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Introduction Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking. Methods A total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay. Results 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63–1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay. Conclusions In hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.

Objectives Cerebral vasospasm after subarachnoid haemorrhage (SAH) is associated with cerebrovascular contractile receptor upregulation resulted from haemolysis in the subarachnoid space. This study developed a new magnesium-rich artificial cerebrospinal fluid (MACSF) formula and investigated its effects on receptor-mediated contraction in rat basilar arteries. Methods Clear and haemorrhagic cerebrospinal fluid (CSF) were collected from patients with hydrocephalus or SAH. MACSF was freshly prepared using clinical intravenous injections. Rat basilar arteries were segmented and incubated with clear CSF, haemorrhagic CSF or MACSF. The contractile responses were studied by myograph. The messenger ribonucleic acid (mRNA) and protein expression of 5-hydroxytryptamine 1B (5-HT1B), endothelin subtype B (ETB) and endothelin subtype A (ETA) receptors were evaluated by real-time polymerase chain reaction (PCR) and Western blot analyses. Results Haemorrhagic CSF exposure shifted the contractile curves induced by 5-hydroxytryptamine (5-HT), sarafotoxins 6c (S6c) and endothelin-1 (ET-1) leftward with increased maximal contraction values. Furthermore, mRNA and protein expression were markedly elevated for 5-HT1B, ETB and ETA receptors on arteries exposed to haemorrhagic CSF. However, the contractile responses to 5-HT, S6c or ET-1 and expression of 5-HT1B, ETB and ETA receptors in rat cerebral arteries exposed to MACSF remained unaffected compared to those exposed to clear CSF. Besides, unlike normal saline which can inactive in-vitro vessels, MACSF can maintain their physiological activity. Conclusion Haemorrhagic CSF induces upregulation of 5-HT1B, ETB and ETA receptors in rat cerebral arteries. However, MACSF can maintain in-vitro rat basilar arteries in good physiological activity and normal expression of contractile 5-HT and ET receptors.

Signal transducer and activator of transcription (STAT) 3 plays a vital role in carcinogenesis and drug response. Platinum-based chemotherapy is the first-line treatment for lung cancer patients, especially those in advanced stages. In the present study, we investigated the association of STAT3 polymorphism rs4796793 with lung cancer susceptibility, platinum-based chemotherapy response, and toxicity. A total of 498 lung cancer patients and 213 healthy controls were enrolled in the study. 467 of them received at least 2-cycle platinum-based chemotherapy. Unconditional logistical regression analysis was used to assess the associations. STAT3 rs4769793 G allele carriers had an increased susceptibility of lung cancer [additive model: adjusted OR (95% CI) 1.376 (1.058–1.789), P = 0.017; recessive model: adjusted OR (95% CI) 1.734 (1.007–2.985), P = 0.047]. Rs4769793 was not significantly associated with platinum-based chemotherapy response in lung cancer patients. STAT3 rs4796793 was associated with an increased risk of severe overall toxicity [additive model: adjusted OR (95% CI) 1.410 (1.076–1.850), P = 0.013; dominant model: adjusted OR (95% CI) 1.638 (1.091–2.459), P = 0.017], especially hematological toxicity [additive model: adjusted OR (95% CI) 1.352 (1.001–1.826), P = 0.049]. STAT3 rs4796793 may be considered as a potential candidate biomarker for the prediction of susceptibility and prognosis in Chinese lung cancer patients. However, well-designed studies with larger sample sizes are required to verify the results.

The strong association between inflammation and cancer is reflected by the high interleukin-6 (IL-6) levels in the tumor microenvironment, where it promotes carcinogenesis by regulating all hallmarks of cancer and multiple signaling pathways. In this study, we investigated the prognostic value of IL-6 and other clinical indexes in inflammatory and cancer patients. All the patients were divided into the inflammation group (n = 400) and the cancer group (n = 672) composed of hematological malignancies group (n = 338) and solid tumors group (n = 334). Continuous variables were measured by one-way ANOVA and t-test, and the independent risk factors for carcinogenesis were determined by multivariate logistic regression analysis. The receiver operating characteristic (ROC) curves subsequently performed the predictive value of significant serological parameters and the Corheatmaps illustrated the correlation of these parameters in every case. Our retrospective study revealed that various serological indexes could reflect carcinogenesis in inflammatory patients, as significant differences existed in many indexes between them. It was notable that indicator composed of IL-6 and neutrophils/lymphocytes ratio (NLR) occupied the superior position of Area Under Curve (AUC) values in cancer cases, especially in patients with solid tumors (AUC = 0.85). The newly-found indicator could also be referred as an independent risk factor, which provided us with novel clues on the investigation of more reliable and affordable clinical indexes in tumor prediction.

