Search

BACKGROUND Visceral leishmaniasis (VL) is a parasitic disease caused by Leishmania and transmitted by infected sand flies. VL has a low incidence in China, and its clinical presentation is complex and atypical. This disease is easily misdiagnosed and can become life-threatening within a short period of time. Therefore, early, rapid and accurate diagnosis and treatment of the disease are essential. CASE SUMMARY A 25-year-old male patient presented with the clinical manifestations of irregular fever, hepatosplenomegaly, increased polyclonal globulin, and pancytopenia. The first bone marrow puncture biopsy did not provide a clear diagnosis. In order to relieve the pressure and discomfort of the organs caused by the enlarged spleen and to confirm the diagnosis, splenectomy was performed, and hemophagocytic syndrome was diagnosed by pathological examination of the spleen biopsy. Following bone marrow and spleen pathological re-diagnosis and metagenomic next-generation sequencing (mNGS) technology detection, the patient was finally diagnosed with VL. After treatment with liposomal amphotericin B, the body temperature quickly returned to normal and the hemocytes recovered gradually. Post-treatment re-examination of the bone marrow puncture and mNGS data showed that Leishmania was not detected. CONCLUSION As a fast and accurate detection method, mNGS can diagnose and evaluate the efficacy of treatment in suspicious cases of leishmaniasis.

BACKGROUND While tuberculosis (TB) itself is a common disease, isolated TB of the liver is a rare entity. Tubercular involvement of the liver is more commonly a part of a disseminated disease of the hepatic parenchyma. In contrast, isolated hepatic TB spread through the portal vein from the gastrointestinal tract is seldom encountered in clinical practice, with only a few sporadic cases and short series available in the current literature. Vascular complications, such as portal vein thrombosis (PVT), have rarely been reported previously. CASE SUMMARY A 22-year-old man was hospitalized with complaints of a 3-mo history of fever and weight loss of approximately 10 kg. He had a 10-year hepatitis B virus (HBV) infection in his medical history. Contrast-enhanced computed tomography (CECT) confirmed hepatosplenomegaly, with hypodensity of the right lobe of the liver and 2.1 cm thrombosis of the right branch of the portal vein. A liver biopsy showed epithelioid granulomas with a background of caseating necrosis. Ziehl-Nelson staining showed acid-fast bacilli within the granulomas. The patient was diagnosed with isolated hepatic TB with PVT. Anti-TB therapy (ATT), including isoniazid, rifapentine, ethambutol, and pyrazinamide, was administered. Along with ATT, the patient was treated with entecavir as an antiviral medication against HBV and dabigatran as an anticoagulant. He remained asymptomatic, and follow-up sonography of the abdomen at 4 mo showed complete resolution of the PVT. CONCLUSION Upon diagnosis of hepatic TB associated with PVT and HBV coinfection, ATT and anticoagulants should be initiated to prevent subsequent portal hypertension. Antiviral therapy against HBV should also be administered to prevent severe hepatic injury.

BACKGROUND Open reduction and internal fixation (ORIF) is the traditional surgical treatment for patellar fractures, and unicompartmental knee arthroplasty (UKA), especially Oxford UKA, has been increasingly used in patients with medial knee osteoarthritis (OA). However, the process of choosing treatment for patients with both patellar fractures and anteromedial knee OA remains unclear. We present the case of a patient with a patellar fracture and anteromedial OA. CASE SUMMARY We present the case of a 72-year-old woman with a history of bilateral medial compartment OA of the knees and a right Oxford UKA. She also experienced a recent left patellar fracture. ORIF and Oxford UKA were performed in a single stage. The patient showed excellent postoperative clinical results. CONCLUSION ORIF and Oxford UKA can be performed simultaneously for patients with patellar fracture and anteromedial OA on the same knee.

BackgroundDiagnostic-related groups (DRGs) are a principle type of hospital payment systems worldwide. Laparoscopic cholecystectomy (LC) is a common surgical procedure for cholelithiasis paid by DRGs. However, acute cholecystitis (AC) patients usually have heterogeneous conditions that can negatively impact the successful implementation of DRGs. We evaluated the quality and efficiency of treating AC patients under the DRG system in Taiwan.MethodsAll AC patients who underwent LC between October 2015 and December 2016 were included. Patient demographics, comorbidities, laboratory tests, AC severity, treatment outcomes and financial results were recorded and compared. Patients were reimbursed by one of the two DRG schemes based on their comorbidities or complications (CC): DRG-1, LC without CC; and DRG-2, LC with CC. Hospitals were reimbursed with the lower threshold if costs were below the lower threshold (sector A); with the outlier threshold if costs were between the lower and outlier thresholds (sector B); and with the outlier threshold plus 80% of the exceeding cost if costs were higher than the outlier threshold (sector C). The lower and outlier thresholds for DRG-1 and DRG-2 were TWD 38,716 and TWD 64,146 and TWD 39,997 and TWD 81,843, respectively (TWD = Taiwan dollars, one US dollar is approximately 30 TWD).ResultsAmong 246 patients, 114 were paid by DRG-1, and 132 were paid by DRG-2. The sex ratio and AC severity were similar between groups, but DRG-2 patients were older and had more comorbidities. In total, 195 of 246 patients (79.3%) underwent LC within one day after admission, and patients with mild AC had shorter hospital stays than those with moderate or severe AC. The complication rate was 7.3%, and there was only one mortality. In total, 105 of 114 patients in DRG-1 and 120 of 132 patients in DRG-2 fell into sector B (the profitable sector). The average margin per patient was 11,032 TWD for DRG-1 and 24,993 TWD for DRG-2.ConclusionsDRGs can be well adopted for acute care surgery. Under such a system, hospitals can still provide efficient and quality medical services without losing profit.Trial registration:None, the current study is not a clinical trail

The GABAB receptor (GABABR) agonist baclofen has been used to treat alcohol and several other substance use disorders (AUD/SUD), yet its underlying neural mechanism remains unclear. The present study aimed to investigate cortical GABABR dynamics following chronic alcohol exposure. Ex vivo brain slice recordings from mice chronically exposed to alcohol revealed a reduction in GABABR-mediated currents, as well as a decrease of GABAB1/2R and G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) activities in the motor cortex. Moreover, our data indicated that these alterations could be attributed to dephosphorylation at the site of serine 783 (ser-783) in GABAB2 subunit, which regulates the surface expression of GABABR. Furthermore, a human study using paired-pulse-transcranial magnetic stimulation (TMS) analysis further demonstrated a reduced cortical inhibition mediated by GABABR in patients with AUD. Our findings provide the first evidence that chronic alcohol exposure is associated with significantly impaired cortical GABABR function. The ability to promote GABABR signaling may account for the therapeutic efficacy of baclofen in AUD.

Objective: To investigate the correlation between cognitive function and quality of life in patients with moderate to severe OSAHS, and to further analyze the impact of cognitive domains on QoL in ...

This study aimed to understand the prevalence of Chinese medicine and other potentially inappropriate medications and to examine if there are relationships with emergency room visits, hospital admissions, and falls in a Chinese nursing home population. This cross-sectional descriptive study was a secondary analysis of data from 531 nursing home residents in Taiwan. Cox proportional hazard regression models were used in the analysis. Use of Chinese medicine in combination with Western medicine was observed in approximately 1% of residents. For every additional Chinese medicine used, the hazard ratio was 3.09 (p=.26) for emergency room visits and 3.22 (p=.21) for hospital admissions. For every additional nonsteroidal antiinflammatory agent used, the hazard ratio for falls was 5.42 (p=.006). Further studies with larger sample sizes are required to understand the appropriate time intervals required between administration of Chinese and Western medicine as well as to understand the drug-drug interactions.

BackgroundRecent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients.MethodsA total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization.ResultsType 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037–5.051;P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377,P r = 0.491,P r = 0.330,P r = 0.194,P = 0.017); and fasting serum insulin (r = 0.167,P = 0.041) and IL-6 (r = 0.311,P ConclusionsOur results suggested that circulating sRAGE is independently risk factor for CRC, and also closely related to inflammation, dyslipidemia in type 2 diabetes patients.

To evaluate the clinical efficacy and safety of Congrong Shujing Granules (苁蓉舒 痉颗粒, CSGs) in treating patients with Parkinson’s disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach. Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson’s Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction. A total of 86 PD patients were selected from the Third Affifiliated People’s Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P 0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B. CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394)

Objective A small thigh circumference is associated with an increased risk of diabetes, cardiovascular diseases, and total mortality. The purpose of this study was to evaluate the association between thigh circumference and hypertension in the middle-aged and elderly population. Methods A total of 9520 individuals aged 40 years and older with measurement of thigh circumference were available for analysis. The measurement of thigh circumference was performed directly below the gluteal fold of the thigh. The association of thigh circumference with hypertension was tested in logistic regression analyses and reported as odds ratio (OR) with 95% CI. Results Thigh circumference was negatively correlated with systolic blood pressure, diastolic blood pressure, fasting glucose, and total cholesterol. Compared with the lowest thigh circumference tertile group, the risk of hypertension was significantly lower in the highest tertile group, both in overweight individuals (OR 0.68; 95% CI 0.59–0.79, P P Conclusion In the present study, large thigh circumference is associated with lower risk of hypertension in overweight and obese Chinese individuals.

