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Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years.To discover more potential active ingredients and evaluate the gastroprotective mechanisms of ZJP.An approach involving UPLC-Q-Orbitrap HRMS and serum pharmacochemistry was established to screen the multiple chemical constituents of ZJP. Male Sprague-Dawley (SD) rats were divided into six groups: normal control, ulcer control, omeprazole (30 mg/kg), and three ZJP groups (1.0, 2.0 and 4.0 g/kg). After oral treatment with ZJP or omeprazole for 7 days, all groups except the normal control group were orally administered 5 mL/kg ethanol to induce gastric ulceration. Histopathological assessment of gastric tissue was performed by haematoxylin and eosin staining. Antioxidant parameters and inflammatory mediators were determined using ELISA Kit and immunohistochemical analysis.Ninety components were identified in ZJP. Among them, 23 prototypes were found in rat serum after oral administration of ZJP. The ulcer inhibition was over 90.0% for all the ZJP groups. Compared with the ulcer control rats, ZJP (4.0 g/kg) enhanced the antioxidant capacity of gastric tissue: superoxide dismutase (1.33-fold), catalase (2.61-fold), glutathione (2.14-fold), and reduced the malondialdehyde level (0.48-fold). Simultaneously, the ZJP meaningfully lowered the content of tumour necrosis factor-α (0.76-fold), interleukin-6 (0.66-fold), myeloperoxidase (0.21-fold), and nuclear factor kappa B (p65) (0.62-fold).This study showed ZJP could mitigate ethanol-induced rat gastric ulcers, which might benefit from the synergistic actions of multiple ingredients. The findings could support the quality control and clinical trials of ZJP.

Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP).ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective-prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed.There were 1633 ICP patients enrolled, with a median follow-up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%-7.9%), 8.0% (95% CI 6.2%-9.8%), and 9.3% (95% CI 6.6%-12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P = 0.003), and aged less than 18 years at onset of ICP (HR 0.095, P 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes.We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high-risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI.

Aims Secondary bleeding and further hematoma expansion (HE) aggravate brain injury after intracerebral hemorrhage (ICH). The majority of HE results from hypertensive ICH. Previous study reported higher iron content in the brains of hypertensive patients. Iron overload exacerbates the risk of hemorrhagic transformation in thromboembolic stroke mice. Whether iron overload during the process of hypertension participates in secondary bleeding of hypertensive ICH remains unclear. Methods Hypertension was induced by continuous infusion of angiotensin II (Ang II) with an osmotic pump into C57BL/6 mice. ICH was simulated by intrastriatal injection of the liquid polymer Onyx‐18. Iron chelation and iron overload was achieved by deferoxamine mesylate or iron dextran injection. Secondary bleeding was quantified by measuring the hemoglobin content in the ipsilateral brain hemisphere. Results Ang II‐induced hypertensive mice showed increased iron accumulation in the brain and expanded secondary hemorrhage after ICH modeling. Moreover, iron chelation suppressed while iron overload aggravated secondary bleeding. Mechanistically, iron exacerbated the loss of contractile cerebral vascular smooth muscle cells (VSMCs), aggravated blood–brain barrier (BBB) leakage in Ang II‐induced hypertensive mice, and increased glial and MMP9 accumulation after ICH. Conclusion Iron overload plays a key role in secondary bleeding after ICH in Ang II‐induced hypertensive mice. Iron chelation during the process of Ang II‐induced hypertension suppresses secondary bleeding after ICH., Iron accumulation in the brain tissues of Ang II‐induced hypertensive mice might exacerbate the loss of contractile VSMCs, enhance perivascular inflammation and BBB leakage. These factors might lead to increased vascular fragility and increased vulnerability to rupture, ultimately causing more secondary bleeding and subsequent HE after ICH.

Prostate cancer (PCa) is one of the leading causes of cancer diagnoses and cancer-related deaths in the United States. Mutations or deletions in the genes involved in the DNA damage response (DDR) are common in aggressive primary PCa (germline alterations) and further enriched in advanced therapy-resistant PCa (somatic alterations). Among the DDR genes, BRCA2 is the most commonly altered (~ 13%) in advanced therapy-resistant PCa. Patients with BRCA2-altered PCas are exquisitely sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis). Indeed, two PARPis-olaparib and rucaparib have recently gained U.S. FoodDrug Administration approval for the treatment of advanced PCas harboring a BRCA2 mutation. This review seeks to explore the role of BRCA2 in DNA damage repair, the pathogenesis and progression of BRCA2 mutant PCa, and the utility of radiation therapy, targeted therapies, and platinum-based chemotherapies for patients with BRCA2 alterations.

Rationale Hematoma expansion (HE) aggravates brain injury after intracerebral hemorrhage (ICH) and hypertension is a key contributor to HE. Plasma kallikrein (PK) is involved in hemorrhagic transformation in ischemic stroke mice. This study was conducted to explore the role of PK in HE in hypertensive ICH. Methods Hypertension was achieved by continuous infusion of angiotensin II (Ang II) with an osmotic pump in C57BL/6 mice. ICH was achieved by stereotactic intrastriatal injection of blood. PK-specific antibody and platelet glycoprotein VI (GPVI) agonists were administered to intervene in hematoma expansion. The hematoma volume was indicated by the erythrocyte components hemoglobin and carbonic anhydrase-1 in the ipsilateral brain hemisphere. Results Ang II-induced hypertensive mice showed enhanced hematoma expansion and worsened neurologic deficits after ICH modeling. Moreover, intrastriatal injection of blood from Ang II-treated mice into normal mice increased the area of secondary hemorrhage more than blood from untreated mice. Mechanistically, elevated PK was found in Ang II-infused mice whereas, inhibition of PK and administration of the GPVI agonist convulxin decreased hematoma expansion and improved neurologic deficits after ICH. Conclusions These findings suggest that PK inhibition and GPVI agonist treatment might serve as potential methods to intervene in HE after ICH.

Objective To compare the clinical efficacy of the direct anterior approach in lateral decubitus position (L‐DAA) and supine position (S‐DAA) for unilateral total hip arthroplasty. Methods A retrospective study was conducted on 89 patients who underwent primary unilateral total hip arthroplasty in our department between August 2016 and December 2017. There were 46 patients who underwent L‐DAA and 43 patients who underwent S‐DAA. The body mass index (BMI), operation time, blood loss, preoperative Hb, first day and third day postoperative Hb, incision length, hospital stay, preoperative and postoperative Harris score, preoperative and postoperative visual analogue scale (VAS) score, radiological evaluation, intraoperative and postoperative complication, postoperative absolute length difference of lower extremity were recorded and analyzed. P 0.05). However, significant differences were detected in BMI, blood loss, first day and third day postoperative Hb, and operation time (P, Lateral decubitus position: A. Surgical position; B. hemostasis of the extrafemoral artery achieved; C. Grinding the acetabulum; D. Position of operation in femur and acetabulum; E. Reaming the femur and acetabulum; F. Length of incision. Supine position: G. Surgical position; H. Skin preparation and draping; I. Position of operation in femoral; J & K. Muscle protection retractors.

This paper elucidates that the AIDS/HIV incidence rate differences exist among different population and regions, especially among the old and college students. Due to the effect of age, the AIDS incidence peak in males aged 20–35 years and 50 years old both in Chongqing and Shenzhen, and the incidence rate and increasing spread in males was higher than that of females under period effect. In the local population in Chongqing and Shenzhen, the incidence rate of males in over 40, below and in the whole age groups are predicted to increase sharply in the future six years, while in females, the incidence rates among over 40-year-old and the whole age groups were predicted to increase as well. The incidence rate among homosexually transmitted patients reaches the peak in the 20–35, the incidence rate of patients transmitted through heterosexual reaches the peak around 50-year-old. Under the effect of period, AIDS/HIV incidence rate of patients transmitted through sexual routes showed an upward trend both in Chongqing and Shenzhen. The incidence rate of patients aged between 41 and 70 years old presents with an upward trend in the future six years. The results show great differences exist in the AIDS/HIV incidence between males and females, therefore it is necessary to take specific measures respectively.