Objectives Recent studies have demonstrated that first-line nurses involved in the coronavirus disease-2019 (COVID-19) crisis may experience sleep disturbances. As breathing relaxation techniques can improve sleep quality, anxiety, and depression, the current study aimed to evaluate the effectiveness of diaphragmatic breathing relaxation training (DBRT) for improving sleep quality among nurses in Wuhan, China during the COVID-19 outbreak. Methods This study used a quasi-experimental (before and after) intervention strategy, with 151 first-line nurses from four wards in Leishenshan hospital. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) to evaluate the effectiveness of DBRT before and after the intervention. Data were examined using the Shapiro–Wilk test, Levene's test, and paired t-test. Results A total of 140 nurses completed the DBRT sessions. First-line nurses achieved significant reductions in global sleep quality (p, Highlights • The COVID-19 epidemic has implications for general public health. • Sleep quality and anxiety are affected in COVID-19 first-line nurses. • DBRT can improve sleep quality and anxiety. • DBRT promotes the development of non-drug therapies in mind-body medicine.

Summary Background Since December 2019, when coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout the world, critically ill patients have a high mortality rate. We aimed to assess the effect of continuous renal replacement therapy (CRRT) on all-cause mortality in patients with COVID-19 undergoing invasive mechanical ventilation. Methods In this retrospective cohort study, we included all patients with COVID-19 undergoing invasive mechanical ventilation at Optical Valley Branch of Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan from February 12th to March 2nd, 2020. Demographic, clinical, laboratory, and treatment data were collected and analyzed. All patients were followed until death or end of follow up (March 9th), and all survivors were followed for at least one week. Findings Of 36 hospitalized COVID-19 patients with invasive mechanical ventilation, the mean age was 69.4 (±1.8) years and 30 (83.3%) were men. 22 (61.1%) patients received CRRT (CRRT group) and 14 cases (38.9%) were managed in conventional strategy (non-CRRT group). There was no difference in age, sex, comorbidities, complications, treatments and most of the laboratory findings, except for patients in the CRRT group with higher levels of aspartate aminotransferase and serum creatinine. During the average follow-up period of 10.4 days, 12 of 22 (54.5%) patients in CRRT group and 11 of 14 (78.6%) patients in non-CRRT group died. Kaplan–Meier analysis demonstrated a prolonged survival in patients in CRRT group than non-CRRT group (P=0.032). The association between CRRT treatment and a reduced risk of mortality remained significant after adjusting for confounding factors in seven different models, with an adjusted hazard ratio (aHR) varying between 0.283 and 0.424. Older age, higher levels of IL-1β, IL-2 receptor, hs-cTnI and NT-proBNP were independently associated with increased risk of mortality in patients with CRRT treatment. Interpretation CRRT may be beneficial for the treatment of COVID-19 patients with invasive mechanical ventilation. Further prospective multicenter studies with larger sample sizes are required. Funding National Natural Science Foundation of China; Science Foundation of Hubei Province of China

Several studies have reported that apolipoprotein A5 (APOA5) is involved in the development of non-alcoholic fatty liver disease (NAFLD). However, no research has been performed regarding the association between APOA5 polymorphisms and the risk of NAFLD. This study aimed to explore the association between APOA5 gene polymorphisms and NAFLD in a Chinese Han population.Genotypes of the SNPs (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 in 232 NAFLD patients and 188 healthy controls were determined using polymerase chain reaction (PCR) analysis. Clinical characteristics were measured using biochemical methods.The five single nucleotide polymorphisms (SNPs) (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 showed no significant association with NAFLD (P 0.05). The rs10750097 with G allele showed a higher serum level of alkaline phosphatase (ALP) compared with C allele in overall series and NAFLD patients (P 0.05). The rs1263173(A/A) carriers showed a higher level of glucose compared to the non-carriers in overall series (P 0.05). The rs17120035(T/T) carriers showed a lower plasma TG level in overall series and NAFLD patients (P 0.05), and the rs662799(G/G) carriers showed higher levels of plasma triglyceride (TG), ALP, and lower level of high-density lipoprotein (HDL) compared to non-carriers in NAFLD patients (P 0.05). No significant difference were observed on the clinic parameters of APOA5 rs3135507(T/T) carriers in both group of overall series and NAFLD patients (P 0.05).The five SNPs (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 gene are not associated with the risk of NAFLD in the Chinese Han population. The genotypes of rs10750097(G/G), rs1263173(A/A), rs17120035(T/T), and rs662799(G/G) performed a significant effect on clinic characteristics in overall series and NAFLD patients, indicating that these polymorphisms may be associated with NAFLD.