Background Nucleus Accumbens (NAc) is a vital brain region for the process of reward and stress, whereas microRNA plays a crucial role in depression pathology. However, the abnormality of NAc miRNA expression during the stress-induced depression and antidepressant treatment, as well as its biological significance, are still unknown. Methods We performed the small RNA-sequencing in NAc of rats from three groups: control, chronic unpredictable mild stress (CUMS), and CUMS with an antidepressant, Escitalopram. We applied an integrative pipeline for analyzing the miRNA expression alternation in different model groups, including differential expression analysis, co-expression analysis, as well as a subsequent pathway/network analysis to discover both miRNA alteration pattern and its biological significance. Result A total of 423 miRNAs were included in analysis.18/8 differential expressing (DE) miRNA (adjusted p 1) were observed in controls Vs. depression/depression Vs. treatment, 2 of which are overlapping. 78% (14/18) of these miRNAs showed opposite trends of alteration in stress and treatment. Two micro RNA, miR-10b-5p and miR-214-3p, appeared to be hubs in the regulation networks and also among the top findings in both differential analyses. Using co-expression analysis, we found a functional module that strongly correlated with stress (R = 0.96, P = 0.003), and another functional module with a moderate correlation with anhedonia (R = 0.89, P = 0.02). We also found that predicted targets of these miRNAs were significantly enriched in the Ras signaling pathway, which is associated with both depression, anhedonia, and antidepressant treatment. Conclusion Escitalopram treatment can significantly reverse NAc miRNA abnormality induced by chronic stress. However, the novel miRNA alteration that is absent in stress pathology also emerges, which means that antidepressant treatment is unlikely to bring miRNA expression back to the same level as the controls. Also, the Ras-signaling pathway may be involved in explaining the depression disease etiology, the clinical symptom, and treatment response of stress-induced depression.

Objective The aims of this study were to compare the clinical outcomes between image-guided percutaneous microwave ablation (MWA) and cryoablation (CRA) in patients with hepatocellular carcinoma (HCC) in high-risk locations and to identify the prognostic factors associated with the two treatment methods. Methods This retrospective study was institutional review board approved. A total of 120 patients (88 men and 32 women) with one hundred and thirty-four HCC lesions in high-risk locations from April 2014 to March 2018 were reviewed. Sixty-four patients underwent MWA and 56 patients underwent CRA. Survival, recurrence and complications were compared between the two groups. Effect of changes in key outcomes (i.e., overall survival (OS), recurrence-free survival (RFS) and local tumor progression (LTP)) was statistically analyzed with the log rank test. Univariate and multivariate analysis were performed on clinicopathological variables to identify factors affecting intermediate-term outcomes. Results The OS and RFS after MWA were comparable to those of CRA (P =0.141, and P=0.469, respectively). The LTP and major complication in MWA group was higher than those in CRA group (P=0.003, and P=0.039). Univariate analysis showed that age (P=0.007), tumor size (P=0.001), and Child-Turcotte-Pugh (CTP) grade (P=0.003) were risk factors for OS, and multivariate analysis results showed that older age (≥65 years) (P=0.002, HR:3.338, 95% CI:1.928-5.281), 3.0-5.0 cm in size (P

Background Corrected QT (QTc) interval has been reported to be associated with type 2 diabetes. This study aimed to explore the relationship between different glucose tolerance and QTc intervals among middle-aged and older Chinese individuals. Methods We conducted a cross-sectional analysis that included 9898 subjects (3194 men and 6704 women) in a Chinese population. Glucose tolerance was studied during the oral glucose tolerance test (OGTT). Insulin, blood pressure, hemoglobin A1c (HbA1c), serum lipids, hepatic transaminases and waist-to-hip ratio were assessed. The QTc interval was derived from ECG recordings, and the subjects were stratified based on different glucose tolerance. Results QTc interval levels were increased significantly in the subjects with abnormal glucose metabolism compared with the normal glucose regulation group. Multiple regression analyses showed that the QTc interval was significantly associated with fasting plasma glucose, 2-h OGTT plasma glucose and HbA1c. The odds ratio of prolonged QTc was 1.396 for impaired glucose regulation (IFG)/impaired fasting glucose (IGT) (95% CI 0.126–1.730), and 1.342 for type 2 diabetes (95% CI 0.142–1.577) after all potential confounders were adjusted. Conclusions Impaired glucose tolerance (IGR) and diabetes are associated with prolonged QTc intervals among middle-aged and older Chinese individuals. Abnormal glucose regulation can be used to monitor the QTc interval in the population.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is now regarded as the hepatic manifestation of metabolic syndrome (MetS). Recent research has suggested that serum creatinine (SCr) may be an indicator of MetS and its related diseases. We aimed to investigate the association between SCr and NAFLD in Chinese adults. METHODS A cross-sectional sample of 8862 subjects aged 40 years or older (40-73 years) from China were analysed in this study. The anthropometric measurements, laboratory tests, and hepatic ultrasonography were conducted. NAFLD presence was defined by hepatic ultrasound in the absence of other liver diseases. RESULTS NAFLD subjects had higher SCr than those without NAFLD (66.8 μmol/L vs. 65.6 μmol/L, p

Extraosseous Ewing’s sarcoma (EES) is a malignant tumor that is classified as a rare disease. EES is common in children and adolescents, with a rarer incidence being present in the elderly. ES of the primary intestine is rare, with only a few reports described in the literature. Here we report a case of a 69-year-old male patient who was experiencing abdominal pain for over 3 months. Ultrasonography (US) revealed a solid hypoechoic lesion with multiple irregular necrotic areas in the left lower abdomen close to the dome of the bladder. Contrast-enhanced ultrasonography (CEUS) showed that the lesion exhibited heterogeneous enhancement and quick peripheral enhanced tissue wash-out classifying this mass as malignant. PET–CT showed a high metabolic mass in the lower abdomen, multiple metabolic nodules in the mesentery, considered as a small intestinal stromal tumor with lymph nodes metastasis, and that a diagnosis of lymphoma should be excluded. Esophagogastroduodenoscopy performed at another hospital 1 month prior to CT showed an abnormal density in the pelvic cavity that was considered as a colonic diverticulum with an abscess. The endoscopy showed no obvious occupying lesions. The mass was removed and postoperative pathology confirmed ES of the small intestine. The patient avoided receiving chemotherapy. After 2 months, skull metastasis was diagnosed and surgical intervention was done. His survival was only six months after the second surgery. To our knowledge, our case is the first report of ultrasound and CEUS manifestation of EES in the small intestine in elderly.

Background Observational studies have identified various associations between neuroimaging alterations and neuropsychiatric disorders. However, whether such associations could truly reflect causal relations remains still unknown. Results Here, we leveraged genome-wide association studies (GWAS) summary statistics for (1) 11 psychiatric disorders (sample sizes varied from n = 9,725 to 1,331,010); (2) 110 diffusion tensor imaging (DTI) measurement (sample size n = 17,706); (3) 101 region-of-interest (ROI) volumes, and investigate the causal relationship between brain structures and neuropsychiatric disorders by two-sample Mendelian randomization. Among all DTI-Disorder combinations, we observed a significant causal association between the superior longitudinal fasciculus (SLF) and the risk of Anorexia nervosa (AN) (Odds Ratio [OR] = 0.62, 95 % confidence interval: 0.50 ~ 0.76, P = 6.4 × 10− 6). Similar significant associations were also observed between the body of the corpus callosum (fractional anisotropy) and Alzheimer’s disease (OR = 1.07, 95 % CI: 1.03 ~ 1.11, P = 4.1 × 10− 5). By combining all observations, we found that the overall p-value for DTI − Disorder associations was significantly elevated compared to the null distribution (Kolmogorov-Smirnov P = 0.009, inflation factor λ = 1.37), especially for DTI − Bipolar disorder (BP) (λ = 2.64) and DTI − AN (λ = 1.82). In contrast, for ROI-Disorder combinations, we only found a significant association between the brain region of pars triangularis and Schizophrenia (OR = 0.48, 95 % CI: 0.34 ~ 0.69, P = 5.9 × 10− 5) and no overall p-value elevation for ROI-Disorder analysis compared to the null expectation. Conclusions As a whole, we show that SLF degeneration may be a risk factor for AN, while DTI variations could be causally related to some neuropsychiatric disorders, such as BP and AN. Also, the white matter structure might have a larger impact on neuropsychiatric disorders than subregion volumes.

