal CNFL was found in 30.6% (63/206) of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P 0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595-0.866, P = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (all P for trend0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic patients.There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.

To investigate the independent risk factors of poor short-term outcomes in patients with lung cancer-associated acute ischemic stroke (LCAIS) and use them to develop an index of prognosis LCAIS (pLCAIS) which could help clinicians identify patients at high risk for poor short-term outcomes.We retrospectively enrolled patients with lung cancer-associated acute ischemic stroke and employed the 90D modified Rankin cale (mRS) to divide them into two groups: good outcomes (score 0-2) and poor outcomes (score 3-6). Propensity score matching (PSM) was used to remove confounding factors, and multivariable logistic regression analysis was used to analyze the independent risk factors of pLCAIS. The receiver operating characteristic (ROC) and area under the ROC curve (AUC) developed a multiple model combining the independent risk factors of pLCAIS.A total of 172 patients were included: 67 (38.9%) with good outcomes and 105 (61.1%) with poor outcomes. After using PSM, there were 33 cases in each group. The results showed that patients with poor short-term outcomes were significantly higher in D-dimer (OR = 1.001, 95% CI: 1.000-1.002, p = 0.048), CRP (OR = 1.078, 95% CI: 1.008-1.153, p = 0.028), and neutrophil count (OR = 14.673, 95% CI: 1.802-19.500, p = 0.012). The ROC curve, used to assess the diagnostic ability of binary classifiers, showed that the product of these three independent risk factors showed high sensitivity and specificity.In this study, we have identified three independent risk factors associated with poor short-term outcomes in pLCAIS: higher NC, CRP, and D-dimer levels. These findings may be helpful for clinicians in identifying poor short-term outcomes patients.

This meta-analysis aimed to assess the position of near-infrared autofluorescence (NIRAF) imaging in the recognition and protection of the parathyroid gland (PG) during thyroidectomy.The PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Library databases were searched up to June 2021. The primary outcome was to evaluate the rates of postoperative hypocalcemia, inadvertent PG resection, and autotransplantation of PG when adopting NIRAF imaging compared with standard naked-eye (N-E) surgery.Eight studies with 2,889 patients were enrolled in the analysis. Our analysis showed that the incidence of transient hypocalcemia was 7.11% (60/844) in the NIRAF group and 22.40% (458/2045) in the N-E group (The application of NIRAF imaging in thyroidectomy can help lower the incidence of inadvertent PG resection and reduce the risk of postoperative hypocalcemia and hypoparathyroidism compared with N-E recognition.

This review aimed to systematically evaluate the effect of transcranial direct current stimulation (tDCS) on poststroke dysphagia.PubMed, Cochrane Library (CENTRAL), Web of Science, VIP, CNKI, and Wanfang databases were systematically searched up to June 2021.Randomized controlled trials (RCTs) on the effects of tDCS on poststroke dysphagia.The extracted data included the author, country of publication, time of publication, key elements of bias risk assessment (such as RCTs and blind methods), sample size and basic information (age, course of disease, stroke location), intervention measures, treatment methods of tDCS (stimulation location, intensity, duration), relevant outcome indicators, and relevant data (SDs).The Cochrane Risk of Bias Assessment Tool and Physiotherapy Evidence Database Scale were used to assess the risk of bias.Sixteen RCTs were included in this meta-analysis. Overall, the results revealed a large and statistically significant pooled effect size (0.80; confidence interval [CI], 0.45-1.14; P.001). The subgroup that explored the course of the disease yielded a large and significant effect size for the chronic phase group (0.80; CI, 0.43-1.16; P.001). For the stimulation intensity, 1 mA and 1.6 mA showed a moderate and significant effect sizes (0.47; CI, 0.13-0.81; P=.006 vs 1.39; CI, 0.69-2.08; P.001). In the subgroup analyses, the affected (0.87; CI, 0.26-1.48; P=.005) vs unaffected (0.61; CI, 0.23-0.99; P=.002) hemisphere showed a significant result, and stimulation of the affected hemisphere had a more obvious effect. Subgroup analysis of stroke location showed that tDCS was effective for dysphagia after unilateral hemispheric stroke, bulbar paralysis, and brainstem stroke but not for dysphagia after ataxic and basal ganglia stroke. However, the subgroup analysis of stroke location revealed a significant result (0.81; CI, 0.44-1.18; P.001).This meta-analysis demonstrated the height and significant beneficial effect of tDCS on improving poststroke dysphagia.

To evaluate the safety and efficacy of covered stents for treatment of visceral artery aneurysms (VAA).This multicenter retrospective study included patients with VAAs who were treated with covered stents between January 2015 and December 2020. A total of 65 patients (mean age, 58 years; range, 27-89 years) with 70 VAAs (60 true aneurysms [86%], 10 pseudoaneurysms [14%]) were included. Of the 65, 48 patients (74%) were asymptomatic. Patient demographics, endovascular treatments, and follow-up results were analyzed.All patients received covered stents. The mean diameter was 2.9 cm (range, 1.0-7.6 cm) for symptomatic aneurysms and 2.5 cm (range, 1.0-9.0 cm) for asymptomatic aneurysms. Of the asymptomatic aneurysms, 89% had a saccular shape. The mean distance between the ostium of the artery in which the aneurysm occurred and the aneurysm was 3.9 cm (median, 3.0 cm; range, 0.5-10 cm). Additional coil embolization was used in 7 aneurysms (10%). During the procedure, 68 (97%) aneurysms were completely excluded, while 2 (3%) had a Type Ib endoleak. After a mean follow-up of 20 months (range, 1-75 months), all patients were asymptomatic. Four endoleaks were recorded and left for close observation. Four stents (7%) had mild restenosis, while the rest of the stents were patent.Placement of covered stents in patients with VAAs excluded aneurysms and maintained artery patency.