We conducted a retrospective analysis of the clinical characteristics and dynamic variations of immune indexes in nine COVID-19 patients in Zigong, China. We used flow cytometry and enzyme-linked immunosorbent assays to measure the absolute levels of CD4 and CD8 lymphocytes and SARS-CoV-2 antibodies, respectively. We found that CRP, LDH, HBDH, CD4/CD8 and IgE levels were increased in 6/9 patients, while PA and the absolute numbers of CD4 and CD8 lymphocytes decreased in 7/9 patients. From disease onset through 63 days of follow-up, SARS-CoV-2 IgG levels were consistently higher than those of SARS-CoV-2 IgM, reaching peaks on days 28 and 13, respectively. IgM levels decreased to normal 35 days after disease onset, while IgG levels remained elevated through day 63. IgE levels varied similarly to SARS-CoV-2 IgM. Our results suggest that SARS-CoV-2 may elicit allergic immune responses in patients and that the levels of CRP, PA, LDH, and HBDH, as well as the absolute numbers of CD4 and CD8 lymphocytes could be used as early diagnostic markers of SARS-CoV-2 infection. Lastly, the dynamic variation of SARS-CoV-2 antibodies could guide the timing of blood collection for plasma exchange.

To develop and validate a clinical nomogram for individualized predicting hematoma expansion (HE) in patients with Intracerebral Hemorrhage (ICH).A total of 1025 patients with ICH were retrospectively enrolled in the development cohort between 2010 and 2016. We identified and integrated significant factors for HE to build a nomogram. The model was subjected to validation with a separate cohort of 397 patients from the 2017-2019. The predictive accuracy and discriminative ability were measured by concordance index (C-index). The primary outcome was HE, defined as hematoma growth more than 6 mL or 33% increase in the volume.A total of 1025 patients were included for univariable analysis. HE occurred in 180 patients (17.6%). The time to initial CT (≤6h vs.6 h; p = 0.001), NIHSS score (0-4 vs. 5-14 vs. ≥15; p = 0.031), CTA spot sign (yes vs. no vs. absent; p = 0.018), hypodensities (p = 0.000), blend sign (p = 0.005), and INR (1.2 vs. ≥1.2; p = 0.009) were identified and entered into the nomogram. The calibration curves for probability of HE showed optimal agreement between nomogram prediction and actual observation. The C-index was 0.751. The validation cohort consisted of 397 patients and HE occurred in 78 patients (19.6%). The C-index was 0.743.We developed and validated a nomogram that can individually predict HE for ICH in Chinese populations. This practical prognostic nomogram may help clinicians make decision of clinical practice and design of clinical studies.

Dynamic functional connectivity (DFC) analysis can capture time‐varying properties of connectivity. However, studies on large samples using DFC to investigate transdiagnostic dysconnectivity across schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are rare. In this study, we used resting‐state functional magnetic resonance imaging and a sliding‐window method to study DFC in a total of 610 individuals (150 with SZ, 100 with BD, 150 with MDD, and 210 healthy controls [HC]) at a single site. Using k‐means clustering, DFCs were clustered into three functional connectivity states: one was a more frequent state with moderate positive and negative connectivity (State 1), and the other two were less frequent states with stronger positive and negative connectivity (State 2 and State 3). Significant 4‐group differences (SZ, BD, MDD, and HC groups; q, We identified three functional connectivity states across multiple psychiatric disorders and healthy controls: one was a more frequent state with weak connectivity, and the other two were less frequent states with strong connectivity. Dysconnectivity in the psychiatric patients was found nearly only in the weak connectivity state. Psychiatric patients spent less time in the weak connectivity state than HC patients.

Backgrounds The novel coronavirus disease (COVID‐19) poses serious threat to global public health and economics. Serial interval (SI), time between the symptom onsets of a primary case and a second case, is a key epidemiological parameter. We estimated SI of COVID‐19 in Shenzhen, China based on 27 records of transmission chains. Methods We adopted three parametric models: Weibull, Lognormal and Gamma distributions and an interval censored likelihood framework. The three models were compared using the corrected Akaike information criterion (AICc). We also fitted the epidemic curve of COVID‐19 to the exponential growth to estimate the reproduction number. Findings Using a Weibull distribution, we estimated mean SI at 5.9 days (95%CI: 3.9−9.6) and a standard deviation (SD) at 4.8 days (95%CI: 3.1−10.1). Using a logistic growth model, we estimated the basic reproduction number in Shenzhen at 2.6 (95%CI: 2.4−2.8). Conclusion The SI of COVID‐19 is relative shorter than that of SARS and MERS, other two beta coronavirus diseases, which suggests the iteration of the transmission was rapid. It is crucial to isolate close contacts promptly to control the spread of COVID‐19 effectively.

This study was to assess the anti-inflammatory potential of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. The EPS was isolated from the Cs-HK1 mycelial fermentation broth by ethanol precipitation and purified by deproteinization and dialysis. The EPS had a total sugar content of 74.8% and a maximum average molecular weight (MW) over 107 Da, and consisted mainly of glucose and mannose, and a small amount of galactose and ribose. In THP-1 and RAW264.7 cell cultures, EPS significantly inhibited lipopolysaccharide (LPS)-induced inflammatory responses of the cells including the release of NF-κB and several pro-inflammatory factors such as NO, TNF-α and IL-1β. In the murine model of LPS-induced acute intestinal injury, the oral administration of EPS to the animals effectively suppressed the expression of major inflammatory cytokines TNF-α, IL-1β, IL-10 and iNOS and alleviated the intestinal injury. The results suggest that the Cs-HK1 EPS has notable anti-inflammatory activity and can be a potential candidate for further development of new anti-septic therapeutics. To the best of our knowledge, this is the first report on the anti-inflammation of an EPS from C. sinensis fungal fermentation.

Aims Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin ‐ (Ang ‐)–induced CSVD were evaluated. Methods To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang ‐, and NR was added to the food of the mice for 28 days. Then, short‐term memory, blood‐brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated. Results Our data showed that mice infused with Ang ‐ exhibited decreased short‐term memory function and BBB leakage due to decreased claudin‐5 expression and increased caveolae‐mediated endocytosis after 28 days. Furthermore, Ang ‐ decreased the expression of α‐smooth muscle actin (α‐SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD‐related damages induced by Ang ‐ were inhibited by NR administration. Moreover, NR administration significantly reduced glial activation around the vessels. Conclusion Our results indicated that NR administration alleviated Ang ‐–induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)–associated cognitive impairment.

Acinetobacter baumannii emerged as one of the most important pathogens that causes nosocomial infections due to its increased multidrug resistance. Identifying capsular epidemiology in A. baumannii can aid in the development of effective treatments and preventive measures against this emerging pathogen. Here we established a wzc-based method, and combined it with wzy-PCR to determine capsular types of A. baumannii causing nosocomial bacteraemia collected at two medical centres in Taiwan from 2015 to 2017. Among the 237 patients with A. baumannii bacteraemia, 98 (41.4%) isolates were resistant to carbapenems. Four prevalent capsular types (KL2, KL10, KL22, and KL52) accounted for 84.7% of carbapenem-resistant A. baumannii (CRAB) and 12.2% of non-CRAB. The rate of pneumonia, intensive care unit admission, APACHE II score, and Pitt bacteraemia score were higher in patients with KL2/10/22/52 infection than in those with non-KL2/10/22/52 infection. Patients with KL2/10/22/52 infection and patients with CRAB infection have a higher cumulative incidence of attributable and all-cause in-hospital 30-day mortality. On multivariate analysis, appropriate empirical antimicrobial therapy within 24 h was associated with a lower risk of 30-day attributable mortality in the KL2/10/22/52 isolates (odds ratio = 0.19, 95% CI: 0.06–0.66, p = 0.008) but not in non-KL2/10/22/52 isolates. Early recognition of carbapenem resistance-associated capsular types may help clinicians to promptly implement appropriate antimicrobial therapy for improving the outcomes in patients with CRAB bacteraemia.