Aims: To evaluate the prospective association of circulating PCSK9 levels with the cardiometabolic risk profiles (high LDL-cholesterol, high triglycerides, low HDL-cholesterol, hypertension, type 2 diabetes, and metabolic syndrome).Methods: A population-based prospective study was conducted among 7,104 Chinese individuals (age 56.2 ± 7.5 years; 32.0% men). Circulating PCSK9 levels were measured using ELISA.Results: Circulating PCSK9 levels were higher in women than men (286.7 ± 90.1 vs. 276.1 ± 86.4 ng/ml, p < 0.001). And circulating PCSK9 was positively correlated with LDL-cholesterol, total cholesterol, and triglycerides both in men and women (all p < 0.001). The positive correlation between PCSK9 and waist circumference, fasting glucose, insulin resistance, systolic blood pressure, diastolic blood pressure and C-reactive protein (all p < 0.01) was observed in women only. According to Cox regression analysis, circulating PCSK9 was positively associated with incidence of high LDL-cholesterol both in men (HR 1.33, 95% CI 1.09–1.65, p < 0.001) and women (HR 1.36, 95% CI 1.12–1.69, p < 0.001). Moreover, PCSK9 was significantly associated with incident high triglycerides (HR 1.31, 95% CI 1.13–1.72, p < 0.001), hypertension (HR 1.28, 95% CI 1.08–1.53, p = 0.011), type 2 diabetes (HR 1.34, 95% CI 1.09–1.76, p = 0.005), and metabolic syndrome (HR 1.30, 95% CI 1.11–1.65, p = 0.009) per SD change in women only. No statistically significant association was observed between circulating PCSK9 and incidence of low HDL-cholesterol (p > 0.1).Conclusions: Elevated circulating PCSK9 was significantly associated with cardiometabolic risk factors and independently contributed to the prediction of cardiometabolic risks in women.

ObjectiveGrowth differentiation factor 15 (GDF-15) is a member of the TGF-β superfamily that has anti-inflammatory properties. The objective of this study was to evaluate the relationship between circulating GDF-15 levels and diabetic retinopathy (DR) in patients with type 2 diabetes.Materials/MethodsA case–control study was performed in which 402 patients with type 2 diabetes were enrolled. Of these, 171 patients had DR and the remaining 231 patients without DR acted as controls. The plasma GDF-15 levels were measured using ELISA, while DR was diagnosed using the canon ophthalmic digital imaging system and the Canon EOS 10D digital camera (Canon, Tokyo, Japan) through a non-pharmacologically dilated pupil.ResultsThe levels of GDF-15 were significantly higher in patients with DR [168.9 (112.9–228.3) pg/ml vs. 127.8 (96.1–202.8) pg/ml, P < 0.001] compared to controls. Results of the Spearman correlation analysis showed that the GDF-15 levels were positively associated with the duration of diabetes morbidity, fasting plasma glucose, systolic blood pressure, albumin/creatinine ratio, creatinine, and liver enzymes, but negatively associated with eGFR (both P < 0.001). The participants in the highest GDF-15 quartile had a significantly increased risk for DR (OR = 2.15, 95% CI 1.53–3.02) after adjusting for potential cofounders.ConclusionsThe circulating GDF-15 levels are positively associated with DR independent of potential cofounders.

Background Neck circumference, a proxy for upper-body subcutaneous fat, is a unique and pathogenic fat depot that confers additional metabolic risk. The purpose of present study was to determine whether neck circumference associates with nonalcoholic fatty liver disease (NAFLD) in postmenopausal women with normal body mass index. Methods A cross-sectional survey (n = 2492) and a 3.1-year follow-up investigation (n = 1354) were conducted among Chinese postmenopausal women with normal BMI (18.5 to 2). Neck circumference was measured horizontally at the lower margin of the laryngeal prominence. Results In the cross-sectional analysis, large neck circumference was associated with the presence of NAFLD (odds ratio 2.28; 95% CI 1.74–2.98; highest tertile versus lowest tertile) after adjustment for confounding factors. Among 1354 subjects without the NAFLD at baseline, 429 (31.7%) incident NAFLD cases occurred at 3.1 years. Neck circumference was positively associated with triglycerides, homeostasis model assessment of insulin resistance, C-reactive protein, and negatively associated with high-density lipoprotein cholesterol and adiponectin. Individuals with large baseline neck circumference had a significantly higher risk of NAFLD than those with small neck circumference. The multivariable adjusted hazard ratio was 1.42 (95% CI 1.15–1.97; p for trend = 0.004) for the highest versus the lowest tertile of neck circumference, and was 1.22 (95% CI 1.10–1.41; p = 0.006) per 1-standard deviation increment in neck circumference. Conclusions Among postmenopausal women with normal BMI, relatively large neck circumference levels are associated with an increased risk of NAFLD.

A 30-year-old man walked into the emergency department after a suicide attempt by firing a nail from a pneumatic nail gun directed at his left temple. He was haemodynamically stable and neurologically intact, able to recall all events and moving all extremities with a Glascow Coma Scale of 15. CT of the brain showed a 6.3 cm nail in the right frontal region without major intracerebral vessel disruption. He was taken to the operating room for left temporal wound washout, debridement of gross contamination and closure with titanium cranial fixation plate. The foreign body was not accessible on initial surgical intervention and was left in place to define anatomy and plan for subsequent removal. Thin slice CT images were used to create 3D reconstructions to facilitate stereotactic navigation and foreign body removal via right craniotomy the following day. The patient tolerated the procedures well and recovered with full neurological function.

Objective Albumin-to-alkaline phosphatase ratio (AAPR), a newly developed blood biomarker, has been reported to have prognostic value in several types of cancer. This study aimed to investigate the predictive value of AAPR in patients with early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) as initial therapy. Methods This retrospective study analyzed 445 patients with newly diagnosed HCC undergoing RFA as initial therapy. A series of survival analyses were performed to evaluate the prognostic value of AAPR. Univariate and multivariate analyses were performed to identify independent prognostic factors. An AAPR-based nomogram was constructed, and its predictive performance was validated. Results Patients with a low AAPR had a significantly reduced recurrence-free survival (RFS) and overall survival (OS) compared with those with a high AAPR. AAPR was found to be an independent prognostic indicator and showed superior discrimination efficacy than other liver function indices. The AAPR-based nomogram had a concordance index value of 0.72 (95% confidence interval [CI]: 0.65–0.79) in the training cohort and 0.72 (95% CI: 0.63–0.81) in the validation cohort, which significantly outperformed other existing staging systems. Conclusions AAPR serves as a promising indicator of prognosis in patients with early-stage HCC undergoing RFA. The AAPR-based nomogram might contribute to individualized prognosis prediction and clinical decision making.

Pemphigus is a life-threatening and skin-specific inflammatory autoimmune disease, characterized by intraepidermal blistering between the mucous membranes and skin. Chinese herbal medicine (CHM) has been used as an adjunct therapy for treating many diseases, including pemphigus. However, there are still limited studies in effects of CHM treatment in pemphigus, especially in Taiwan. To more comprehensively explore the effect of long-term CHM treatment on the overall mortality of pemphigus patients, we performed a retrospective analysis of 1,037 pemphigus patients identified from the Registry for Catastrophic Illness Patients database in Taiwan. Among them, 229 and 177 patients were defined as CHM users and non-users, respectively. CHM users were young, predominantly female, and had a lesser Charlson comorbidity index (CCI) than non-CHM users. After adjusting for age, sex, prednisolone use, and CCI, CHM users had a lower overall mortality risk than non-CHM users (multivariate model: hazard ratio (HR): 0.422, 95% confidence interval (CI): 0.242–0.735, p = 0.0023). The cumulative incidence of overall survival was significantly higher in CHM users than in non-users (p = 0.0025, log rank test). Association rule mining and network analysis showed that there was one main CHM cluster with Qi–Ju–Di–Huang–Wan (QJDHW), Dan–Shen (DanS; Radix Salviae miltiorrhizae; Salvia miltiorrhiza Bunge), Jia–Wei–Xiao–Yao-–San (JWXYS), Huang–Lian (HL; Rhizoma coptidis; Coptis chinensis Franch.), and Di–Gu–Pi (DGP; Cortex lycii; Lycium barbarum L.), while the second CHM cluster included Jin–Yin–Hua (JYH; Flos lonicerae; Lonicera hypoglauca Miq.) and Lian–Qiao (LQ; Fructus forsythiae; Forsythia suspensa (Thunb.) Vahl). In Taiwan, CHMs used as an adjunctive therapy reduced the overall mortality to approximately 20% among pemphigus patients after a follow-up of more than 6 years. A comprehensive CHM list may be useful in future clinical trials and further scientific investigations to improve the overall survival in these patients.