Gastric cancer (GC) is among the most common malignant tumors. Numerous studies have reported that microRNAs (miRNAs) play significant roles in carcinogenesis and treatment. An miRNA, miR-520-3p, has been identified as a cancer-suppressing gene in several cancers. However, the role and underlying mechanism of miR-520-3p regulation of GC remain unknown. In this study, the expression levels of miR-520-3p in cancer tissues of patients with GC - and in adjacent normal tissues, gastric cancer cell lines, and human normal gastric epithelial cells - were detected by qRT-PCR. RNA interference was performed in GC cell lines. After the corresponding treatment, the cells were characterized in vitro or in vivo to evaluate their molecular function. CCK-8, cell colony formation, and a Transwell assay were used to detect cell proliferation rate, viability, and invasion ability. A dual-luciferase reporter gene experiment was used to explore the potential molecular mechanisms of miR-520-3p. The results showed that the expression of miR-520-3p was significantly downregulated in GC tissues and cells, and upregulation of miR-520-3p could inhibit the proliferation, vitality, and invasion of GC cells both in vivo and in vitro. The expression of Kruppel-like factor 7 (KLF7) was greatly upregulated in GC tissues. MiR-520-3p can adsorb KLF7 in GC cells, and KLF7 can reverse the inhibitory effect of miR-520-3p overexpression on the proliferation of GC cells. This study revealed that miR-520-3p plays a significant role in inhibiting the proliferation, invasion, and migration of GC cells by targeting KLF7. These data demonstrate that miR-520-3p may serve as a novel prognostic biomarker and a potential therapeutic target for GC.

Neural precursor cell (NPC) dysfunction has been consistently implicated in autism. Induced pluripotent stem cell (iPSC)-derived NPCs from two autism groups (three idiopathic [I-ASD] and two 16p11.2 deletion [16pDel]) were used to investigate if proliferation is commonly disrupted. All five individuals display defects, with all three macrocephalic individuals (two 16pDel, one I-ASD) exhibiting hyperproliferation and the other two I-ASD subjects displaying hypoproliferation. NPCs were challenged with bFGF, and all hyperproliferative NPCs displayed blunted responses, while responses were increased in hypoproliferative cells. mRNA expression studies suggest that different pathways can result in similar proliferation phenotypes. Since 16pDel deletes MAPK3, P-ERK was measured. P-ERK is decreased in hyperproliferative but increased in hypoproliferative NPCs. While these P-ERK changes are not responsible for the phenotypes, P-ERK and bFGF response are inversely correlated with the defects. Finally, we analyzed iPSCs and discovered that 16pDel displays hyperproliferation, while idiopathic iPSCs were normal. These data suggest that NPC proliferation defects are common in ASD.

CD2 is a costimulatory protein expressed in all mature T/NK-cells, in particular memory T-cells. CD58 (or LFA-3) is the receptor for CD2 and is ubiquitously expressed. CD2-CD58 interaction has key functions in T-cell activation and organization of the immunological synapse between T- and antigen-presenting cells. Cancer cells have developed multiple mechanisms to evade immune surveillance. Loss of CD58 expression is one frequently reported in diffuse large B-cell lymphomas (DLBCL). On the other hand, in non-hematological neoplasms, tumor infiltrating lymphocytes (TILs) with reduced expression of CD2 have been associated with defective cytotoxicity and T-cell exhaustion. Here, we reported a case of DLBCL involving the jejunal mucosa associated with a rim of cytotoxic reactive T-cells with features of immune evasion (CD2- and TCR-) and T-cell exhaustion (PD1 + high). This case likely exemplifies a previously unrecognized immune evasion mechanism in lymphoma involving a decreased CD2 expression in the lymphoma-associated T-cells.

Osteoarthritis (OA) is a severe disabling condition that causes major health problems. The roles of long non-coding RNAs (lncRNAs) in regulating OA progression have been increasingly researched. Based on previously published microarray analysis, LINC00707 is upregulated in OA. This research was done to uncover the function of LINC00707 in IL-1β-induced chondrocyte injury and its possible mechanisms.LINC00707, miR-330-5p, and follicle-stimulating hormone receptor (FSHR) expression in OA cartilage tissues were assessed by RT-qPCR. Primary chondrocytes were isolated from OA tissues and treated with IL-1β to establish anLINC00707 and FSHR were elevated, and miR-330-5p was reduced in cartilage tissues of OA patients and in IL-1β-treated primary chondrocytes. Silencing LINC00707 hampered chondrocytes apoptosis, senescence, ECM degradation, and inflammation. LINC00707 acted as a ceRNA to regulate FSHR through controlling miR-330-5p availability. Additionally, both miR-330-5p depletion and FSHR overexpression diminished the effects of silencing LINC00707 in OA progression.Silencing LINC00707 mitigates chondrocyte injury in osteoarthritis

The aim of this study was to evaluate the correlation between tibial tuberosity-trochlear groove distance (TT-TG) and body height or knee size, and to find height-related pathologic thresholds of increased TT-TG.One-hundred and fifty-three patients with recurrent patellar instability and 151 controls were included. The TT-TG was measured on axial computed tomography (CT) images. Femora width and tibial width were selected to represent knee size. The correlation of TT-TG and gender, body height, femora width, and tibial width was evaluated. The height-related pathologic threshold of increased TT-TG was produced according to Dejour's method. To combine TT-TG with body height and knee size, three new indexes were introduced, ratio of TT-TG to body height (RTH), ratio of TT-TG to femoral width (RTF), and ratio of TT-TG to tibial width (RTT). The ability to predict patellar instability was assessed by the receiver-operating characteristic (ROC) curve, odds ratios (ORs), sensitivity, and specificity.In patients with patellar instability, TT-TG showed significantly correlation with patient height, femoral width, and tibial width respectively (range r = 0.266-0.283). This correlation was not found in the control group. The pathologic threshold of TT-TG was 18 mm in patients 169 cm (53%), and the mean TT-TG was 21 mm in patients ≥ 169 cm (54%). There was significant difference in RTH, RTF, and RTT between the two groups. RTH, RTF and RTT have similar large area under the curve (AUC) with TT-TG.TT-TG showed significant correlation with body height and knee size, respectively. The pathologic threshold of increased TT-TG was suggested to be 21 mm for patients [Formula: see text] 169 cm and 18 mm for patients [Formula: see text] 169 cm. Body height-related pathologic threshold provided a supplement for indications of tibial tuberosity medialization.IV.