Terrible triad of the elbow injury is difficult to manage, and the role of the coronoid process in instability is very important. We describe a simple, modified suture technique to fix a coronoid process fragment using suture anchor fixation.Eight patients (three female and five male) with coronoid process injuries with the fragment involving50% of the total height (Regan-Morrey type I/II) in terrible triad of elbow injury were included. Patients were treated operatively via a lateral Kocher's approach, and coronoid process fractures were repaired with a single pulley double-strand suture technique. Structures were addressed in a sequential fashion-the coronoid process, radial head, lateral ulnar collateral ligament.All patients were treated with the single pulley double-strand anchor suture technique and the coronoid process fragment was found to be in good contact with the original avulsion site using the method. The final Mayo Elbow Performance Score was excellent (90) in six patients and good (between 85 and 89) in two patients after operation 6 months.The single pulley double-strand suture tie method using a suture anchor is a less invasive and simpler fixation method for the repair of coronoid process fractures in patients with terrible triad of the elbow injuries and results in good outcomes.

Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10−15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10−3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10−16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Objective To predict the trend of AIDS in specific age groups and to determine the objective population for AIDS screening, this study explored the three transmission routes and characterized each patient group using the APC model based on the whole, local, and immigrant populations in Zhejiang, China. Methods The data recruited in this paper was obtained from the national Comprehensive AIDS Prevention and Control Information System - Antiviral Therapy Management database and the Chinese Disease Prevention and Control Information System and the Statistical Yearbook of Zhejiang, China. An APC model was used to estimate the impact of age, period, and cohort on the incidence of AIDS, as well as to predict the AIDS incidence in specific age groups based on different sexes with different transmission routes. Results The AIDS incidence peaked in males aged 20–35 years; the incidence of males was higher than that of females due to the impact of period; obvious cohort effect was observed among the immigrants. In the whole and local populations, the incidences of males in all age groups and females in both the 35-year-old group and the whole age group were predicted to increase sharply in 5 years. In the immigrant population, the AIDS incidences in both sexes in all age groups were expected to increase significantly in 5 years. Under the influence of period, the incidence of AIDS via homosexual transmission in the whole population and the local population increased and remained stable after 2015. At the same time, the incidence of AIDS transmitted by homosexual and heterosexual routes in the immigrants also showed an increasing trend. Conclusions The results elucidate that there are sex differences in AIDS incidence, and the incidence of AIDS through various transmission routes in all groups is predicted to exhibit an upward trend in the 5 years to come. Effective intervention strategies should be developed and implemented by the public health departments in Zhejiang to control the epidemic of AIDS.

Background Pulmonary hypertension (PH) is a deadly disease characterized by vascular stiffness and altered cellular metabolism. Current treatments focus on vasodilation and not other root causes of pathogenesis. Previously, it was demonstrated that glutamine metabolism, as catalyzed by GLS1 (glutaminase 1) activity, is mechanoactivated by matrix stiffening and the transcriptional coactivators YAP1 (yes‐associated protein 1) and transcriptional coactivator with PDZ‐binding motif (TAZ), resulting in pulmonary vascular proliferation and PH. Pharmacologic inhibition of YAP1 (by verteporfin) or glutaminase (by CB‐839) improved PH in vivo. However, systemic delivery of these agents, particularly YAP1 inhibitors, may have adverse chronic effects. Furthermore, simultaneous use of pharmacologic blockers may offer additive or synergistic benefits. Therefore, a strategy that delivers these drugs in combination to local lung tissue, thus avoiding systemic toxicity and driving more robust improvement, was investigated. Methods and Results We used poly(lactic‐co‐glycolic) acid polymer‐based microparticles for delivery of verteporfin and CB‐839 simultaneously to the lungs of rats suffering from monocrotaline‐induced PH. Microparticles released these drugs in a sustained fashion and delivered their payload in the lungs for 7 days. When given orotracheally to the rats weekly for 3 weeks, microparticles carrying this drug combination improved hemodynamic (right ventricular systolic pressure and right ventricle/left ventricle+septum mass ratio), histologic (vascular remodeling), and molecular markers (vascular proliferation and stiffening) of PH. Importantly, only the combination of drug delivery, but neither verteporfin nor CB‐839 alone, displayed significant improvement across all indexes of PH. Conclusions Simultaneous, lung‐specific, and controlled release of drugs targeting YAP1 and GLS1 improved PH in rats, addressing unmet needs for the treatment of this deadly disease.

Purpose: Protein kinases are known to play a prominent role in oncogenic progression across multiple cancer subtypes, yet their role in prostate cancer progression remains underexplored. The purpose of this study was to identify kinases that drive prostate cancer progression. Experimental Design: To discover kinases that drive prostate cancer progression, we investigated the association between gene expression of all known kinases and long-term clinical outcomes in tumor samples from 545 patients with high-risk disease. We evaluated the impact of genetic and pharmacologic inhibition of the most significant kinase associated with metastatic progression in vitro and in vivo. Results: DNA-dependent protein kinase (DNAPK) was identified as the most significant kinase associated with metastatic progression in high-risk prostate cancer. Inhibition of DNAPK suppressed the growth of both AR-dependent and AR-independent prostate cancer cells. Gene set enrichment analysis nominated Wnt as the top pathway associated with DNAPK. We found that DNAPK interacts with the Wnt transcription factor LEF1 and is critical for LEF1-mediated transcription. Conclusions: Our data show that DNAPK drives prostate cancer progression through transcriptional regulation of Wnt signaling and is an attractive therapeutic target in aggressive prostate cancer.

Background/Purpose: Early detection of suicide risk is a challenge in suicide prevention. A comprehensive yet efficient tool providing timely identification of key risk factors allows healthcare providers to initiate interventions. The study aims to validate the 9-item Concise Mental Health Checklist (CMHC-9). Methods: A series of cross-sectional surveys were conducted in 3982 participants from psychiatric outpatient (n = 931), medical outpatient (n = 931) and community (n = 2120) populations. The factor analysis with internal consistency coefficients (Cronbach's α) and receiver operating characteristic (ROC) analysis were performed to evaluate the scale's reliability and validity. Results: The internal consistency of the CMHC-9 was satisfactory based on Cronbach's α values for the total sample (α = 0.79) and the three sub-samples (i.e., α = 0.76 for psychiatric subjects; 0.67 for community subjects; and 0.69 for medical outpatient subjects). Hierarchical exploratory factor analysis revealed that the CMHC-9 was a single-dimensional scale with two-factor structure of psychopathology and suicidality. The two-factor solution was confirmed by confirmatory factor analysis. The optimal cut-off of 3/4 obtained from the ROC analysis represented a satisfactory sensitivity (92%) and specificity (82%) in identifying recent suicide ideation. Conclusion: This large-scale study confirmed the CMHC-9 as a brief and effective tool for suicide risk detection. It is recommended that CMHC-9 can be used for care engagement and risk identification in both medical and community settings among people at risk for suicide. Keywords: Mental health, Psychometric evaluation, Suicidal ideation, Suicide prevention

Objective Impaired social interaction is one of the core characteristics of autism spectrum disorder (ASD). This study was conducted to compare the facial emotion recognition (FER) abilities and emotional interference of adolescents with and without high-functioning ASD by performing the FER Task (FERT) using the faces of Taiwanese people and the Implicit Association Test (IAT), respectively. Methods This study recruited 71 adolescents with high-functioning ASD who aged at 11 to 18 years old as the ASD group and 63 adolescents without ASD from the Taiwanese community as the non-ASD group. We investigated FER abilities by conducting the FERT on six types of emotional expression with a three-level intensity rating, and we performed the IAT for evaluating the strength of a person's automatic association with mental representations of emotions in memory. Results Compared with the non-ASD group, the ASD group performed significantly worse on facial emotion differentiation and the ranking and rating of emotional intensity in the FERT. The ASD group had higher IAT scores than the non-ASD group. Conclusion The results suggest that adolescents with high-functioning ASD have subtle deficits in facial emotion processing and emotional interference.