Although genome-wide association studies have greatly advanced our understanding of the contribution of common noncoding variants to leprosy susceptibility, protein-coding variants have not been systematically investigated. We carried out a three-stage genome-wide association study of protein-coding variants in Han Chinese, of whom were 7,048 leprosy patients and 14,398 were healthy control subjects. Seven coding variants of exome-wide significance were discovered, including two rare variants: rs145562243 in NCKIPSD ( P = 1.71 × 10 –9 , odds ratio [OR] = 4.35) and rs149308743 in CARD9 ( P = 2.09 × 10 –8 , OR = 4.75); three low-frequency variants: rs76418789 in IL23R ( P = 1.03 × 10 –10 , OR = 1.36), rs146466242 in FLG ( P = 3.39 × 10 –12 , OR = 1.45), and rs55882956 in TYK2 ( P = 1.04 × 10 –6 , OR = 1.30); and two common variants: rs780668 in SLC29A3 ( P = 2.17 × 10 –9 , OR = 1.14) and rs181206 in IL27 ( P = 1.08 × 10 –7 , OR = 0.83). Discovered protein-coding variants, particularly low-frequency and rare ones, showed involvement of skin barrier and endocytosis/phagocytosis/autophagy, in addition to known innate and adaptive immunity, in the pathogenesis of leprosy, highlighting the merits of protein-coding variant studies for complex diseases.

Huperzine A is a potent, reversible, and blood-brain barrier permeable acetylcholinesterase inhibitor. The aim of this study was to compare the pharmacokinetics, tolerability, and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting, healthy Chinese male population. This was a randomized, single-dose, 3-period, 6-sequence crossover study. The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry. Tolerability was assessed based on subject interview, vital sign monitoring, physical examination, and routine blood and urine tests. The mean (SD) pharmacokinetic parameters of the reference drug were Cmax, 1.550 (0.528) ng/mL; t1/2, 12.092 (1.898) h; AUC0-72h, 17.550 (3.794) ng·h/mL. Those of the test formulation A and test formulation B were Cmax, 1.412 (0.467), 1.521 (0.608) ng/mL; t1/2, 12.073 (2.068), 12.271 (1.678) h; AUC0-72h, 15.286 (3.434) ng·h/mL, 15.673 (3.586) ng·h/mL. The 90% confidence intervals for the AUC0-72h and Cmax were between 0.80 and 1.25. No adverse events were reported by the subjects or found with results of clinical laboratory test. The test and reference products met the regulatory criteria for bioequivalence in these fasting, healthy Chinese male volunteers. All three formulations appeared to be well tolerated.

AIM To investigate the inhibitory effect of Liuwei Dihuang Pill (LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea (MNU) in diabetic mice. METHODS Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP. MNU was administrated for 20 wk to induce gastric carcinogenesis. LDP was administrated for 10 wk for improvement of insulin resistance. Body weight and food intake were measured every week. Blood samples were collected for assays of fasting blood glucose, insulin, insulin-like growth factor (IGF)-1, adiponectin and leptin. Stomach tissues were collected for histopathological analysis, immunohistochemical staining of Ki67, quantitative reverse transcription-polymerase chain reaction and western blotting. RESULTS The incidence of MNU-induced gastric dysplasia was significantly elevated in diabetic (db/db) mice relative to the control (db/m) mice. The incidence of gastric dysplasia was significantly reduced by LDP with suppression of cell proliferation, as demonstrated by a decrease in Ki67 staining. Hyperglycemia, hyperinsulinemia and serum IGF-1 were inhibited by LDP. Expression of IGF-1 and insulin receptor mRNAs was decreased, phosphorylation of IGF-1 receptor and AKT protein was reduced in the stomach tissues by LDP. In addition, adiponectin was increased and leptin was decreased in the serum by LDP. CONCLUSION LDP decreased risk of gastric dysplasia in type 2 diabetic mice by down-regulation of IGF and insulin activity and correction of adipokines disorders.