Background: Primary duct closure (PDC) after laparoscopic common bile duct exploration (LCBDE) has been widely applied for choledocholithiasis. However, there has been controversy over the placement of endoscopic nasobiliary drainage (ENBD) during operation. To date, few studies compare the clinical effect of PDC without and with ENBD. The aim of this study was to assess the safety and efficacy of PDC without ENBD for choledocholithiasis. Methods: From January 2016 to December 2018, a total of 164 patients meeting the inclusion criteria were enrolled and divided into group A (undergone LCBDE + PDC without ENBD, 81 cases) and group B (undergone LCBDE + PDC with ENBD, 83 cases) in this study. The intraoperative conditions and postoperative complications were compared between the 2 groups. Results: In group A, the time of operation, postoperative first flatus, extubation, antibiotics, and discharge were shorter than in group B (t = −17.775, p = 0.000; t = −7.649, p = 0.000; t = −5.807, p = 0.000; t = −9.247, p = 0.000; t = −9.322, p = 0.000, respectively). Furthermore, intraoperative blood loss was less (t = −2.199, p = 0.029) and hospital costs were lower (t = −6.685, p = 0.000). However, there was no significant difference in postoperative complications between the 2 groups (p > 0.05). Conclusions: In patients who meet the screening criteria, PDC without ENBD after LCBDE is safe and effective and worthy of clinical application.

The survival of patients with HIV has greatly improved, due to Anti-Retroviral Therapy (ART). However, long-term HIV survivors often develop serious bone abnormalities, possibly due to the interplay of osteoblasts, osteoclasts, HIV ad ART. We evaluated in a nation-wide study in Taiwan the effect of Chinese herbal medicine (CHM) on overall mortality in HIV patients with osteoporosis or fractures. Enrollment period was between 1998 and 2011. Patients with osteoporosis or fractures before the HIV infection, and those with less than 14 days CHM use, were excluded. This left 498 patients, 160 CHM users, 338 without CHM. Univariate Kaplan-Meier and multivariate Cox regression analysis were used to compare the overall mortality in these 2 groups. Due to the nature of Chinese medicine, CHMs inevitably varied. We therefore also used rule mining and network analysis to determine which major CHM clusters were prescribed to the patients. CHM users had a much Lower mortality (hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.24–0.77, p < 0.005) and higher survival (p = 0.004, log-rank test). Although the CHMs greatly varied, network analysis identified one main cluster of strongly related CHM combinations (Chuan-Xiong-Cha-Tiao-San (CXCTS), Gan-Cao (GC; Glycyrrhiza uralensis Fisch.), Liu-He-Tang (LHT), Huang-Qin-Tang (HQT), Jia-Wei-Ping-Wei-San (JWPWS), and Dang-Gui-Long-Hui-Wan (DGLHuiW)). CHM as an additional treatment strongly improves overall survival in HIV-infected patients with osteoporosis and fractures.

Hypothyroid myopathy is a skeletal muscle disease caused by hypothyroidism. However, patients with hypothyroidism are often misdiagnosed as polymyositis if they do not have a clear history of thyroid gland or obvious hypometabolic symptoms, but with myasthenia and myalgia as the main symptoms or the first symptoms. Moreover, hypothyroid myopathy with periodic paralysis as the first symptom is rare in clinic. In this study, we summarized the clinical data of 1 case of hypothyroid myopathy with periodic paralysis as the first symptom in our clinical diagnosis and treatment. A 27-year-old male patient with recurrent periodic paralysis was found with hypothyroidism during a most recent attack of myasthenia and was diagnosed with hypothyroid myopathy, which was relieved after oral administration of levothyroxine. We also found 13 similar cases reported internationally, and summarized their clinical characteristics, diagnosis, and treatment methods to provide reference for the clinical diagnosis and treatment of such cases. In general, periodic paralysis may be the main symptom or even the first symptom of hypothyroid myopathy, which is easy to be confused with renal tubular acidosis (RTA) or other autoimmune diseases. The diagnosis is mainly based on the detection of thyroid function and thyroid autoantibodies. Timely supplement of thyroxine and correction of electrolyte disorders are the key to treatment.

Background: Heart failure (HF) is associated with type 2 diabetes mellitus (T2DM). Antihyperglycemic drugs have interaction with heart failure among diabetic patients. To date, the data on real world use of diabetic medication in Malaysian heart failure patients with T2DM has not been elucidated. Objective: This study aims to identify the prescribing pattern of antihyperglycemic regimens in HF patients with T2DM, and to investigate the association between glycemic control and other factors such as demographic and clinical characteristics with left ventricular ejection fraction (LVEF) in these patients. Methods: This retrospective observational study involved patients diagnosed to have HF and T2DM who were seen in the outpatient clinic in a government tertiary hospital in Malaysia. Patients receiving at least one oral antidiabetic agent and/or insulin for at least 3 months prior were included. The differences and association between study outcomes were examined and analyzed using Pearson's Chi-square test, One-Way ANOVA, Binary Logistic Regression and multiple Multinomial Logistic Regression models. Results: From July to December 2019, 194 patients were included in this study. The majority (52.1%) of the patients had HF with preserved ejection fraction (HFpEF), 20.6% had HF with mid-range EF (HFmrEF), and 27.3% had HF with reduced EF (HFrEF). Overall, metformin (59.8%) was the commonest antihyperglycemic agent prescribed, followed by insulins (54.0%), and sulphonylureas (44.9%). The most prescribed agents for HFpEF, HFmrEF, and HFrEF patients were metformin (65.3%), insulins (62.5%), and sulphonylureas (60.4%), respectively. The prescribing trend of sulphonylureas was found to be significantly associated with patients' LVEF status (p = 0.033). The odds for sulphonylurea prescription among the HFrEF patients were 2.42 times higher compared to the HFpEF patients [95% confidence interval [CI], 1.23–4.79]. There was no association found between glycemic control with patients' LVEF. Conclusion: Our findings reported metformin as the most commonly prescribed antihyperglycemic agent, sodium glucose linked transporter-2 (SGLT-2) inhibitor being under-prescribed, and detected poorly controlled diabetes in majority of patients with T2DM and HF. Understanding the prescribing pattern of antihyperglycemic agents supports the implementation of evidence-based treatment in HF patients with T2DM to improve patients' outcomes.

This study was to evaluate the impact of the symptoms of overactive bladder (OAB) syndrome on female sexual function. Seventy nine patients with OAB (OAB group) and 79 healthy women (control group) underwent physical examination at our center, and had their sexual function evaluated using the female sexual function index (FSFI). In accordance with the presence or absence of urge incontinence, the OAB group was further divided into the wet and dry groups. The sexual function was evaluated again after 3 months of pharmacotherapy. We investigate the difference of sexual function between OAB and control group. The effect of OAB severity and OAB pharmacotherapy on sexual function was also explored. There were no significant differences between OAB group and control group, including age, body mass index (BMI), education, occupation, fertility, parity, childbirth, and menopause. Compared with the control group, the OAB group had significantly lower FSFI scores. The respective mean ± standard error FSFI scores in the control group and the OAB group were 2.98 ± 1.07 and 2.27 ± 0.96 for desire, 3.48 ± 1.16 and 2.32 ± 1.44 for arousal, 4.60 ± 1.13 and 3.10 ± 1.95 for lubrication, 3.37 ± 0.87 and 2.63 ± 1.04 for orgasm, 3.58 ± 1.02 and 2.41 ± 1.35 for sexual satisfaction, 3.58 ± 1.02 and 2.41 ± 1.35 for sexual pain, and 22.24 ± 5.29 and 15.59 ± 7.47 for the total score (P

Acute cholecystitis (AC) is a common surgical emergency. The Tokyo Guidelines 2018 (TG18) provides a reliable algorithm for the treatment of AC patients to achieve optimal outcomes. However, the economic benefits have not been validated. We hypothesize that good outcomes and cost savings can both be achieved if patients are treated according to the TG18. This retrospective study included 275 patients who underwent cholecystectomy in a 15-month span. Patients were divided into three groups (group 1: mild AC; group 2: moderate AC with American Society of Anesthesiologists (ASA) physical status class ≤ 2 and Charlson Comorbidity Index (CCI) score ≤ 5; and group 3: moderate AC with ASA class ≥ 3, CCI score ≥ 6, or severe AC). Each group was further divided into two subgroups according to management (followed or deviated from the TG18). Patient demographics, clinical outcomes, and hospital costs were compared. For group 1 patients, 77 (81%) were treated according to the TG18 and had a significantly higher successful laparoscopic cholecystectomy (LC) rate (100%), lower hospital cost ($1896 vs $2388), and shorter hospital stay (2.9 vs 8 days) than those whose treatment deviated from the TG18. For group 2 patients, 50 (67%) were treated according to the TG18 and had a significantly lower hospital cost ($1926 vs $2856), shorter hospital stay (3.9 vs 9.9 days), and lower complication rate (0% vs 12.5%). For group 3 patients, 62 (58%) were treated according to the TG18 and had a significantly lower intensive care unit (ICU) admission rate (9.7% vs 25%), but a longer hospital stay (12.6 vs 7.8 days). However, their hospital costs were similar. Early LC in group 3 patients did not have economic benefits over gallbladder drainage and delayed LC. The TG18 are the state-of-the-art guidelines for the treatment of AC, achieving both satisfactory outcomes and cost-effectiveness.