Postoperative intra-abdominal septic complications in patients with Crohn's disease undergoing intestinal resection and anastomosis are frequent and difficult to manage.This study sought to explore the value of preoperative CT enterography to predict intra-abdominal septic complications.This was a retrospective and prospective observational study.This study was conducted in a tertiary referral hospital.Patients with Crohn's disease undergoing primary intestinal resection were enrolled in our study.The CT enterography severity index was calculated and its ability to predict intra-abdominal septic complications evaluated by multivariate analyses. A prospective study was then performed to assess the reliability of this CT enterography index.The incidence of postoperative intra-abdominal septic complications in patients undergoing a 1-stage procedure was significantly higher than those undergoing a 2-stage procedure (3/103 vs 24/241; 2.9% vs 10.0%; p = 0.026). A multivariate analysis identified 5 CT enterography parameters, including mesenteric fibrofatty proliferation, intra-abdominal abscess or phlegmon, intestinal fistula, peritoneal effusion, and intestinal dilatation with stricture to be independent predictors of intra-abdominal septic complications (p0.001). A nomogram model based on these 5 parameters was constructed. A receiver operating characteristic analysis identified a CT enterography nomogram score cutoff of 175 as a predictor of intra-abdominal septic complications with a sensitivity of 83.3% and a specificity of 85.3%. In the prospective study, those patients with a CT enterography nomogram score175 were assigned to the 2-stage group, which resulted in a similar intra-abdominal septic complication incidence in those undergoing intestinal resection with or without anastomosis (2/82 vs 2/34; p = 0.355).This study was limited by its single-center scope.Preoperative CT enterography findings may predict postoperative outcomes and help determine surgical approach in Crohn's disease. Patients with worse intra-abdominal findings confirmed by CT enterography may benefit from stoma creation after intestinal resection. See Video Abstract at http://links.lww.com/DCR/B588.ANTECEDENTES:Las complicaciones sépticas intra-abdominales postoperatorias en pacientes con enfermedad de Crohn sometidos a resección intestinal y anastomosis son frecuentes y difíciles de manejar.OBJETIVO:Este estudio buscó explorar el valor del índice enterográfico por tomografía computada en el pré-operatorio y así poder predecir futuras complicaciones sépticas intra-abdominales.DISEÑO:Estudio observacional retro-prospectivo.AJUSTE:Investigación realizada en un hospital de referencia terciaria.PACIENTES:Se incluyeron en nuestro estudio pacientes con enfermedad de Crohn sometidos a una resección intestinal primaria.PRINCIPALES MEDIDAS DE RESULTADO:Se calculó el índice de gravedad de la enterografía por tomografía axial computada y se evaluó su capacidad para predecir las complicaciones sépticas intra-abdominales mediante un análisis multivariado. Luego se realizó un estudio prospectivo para evaluar la confiabilidad del índice enterográfico por tomografía axial computada.RESULTADOS:La incidencia de complicaciones sépticas intra-abdominales postoperatorias en pacientes sometidos a un procedimiento de un solo tiempo fue significativamente mayor que aquellos sometidos a un procedimiento de dos tiempos (3/103 frente a 24/241; 2,9% frente a 10,0%; p = 0,026). El análisis multivariado identificó cinco parámetros enterográficos por tomografía axial computada, incluidos la proliferación fibrograsa mesentérica, el absceso o flegmón intra-abdominal, la fístula entérica, el derrame peritoneal y la dilatación intestinal debido a estenosis como predictores independientes de complicaciones sépticas intra-abdominales (p0,001). Se construyó un modelo de Nomograma basado en estos cinco parámetros. Un análisis de las características operatorias del receptor identificó una puntuación de cohortes del nomograma de la enterografía por tomografía axial computada de 175 como predictor de complicaciones sépticas intra-abdominales con una sensibilidad del 83,3% y una especificidad del 85,3%. En el estudio prospectivo, los pacientes con puntuación de nomograma enterográfico por tomografía axial computada superior a 175 fueron asignados al grupo en dos tiempos, lo que resultó en una incidencia similar de complicaciones sépticas intra-abdominales en aquellos sometidos a resección intestinal con o sin anastomosis (2/82 vs. 2/34; p = 0,355).LIMITACIONES:Este estudio estuvo limitado por su alcance unicéntrico.CONCLUSIÓN:Los hallazgos enterográficos por tomografía axial computada pré-operatoria pueden predecir ciertos resultados postoperatorios y ayudar a determinar el abordaje quirúrgico en la enfermedad de Crohn. Los pacientes con peores hallazgos intra-abdominales confirmados por enterografía en la tomografía axial computada podrían beneficiarse de la creación de un estoma después de la resección intestinal. Consulte Video Resumen en http://links.lww.com/DCR/B588. (Traducción-Dr Xavier Delgadillo).

Community-acquired pneumonia (CAP) causes substantial morbidity and mortality in adults worldwide. The etiology of CAP often remains uncertain, and therapy is empirical. Thus, there is still room for improvement in the diagnosis of pneumonia.Adults aged20 years who presented at the outpatient or emergency departments of Linkou and Keelung Chang Gung Memorial Hospital with CAP were prospectively included between November 2016 and December 2018. We collected respiratory specimens for culture and molecular testing and calculated the incidence rates of CAP according to pathogens.Of 212 hospitalized adult patients with CAP, 69.3% were male, and the median age of the patients was 67.8 years. Bacterial pathogens were detected in 106 (50%) patients, viruses in 77 (36.3%), and fungal pathogens in 1 patient (0.5%). The overall detection rate (culture and molecular testing method) was 70.7% (n = 150). Traditional microbial culture yielded positive results in 36.7% (n = 78), molecular testing in 61.3% (n = 130). The most common pathogens were influenza (16.1%), followed by Klebsiella pneumoniae (14.1%), Pseudomonas aeruginosa (13.6%), human rhinovirus (11.8%), and Streptococcus pneumoniae (9.9%). Multiple pathogen co-infections accounted for 28.7% (n = 61), of which co-infection with K. pneumoniae and human rhinovirus comprised the largest proportion.Molecular diagnostic testing could detect 23.6% more pathogens than traditional culture techniques. However, despite the current diagnostic tests, there is still the possibility that no pathogen was detected.