β-Amyloid (Aβ) deposition has a central role in the pathogenesis of Alzheimer disease (AD). Previous studies have indicated that as a risk factor for AD, diabetes mellitus (DM) could induce Aβ deposition in the brain, but the mechanism is not fully elucidated. Autophagy-lysosome is a cellular pathway involved in protein and organelle degradation. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether autophagy-lysosome is related to Aβ1-42 clearance in DM. We found that DM rats had a longer escape latency and less frequent entry into the target zone than that of the control group (p

This study aimed to evaluate the associations between phthalate concentrations and thyroid function in preschool children. We collected demographic data and biological samples from 216 children aged 5–7 years. We calculated urinary concentrations of eight mono-phthalate metabolites (mPAEs) separately for children from urban and rural areas and investigated their associations with thyroid function and growth hormones. mPAE concentrations were higher in children from the urban area than in those from the rural area, and most mPAEs were positively associated with free triiodothyronine and free thyroxine. The insulin-like growth factor 1 (IGF-1) concentration decreased 0.082 ng/mL (95% confidence interval [CI]: − 1.34, − 0.113) with each 1 ng/mL increase in monomethyl phthalate (MMP) and 0.132 ng/mL (95% CI: − 0.209, − 0.055) with each 1 ng/mL increase in mono- n -butyl phthalate. The insulin-like growth factor binding protein 3 concentration decreased by 0.01 mg/L (95% CI: − 0.001, − 0.000) or 0.01 mg/L (95% CI: − 0.003, − 0.000) with each 1 ng/mL increase in MMP or monoethyl phthalate, respectively. Exposure to some phthalates at 5–7 years of age might interfere with thyroid hormones and growth.

Although previous studies showed that children are widely exposed to phthalates, the sources of phthalate exposure for school-aged children in China are not well understood. This study aimed to assess phthalate metabolite levels and explore the factors influencing exposure in children. We collected demographic data and biological samples from 336 children aged 6-12 years. We calculated urinary concentrations of 14 mono-phthalate metabolites and conducted chi-square (χ2) tests and logistic regression analysis to determine the variables associated with phthalate levels. Mono-n-butyl phthalate (MnBP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were the most abundant urinary phthalate metabolites. In addition, housing type, decorating materials in the home, and frequency of canned food consumption were associated with exposure to low molecular weight phthalates. Water source, duration of time spent playing with toys, residential area, and frequency of canned food consumption were associated with exposure to high molecular weight phthalates. Based on these results, potential strategies to reduce exposure to phthalates include avoiding plastic food containers and chemical fragrances as well as eating fewer processed foods, especially canned foods, and foods in plastic packaging.

Background Putative endothelial progenitor cells (pEPCs) have been confirmed to participate in alleviation of renal fibrosis in several ischaemic diseases. However, their mechanistic effect on renal fibrosis, which is characterized by vascular regression and further rarefaction-related pathology, remains unknown. Methods To explore the effect and molecular mechanisms by which pEPCs act on unilateral ureteral obstruction (UUO)-induced renal fibrosis, we isolated pEPCs from murine bone marrow. In vivo, pEPCs (2 × 105 cells/day) and pEPC-MVs (microvesicles) were injected into UUO mice via the tail vein. In vitro, pEPCs were co-cultured with renal-derived pericytes. Pericyte-myofibroblast transition was evaluated using the myofibroblast marker α-smooth muscle actin (α-SMA) and pericyte marker platelet-derived growth factor receptor β (PDGFR-β). Results Exogenous supply of bone marrow-derived pEPCs attenuated renal fibrosis by decreasing pericyte-myofibroblast transition without significant vascular repair in the UUO model. Our results indicated that pEPCs regulated pericytes and their transition into myofibroblasts via pEPC-MVs. Co-culture of pericytes with pEPCs in vitro suggested that pEPCs inhibit transforming growth factor-β (TGF-β)-induced pericyte–myofibroblast transition via a paracrine pathway. Conclusion pEPCs effectively attenuated UUO-induced renal fibrosis by inhibiting pericyte–myofibroblast transition via a paracrine pathway, without promoting vascular repair. Electronic supplementary material The online version of this article (10.1186/s13287-019-1201-5) contains supplementary material, which is available to authorized users.