We proposed a novel continuous glucose monitoring (CGM)-based metric, area under the curve in range (AucIR), for integrating both the amplitude and duration of dysglycemia, and further compared AucIR with the emerging key CGM-derived metric, time in range (TIR).A total of 2,030 adult patients with type 2 diabetes were enrolled during May 2020 to October 2021. AucIR and TIR were measured with 7-day CGM data. Logistic regression analysis and the C-statistic was carried out to assess the association of AucIR and TIR with diabetic retinopathy (DR).Both AucIR (r = -0.89) and TIR (r = -0.95) were strongly correlated with mean glucose levels. Compared with TIR, AucIR showed a tighter relationship with parameters of glycemic variability, including the coefficient of variation (r = -0.56), standard deviation (r = -0.89) and mean amplitude of glycemic excursions (r = -0.70). For each absolute 10% decrease in AucIR, the risk of DR was increased by 7% (95% confidence interval 1.02-1.13) after adjustment for confounders. With respect to TIR, each absolute 10% decrease was associated with an 8% (95% confidence interval 1.03-1.14) increased risk of DR. The model discrimination for DR, as measured by C-statistic, did not differ significantly between the two metrics (P 0.05).AucIR did not provide added benefit over TIR in the assessment of DR risk among patients with type 2 diabetes. The potential value of AucIR needs to be explored in future studies.

Background: Cell division cycle 45 (CDC45) plays an important role in the occurrence and development of numerous carcinomas, but its effect in laryngeal squamous cell carcinoma (LSCC) remains uncle...

Inflammation and immunity play an essential role in disease pathogenesis. 3-N-Butylphthalide (NBP), a group of compounds extracted from seeds of Apium graveolens (Chinese celery), has been demonstrated as an efficient and effective therapy for ischemic stroke. The amount of research on NBP protective effect is increasing at pace, such as microcircular reconstruction, alleviating inflammation, ameliorating brain edema and blood-brain barrier (BBB) damage, mitochondrial function protection, antiplatelet aggregation, antithrombosis, decreasing oxidative damage, and reducing neural cell apoptosis. There has been increasing research emphasizing the association between NBP and immunity and inflammation in the past few years. Hence, it is aimed at reviewing the related literature and summarizing the underlying anti-inflammatory and immunoregulatory function of NBP in various disorders.

To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China.Retrospective cohort study.This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors.A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P.001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P.001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure.Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

Prescribing rate of antipsychotics in elderly patients with psychiatric illnesses has been increasing all over the world. However, there is a lack of research examining the use of antipsychotics at psychiatric hospitals. We aim to find out long-term trends in antipsychotic prescriptions and factors associated with the use of antipsychotics in the elderly population. All outpatient visits with patients aged over 65 years between 2006 and 2015 in a psychiatric hospital were included in the analysis. Demographic and clinical data, including patient age, sex, National Health Insurance status, psychiatric diagnosis and antipsychotic prescription, were retrieved through the electronic medical information system. In this study, we found that prescribing rate of antipsychotics has increased around 5.07% through the study period (from 57.25% in 2006 to 60.15% in 2015, P 0.001). Among all antipsychotics, there was an increase in the use of second-generation antipsychotics with a simultaneous decline in the use of first-generation antipsychotics. Logistic regression analysis showed advanced age, female gender and certification for catastrophic illnesses were positively associated with the use of antipsychotics. Furthermore, patients most likely to be prescribed an antipsychotic were those with psychotic disorders, followed by dementia, and then affective or neurotic disorders. The results of this study were consistent with the worldwide trend of increasing prescriptions of second-generation antipsychotics among elderly patients with psychiatric illnesses. Despite the potential benefits of these medications on certain psychiatric symptoms, clinicians need to exercise due caution as they may also cause potentially serious side effects among the elderly population.

Dense tumor stroma is the physiological barrier in drug delivery that prevents anticancer drugs from entering the tumor, thereby seriously limiting the drugs' therapeutic effect. In this study, a Janus nanoplatform consisting of periodic mesoporous organosilica-coated platinum nanoplatforms (JPMO-Pt) and anti-stroma drug halofuginone (HF) (denoted as JPMO-Pt-HF), was developed to deplete the tumor stroma and synergistically treat breast cancer in BALB/c mice. The prepared JPMO-Pt had a uniform size of 245 nm, a good dispersion, an excellent in vitro and in vivo biocompatibility, and a high loading capacity for HF (up to 50 μg/mg). The antitumor experiments showed that the survival rate of 4T1 cells exhibited an obvious downward trend when the cells were incubated with the JPMO-Pt-HF and irradiated with 808 nm laser. Moreover, the cell survival rate was only about 10% at 48 h when the HF concentration was 2.0 μg/mL. Notably, JPMO-Pt-HF under irradiation had an excellent synergistic therapeutic effect on tumor cells. In vivo antitumor experiment further showed that the JPMO-Pt-HF, in combination with laser irradiation, could minimize tumor growth, showing significantly better effects than those observed for the case of monotherapy involving photothermal therapy (PTT) (152 vs. 670 mm3, p

Objectives To evaluate inter- and intra- scan mode and scanner repeatability and reproducibility of radiomics features within and between single-energy CT (SECT) and dual-energy CT (DECT). Methods A standardized phantom with sixteen rods of clinical-relevant densities was scanned on seven DECT-capable scanners and three SECT-only scanners. The acquisition parameters were selected to present typical abdomen-pelvic examinations with the same voxel size. Images of SECT at 120 kVp and corresponding 120 kVp-like virtual monochromatic images (VMIs) in DECT which were generated according to scanners were analyzed. Regions of interest were drawn with rigid registrations to avoid variations due to segmentation. Radiomics features were extracted via Pyradiomics platform. Test-retest repeatability was evaluated by Bland-Altman analysis for repeated scans. Intra-scanner reproducibility for different scan modes was tested by intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). Inter-scanner reproducibility among different scanners for same scan mode was assessed by coefficient of variation (CV) and quartile coefficient of dispersion (QCD). Results The test-retest analysis presented that 92.91% and 87.02% of the 94 assessed features were repeatable for SECT 120kVp and DECT 120 kVp-like VMIs, respectively. The intra-scanner analysis for SECT 120kVp vs DECT 120 kVp-like VMIs demonstrated that 10.76% and 10.28% of features were with ICC > 0.90 and CCC > 0.90, respectively. The inter-scanner analysis showed that 17.09% and 27.73% of features for SECT 120kVp were with CV < 10% and QCD < 10%, and 15.16% and 32.78% for DECT 120 kVp-like VMIs, respectively. Conclusions The majority of radiomics features were non-reproducible within and between SECT and DECT. Key Points • Although the test-retest analysis showed high repeatability for radiomics features, the overall reproducibility of radiomics features within and between SECT and DECT was low. • Only about one-tenth of radiomics features extracted from SECT images and corresponding DECT images did match each other, even their average photon energy levels were considered alike, indicating that the scan mode potentially altered the radiomics features. • Less than one-fifth of radiomics features were reproducible among multiple SECT and DECT scanners, regardless of their fixed acquisition and reconstruction parameters, suggesting the necessity of scanning protocol adjustment and post-scan harmonization process.