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are involved in the progression of laryngeal squamous cell carcinoma (LSCC). Here, we aimed to disclose the role of MNX1-AS1 in LSCC progression, and explore whether MNX1-AS1 participates in LSCC progression via targeting miR-744-5p to active BCL9/β-catenin signaling. Sixty-five human LSCC tissues and the paracancerous normal tissues were recruited to determine the levels of MNX1-AS1, miR-744-5p and BCL9 using qRT-PCR. The interaction of miR-744-5p and MNX1-AS1/BCL9 was determined by using the RNA immunoprecipitation (RIP) assay and/or luciferase gene reporter assay. Cell viability, in vivo tumor formation, invasion and migration abilities were detected by MTT, Xenograft models and Transwell assays. MNX1-AS1 level was increased significantly in human LSCC tissues as compared with the normal tissues, which showed a positive correlation with BCL9 level while a negative correlation with miR-744-5p level. High level of MNX1-AS1 predicted a poor prognosis and an advanced clinical process in LSCC patients. miR-744-5p targeted upregulation weakened the luciferase activity of MNX1-AS1 and /BCL9, and downregulated their expression levels-wt, while showed no effect when the binding sites were mutated. Knockdown of MNX1-AS1 markedly weakened cell viability, migration, and invasion abilities, while BCL9 overexpression abolished these tendencies. In addition, MNX1-AS1 downregulation induced decreases in tumor volumes and weights in vivo, accompanied by reductions in BCL9, Ki-67 and β-catenin expression and an increase in miR-744-5p expression. Collectively, this study reveals that MNX1-AS1 contributes to cell growth and migration by regulating miR-744-5p/BCL9/β-catenin axis in LSCC.

Objective To provide guidelines for surgery and reduce the incidence of fracture, this study analyzed the relationship between femoral fracture and related factors in direct anterior approach (DAA) total hip arthroplasty (THA) in the lateral decubitus position. Method A retrospective series of 273 consecutive patients who underwent THA with the DAA in the lateral decubitus position was analyzed. Each surgery was performed by the same surgeon with a conventional operation bed and femoral stem. The correlations between the incidence of fracture and sex, age, body mass index (BMI), height, osteoporosis, the anterior superior iliac spine-greater trochanter distance (ASIS-GTD), and hip joint disease were analyzed by univariate analysis and logistic regression analysis. Results Among all hip arthroplasty procedures, 35 hips had femoral fractures, including 30 greater trochanter fractures, 4 proximal femoral splits, and 1 femoral perforation. The incidence of fracture was 12.82%. Univariate analysis showed no significant difference in the incidence of fracture by sex, BMI, or age. However, osteoporosis caused an increase in the incidence of fracture, while the incidence of fracture decreased as height and the ASIS-GTD increased. The incidence of femoral neck fracture was lower in cases of osteonecrosis of the femoral head than in cases of other diseases. Logistic regression showed a significant correlation between osteoporosis, the ASIS-GTD, and fractures. Patients with osteoporosis had a high possibility of fracture (OR = 2.414); the possibility of fracture decreased with increasing ASIS-GTD (OR = 0.938). Conclusion Lateral decubitus DAA THA can be successfully performed using a conventional operation bed and stem, effectively saving medical resources. Osteoporosis and a shorter ASIS-GTD were independent risk factors for femoral fracture.

This study aimed to analyze and compare the clinical and functional outcomes of distal tibia fractures treated with intramedullary nailing (IMN) using the suprapatellar (SP) and infrapatellar (IP) surgical approaches.A retrospective analysis was performed in 63 patients with distal fractures that were treated with IMN between August 2014 and August 2018. A total of 27 and 36 patients underwent IMN using the SP and IP techniques, respectively. The surgical time, blood loss, closed reduction rate, rate of adjuvant reduction technique, fracture healing time, and complications were reviewed in this study. Anterior knee pain was assessed using the visual analog scale. The Lysholm Knee Scoring Scale and American Orthopaedic Foot and Ankle Society (AOFAS) scale were used as clinical measurements.A total of 63 patients, with a minimum follow-up of 12 months, were evaluated. The average surgical time, blood loss, rate of adjuvant reduction technique, closed reduction rate, fracture healing time, and Lysholm Knee Scoring Scale score were insignificantly different (P0.05) between the two groups. However, the SP approach was superior to the IP approach in terms of pain score, AOFAS score, and fracture deformity rate (P0.05).In the treatment of distal tibia fractures, the SP IMN technique is associated with a significantly higher functional outcome, lower knee pain, and lower rate of fracture deformity than the IP IMN technique.

Stiff-person syndrome (SPS) is highly associated with anti-glutamic acid decarboxylase (GAD) antibody. However, GAD antibodies alone appear to be insufficient to cause SPS, and they possibly are involved in only part of its pathophysiology. It is suspected that the symptoms of SPS get precipitated by external stimuli. Here, we briefly introduce the case of a patient with latent autoimmune diabetes who developed SPS through the action of subcutaneously injected insulin. A 43-year-old man was diagnosed with diabetes and initially well-controlled with oral hypoglycemic agents but progressed to requiring insulin within 1 year of diagnosis. Two months after the initiation of basal insulin therapy, he presented with abdominal stiffness and painful muscle spasms, involving the lower limbs, which resulted in walking difficulty, and thus, he refused insulin injections thereafter. He had been treated with oral anti-diabetic agents instead of insulin for 10 years until premixed insulin twice daily was started again due to poor diabetes control. Immediately after insulin injection, abdominal muscle rigidity and spasms were noted. When insulin was not administered, frequent episodes of diabetic ketoacidosis occurred. Serum GAD antibody test was positive and there was no positivity for islet antigen-2 antibody. A glucagon stimulation test demonstrated relative insulin deficiency, indicative of latent autoimmune diabetes in adults (LADA). Tolerable muscle rigidity was achieved when the dosage of basal insulin was split into two separate daily injections with lower amounts of units per injection. This case highlights a different form of autoimmune diabetes in SPS. To our knowledge, this is the first report of SPS described shortly after the initiation of insulin therapy that required basal insulin to achieve tolerable muscle symptoms and better glucose control, without the development of diabetic ketoacidosis.

Purpose: The current study was intended to assess the effect of a facilitated behavioral intervention based on the extended theory of planned behavior (TPB) on psychological constructs and physical activity among adolescents over a period of eight weeks. Methods: Students (n = 51, 12 &plusmn, 0.3 years of age) in the seventh grade at a junior middle school in China were randomly assigned to two groups: the intervention group (n = 24) and the control group (n = 27). Both groups were pre- and post-tested with the related psychological constructs of the extended TPB, along with behavioral measures of the Physical Activity Scale and ActiGraph accelerometer (model wGT3X-BT). The intervention group took part in 45 min classes once per week for 8 weeks, including five indoor theoretical courses and three outdoor basketball matches. The control group was not required to make any change to their normal school day. Also, 2 &times, 2 repeated measures analysis of variance (ANOVA) was conducted to compare the differences between the two groups, and then t-test was employed to compare the independent and paired differences. Results: Significant increases in pre&ndash, post subjective norms (SN) (p = 0.041, Cohen&rsquo, s d = 0.62), perceived behavior control (PBC) (p = 0.023, Cohen&rsquo, s d = 0.72), exercise intention (EI) (p = 0.043, Cohen&rsquo, s d = 0.61), and self-efficacy (SE) (p = 0.035, Cohen&rsquo, s d = 1.36) were observed in the intervention group. In addition, participants in the intervention group increased their exercise frequency (p &lt, 0.001, Cohen&rsquo, s d = 1.25) and intensity (p = 0.028, Cohen&rsquo, s d = 0.68), especially their time spent on light intensity physical activity (light-PA%, p = 0.031, Cohen&rsquo, s d = 0.68), and their percentage of sedentary time (SB%) was also reduced (from 68% &plusmn, 10% to 58% &plusmn, 7%, p &lt, s d = 1.17). Furthermore, the intervention group showed significantly better performance in PBC (p = 0.032, Cohen&rsquo, s d = 0.62), EI (p &lt, s d = 1.32), SE (p &lt, s d = 1.15), SB% (p &lt, s d = 1.22), light-PA% (p &lt, s d = 1.12), and total physical activity (TPA) (p = 0.015, Cohen&rsquo, s d = 0.72) compared to the control group at the post-test. No significant pre post differences were observed for any psychological or behavioral variables in the control group, except for exercise frequency, but the values were still lower than those in the intervention group after the 8-week intervention (3.70 &plusmn, 0.72 versus 3.92 &plusmn, 0.83). Conclusion: The combined theory-based intervention was effective at improving psychological constructs and physical activity among seventh-grade adolescents in 8 weeks.