The relationship between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and lung cancer remains unclear. A 66-year-old man presented with pulmonary nodules. Histological examination of a specimen from computed tomography-guided percutaneous transthoracic biopsy revealed adenocarcinoma. The patient was treated using cryoablation and systemic chemotherapy. Sixteen months later, the patient presented with fever, nasal inflammation, recurrent lung lesions, elevated serum creatinine levels, and high levels of ANCA. Histological examination of a specimen from ultrasound-guided percutaneous renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis. The patient responded to treatment, but granulomatosis with polyangiitis recurred and he later died. This case highlights the possibility of sequential AAV with lung cancer. Although this is relatively rare, further research is needed to better understand the association or pathophysiological link between lung cancer and AAV.

Context: Pancreatic cancer portal hypertension (PCPH) is a rare cause of gastrointestinal bleeding. This study retrospectively assessed gastrointestinal bleeding risk factors in 57 PCPH patients diagnosed via multidetector computed tomography (MDCT). Materials and Methods: The data of patients with pancreatic cancer from January 2008 to January 2018 at Qingdao Municipal Hospital were reviewed. PCPH patients were screened with MDCT and followed up. MDCT findings (e.g., the location of the venous obstruction, type of variceal veins pathway, and splenomegaly) were recorded. Variceal hemorrhage was recorded. The MDCT findings and clinical data of the PCPH patients were used in this analysis to explore the risk factors of variceal hemorrhage using binary logistic regression and multivariate logistic regression model. Results: Fifty-seven of the 182 patients were diagnosed with PCPH. A total of 7 draining routes and 11 types of varices were found. Of these patients, eight experienced variceal hemorrhage. Univariate analysis showed that splenomegaly (odds ratio [OR] = 10.364, P = 0.003) was significantly associated with an increased risk of variceal hemorrhage. Multivariate analysis showed that splenomegaly (OR = 66.491, 95% confidence interval: 2.790–1584.643, P = 0.009) was an independent influencing factor for variceal hemorrhage in PCPH patients. Conclusions: Patients with pancreatic cancer have high morbidity of PCPH. The splenomegaly is more prone to hemorrhage. Splenomegaly was an independent risk factor of variceal hemorrhage. MDCT can provide insight into the stenosis and occlusion of the portal vein system and the drainage routes of variceal veins and is one of the best ways to diagnose PCPH.

Background Many researches on gender differences in leprosy found that female patients were detected with the disease later and had more serious disabilities than male patients. We analyzed the gender differences related to epidemiological characteristics of new leprosy cases detected from 2000 to 2015 in Sichuan Province, China. Methods A retrospective study was undertaken to analyze the gender differences with respect to age, delay in disease detection, the main modes of detection, and disability grade. The chi-squared test and t test were applied for the comparison using Epi Info 7.2 with a significance level of a = 0.05. The data were collected from the Leprosy Management Information System in China. Results A total of 2900 new leprosy cases were detected from 2000 to 2015, of whom 2075 (71.6%) were male and 825 (28.4%) were female with a gender ratio of 2.5. The gender ratio of patients aged 15-30 was significantly lower than that of patients aged 31-45 and 46-60. Male cases were older than female cases when they were detected. The proportion of Grade 2 Disability (G2D) among men (20.6%) was significantly higher than that among women (17.3%). The average period of delay in detection among male cases was similar with that among females cases. Conclusions Gender-related differences existed among the leprosy cases detected from 2000 to 2015. Female patients were younger than male patients. The detection of leprosy in women was not later than in the case of men. The disability situation in men was more serious than in women.

Objective To explore the characteristics of blood glucose excursions of type 2 diabetes mellitus patients with three different Traditional Chinese Medicine (TCM) syndromes. Methods One hundred and nine patients with type 2 diabetes mellitus were recruited from the Department of Endocrinology and the Department of TCM of the Sixth People's Hospital affiliated to Shanghai Jiao Tong University. Subjects were divided into three groups according to TCM syndrome: intrinsic Damp ( n = 42), Yin deficiency and internal Heat ( n = 25), and Qi and Yin deficiency ( n = 42). Subcutaneous interstitial glucose was monitored with a continuous glucose monitoring system for 3 consecutive days to investigate the glycemic profile in each group. Plasma C-peptide levels were measured, and an arginine test was taken in 10 patients randomly selected from each group. Glucose data and glycemic variability were analyzed to investigate the differences among the groups. The change in C-peptide levels and the results from arginine trial were used to evaluate β cell function. Results Indicators reflecting blood glucose level were the highest in subjects with Yin deficiency and internal Heat syndrome, and parameters reflecting glycemic variability were the lowest in those with Qi and Yin deficiency syndrome. The change in C-peptide levels showed that subjects with Qi and Yin deficiency syndrome had the best β cell function among the three groups; this was confirmed by the arginine trial. Conclusion Patients with Qi and Yin deficiency syndrome had a more stable blood glucose profile, as glycemic variability was higher in those with intrinsic Damp syndrome and those with Yin deficiency and internal Heat syndrome.