The identification of high recurrence risk stage II colon cancer patients was critical to adjuvant chemotherapy decision. However, current definition of high-risk features remains inadequate. This study aimed to construct a model for predicting recurrence risk based on tumor enhancement ratio (TER) on abdominal contrast-enhanced CT scan.282 stage II colon cancer patients were included and randomly divided into training and validation sets in the ratio of 7:3. TER was calculated using maximum tumor attenuation value in contrast-enhanced CT scan divided by the minimum. Kaplan-Meier survival analyses were adopted to evaluate the prognostic value of variables. A model based on TER was built to predict recurrence risk through the LASSO Cox model. The recurrence risk score of patients was calculated based on this model.The optimal cut-off value of TER was 1.83 derived from the time-dependent ROC (tdROC) curve. Patients with high-TER showed increasingly poorer disease-free survival (DFS) in both training (p 0.001) and validation (p 0.001) sets. A model was built based on TER demonstrated satisfactory performance to recurrence risk prediction (C-index: 0.784 in the training set and 0.725 in the validation set). Patients were regrouped into modified high-risk and non-high risk according to recurrence risk score (cut-off value: 1.75) and a significant DFS difference was observed (training set: p 0.001; validation set: p 0.001).TER can serve as a high-risk feature of stage II colon cancer. And a model based on TER provided a new approach to assess recurrence risk of stage II disease.

Background Repetitive exertion in supination/pronation could increase the risk of forearm diseases due to fatigue. Kinesio taping (KT) is a physical therapy technique that decreases muscle tone and musculoskeletal disorders (MSDs) risk. Many assumptions about taping have been made and several studies have considered the taping applications; however, the effect of KT on strength and fatigue of the forearm supination/pronation remains unclear. The purpose of this study was to evaluate the effect of KT on forearm performance fatigability. Methods A screwing test was constructed to measure the forearm force loss and screwing efficiency during repetitive supination/pronation. Data from 18 healthy adults who underwent both KT and no taping (NT) sessions were used to investigate the forearm strength change in terms of grip force (GF), driving torque (DT), and push force (PF). The maximal isometric forces before and after the screwing test and force decreasing rate (efficiency) during screwing were evaluated to assess the performance fatigability in KT and NT conditions. Results A statistically significant force loss (FL) in maximal isometric GF (p = 0.039) and maximal isometric DT (p = 0.044); however, no significant difference was observed in maximal isometric PF (p = 0.426) between NT and KT. KT provides greater screwing efficiency than NT. Conclusions KT could not improve FL in the maximal muscle strength of the forearm in healthy subjects. KT on the forearm was associated with a lesser decline in DT efficiency than NT, implying that KT could decrease the loss rate of muscle strength and delay the development of fatigue; however, the KT did not yield improvements in PF while performing screwing tasks.

Heart failure is a leading cause of fatality in Duchenne muscular dystrophy (DMD) patients. Previously, we discovered that cardiac and skeletal-muscle-enriched CIP proteins play important roles in cardiac function. Here, we report that CIP, a striated muscle-specific protein, participates in the regulation of dystrophic cardiomyopathy. Using a mouse model of human DMD, we found that deletion of CIP leads to dilated cardiomyopathy and heart failure in young, non-syndromic mdx mice. Conversely, transgenic overexpression of CIP reduces pathological dystrophic cardiomyopathy in old, syndromic mdx mice. Genome-wide transcriptome analyses reveal that molecular pathways involving fibrogenesis and oxidative stress are affected in CIP-mediated dystrophic cardiomyopathy. Mechanistically, we found that CIP interacts with dystrophin and calcineurin (CnA) to suppress the CnA-Nuclear Factor of Activated T cells (NFAT) pathway, which results in decreased expression of Nox4, a key component of the oxidative stress pathway. Overexpression of Nox4 accelerates the development of dystrophic cardiomyopathy in mdx mice. Our study indicates CIP is a modifier of dystrophic cardiomyopathy and a potential therapeutic target for this devastating disease.

Despite the clinical importance of glycemic variability and hypoglycemia, thus far, there is no consensus on the optimum method for assessing glycemic variability and risk of hypoglycemia simultaneously.A novel metric, the gradient variability coefficient (GVC), was proposed for characterizing glycemic variability and risk of hypoglycemia. A total of 208 daily records of CGM encompassing 104 patients with T1DM and 2380 daily records from 1190 patients with T2DM were obtained in our study. Simulated CGM waveforms were used to assess the ability of GVC and other metrics to capture the amplitude and frequency of glucose fluctuations. In addition, the association between GVC and the risk of hypoglycemia was evaluated by receiver operating characteristic (ROC) curve.The results of simulated CGM waveforms indicated that, compared with the widely used metrics of glycemic variability including standard deviation of sensor glucose (SD), coefficient of variation (CV), and mean amplitude of glycemic excursion (MAGE), GVC could reflect both the amplitude and frequency of glucose oscillations. In addition, the area under the curve (AUC) of ROC was 0.827 in T1DM and 0.873 in T2DM, indicating good performance in predicting hypoglycemia.The proposed GVC might be a clinically useful tool in characterizing glycemic variability and the assessment of hypoglycemia risk in patients with diabetes.

SHP2, encoded by the PTPN11 gene, participates in multiple cell functions including cell proliferation, movement, and differentiation. PTPN11 loss-of-function and gain-of-function mutations are both associated with diseases, such as Noonan syndrome, whose manifestations include bone defects, suggesting a crucial role for SHP2 in the skeleton. However, the exact mechanisms by which SHP2 regulates bone development remain unclear. This review focuses on the current understanding of the regulation of SHP2 and highlights the vital roles of SHP2 in skeletal development, especially its roles in ossification. Overall, a better understanding of the functions of SHP2 in ossification will provide a new avenue to treat-related skeletal diseases.