Aims The 2014 World Health Organization report on global suicide identified large differences in the male-to-female ratio of suicide rates between countries: most high-income countries (HICs) report ratios of 3:1 or higher while many low- and middle-income countries (LMICs) – including China and India – report ratios of less than 1.5:1. Most authors suggest that gender-based social-cultural factors lead to higher rates of suicidal behaviour among women in LMICs and, thus, to relatively high female suicide rates. We aim to test an alternative hypothesis: differences in the method and case-fatality of suicidal behaviour – not differences in the rates of suicidal behaviour – are the main determinants of higher female suicide rates in LMICs. Methods A prospective registry of suicide attempts treated in all 14 general hospitals in a rural county in China was established and data from the registry were integrated with population and mortality data from the same county from 2009 to 2014. Results There were 160 suicides and 1010 medically-treated suicidal attempts in the county; 84% of female suicides and 58% of male suicides ingested pesticides while 73% of female attempted suicides and 72% of male attempted suicides ingested pesticides. The suicide rate (per 100 000 person-years of exposure) was 8.4 in females and 9.1 in males (M:F ratio = 1.08:1) while the incidence of ‘serious suicidal acts’ (i.e. those that result in death or received treatment in a hospital) was 81.5 in females and 47.7 in males (M:F ratio = 0.59:1). The case-fatality of serious suicidal acts was higher in males than in females (19 v. 10%), increased with age, was highest for violent methods (92%), intermediate for pesticide ingestion (13%) and lowest for other methods (5%). Conclusions The incidence of medically serious suicidal behaviour among females in rural China was similar to that reported in HICs, but the case-fatality was much higher, primarily because most suicidal acts involved the ingestion of pesticides, which had a higher case-fatality than methods commonly used by women in HICs. These findings do not support sociological explanations for the relatively high female suicide rate in China but, rather, suggest that gender-specific method choice and the case-fatality of different methods are more important determinants of the demographic profile of suicide rates. Further research that involves ongoing monitoring of the changing incidence, demographic profile and case-fatality of different suicidal methods in urban and rural parts of both LMICs and HICs is needed to confirm this hypothesis.

Myeloid cells, such as neutrophils, are produced in the bone marrow in high quantities and are important in the pathogenesis of vascular diseases such as pulmonary hypertension (PH). Although neutrophil recruitment into sites of inflammation has been well studied, the mechanisms of neutrophil egress from the bone marrow are not well understood. Using computational flow cytometry, we observed increased neutrophils in the lungs of patients and mice with PH. Moreover, we found elevated levels ofIL-6 in the blood and lungs of patients and mice with PH. We observed that transgenic mice overexpressingIl-6 in the lungs displayed elevated neutrophil egress from the bone marrow and exaggerated neutrophil recruitment to the lungs, resulting in exacerbated pulmonary vascular remodeling, and dysfunctional hemodynamics. Mechanistically, we found that IL-6-induced neutrophil egress from the bone marrow was dependent on interferon regulatory factor 4 (IRF-4)-mediated CX3CR1 expression in neutrophils. Consequently, Cx3cr1 genetic deficiency in hematopoietic cells in Il-6-transgenic mice significantly reduced neutrophil egress from bone marrow and decreased neutrophil counts in the lungs, thus ameliorating pulmonary remodeling and hemodynamics. In summary, these findings define a novel mechanism of IL-6-induced neutrophil egress from the bone marrow and reveal a new therapeutic target to curtail neutrophil-mediated inflammation in pulmonary vascular disease.

Objective To determine whether suicidal ideation or suicide attempts are linked to poor neurocognitive function among individuals with first-episode schizophrenia (FES). Method We performed a cross-sectional study on 159 Chinese inpatients (Mage = 27.1 years; 52.2% females) with minimal-treated FES and collected their suicidal history through interviews and medical records. Neurocognitive performance, psychopathology, and depressive symptoms were assessed using the MATRICS Consensus Cognitive Battery, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale for Schizophrenia, respectively. Results Approximately 1/10 FES inpatients had any suicide attempts, and more than 1/4 reported lifetime suicidal ideation. Inpatients with a suicide attempt or suicidal ideation scored significantly worse in the overall seven neurocognitive domains compared with those without past suicidal ideation or a suicide attempt. Linear regression suggested that suicide attempts were mainly associated with lower scores in working memory and speed of processing, after adjusting for education levels. The associations remained robust after further controlling for psychopathological and depressive symptoms. Conclusion First-episode schizophrenia patients with suicide attempts had more severely impaired neurocognitive performances in specific domains. Fundamental neurocognitive dysfunctions should be assessed, detected, and treated after their suicide risk assessments.

Persistent chronic inflammation and delayed epithelialization lead to stalled healing in diabetic ulcers (DUs). PD-L1 shows anti-inflammatory and proliferative activities in healing defects, whereas its function in DU pathogenesis remains unknown. Lower levels of PD-L1 were found in DU tissues, and exogenous PD-L1 has therapeutic effects in the healing process by accelerating re-epithelialization and attenuating prolonged inflammation, which contributed to the delayed wound closure. We detected the downstream effectors of PD-L1 using transcriptional profiles and screened the interacting proteins using immunoprecipitation in combination with mass spectrometry and coimmunoprecipitation assays. The biological functions of eIF3I‒PD-L1‒IRS4 axis were tested both in vivo and in vitro. Finally, we validated the expression levels of eIF3I, PD-L1, and IRS4 in DU tissues from human clinical samples by immunohistochemistry staining. Mechanistically, PD-L1 binds to eIF3I and promotes cutaneous diabetic wound healing by downregulating IRS4. These findings identify that the eIF3I‒PD-L1‒IRS4 axis contributes to wound healing defects, which can serve as a potential therapeutic target in DUs.

This exploratory study examined the relationship of five patient demographic characteristics (residence in an urban or rural site, gender, age group, marital status, and education level) with the patients' (1) perceived importance of, (2) desire to, (3) ability to perform four patient engagement self-care actions that result in finding safe and decent care.Equitable access to health care is essential in a humanized health care system. Healthcare providers must engage patients in discussions about their desires for their care to create person-centered care plans reflecting patient values and wishes.This secondary data analysis from a cross-sectional survey project surveyed community-dwelling adults living in the southern United States, 2015-2016. This paper only includes responses of participants aged 65 years and older (N = 123). Data collected in The Patient Action Inventory for Self-Care and demographic questions were used. Chi-square tests and multiple logistic regression analyses were used.As revealed in the Chi-square and logistic regression findings, self-care actions of "finding a doctor or practitioner who meets your needs," "using available information to choose a doctor or practitioner," and "using data to choose a hospital or clinic" showed some associations with whether seniors resided in an urban or rural community, age group, and marital status (P 0.05). No significant associations between these four self-care actions with gender or education were found.A community-based solution is warranted to leverage between patient demographic characteristics and their perceived self-care actions by harnessing local factors in collaboration with identified patient needs.

The incidence of inflammatory bowel disease (IBD) has markedly increased. Our research findings during the past showed that medicinal plant extracts and the derived phytochemical components from Wedelia chinensis (WC) can have strong anti-colitis activities. Here, we further identified the key component phytochemicals from active fractions of different WC preparations (WCHA) that are responsible for the protective effect of WCHA in colitis mice. Of the 3 major compounds (wedelolactone, luteolin and apigenin) in this fraction, luteolin had the highest anti-inflammatory effect in vivo. Using a next-generation sequencing (NGS) (e.g., RNA-seq) system to analyze the transcriptome of colorectal cells/tissues in mice with dextran sulfate sodium (DSS)-induced colitis with/without phytochemicals treatment, luteolin was found to strongly suppress the DSS-activated IL-17 pathway in colon tissue. In addition, co-treatment with wedelolactone and luteolin had a synergistic effect on the expression level of some IL-17 pathway-related genes. Interestingly, our NGS analyses also indicated that luteolin and wedelolactone can specifically suppress the expression of NLRP3 and NLRP1. Using a 3-dimensional cell co-culture system, we further demonstrated that luteolin could efficiently suppress NLRP3 expression via disruption of IL-17A signaling in inflamed colon tissue, which also indicates the pharmacological potential of luteolin and wedelolactone in treating IBD.