The aim of this study is to evaluate the relationship between maternal single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine (HCY) level and offspring congenital heart diseases (CHDs). 338 mothers with offspring CHDs as case group and 306 mothers of normal children as control group were recruited. Their pregnant histories were interviewed by questionnaire and the MTHFR rsl801133 and rsl801131 were genotyped. The case–control analysis was used to find out the relationship between maternal SNPs of MTHFR gene and offspring CHDs. And the plasma HCY concentration of the mothers of CHDs children was detected. This case–case study was intended to find out the relevance between maternal HCY level and SNPs of MTHFR gene. There were significant differences in the gender of children, occupation of mothers, family history with CHDs, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHDs group and control group (P

Objective: Systemic hypoperfusion is intricately involved in neurohormone secretion, vascular calcification (VC) related impaired vasodilation, and luminal stenosis. We aimed to conduct a joint evaluation of vasopressin-neurophysin II-copeptin peptide (VP) and advanced aortic arch calcification (AAC) on all-cause and cardiovascular (CV) mortality in maintenance hemodialysis (MHD) patients. Methods: Unadjusted and adjusted hazard ratios (aHRs) of mortality risks were analyzed for different groups of VP and AAC in 167 MHD patients. The modification effect between higher VP and advanced AAC on mortality risk was examined using an interaction product term. Results: Interactions between VP and AAC with respect to all-cause and CV mortality were statistically significant. In multivariable analysis, higher VP predicted all-cause and CV mortality [aHR: 2.2 (95% confidence interval (CI): 1.1–4.5)] and 2.6 (95% CI: 1.1–4.6), respectively. Advanced AAC was associated with incremental risks of all-cause and CV mortality [aHR: 2.1 (95% CI: 1.1–4.0)and 2.5 (95% CI: 1.0–4.3), respectively]. Patients with combined higher VP (>101.5 ng/mL) and advanced AAC were at the greatest risk of all-cause and CV mortality [aHR: 4.7 (95% CI: 1.2–16.2)and 4.9 (95% CI: 1.1–18.9), respectively]. Conclusion: Combined VP and advanced AAC predict not only all-cause but also CV death in MHD patients, and a joint evaluation is more comprehensive than single marker. In light of hypoperfusion and ischemic events in vital organs, VP and AAC could act as more robust dual marker for prognostic assessment.

Background: Uremic vascular calcification (UVC) is reminiscent of osteogenesis and apoptosis in vascular smooth muscle cell (VSMC). We aimed to identify how circulating procalcific particles dramatically leak into VSMC layer in human tissue models of vascular rings. Methods: According to baseline estimated glomerular filtration rate (eGFR), patients following lower extremity amputation were divided into three groups: normal renal function (eGFR ≧ 60 ml/min), mild-to-moderate (15 ml/min < eGFR ≧ 60 ml/min) and severe chronic kidney disease (CKD) (eGFR ≦ 15 ml/min). Arterial specimens with immunohistochemistry stain were quantitatively analyzed for UVC, internal elastic lamina (EL) disruption, α-SMA, osteogenesis, apoptosis, and oxidative injury. Correlations among UVC severity, eGFR, EL disruption, osteogenesis, and oxidative injury were investigated. Results: CKD arteries were associated with eGFR-dependent EL disruption corresponding to UVC severity. CKD arteries exhibited lower α-SMA, higher expressions of caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), indicative of contractile VSMC loss, and apoptosis. Enhanced expressions of alkaline phosphatase and Runx2 were presented in VSMCs of CKD arteries, indicative of osteogenic differentiation. Above eGFR-dependent UVC and EL disruption correlated expressions of 8-hydroxy-2'-deoxyguanosine (8-OHdG), indicating oxidative EL injury promoted procalcific processes. Conclusions: Circulating uremic milieu triggers vascular oxidative stress, leading to progressive internal EL disruption as a key event in disabling VSMC defense mechanisms and catastrophic mineral ion influx into VSMC layer. Oxidative EL injury begins in early CKD, corresponding with active VSMC re-programming, apoptosis, and ultimately irremediable UVC. In light of this, therapeutic strategies targeting oxidative tissue injury might be of vital importance to hinder the progression of UVC related cardiovascular events.

This study investigated the effects of the Cong Rong Shu Jing (CRSJ) compound on endoplasmic reticulum stress in a rat model of Parkinson's disease (PD). A total of 40 rats were subcutaneously injected with rotenone-sunflower oil emulsion into the back of the neck to establish a rat model of PD. These PD rats were randomly divided into low-, medium-, and high-dose groups (intragastric administration of 0.5, 1, and 2 g/kg CRSJ, respectively) and a model group (intragastric administration of the solvent; 10 rats per group). Furthermore, 10 rats each were attributed to the control and vehicle groups (both received intragastric administration of the CRSJ solvent, and the vehicle group were injected additionally with sunflower oil alone). A traction test was conducted two times, after the PD model establishment and after 14 days of CRSJ gavage. The numbers of tyrosine hydroxylase- (TH-) positive cells and the dopamine levels in the substantia nigra were assessed using immunohistochemistry and high-performance liquid chromatography, respectively. Western blotting detected the expression levels of α-synuclein, endoplasmic reticulum stress pathways-related proteins, cerebral dopamine neurotrophic factor (CDNF), mesencephalic astrocyte-derived neurotrophic factor (MANF), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related proteins. Compared with the model group, the number of TH-positive cells in the substantia nigra was increased in the CRSJ groups. The expression levels of α-synuclein and the endoplasmic reticulum stress pathways-associated proteins glucose regulatory protein 78, inositol-requiring enzyme 1, apoptosis signal-regulating kinase 1, phosphorylated c-Jun N-terminal kinase, and caspase-12 were reduced. However, CRSJ administration elevated the expression levels of the neurotrophic factors CDNF and MANF, as well as those of p-PI3K and p-AKT. The CRSJ compound can relieve endoplasmic reticulum stress in PD rats and exerts protective effects in this animal model. These effects may be related to increased expression of neurotrophic factors and activation of the PI3K/AKT pathway.

Nonalcoholic fatty liver disease (NAFLD) is a very common liver disease, and its incidence has significantly increased worldwide. The liver X receptor α (LXRα) is a multifunctional nuclear receptor that controls lipid homeostasis. Inhibition of LXRα transactivation may be beneficial for NAFLD and hyperlipidemia treatment. Ursolic acid (UA) is a plant triterpenoid with many beneficial effects; however, the mechanism of its action on LXRα remains elusive. We evaluated the effects of UA on T0901317 (T090)-induced LXRα activation and steatosis. UA significantly decreased the LXR response element and sterol regulatory element-binding protein-1c ( SREBP-1c) gene promoter activities, mRNA, protein expression of LXRα target genes, and hepatic cellular lipid content in a T090-induced mouse model. A molecular docking study indicated that UA bound competitively with T090 at the LXRα ligand binding domain. UA stimulated AMP-activated protein kinase (AMPK) phosphorylation in hepatic cells and increased corepressor, small heterodimer partner-interacting leucine zipper protein (SMILE) but decreased coactivator, steroid receptor coactivator-1 (SRC-1) recruitment to the SREBP-1c promoter region. In contrast, UA induced SRC-1 binding but decreased SMILE binding to reverse cholesterol transport-related gene promoters in intestinal cells, increasing lipid excretion from intestinal cells. Additionally, UA reduced valproate-induced LXRα mediated and rifampin-induced pregnane X receptor mediated lipogenesis, offering potential treatments for drug-induced hepatic steatosis. Thus, UA displays liver specificity and can be selectively repressed while RCT stimulation by LXRα is preserved and enhanced. This is a novel therapeutic option to treat NAFLD and may be helpful in developing LXR agonists to prevent atherosclerosis.