Dialysate potassium concentration directly affects the serum potassium level and safety of hemodialysis patients. In most dialysis centers in China, a single dialysate potassium concentration is used for dialysis, but there is no data on whether this is reasonable or not.Serum potassium values before and after dialysis in maintenance hemodialysis (MHD) patients between 2019 and 2020 were collected from 5 hemodialysis centers in Shanghai, which uniformly use dialysate with a potassium concentration (KD) of 2.0 mmol/L, and data were collected 3 times per patient for analysis. Serum potassium fluctuation was analyzed after administration of individualized KD dialysate.In all, 1,296 MHD patients were included in the study. Predialysis serum potassium was lower than 4.5 mmol/L in 38.0% and higher than 5.5 mmol/L in 14.6% of patients. Postdialysis serum potassium was lower than 3 mmol/L in 11.3% and higher than 4 mmol/L in 10.4% of patients. Pre-dialysis serum potassium was below 4.5 mmol/L and post- dialysis serum potassium was below 3 mmol/L in 9.54% of patients. Compared with patients younger than 40 years, patients80 years more often exhibited predialysis serum potassium below 4.5 mmol/L and Postdialysis serum potassium below 3 mmol/L. A total of 668 patients underwent a trial of hemodialysis with individualized KD dialysate. When receiving individualized KD, compared with uniform KD 2.0 mmol/L, the number of patients with postdialysis serum potassium less than 3 mmol/L significantly decreased, the following predialysis serum potassium level was not significantly different from baseline, and the proportion of patients with predialysis serum potassium less than 4.5 mmol/L and postdialysis serum potassium less than 3 mmol/L significantly decreased.Hypokalemia and fluctuations of serum potassium are common in MHD patients. KD 2.0 mmol/L dialysate should not be used for all patients, and individualized KD dialysate for patients with low serum potassium reduces the incidence of hypokalemia.

Toll-like receptors (TLRs) are evolutionarily conserved proteins of pattern recognition receptors (PRRs) and play a crucial role in innate immune systems recognition of conserved pathogen-related molecular samples (PAMPs). We identified and characterized TLR18 from Nile tilapia (Oreochromis niloticus), OnTLR18, to elucidate its role in tissue expression patterns, modulation of gene expression after microbial challenge and TLR ligands, subcellular localization in fish and human cells, and the possible effectors TLR18 induces in a melanomacrophage-like cell line (tilapia head kidney (THK) cells). OnTLR18 expression was detected in all tissues examined, with the highest levels in the intestine and the lowest in the liver. OnTLR18 transcript was up-regulated in immune-related organs after bacterial and polyinosinic-polycytidylic acid (poly I:C) challenges and in the THK cells after lipopolysaccharide (LPS) stimulation. In transfected THK and human embryonic kidney (HEK) 293 cells, OnTLR18 localizes in the intracellular compartment. OnMyD88 and OnTRIF, but not OnTIRAP, were co-immunoprecipitated with OnTLR18, suggesting that the former two molecules are recruited by OnTLR18 as adaptors. The constitutively active form of OnTLR18 induced the production of pro-inflammatory cytokines, type I interferon (IFN), and antimicrobial peptides such as tumor necrosis factor α, interferon (IFN) d2.13, tilapia piscidin (TP)2, TP3, TP4, and hepcidin in THK cells. Our results suggest that OnTLR18 plays an important role in innate immunity through initiating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and IFN signaling pathways via OnMyD88 and OnTRIF and induces the production of various effectors in melanomacrophages.

Background Fabry disease (FD) remains poorly recognized, especially in children in China. Considering the diversity and nonspecific clinical manifestations accompanying with life-threatening aspect of this disease, methods to improve effective screening and management of the suspects are needed. This study aims to explore how it can be done effectively from a multidisciplinary perspective for children with FD at a tertiary children’s hospital in China. Methods A multidisciplinary team (MDT) of pediatric FD experts was launched at Children’s Hospital of Fudan University. Children with high-risk characteristics were referred by the MDT screening team using the dried blood spot (DBS) triple-test (α-galactosidase A, globotriaosylsphingosine, GLA gene). For newborns who were undergoing genetic testing in the hospital, the GLA gene was listed as a routine analysis gene. Evaluation, family screening, and genetic counselling were implemented after screening by the MDT management team. Results Before the establishment of the MDT, no case was diagnosed with FD in the hospital. However, twelve months following the MDT program's implementation, thirty-five children with high-risk profiles were referred for screening by DBS triple-test, with a yield of diagnosis of 14.3% (5/35). These 5 diagnosed children were referred due to a high-risk profile of pain accompanied by dermatological angiokeratoma and hypohidrosis (n = 2), pain accompanied by abnormal liver function (n = 1), pain only (n = 1), and unexplained renal tubular dysfunction (n = 1). Two neonates were detected early with GLA mutations in the hospital, with a yield of detection of 0.14% (2/1420). Furthermore, another 3 children diagnosed with FD were referred from other hospitals. Family screening of these 10 diagnosed children indicated that 9 boys inherited it from their mothers and 1 girl inherited it from her father. Four of them started to receive enzyme replacement therapy. Conclusion Screening and management of children with FD is effective based on a defined screening protocol and a multidisciplinary approach. We should pay more attention to the high-risk profiles of pain, angiokeratoma, decreased sweating, and unexplained chronic kidney disease in children.

Binding and unbinding of transcription factors to DNA are kinetically controlled to regulate the transcriptional outcome. Control of the release of the transcription factor NF-κB from DNA is achieved through accelerated dissociation by the inhibitor protein IκBα. Using single-molecule FRET, we observe a continuum of conformations of NF-κB in free and DNA-bound states interconverting on the subseconds to minutes timescale, comparable to in vivo binding on the seconds timescale, suggesting that structural dynamics directly control binding kinetics. Much of the DNA-bound NF-κB is partially bound, allowing IκBα invasion to facilitate DNA dissociation. IκBα induces a locked conformation where the DNA-binding domains of NF-κB are too far apart to bind DNA, whereas the loss-of-function IκBα mutant retains the NF-κB conformational ensemble. Overall, our results suggest a novel mechanism with a continuum of binding modes for controlling association and dissociation of transcription factors.