Background The incidence of early postoperative complications of displaced intracapsular hip fractures is high. The purpose of this study was to compare the early postoperative complications and assess the incidence of femoral neck shortening on using a newly designed proximal femoral cannulated screw locking plate (CSLP) versus multiple cancellous screws (MCS) in the treatment of displaced intracapsular hip fractures in young adults. Methods Sixty-eight young adult patients with displaced intracapsular hip fractures were randomly assigned to either the CSLP group or the MCS group and treated routinely by internal fixation with either the CSLP or the MCS. Harris Hip Score, nonunion, failure of fixation, overall complications, and femoral neck shortening were recorded and compared. Results Two patients (5.88%) in the CSLP group and eight (23.53%) in the MCS group had postoperative nonunion (P 0.05). Three patients (8.82%) in the CSLP group and 11 (32.35%) in the MCS group had overall complications (P

Circulating microRNAs (c-miRNAs), plasma-based noncoding RNAs that control posttranscriptional gene expression, mediate processes that underlie phenotypical plasticity to exercise. The relationship and biological relevance between c-miRNA expression and variable dose exercise exposure remains uncertain. We hypothesized that certain c-miRNAs respond to changes in exercise intensity and/or duration in a dose-dependent fashion. Muscle release of such c-miRNAs may then deplete intracellular stores, thus facilitating gene reprogramming and exercise adaptation. To address these hypotheses, healthy men participated in variable intensity ( n = 12, 30 × 1 min at 6, 7, and 8 miles/h, order randomized) and variable duration ( n = 14, 7 × 1 mile/h for 30, 60, and 90 min, order randomized) treadmill-running protocols. Muscle-enriched c-miRNAs (i.e., miRNA-1 and miRNA-133a) and others with known relevance to exercise were measured before and after exercise. c-miRNA responses followed three profiles: 1) nonresponsive (miRNA-21 and miRNA-210), 2) responsive to exercise at some threshold but without dose dependence (miRNA-24 and miRNA-146a), and 3) responsive to exercise with dose dependence to increasing intensity (miRNA-1) or duration (miRNA-133a and miRNA-222). We also studied aerobic exercise-trained mice, comparing control, low-intensity (0.5 km/h), or high-intensity (1 km/h) treadmill-running protocols over 4 wk. In high- but not low-intensity-trained mice, we found increased plasma c-miR-133a along with decreased intracellular miRNA-133a and increased serum response factor, a known miR-133a target gene, in muscle. Characterization of c-miRNAs that are dose responsive to exercise in humans and mice supports the notion that they directly mediate physiological adaptation to exercise, potentially through depletion of intracellular stores of muscle-specific miRNAs. NEW & NOTEWORTHY In this study of humans and mice, we define circulating microRNAs in plasma that are dose responsive to exercise. Our data support the notion that these microRNAs mediate physiological adaptation to exercise potentially through depletion of intracellular stores of muscle-specific microRNAs and releasing their inhibitory effects on target gene expression.

Pulmonary inflammation, which is characterized by the presence of perivascular macrophages, has been proposed as a key pathogenic driver of pulmonary hypertension (PH), a vascular disease with increasing global significance. However, the mechanisms of expansion of lung macrophages and the role of blood-borne monocytes in PH are poorly understood. Using multicolor flow cytometric analysis of blood in mouse and rat models of PH and patients with PH, an increase in blood monocytes was observed. In parallel, lung tissue displayed increased chemokine transcript expression, including those responsible for monocyte recruitment, such as Ccl2 and Cx3cl1, accompanied by an expansion of interstitial lung macrophages. These data indicate that blood monocytes are recruited to lung perivascular spaces and differentiate into inflammatory macrophages. Correspondingly, parabiosis between congenically different hypoxic mice demonstrated that most interstitial macrophages originated from blood monocytes. To define the actions of these cells in PH in vivo, we reduced blood monocyte numbers via genetic deficiency of cx3cr1 or ccr2 in chronically hypoxic male mice and by pharmacologic inhibition of Cx3cl1 in monocrotaline-exposed rats. Both models exhibited decreased inflammatory blood monocytes, as well as interstitial macrophages, leading to a substantial decrease in arteriolar remodeling but with a less robust hemodynamic effect. This study defines a direct mechanism by which interstitial macrophages expand in PH. It also demonstrates a pathway for pulmonary vascular remodeling in PH that depends upon interstitial macrophage-dependent inflammation yet is dissociated, at least in part, from hemodynamic consequences, thus offering guidance on future anti-inflammatory therapeutic strategies in this disease.

Previous neuroimaging studies have reported brain morphological alterations and the occurrence of mental disorders in primary insomnia (PI) patients. However, studies of the effect of disrupted sleep on brain structure have showed inconsistent results. In this study, DARTEL-VBM was used to evaluate the changes in gray matter volume from 60 PI patients and 53 controls. Voxel-wise statistics was performed in two ways. One is a more liberal statistical analysis using an uncorrected P

Summary BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin reader proteins that bind acetylated histones and regulate gene expression. Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We show that BRD4 is essential for the repair of DNA double-strand breaks (DSBs) and mediates the formation of oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced acetylation of histone H4, leading to BRD4 recruitment, and stable establishment of the DNA repair complex. In support of this, we also show that, in clinical tumor samples, BRD4 protein levels are negatively associated with outcome after prostate cancer (PCa) radiation therapy. Thus, in addition to regulating gene expression, BRD4 is also a central player in the repair of DNA DSBs, with significant implications for cancer therapy., Graphical abstract The classic function of BRD4 is to regulate gene expression. Li et al. present experimental and clinical data to suggest that BRD4 is also a key player in DNA repair and is associated with the development of CRPC after radiation therapy.

Codeine-containing cough syrups (CCS) have become one of the most popular drugs of abuse in young population worldwide. However, the neurobiological mechanisms underlying CCS-dependence are yet ill-defined. Therefore, understanding the brain abnormalities in chronic users of CCS is crucial for developing effective interventions. The present study depicted the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in chronic users of CCS. In addition, the degree centrality (DC) changes were correlated to the Barratt Impulsiveness Scale (BIS-11) total score, dose, duration of CCS use, and the age at first use of cough syrups. The current study included 38 chronic CCS users and 34 matched control subjects. All patients were evaluated using the BIS-11. Next, resting-state functional magnetic resonance imaging (rs-fMRI) datasets were acquired from these CCS users and controls. Whole-brain connectivity was analyzed using a graph theory approach: degree centrality (DC). CCS-dependent individuals exhibited low DC values in the left inferior parietal lobule and the left middle temporal gyrus, while high DC values were noted in the right pallidum and the right hippocampus (P, Highlights • The abuse of CCS has gained a severe foothold among young individuals worldwide. • DC is one of the more reliable and compelling measures among several nodal network metrics. • The present study depicted intrinsic dysconnectivity pattern of whole-brain functional networks in CCS-dependent individuals. • CCS-dependent individuals showed altered DC in the right pallidum, right hippocampus, left IPL and left middle temporal gyrus. • Significant correlations were established between average DC value in the left IPL and attentional impulsivity scores and the age at first CCS use.