Liver X receptor α (LXRα) controls important biological and pathophysiological processes such as lipid homeostasis. Inhibiting LXRα transactivation may beneficial in the treatment of nonalcoholic fatty liver disease (NAFLD), which is one of the main causes of liver diseases and hyperlipidemia. Oleanolic acid (OA) is a naturally occurring triterpenoid found in many plants. It has several beneficial effects on biological pathways; however, the mechanisms underlying its effects on LXRα are unclear. Therefore, we evaluated the effects of OA on T0901317-induced LXRα activation and explored whether OA can attenuate hepatic lipogenesis. The results showed that OA significantly decreased the promoter activities of LXR response element and sterol regulatory element binding protein-1c (SREBP-1c). It also decreased the mRNA and protein expression of LXRα target genes. These resulted in reduced hepatocellular lipid content. Our results also revealed that the overall binding pose of OA is similar to the X-ray pose of T0901317. Furthermore, OA stimulated AMP-activated protein kinase phosphorylation in hepatic cells. Additionally, it increased small heterodimer partner-interacting leucine zipper protein (SMILE) but decreased steroid receptor coactivator-1 (SRC-1) recruitment to the SREBP-1c promoter region. OA also enhanced LXRα-mediated induction of reverse cholesterol transport (RCT)-related gene, ATP-binding cassette transporter (ABC) A1, and ABCG1 expression in intestinal cells. It was found that OA increased the binding of SRC-1 but decreased SMILE recruitment to the ABCG1 gene promoter region. Furthermore, it reduced valproate- and rifampin-induced LXRα- and pregnane X receptor-mediated lipogenesis, respectively, which indicates its potential benefit in treating drug-induced hepatic steatosis. The results also show that OA is liver-specific and can be selectively repressed of lipogenesis. Moreover, it preserves and enhances LXRα-induced RCT stimulation. The results show that OA may be a promising treatment for NAFLD. Additionally, it can be used in the development of LXRα agonists to prevent atherosclerosis.

Numerous experimental studies and clinical observations suggest that cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD). Two-vessel occlusion caused cerebral ischemia model is often used in the study of vascular dementia (VaD). But how cerebral ischemia works on AD rat model which induced by intracerebroventricular injection of Aβ1-42 remains unclear. In the following study, we investigated the characteristics of rat model caused by intracerebroventricular injection of Aβ1-42 or two-vessel occlusion (2-VO) only and by both of the two operations. The animal cognitive functions were accessed by the Morris water maze. Regional cerebral blood flow was detected by Laser Doppler Blood Flowmeter. HE&Nissl staining, Congo red staining and immunohistochemistry were used to observe the status of neuronal loss, Aβ deposition and the phosphorylated tau expression in hippocampus, respectively. We also measured the contents of AchE and ChAT in serum and hippocampus by Enzyme Linked Immunosorbent Assay. The MWM results showed that rats of Aβ1-42+2-VO group had a disorder in cognitive functions, at an early stage of one week after modeling, comparing with rats of sham group. The regional cerebral blood flow (rCBF) was significantly reduced in Aβ1-42+2-VO and 2-VO group one week after modeling, and still maintained low perfusion levels four weeks after modeling. HE and Nissl staining showed that Aβ1-42+2-VO rats' hippocampal CA1 neurons were in disorder, degeneration and necrosis, severe neuronal loss from the first week to the fourth week, while this phenomenon only appeared in the fourth week after modeling in rats of Aβ1-42 group and 2-VO group. Congo red staining showed that Aβ1-42 + 2-VO group rats' hippocampus CA1 had amyloid deposits from the first week to the fourth week, Aβ1-42 group were not find amyloid deposition significantly until four weeks after modeling, however, 2-VO group had no significant amyloid deposition all the time. Notably, IHC showed that, two weeks after modeling, the p-tau positive total area and integrated optical density of hippocampal CA1 region were significantly increased in Aβ1-42 + 2-VO group rats, while 2-VO group and Aβ1-42 group rats had no significantly changes all the time. We also found that the content of AchE was increased both in serum and hippocampus of Aβ1-42 + 2-VO group rats, and ChAT was decreased. However, there was no significantly change in cortex of content of AchE: acetylcholinesterase (AchE) and choline acetylase (ChAT) all three groups. Together, our study suggest that intracerebroventricular injection of Aβ1-42 combined with two-vessel occlusion may accelerate Alzheimer's disease development in rats. Also, this may serve as a less-time consuming new model to study the Alzheimer's disease and especially AD accompanied by cerebral ischemia.

Background Chronic rhinosinusitis (CRS) is a multi-factorial disorder that causes systemic symptoms beyond rhinologic symptoms alone. A possible association between autonomic nervous system (ANS) dysfunction and CRS has been identified; however, few studies have confirmed this observation. In this study, we prospectively measured changes in ANS dysfunction symptoms following functional endoscopic sinus surgery (FESS) and explored the impact of ANS dysfunction on surgical outcomes of CRS. Methodology Patients diagnosed with CRS who consented to surgical intervention were included prospectively. All patients completed the Sino-nasal Outcome Test-22 (SNOT-22) and the 31-item Composite Autonomic Symptom Score (COMPASS 31) questionnaires before the operation and during the follow-up period. Clinical demographic data, Lund-Mackay, and modified Lund-Kennedy scores were recorded and measured. Results A total of 102 patients were enrolled. The median SNOT-22 and COMPASS 31 scores significantly improved following FESS from 43.0 to 14.0 and 21.0 to 11.2 (all P less than 0.001), respectively. FESS led to a significant reduction in the prevalence of various ANS dysfunction symptoms. In multivariate analyses, revision surgeries (odds ratio [OR] 5.012, 95% confidence interval [CI] 1.52416.489; P=0.008), CRS with nasal polyps (OR 4.071, 95% CI 1.454-11.40; P=0.008), and higher Pre-FESS COMPASS 31 scores (OR 1.043, 95% CI 1.003-1.084; P=0.036) were independent risk factors for uncontrolled inflammation following FESS. Conclusions ANS dysfunction symptoms are prevalent in CRS and higher preoperative COMPASS 31 scores correspond with poor surgical outcomes. Following FESS, the majority of ANS dysfunction symptoms can be alleviated. Further investigations are required to explore the possible mechanism of how ANS is involved in the pathogenesis of CRS.

Objective It has been identified that the smoking rate is higher in schizophrenic patients than general population. This study aimed to explore the association between schizophrenia and tobacco use, and provide rational recommendations for clinical care of schizophrenia. Methods We recruited 244 patients with schizophrenia and 225 healthy controls. Of schizophrenia patients, 54 patients were untreated with any antipsychotics over the previous 6 months or first‐episode and drug‐naïve. These patients (nonmedication subgroup) were followed up for 8 weeks. The associations between tobacco use and susceptibility to schizophrenia and psychotic symptoms were analyzed. Results Although there was no significant difference between schizophrenia patients and healthy controls in the entire sample, stratification analysis showed the rate of smoking was higher in male patients versus healthy controls and that male smokers exhibited higher odds ratios for schizophrenia than nonsmokers. Next, when we repeated analyses in first‐episode patients and healthy controls, significant differences were not observed, indicating tobacco use is an outcome rather than a cause of schizophrenia. Furthermore, among nonmedication subgroup, smokers presented with more severe psychotic symptoms at baseline, and better improvement after medication than nonsmokers, suggesting patients with worse symptoms tend to smoke to relieve symptoms. Conclusion This study supports the self‐medication hypothesis. Nonetheless, considering the serious health hazard associated with tobacco use, we should encourage patients to stop smoking. Further investigations are warranted to determine the tobacco constituents that are beneficial or harmful to schizophrenia., This study investigated the association between tobacco use and susceptibility to schizophrenia and psychotic symptoms. It provides evidence to support the self‐medication hypothesis and provides guidance for clinical care and rehabilitation of schizophrenia.

The mechanism of upper tract recurrence after local excision of bladder cancer remains unknown. This study was designed to identify risk factors for upper tract urothelial recurrence following local tumor excision of bladder cancer. To identify 76 597 bladder cancer patients, comprising 76 537 nonrecurrence and 60 recurrence patients, the Surveillance, Epidemiology, and End Results database was used. Kaplan‐Meier analysis and univariate and multivariate Cox proportional hazards regression models were used to determine the risk factors. Compared with the nonrecurrence group, the recurrence group was associated with older age, higher grade, high T stage, and higher proportional squamous cell carcinomas. Univariate Cox proportional hazards regression model showed that age, grades III and IV, T stage, and pathology were significantly associated with worse upper tract urothelial recurrence (UTUR) survival. However, after adjusting for prognostic factors, grade was no longer an independent prognostic factor in multivariate analysis. This study demonstrates that clinical prognosis of UTUR after local bladder tumor excision has significant independent risk factors that include age ≥60 years, T1 and T2 stage, and squamous cell carcinoma, and will require more careful consideration during follow‐up.