Although concomitant nonalcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear. We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment.In the post-hoc analysis of a multicenter trial, naïve CHB patients receiving 72-week entecavir treatment were enrolled. We evaluated the biochemical, viral and histopathological responses of these patients. The histopathological features of NASH were also evaluated, using paired liver biopsies at baseline and week 72.A total of 1000 CHB patients were finally enrolled for analysis, with 18.2% of whom fulfilling the criteria of NASH. A total of 727 patients completed entecavir antiviral treatment and received the second biopsy. Serum HBeAg loss, HBeAg seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH (P0.05). Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up (all P0.001), 46% (63/136) achieved NASH resolution. Patients with baseline body mass index (BMI) ≥ 23 kg/mLower BMI and weight reduction but not virologic factors determine NASH resolution in CHB. The value of weight management in CHB patients during antiviral treatment deserves further evaluation.

Background: Little was known about the association among time in range (TIR), time above range (TAR), time below range (TBR), and cancer mortality among patients with type 2 diabetes. We aimed to investigate the association among TIR, TAR, TBR, and the risk of cancer mortality among patients with type 2 diabetes. Methods: A total of 6225 patients with type 2 diabetes were prospectively recruited in Shanghai, China. TIR was measured with continuous glucose monitoring at baseline and was defined as the average percentage of time in the target glucose range during a 24 h period. Cox proportion hazard regression analysis was used to determine the association between TIR and the risk of cancer mortality. Results: During a mean follow-up of 7.10 years, we confirmed 237 death events related to cancer. The multivariable-adjusted hazard ratio (HR) for cancer mortality was 1.32 (95% confidence interval [CI]: 1.01–1.75) in patients with TIR ≤70% compared with those with TIR >70%. When TIR was considered as a continuous variable, the multivariable-adjusted HR for cancer mortality associated with each 10% decrease in TIR was 1.07 (95% CI: 1.02–1.14). In the site-specific analysis, a significant association between TIR as a continuous variable and the risk of hepatocellular cancer was found (HR: 1.24; 95% CI: 1.09–1.41). However, no relationship between hemoglobin A1c and cancer mortality was observed (HR: 1.04; 95% CI: 0.97–1.10). Conclusions: The present study found an inverse association of TIR with the risk of cancer mortality among patients with type 2 diabetes. New evidence of TIR was added into the clinical practice that TIR may be an optimal target of glycemic control among patients with type 2 diabetes.

Infantile pneumonia is a common inflammatory disease with the infections of various pathogens in lower respiratory tracts. Here, the role and working mechanism of circular RNA (circRNA) ubiquinol-cytochrome c reductase core protein 2 (circ-UQCRC2; hsa_circ_0038467) in infantile pneumonia were investigated. Cell viability, apoptosis, and inflammatory response were assessed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). Cell oxidative stress was analyzed by measuring the production of malondialdehyde (MDA) and superoxide dismutase (SOD). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were performed to determine the expression of RNAs and proteins. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the interaction between microRNA-495-3p (miR-495-3p) and circ-UQCRC2 or myeloid differentiation primary response protein 88 (MYD88). Lipopolysaccharide (LPS) treatment suppressed the viability while induced the apoptosis, inflammation, and oxidative stress of 16HBE cells in a dose-dependent manner. LPS exposure dose-dependently up-regulated the expression of circ-UQCRC2 in 16HBE cells. Circ-UQCRC2 absence attenuated LPS-induced injury in 16HBE cells. miR-495-3p was a target of circ-UQCRC2, and circ-UQCRC2 silencing-mediated protective effects in LPS-induced 16HBE cells were partly reversed by anti-miR-495-3p. MYD88 was a target of miR-495-3p, and MYD88 overexpression partly counteracted miR-495-3p accumulation-mediated influences in 16HBE cells upon LPS exposure. Circ-UQCRC2 interference decreased the protein expression of MYD88 partly by up-regulating miR-495-3p in LPS-induced 16HBE cells. In conclusion, circ-UQCRC2 contributed to LPS-induced injury of 16HBE cells by targeting miR-495-3p/MYD88 signalling-mediated inflammatory response and oxidative stress.

Achieving secure fixation and preventing retear have been recognized as fundamental in arthroscopic repair of rotator cuff tears. Moreover, reducing internal implantation can lower medical expenses and minimize the operation time, which is essential for the surgical safety and postoperative rehabilitation of the patients. We have recently proposed the point union bridge (PUB) suture configuration as a novel method for not only providing equivalent fixation but also decreasing the operation time and medical expenses. However, no comparative clinical studies have been performed.From March 2014 to September 2016, a total of 88 patients with diagnoses of medium-size rotator cuff tears underwent arthroscopic repair with a randomly assigned technique-either the PUB technique (n = 42) or the double-row suture bridge (DRSB) technique (n = 46). All patients underwent a minimal 2-year follow-up. We used the Constant-Murley score (CMS), American Shoulder and Elbow Surgeons (ASES) score, active and passive range of motion, and visual pain-simulation score (visual analog scale [VAS] score) to assess the functional outcomes. In addition, we recorded the arthroscopic operation time, medical costs, and postoperative complications. All patients received magnetic resonance imaging at the 6-month and 2-year postoperative evaluations to assess structural integrity and tendon healing.At the 2-year follow-up, all scoring parameters evaluated (CMS, ASES score, and VAS score), as well as active and passive range of motion, improved significantly in both groups as compared with preoperative assessments. The PUB technique significantly decreased the operation time (55.9 ± 14.1 minutes vs. 72.2 ± 14.2 minutes for PUB vs. DRSB, P.001) and medical expenses ($2608.0 ± $391.1 vs. $4056.9 ± $350.9 for PUB vs. DRSB, P.001). However, no significant differences between the 2 techniques were found in any functional assessments of the shoulder (CMS, ASES score, and VAS score), repair integrity, or the retear rate at the 2-year follow-up.Arthroscopic repair of the medium-size rotator cuff tear with either the PUB or DRSB technique could yield both satisfactory improvements in the shoulder function of patients and equivalent tendon integrity. With less consumption of internal implants, the PUB technique significantly reduced the operation time and decreased medical expenses.