Background Venous thromboembolism (VTE) is a preventable complication in which early ambulation is expected after head and neck surgery. Thus, the role of VTE prophylaxis is questionable and needs further assessment. The purpose of this study was to specify the relative contributing risk factors for patients who underwent head and neck cancer ablation with immediate reconstruction. Methods A retrospective analysis was conducted of consecutive head and neck cancer ablations with immediate reconstructions between 2008 and 2013. Dextran and prostaglandin E2 (PGE2) were routinely given as flap thromboprophylaxis. Logistic regression was applied to analyze the potentially significant risk factors. Results Of 1953 subjects, the incidence of symptomatic VTE was 2.2% with 0.1% mortality rate. Prolonged surgery (>592.5 minutes; P = .048), immobilization (>4 days; P = .019), and subjects without postoperative flap thromboprophylaxis (P = .002) are significant risk factors for VTE development. Conclusion Our flap thromboprophylaxis regime might have played a crucial role in keeping the incidence of VTE low. Despite prolonged immobilization in fibula flap reconstruction, the incidence of VTE remained low when flap thromboprophylaxis was given.

Background The Tokyo Guidelines 2007 (TG07) first presented the diagnostic and severity grading criteria for acute cholangitis. Subsequently updated in 2013, the Tokyo Guidelines (TG13) have been widely adopted throughout the world as global standard guidelines. We set out to verify the efficacy of these TG13 criteria in an international multicenter study. Methods We reviewed 6,063 patients who were clinically diagnosed with acute cholangitis in Japan and Taiwan over a 2-year period. The TG13 diagnostic and severity grading criteria were retrospectively applied, and 30-day mortality was investigated. Results A diagnosis of acute cholangitis was made in 5,454 (90.0%) patients on the basis of the TG13 criteria, and in 4,815 (79.4%) patients on the basis of the TG07 criteria. The 30-day mortality rates of patients with Grade III, Grade II, and Grade I were 5.1%, 2.6%, and 1.2%, respectively, and increased significantly along with disease severity. The mortality rate in the 1,272 Grade II cases where urgent or early biliary drainage was performed was 2.0% (n = 25), which was significantly lower than that of 3.7% (n = 28) in the other 748 cases. Conclusion By using the TG13 diagnostic and severity grading criteria, more patients with possible acute cholangitis can be diagnosed, and patients whose prognosis can potentially be improved by early biliary drainage can be identified. The TG13 criteria are appropriate and useful for clinical practice.

Background The collaborative multicenter retrospective study of acute cholecystitis (AC) was performed in Japan and Taiwan. The aim for this study was evaluation of the clinical value of TG13 severity grading for AC. Method The study was designed as an international multicenter retrospective study of AC from 2011 to 2013. Based on the data, we investigated the TG13 severity grading by analyzing the correlations between grade and prognosis, surgical procedures, histopathology, and organ dysfunction and prognosis. Results An investigation revealed that 30-day overall mortality rate was 1.1% for Grade I, 0.8% for Grade II, 5.4% for Grade III. The mortality rate for Grade III was significantly higher than lower grades (P

Background Since the publication of the Tokyo Guidelines (TG13) for the management of acute cholecystitis (AC), multidirectional studies have been published. However, epidemiological research about AC with big data was not projected. The aim of this study was to reveal the actual clinical conditions of AC. Method The study was designed as an international multicenter retrospective study of AC in Japan and Taiwan from 2011 to 2013. The factors investigated comprised data related to demographic, history, physical examinations, laboratory and imaging findings. Based on these data, we investigated the various values of AC, and real situation with respect to severity and treatment. Results A total of 5,459 patients with AC were reviewed. Thirty-day mortality rate was 1.1%. Based on the diagnostic criteria, 4,088 patients had a definite diagnosis and 291 had a suspected diagnosis. According to the severity grading, 939 patients were classified as Grade III, 2,308 as Grade II, and 2,130 as Grade I. Cholecystectomy was performed in total of 4,266 patients and 2,765 patients had laparoscopic cholecystectomy. The main etiologies were gallbladder stones in 4,623 cases. Conclusion This epidemiological study with large population will undoubtedly contribute to establish the best practice for managing AC worldwide.

Diabetes is a risk factor that increases the occurrence and severity of cardiovascular events. Cardiovascular complications are the leading cause of mortality of 75% of patients with diabetes >40 years old. Sesamin, the bioactive compound extracted from Sesamum indicum, is a natural compound that has diverse beneficial effects on hypoglycemia and reducing cholesterol. The aim of this study is to investigate sesamin effects to diabetes-inducing cardiac hypertrophy. In the present study bioinformatics analysis demonstrated cardiac hypertrophy signaling may be the most important pathway for upregulating genes in sesamin-treated groups. To verify the bioinformatics prediction, sesamin was used as the main bioactive compound to attenuate the impact of diabetes induced by streptozotocin (STZ) on cardiac function in a rat model. The results revealed that oral administration of sesamin for 4 weeks (100 and 200 mg/kg body weight) marginally improved blood glucose levels, body weight and significantly ameliorated the effects on heart rate and blood pressure in rats with type 1 diabetes relative to control rats. The QT interval of sesamin was also reduced relative to the control group. The findings indicated that sesamin has potential cardioprotective effects in the STZ-induced diabetes model. This suggested that this can be used as a novel treatment for patients with diabetes with cardiac dysfunction complication.

Background Generally, surgeons’ perceptions of surgical safety are based on experience and institutional policy. Our recent pilot survey demonstrated that the acceptable duration of surgery and criteria for open conversion during laparoscopic cholecystectomy (LC) vary among workplaces. Methods A web-based survey was distributed to 554 expert LC surgeons in Japan, Korea, and Taiwan. The questionnaire covered LC experience, safety measures and recognition of landmarks, decision-making regarding conversion to open/partial cholecystectomy and the implications of this decision. Overall responses were compared among nations, and then stratified by LC experience level (lifetime cases 200–499, 500–999, and ≥1000). Results The response rate was 92.6% (513/554); 67 surgeons with ≤199 LCs were excluded, and responses from 446 surgeons were analyzed. We observed significant differences among nations on almost all questions. Differences that remained after stratification by LC experience were on questions related to acceptable duration of surgery, adoption rates of intraoperative cholangiography, the “critical view of safety” technique, identification of Rouviere's sulcus, recognition of the SS-Inner layer theory, and intraoperative judgment to abandon conventional LC. Conclusions Even among experts, surgeons’ perceptions during LC are workplace-dependent. A novel grading system of surgical difficulty and standardized LC procedures are paramount to generate high-level evidence. This article is protected by copyright. All rights reserved.

Background Percutaneous cholecystostomy (PC) followed by definitive cholecystectomy is an alternative treatment for acute cholecystitis (AC). We retrospectively investigated the impact of PC tube removal before definitive cholecystectomy on surgical outcomes. Methods From 2012 to 2017, 942 AC patients underwent PC at a single institute. Eligible patients were selected according to inclusion criteria. Demographic data, clinical and laboratory parameters, and treatment outcomes were extracted from medical records. Categorization of patients and subsequent subgroup analysis were based on cholangiography. Results The rate of emergent cholecystectomy in the PC tube removal group was higher than that in the PC tube preserved group (OR = 2.969, 95% CI 1.334-6.612, P = 0.008). In subgroup analysis of patients with patent bile flow under cholangiography, the rate of emergent cholecystectomy was higher in the PC tube removal group (OR = 3.173, 95% CI 1.182-8.523, P = 0.022), though the incidence of complications was higher in the PC tube preserved group (P = 0.012). In addition, routine preoperative cholangiography had no clinical impact on surgical outcome. Conclusion Percutaneous cholecystostomy tube can be removed before subsequent LC to avoid postoperative complications, though removal of the PC tube is associated with an increased likelihood of emergent cholecystectomy.