// Yu-Chuen Huang 1, 8, * , Wen-Ling Liao 2, 9, * , Jane-Ming Lin 3, 8 , Ching-Chu Chen 4, 8 , Shih-Ping Liu 5, 10, 14 , Shih-Yin Chen 1, 8 , Yu-Ning Lin 1 , Yu-Jie Lei 1 , Huan-Ting Liu 1 , Yu-Jen Chen 1, 11, 12, 13 and Fuu-Jen Tsai 1, 6, 7, 15 1 Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan 2 Center for Personalized Medicine, China Medical University Hospital, Taichung 404, Taiwan 3 Department of Ophthalmology, China Medical University Hospital, Taichung 404, Taiwan 4 Division of Endocrinology and Metabolism, China Medical University Hospital, Taichung 404, Taiwan 5 Center for Translational Medicine, China Medical University Hospital, Taichung 404, Taiwan 6 Children's Hospital of China Medical University, Taichung 404, Taiwan 7 Department of Medical Genetics, China Medical University Hospital, Taichung 404, Taiwan 8 School of Chinese Medicine, China Medical University, Taichung 404, Taiwan 9 Graduate Institute of Integrated Medicine, China Medical University, Taichung 404, Taiwan 10 Graduate Institute of Biomedical Science, China Medical University, Taichung 404, Taiwan 11 Department of Radiation Oncology, Mackay Memorial Hospital, Taipei 104, Taiwan 12 Department of Medical Research, Mackay Memorial Hospital, New Taipei City 251, Taiwan 13 Institute of Traditional Medicine, National Yang-Ming University, Taipei 112, Taiwan 14 Department of Social Work, Asia University, Taichung 413, Taiwan 15 Department of Biotechnology, Asia University, Taichung 413, Taiwan * These authors contributed equally to this work Correspondence to: Fuu-Jen Tsai, email: d0704@mail.cmuh.org.tw Yu-Jen Chen, email: chenmdphd@gmail.com Keywords: type 2 diabetes; diabetic retinopathy; circulating endothelial progenitor cells; ARHGAP22 Received: July 03, 2017 Accepted: September 21, 2017 Published: April 03, 2018 ABSTRACT Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Circulating endothelial progenitor cells (EPCs) are derived from bone marrow and are characterized by pathological retinal neovascularization. Rho GTPase Activating Protein 22 ( ARHGAP22 ) is a DR susceptibility gene that interacts with its downstream regulatory protein ras-related C3 botulinum toxin substrate 1 (Rac1), to assist in endothelial cell angiogenesis and increasing capillary permeability. The aim of this study was to elucidate the relationship between ARHGAP22 expression and EPC levels in type 2 diabetes (T2D) patients with DR. Fifty T2D patients with DR were recruited. Circulating EPCs were characterized as CD31 + /vascular endothelial growth factor-2 + /CD45 dim /CD133 + and were quantified using triple staining flow cytometry. Real-time polymerase chain reaction tests were used to quantify ARHGAP22 expression. We found that T2D patients with proliferative DR had significantly lower EPC levels than those with non-proliferative DR ( P = 0.028). T2D patients with EPC levels above the median value (> 4 cells/10 5 events) had higher levels of ARHGAP22 expression ( P = 0.002). EPC levels were positively correlated with ARHGAP22 expression ( r = 0.364, P = 0.009). Among T2D patients with DR, a higher expression of ARHGAP22 was associated with higher levels of EPCs. ARHGAP22 may be involved in the mobilization or active circulation of EPCs, thus contributing to neovascularization during DR development.

Pemphigus foliaceus (PF) is a chronic autoimmune blistering dermatosis (ABD) that often involves the face, scalp and trunk. Kaposi's varicelliform eruption (KVE) is a viral vesicular dermatosis that rarely complicates ABD. In addition, KVE infrequently causes ocular involvement including herpes simplex keratitis (HSK). Timely diagnosis of KVE may be difficult in patients with PF due to their overlapping clinical features. In this report, we described a 79-year-old female with PF complicated by KVE and bilateral HSK. This report reminds physicians that KVE should be considered in patients with refractory PF and other ABD.

Background Endovascular treatment of middle cerebral artery (MCA) aneurysms has traditionally been considered difficult due to complex branching patterns, frequent involvement of parent vessels within the aneurysm neck, and a high incidence of thromboembolic complications. Methods The cases of 93 MCA aneurysms treated with endovascular intervention at our institution between 2003 and 2015 were retrospectively reviewed. Demographic, clinical, and radiographic variables were recorded and analyzed. Results Immediate complete or near-complete occlusion was achieved in 81 (90%) cases. At the longest follow up of 6 months or greater, 83.3% of the aneurysms were stable-to-improved in the Raymond occlusion classification, 8.3% were found to have minor recanalization not requiring retreatment, and 8.3% required retreatment due to significant recanalization. Thromboembolic events occurred in 18 (19.3%) of cases, but only 1 resulted in permanent vessel occlusion and only 1 resulted in permanent neurologic impairment. Thrombus was resolved with intra-arterial thrombolysis or mechanical thrombectomy in 17 of the 18 cases. There were only two cases resulting in morbidity (2.15%). There was no statistically significant correlation between aneurysm location, size, morphology, or use of adjuvant device with radiographic outcome or thromboembolic event. Conclusions While the rate of thromboembolic events in our series was 19%, the overall morbidity was only 2%. This highlights the fact that even complex MCA aneurysms can safely and effectively be treated by endovascular means with or without the use of balloon or stent assistance, as long as the interventionalist is astutely aware of the possibility of thrombus formation and acts accordingly with thrombolytic therapy when necessary.

// Tianfu Yu 1, * , Yingyi Wang 1, * , Qi Hu 1, * , WeiNing Wu 1, * , Youzhi Wu 2 , Wenjin Wei 3 , Dongfeng Han 4 , Yongping You 1 , Ning Lin 5 and Ning Liu 1 1 Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 2 Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China 3 Department of Neurosurgery, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi Province, China 4 Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, China 5 Department of Neurosurgery, The First People’s Hospital Chuzhou, Chuzhou, China * These authors have contributed equally to this work Correspondence to: Ning Lin, email: lin2007512@vip.163.com Ning Liu, email: liuning0853@126.com Keywords: EZH2; EZH2 inhibitor; epigenetics; glioma; glioma stem cell Received: April 18, 2017 Accepted: August 04, 2017 Published: September 27, 2017 ABSTRACT Enhancer of zeste homolog 2 (EZH2) is the catalytic unit of polycomb repressive complex 2 (PRC2) which epigenetically silences many genes involved in tumor-suppressive mechanisms via the trimethylation of lysine 27 of histone H3 (H3K27me3). We recently found that overexpression of EZH2 was associated with poor outcome of glioblastoma (GBM). In this study, we examined the antitumor effects of the EZH2 inhibitor GSK343 on glioma cells in vitro and in vivo . The proliferation and cell cycle of glioma cells was measured. Wound healing assay and transwell invasion assay were performed to evaluate the capacity of migration and invasion of glioma cells. Western blot, qPCR, immunoprecipitation and fluorescent staining were used to test the levels of EZH2 and associated proteins. Spheroid formation assay and clonogenic assays were conducted to assess the stemness of glioma stem cells. Finally, the effect of GSK343 was measured through a nude mice model with intracranially xenotransplanted glioma. We found that GSK343 reduced proliferation, attenuated cell motility and reversed epithelial-mesenchymal transition in U87 and LN229 glioma cells. GSK343 also suppressed the stemness of cell lines and patient derived glioma stem cells. Further, GSK343 inhibited histone H3K27 methylation and upregulated the expression of EZH2 target genes thereby regulating the levels of markers involved in epithelial-mesenchymal transition and stemness. Taken together, our results indicate that GSK343 could be a potential drug against glioblastoma.

The molecular mechanism by which 17β-oestradiol (E2) increases urethral tone is unclear. As human tissue is limited in availability, we explored changes in the urethras of ovariectomized (OVX) mice. Twenty-four virgin female mice were randomised into three groups: mice with a sham operation only (control), OVX mice without E2 replacement (OVX), and OVX mice with E2 replacement (OVX + E2). Two weeks after the ovariectomy, mice received either E2 or placebo for 4 weeks. Leak point pressure (LPP) and maximum urethral closure pressure (MUCP) were assessed in these mice at 6 weeks after OVX, under anaesthesia. After measurements were recorded, the animals were sacrificed and the urethras were removed for proteomic and further analyses. LPP and MUCP values were significantly higher in OVX + E2 group than in OVX group. Fourteen differentially expressed proteins within the urethras of mice from OVX and OVX + E2 groups were identified; six proteins were upregulated and eight proteins were down-regulated. Most E2-induced proteins are involved in proteolysis, development, neurophysiological processes, transcription, and the cell cycle. Expression of survival motor neuron (SMN) protein in the urethra was significantly increased in OVX + E2 group compared to OVX group. OVX can impair urethral tone in female mice. E2 supplementation in OVX mice rescued urethral tone. E2-mediated increase in urethral tone in OVX mice involves overexpression of SMN, decreased proteolysis and promotion of development, neurophysiological processes, and transcription in the urethra. The urethra actively undergoes multiple biological processes in response to OVX and OVX with E2 stimuli. Impact statement Estrogens are known to modulate lower urinary tract trophicity. Although treatments with 17β-oestradiol (E2) result in an increase in urethral tone, the mechanism by which E2 increases urethral tone is still not completely understood. Ovariectomy can impair urethral tone in female mice. E2 supplementation in ovariectomized mice rescued urethral tone. E2-mediated increase in urethral tone in ovariectomized mice involves overexpression of survival motor neuron, decreased proteolysis and promotion of development, neurophysiological processes, and transcription in the urethra. This information will offer clues about pathogenesis of stress urinary incontinence after menopause and will open additional avenues for novel research and potential therapies.