Objective To investigate the clinical and radiographic short‐term results of arthroscopic treatment for posterior labrum tears with an attached bony fragment after traumatic posterior hip dislocation. Methods Between July 2014 and May 2019, a consecutive series of nine patients diagnosed with a posterior labrum tear with an attached bony fragment after traumatic posterior hip dislocation were treated by hip arthroscopic techniques. The patients had been injured in traffic accidents (n = 6) or high falls (n = 3). All patients were provided primary treatment at the emergency department of our institution, and then were transferred to our department for arthroscopy. Demographic data (e.g. gender, age, etc), intraoperative findings, the preoperative and postoperative multiple clinical scores and radiological results were subsequently assessed. Visual analogue scale for pain (VAS) and modified Harris hip scores (mHHSs) were measured and compared before surgery, and at the last follow‐up. Results A total of nine patients were enrolled, all of them were male, with a mean age at surgery of 32.2 ± 5.6 years (range, 22–65 years). The patients were followed‐up for an average of 26.5 ± 4.1 (range, 24 to 50 years). During the arthroscopic surgery, all patients had labral tears with posterior acetabular rim fracture. All patients had loose osteochondral fragments. Five had partial or complete tears of ligamentum teres. Two patients had osteochondral damage. Two had capsular rupture. Postoperative X‐ray films and three dimension computed tomography (3D‐CT) showed satisfactory reduction of posterior acetabular wall fractures. The mHHS before surgery and at 1 year and 2 years after surgery were 51.8 ± 4.3, 81.8 ± 2.0 and 87.5 ± 1.9 respectively; VAS scores were 5.6 ± 0.5, 1.3 ± 0.3 and 0.7 ± 0.3 respectively. As compared with the condition before surgery, there was a significant improvement in the mHHS and VAS scores at 1 year and 2 years after surgery (P, A 22 year old male underwent arthroscopic treatment for acetabular rim fracture caused by posterior hip dislocation. (A1) X ray showed posterior hip dislocation; X ray (A2) and 3D‐CT (A3) showed posterior acetabular rim fracture after hip reduction; (B1) arthroscopic view of acetabular fracture; (B2) The fracture fragment was fixed with anchor; B3: arthroscopic view of acetabular fracture after reduction. X ray (C1) and 3D‐CT (C2) on the second postoperative day showed well reduction; (C3) 3D‐CT on the 3 months postoperative day showed the complete fracture union.

Rationale: Patients with newly diagnosed tuberculosis often have inconsistent glycemic measurements during and after treatment. Distinct glycemic trajectories after the diagnosis of tuberculosis ar...

Objective: The easy liver fibrosis test (eLIFT) is a novel predictor of liver fibrosis in chronic liver disease (CLD). This study aimed to evaluate the predictive value of the eLIFT for liver inflammation and fibrosis in CLD patients. Methods: We enrolled 1125 patients with CLD who underwent liver biopsy. The predictive accuracy for liver inflammation and fibrosis of the eLIFT was assessed and compared to that of the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 score (FIB-4), and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) by ROC (Receiver Operating Characteristic) analysis and decision curve analysis (DCA). Results: The areas under the ROC curves (AUROCs) of the eLIFT for assessing liver inflammation G ≥ 2 and G ≥ 3 were 0.77 (0.75-0.80) and 0.81 (0.79-0.84), with cut-offs of 8.0 and 11.0, respectively. The AUROCs of the eLIFT for predicting fibrosis stages S ≥ 2 and S4 were 0.72 (0.70-0.76) and 0.76 (0.72-0.80), with cut-offs of 9.0 and 10.0, respectively. In discriminating G≥2 inflammation, the AUROC of the eLIFT was better than that of the FIB-4, with no difference compared with the GPR, but lower than that of the APRI. When discriminating G≥3 inflammation, the AUROC of the eLIFT was comparable to that of the APRI and GPR but superior to that of the FIB-4. There were no significant differences between the four indexes for predicting S≥2 and S4. Conclusion: The eLIFT is a potentially useful noninvasive predictor of liver inflammation and fibrosis in patients with CLD.

The incidence rate and mortality rate of lung cancer (LC) are very high. This study aimed to analyze the T lymphocyte subsets and programmed death-1 (PD-1) expression on lymphocytes in the peripheral blood of non-small cell lung cancer (NSCLC) patients and explore whether there were changes in cellular immunity in NSCLC. Peripheral blood samples were collected from newly diagnosed NSCLC patients and healthy individuals. The T lymphocyte subsets and PD-1 expression were evaluated using flow cytometry. Single-sample gene set enrichment analysis (ssGSEA) was performed to explore the correlations of PD-1 expression with infiltration patterns for tumor-infiltrating T immune cells. By flow cytometry, two populations of lymphocytes in NSCLC patients were observed. Apart from a population of normal volume lymphocytes (Lym1), the other population had larger volume and more particles (Lym2). Compared with the healthy group, the proportion of CD4+ T cells and PD-1 expression on Lym1 was higher, and that of CD8+ T cells was lower in the NSCLC group. In the NSCLC group, the proportions of CD3+ T cells, CD8+ T cells, CD4+CD8+ T (DPT) cells, and PD-1 expression were higher on Lym2 than those on Lym1 (P .05). ssGSEA showed that tumor infiltrating immune T cells were positively correlated with PD-1 expression. The PD-1 expression on lymphocytes increased in recurrent patients who treated with PD-1 inhibitor. Lym2 may be tumor-infiltrating lymphocytes (TILs) which upregulated PD-1 expression in NSCLC. PD-1 expression on lymphocytes may be used as a recurrence indicator for NSCLC patients treated with PD-1 inhibitors.