Subependymal giant cell astrocytomas (SEGAs) are histologically benign tumors most frequently associated with tuberous sclerosis complex (TSC). Despite their benign histopathological appearance, they may cause unfavorable outcomes due to their intraventricular location. Rarely, SEGA may be associated with hyperproteinorrhachia (high levels of proteins in the cerebrospinal fluid [CSF]), which causes malresorptive, communicating hydrocephalus; certainly, this scenario makes shunt obstruction likely in this patient population. In this report, we illustrate the case of hyperproteinorrhachia in an SEGA patient with known TSC, who presented repeatedly with shunt failure from proteinaceous shunt obstruction. Subsequent surgical resection of the main intraventricular lesion resulted in a dramatic drop in the CSF protein levels and has since prevented further shunt failures. Different treatment concepts and possible pathophysiology are discussed and the pertinent literature is reviewed.

China currently has the most populous and rapidly aging nation in the world. In the next few decades, China will have to increase the throughput, quality, and scope of its neurosurgical training programs to meet forecasted demand. Until recently, China lacked national education standards in neurosurgery that fostered imbalances in medical and pedagogical resources, quality of care, and education between different regions and introduced significant heterogeneity in neurosurgical competency. In 2010, Shanghai implemented the first new standards-based comprehensive neurosurgery training program, which spans 7 years broken down into 2 blocks. This model was selected subsequently for nationwide adoption by the Chinese Congress of Neurological Surgeons, with initial implementation in 2015 and full nationwide adoption by 2020. Establishment of a national standardized training system represents a significant milestone in the development and evolution of neurosurgery in China and establishes a comprehensive standards-based system that will help reduce nationwide diversity in neurosurgical training. Although this program is still in its infancy and will not see its first graduating class until 2017 in Shanghai, it represents an essential step toward meeting China's growing demand for quality and consistent neurosurgical care. We review the history of neurosurgical training in Mainland China and describe the new Neurosurgical Specialist Standardized Training Program.

Our previous study revealed that miR‑148a, a cyclic adenosine monophosphate‑response element binding protein‑modulated microRNA that promotes adipocyte differentiation by inhibiting Wnt1, is a biomarker of obesity in human subjects and a mouse model. The present study investigated the expression of miR‑148a in human adipose tissue‑derived mesenchymal stem cells (hMSCs‑Ad) in response to inflammatory cytokines and adipokines to clarify its underlying mechanism. miR‑148a expression was detected using reverse transcription‑quantitative polymerase chain reaction analysis and its promoter activity was detected with a luciferase assay. miR‑148a expression levels decreased when differentiated hMSCs‑Ad were exposed to inflammatory cytokines or adipokines, which suggested that miR‑148a may be important in adipocyte metabolism and inflammation. Furthermore, the promoter activity of miR‑148a decreased following treatment of cells with inflammatory cytokines or adipokines. The results of the present study indicated a novel role of miR‑148a in adipocyte inflammation; therefore, miR‑148a may be involved in obesity complications via its own underlying transcriptional mechanism.

Study design The clinical and radiologic data of total disk allografting (TDA) cases were collected and analyzed to explore the correlation between neurological function improvements and imaging changes. Objective The aim of the study was to assess the medium-term and long-term outcome and radiographic character after TDA, and, furthermore, to explore the significance of the changes of imaging signs after the transplantation. Summary of background data Spinal fusion may result in the adjacent segment degeneration. The anxiousness urged the necessity for the development of TDA to reduce the risk of adjacent segment degeneration. Both animal studies and recent clinical trials have shown promising results to support the use of intervertebral disk allograft as a natural mobile disk replacement. Methods The conditions of 13 cases that underwent TDA after cervical discectomy were recorded in detail. Axial symptoms and neurological function in various periods were assessed, and, meanwhile, radiologic examination was performed for the comprehensive evaluation of the relevant indicators before and after surgery. Results (1) There was significant improvement in the neurological function after TDA. Postoperatively, the Visual Analog Score of axial symptoms did not increase significantly. (2) Both the entire and local segment maintained a satisfactory curve after allografting. There was no obvious correlation between the neurological function recovery and the cervical curve. Besides, the motion of the cervical spine did not change postoperatively. (3) Postoperatively, the spinal cord area at the index level increased significantly, whereas the signal value of the transplanted disk decreased sharply. Conclusions (1) Disk allografting is one of the effective and safe methods in treating the diseases of cervical disk herniation. (2) Although some degeneration occurs in the transplanted disk, the allograft can still be alive and can successfully maintain and improve the biological characters of the cervical spine in both radiologic and practical aspects.

Background The mid-upper arm circumference (MUAC) is a proxy for subcutaneous fat in the upper body and is a reliable screening measure for identifying individuals with abnormal regional fat distribution. The purpose of this study was to evaluate the association between MUAC and metabolic syndrome (MetS) in middle-aged and elderly individuals. Methods We measured the MUAC in a cross-sectional sample with a total of 9787 subjects aged 40 years and older. The measurement of MUAC is performed on the right arm using a non-elastic tape held midway between the acromion and the olecranon processes in duplicate, with the arm hanging loosely at the side of the body. The MetS was defined according to the Joint Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Results MUAC was positively correlated with waist circumference (r = 0.437, P P P Conclusion Large mid-upper arm circumference is significantly associated with metabolic syndrome in middle-aged and elderly individuals.

Emerging evidence suggests that obsessive-compulsive disorder (OCD) is caused by a combination of genetic predisposition and environmental factors. In this regard, abnormity of progranulin (PGRN, a key regulator of brain inflammation) and a history of childhood trauma have both been linked to an increased risk of developing OCD. This study is aimed to investigate the association between PGRN and childhood trauma in the development of OCD.We genotyped four single nucleotide polymorphisms (SNPs) covering PGRN in 484 OCD patients and 368 healthy controls. Among the OCD patients, 335 of them accepted clinical assessments in details. Generalized multifactor dimensionality reduction (GDMR) analysis and a general linear model were used to identify gene-environment interactions. The Braineac expression Quantitative Trait Loci (eQTL) dataset was used to analyze the differences in PGRN expression in various brain regions among different genotypes.Our linkage disequilibrium analysis revealed that rs3859268-rs2879096-rs3785817 combined OCD and control groups constructed one haplotype block. The haplotype analysis suggested that TCA haplotype frequency was associated with the risk of developing OCD (Padj=0.03). The Braineac eQTL database revealed that rs2879096 and rs3785817 might be associated with PGRN expression in the hippocampus (Padj=0.00085, Padj=0.007). Emotional abuse was positively correlated with the obsession subscale and Y-BOCS total scores. Except for common trauma, physical abuse, emotional abuse and sexual trauma were all positively correlated with the BAI and BDI-II scores of OCD patients (all P0.05). The interaction between emotional abuse and PGRN haplotype was associated with the development of depression symptoms in OCD patients corrected by age (Padj=0.043).The PGRN gene and childhood trauma may be closely related to the incidence of OCD, and OCD patients who have experienced more childhood trauma may exhibit a more severe clinical symptom. The interaction between PGRN and the early trauma may play a critical role in the development of depression symptom in OCD patients.

Obesity is associated with metabolic endotoxemia, reactive oxygen species (ROS), chronic inflammation, and obese kidney fibrosis. Although the fat&ndash, intestine&ndash, kidney axis has been documented, the pathomechanism and therapeutic targets of obese kidney fibrosis remain unelucidated. To mimic obese humans with metabolic endotoxemia, high-fat-diet-fed mice (HF group) were injected with lipopolysaccharide (LPS) to yield the obese kidney fibrosis&ndash, metabolic endotoxemia mouse model (HL group). Therapeutic effects of ROS, cytosolic phospholipases A2 (cPLA2) and cyclooxygenase-2 (COX-2) inhibitors were analyzed with a quantitative comparison of immunohistochemistry stains and morphometric approach in the tubulointerstitium of different groups. Compared with basal and HF groups, the HL group exhibited the most prominent obese kidney fibrosis, tubular epithelial lipid vacuoles, and lymphocyte infiltration in the tubulointerstitium. Furthermore, inhibitors of nonspecific ROS, cPLA2 and COX-2 ameliorated the above renal damages. Notably, the ROS-inhibitor-treated group ameliorated not only oxidative injury but also the expression of cPLA2 and COX-2, indicating that ROS functions as the upstream signaling molecule in the inflammatory cascade of obese kidney fibrosis. ROS acts as a key messenger in the signaling transduction of obese kidney fibrosis, activating downstream cPLA2 and COX-2. The given antioxidant treatment ameliorates obese kidney fibrosis resulting from a combined high-fat diet and LPS&mdash, ROS could serve as a potential therapeutic target of obese kidney fibrosis with metabolic endotoxemia.