Thyroid dysfunction is associated with both vitamin D deficiency and iodine; however, it is unclear whether they interact. This study aimed to investigate whether and to what extent the interactions between vitamin D and iodine contribute to the risk of thyroid disorder. Participants (n = 4280) were chosen using multistage, stratified random sampling from Shanghai. Fasting blood was drawn for the 25(OH)D and thyroid parameter tests. Spot urine samples were gathered to test for urine iodine. To evaluate the interactive effects of vitamin D and iodine, crossover analysis was carried out. Pregnant women with a high urinary iodine concentration (UIC) and severe vitamin D deficiency had a significantly higher risk of thyrotropin receptor antibody (TrAb) positivity (odds ratio = 2.62, 95% confidence interval (CI): 1.32, 5.22) in the first trimester. Severe vitamin D deficiency and high UIC interacted positively for the risk of TrAb positivity (relative excess risk due to interaction = 1.910, 95%CI: 0.054, 3.766; attributable proportion = 0.700, 95%CI: 0.367, 1.03). Severe vitamin D deficiency combined with excess iodine could increase the risk of TrAb positivity in pregnant women in the first trimester.

ObjectiveTo evaluate determinants of prolonged viral RNA shedding in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection.Materials and methodsHospitalized patients tested SARS-CoV-2 positive by nasopharyngeal real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were included in the single-center, retrospective study. Patients were divided into 2 groups according to the timing of viral clearance (≤ 8 days, “early clearance” and ≥15 days, “late clearance”).Results4,084 patients were included in the study (1,023 late clearance, 3,061 early clearance), with median age of 50 years and a higher proportion (61.4%) of male. Univariate analyses showed that comorbidities (including hypertension, diabetes, and coronary heart disease), receiving vaccine, the number of vaccinations, cycle threshold (Ct) open reading frame 1ab (ORF 1ab), and nucleocapsid protein (N) gene values on admission were associated with late viral clearance. In the multivariable analysis, the number of vaccinations (P = 0.010) and Ct ORF 1ab gene (P < 0.001) values on admission were significantly associated with late viral clearance. Generalized Estimating Equations (GEE) analysis showed that the Ct value of ORF 1ab gene and N gene remained unchanged within 3 days, and showed progressively higher values with increasing days during late viral RNA clearance.ConclusionThe number of vaccinations and Ct values of ORF 1ab gene were independently associated with a prolonged SARS-CoV-2 RNA shedding.

Different from the traditional medical market, the online medical market allows physicians considerable discretion in setting prices of their services, which is beginning to be paid close attention to. Physicians face a challenge with the introduction of various service styles. Guided by transaction utility theory and price fairness, this study aims to investigate the influence of pricing strategy on service demands from the price difference perspective by focusing on two typical service models: individual service and team-based service. Moreover, team characteristics (response speed and team size) are also considered. The data collection was done in March 2018 and repeated in May 2018, and physicians who provide both individual service and team-based services are included in our study. Finally, a dataset consisting of 1,100 teams with 1,100 physician leaders from 14 departments such as obstetrics and gynecology department were collected from an online medical platform in China. Empirical results support most of our hypotheses. A negative influence of team-based price was observed. As a substitute service, a higher individual service price will make patients turn to team-based service. Moreover, individual service prices negatively moderated the relationship between team-based service prices and demands. By calculating the price difference between the individual service price and the team-based service price, we found a negative role of the price difference affecting patient purchase decisions. Although we did not find a significant effect of team size, a quick response can attract more patients. Price fairness provides a proper framework for understanding pricing strategy in individual and team-based service in an online environment. Understanding the effects of prices from a price difference perspective has both theoretical and practical contributions. Specifically, this study contributes to knowledge on price fairness, online medical platforms, and virtual teams, and provides management suggestions.

Aim: To explore the effectiveness of home-based exercise programs with e-devices (HEPEs) on falls among community-dwelling older adults. Methods: Twelve randomized controlled trials were included in the meta-analysis considering four fall-related outcomes. Results: HEPEs significantly reduced the rate of falls (risk ratio: 0.82; 95% CI: 0.72–0.95; p = 0.006) and improved lower extremity strength (mean difference: -0.94; 95% CI: -1.71 to -0.47; p < 0.001). There was a significant improvement favoring HEPEs on balance if the participants were aged >75 years (mean difference: -0.55; 95% CI: -1.05 to -0.05; p = 0.03), or the intervention duration was at least 16 weeks (mean difference: -0.81; 95% CI: -1.58 to -0.05; p = 0.04). Conclusion: HEPEs demonstrated an overall positive effect on falls among community-dwelling older adults.

In recent years, the prevalence of diabetes is on the rise, globally. Resistant starch (RS) has been known as a kind of promising dietary fiber for the prevention or treatment of diabetes. Therefore, it has become a hot topic to explore the hypoglycemic mechanisms of RS. In this review, the mechanisms have been summarized, according to the relevant studies in the recent 15 years. In general, the blood glucose could be regulated by RS by regulating the intestinal microbiota disorder, resisting digestion, reducing inflammation, regulating the hypoglycemic related enzymes and some other mechanisms. Although the exact mechanisms of the beneficial effects of RS have not been fully verified, it is indicated that RS can be used as a daily dietary intervention to reduce the risk of diabetes in different ways. In addition, further research on hypoglycemic mechanisms of RS impacted by the RS categories, the different experimental animals and various dietary habits of human subjects, have also been discussed in this review.

BackgroundSince the 2019 novel coronavirus (COVID-19) pneumonia outbreak in late 2019, an endless stream of research has emerged surrounding physical activity. This study analyzes the 50 most influential articles on COVID-19 and physical activity over the past 2 years to describe the research landscape and hotspots from bibliometric citation analysis.MethodsThe top-50 cited articles were extracted from the Web of Science Core Collection database, and bibliometric citation analysis was performed by Excel 2019 and VOSviewer software.ResultsThe top-50 articles were cited 160.48 ± 106.90 (range: 70–587). Most of the articles were from the United States (14), followed by Italy (11) and England (9). The International Journal of Environmental Research and Public Health (n = 10) is the journal with the top-50 cited articles. The collaboration between authors was mainly among three teams, including Smith L, Musumeci G, and Napoli C. The hotspot of research around COVID-19 and physical activity focused on lifestyle change (sedentary behavior, sitting time), mental health (depressive, anxiety, loneliness), the credibility of physical activity assessment tools (reliability, validity), and physical activity of different populations (gender, youth, children).ConclusionsBased on a bibliometric analysis of high-impact articles on COVID-19 and physical activity highlights physical activity as an essential lifestyle change and developments and hotspots in this field. These data will provide insights for future researchers regarding the direction of physical activity research in the COVID-19 pandemic.