Background A significant association between single nucleotide polymorphisms in NOD2, C13orf31, and CCDC122 genes and leprosy has been reported in a previous genome-wide association study of leprosy in the Chinese Han population. However, it remains unknown whether this association exists among the Chinese Yi population. The aim of this study was to investigate whether single nucleotide polymorphisms in NOD2, C13orf31, and CCDC122 genes are associated with leprosy among the Chinese Yi population in China. Methods We genotyped rs9302752, rs7194886, rs8057341, and rs3135499 in the NOD2 gene; rs3764147 and rs10507522 in the C13orf31 gene; and rs3088362 and rs9533634 in the CCDC122 gene in a Chinese Yi cohort comprised of 319 patients with leprosy and 355 ethnic-matched controls. The differences between the patients and healthy controls were analyzed using chi-squared analysis. Results Significant differences of rs3135499 in NOD2, rs3764147 and rs10507522 in C13orf31, and rs3088362 and rs9533634 in CCDC122 were observed between the patients and the healthy control groups in the cohort. The allelic P values and odd ratios were as follows: rs3135499, 1.0 × 10−8 and 2.55; rs3764147, 1.7 × 10−7 and 1.88; rs10507522, 1.16 × 10−5 and 1.95; rs3088362, 8.2 × 10−4 and 1.51; rs9533634, 5.34 × 10−5 and 1.73. No significant differences were found in the distributions of rs9302752, rs7194886, and rs8057341 between the patients and healthy controls. Conclusions We demonstrated that genetic variants in the NOD2, C13orf31, and CCDC122 genes are closely associated with leprosy among the Chinese Yi population, which implicates the pathogenic role of NOD2, C13orf31, and CCDC122 genes in a different ethnicity.

Ethnopharmacological relevance St John׳s Wort (Hypericum perforatum, SJW) is a widely used herbal medicine in western countries but also an important Uygur drug in China. Hypericin (HY) is the main components in SJW extracts, which is used to treat fatigue, weakness, and mild depression. The aim of this study was to investigate the anti-depression effects of HY on chronic unpredictable mild stress (CUMS) model rats and identify the possible mechanisms. Materials and methods In this study, the protective effects of HY on CUMS-induced depression in rats were investigated by using a combination of behavioral assessments and urinary metabolites analysis. Urinary metabolites analyses were performed using LC–MS/MS in conjunction with principal components analysis (PCA) after oral administration of either HY or Venlafaxine (VF) for 27 days. During the procedure of experiment, food consumption, body weight, adrenal gland, thymus and spleen indices, behavior scores, sucrose consumption, and stress hormone levels were measured. Results Changes in the classic behavioral tests and pharmacological biochemical indices reflected that HY alleviated the symptoms of depression in a shorter period than VF, which was used as positive control for antidepression. Metabolites analysis of urine revealed that HY affected excitatory amino acids and monoamine neurotransmitter metabolites. Remarkably, urinary valine was increased remarkably by HY, even much higher than CUMS group. These results provide important mechanistic insights into the protective effects of HY against CUMS-induced depression and metabolic dysfunction. Conclusion As the most important active ingredient in SJW extracts, HY possesses the better protective effect against CUMS-induced depression symptoms and metabolic disturbances.

To investigate the subchronic oral toxicity of silica nanoparticles (NPs) and silica microparticles (MPs) in rats and to compare the difference in toxicity between two particle sizes.Sprague-Dawley rats were randomly divided into seven groups: the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7, 500, and 1,500 mg/(kg•bw•day)]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver, kidneys, and testis were determined.There were no toxicologically significant changes in mortality, clinical signs, body weight, food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups.Our study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.

Type 2 diabetes can elevate risk of gastric cancer and metformin, an anti-diabetic agent, has an inhibitory effect against gastric cancer cell in vitro. However, the effect of metformin on type 2 diabetes-related gastric tumorigenesis in vivo is still not clear. In the present study, we aim to detect whether metformin can inhibit increased risk of gastric cancer in diabetic db/db mice and which the potential anti-cancer mechanisms of metformin are. 4-week-old mice were divided into 3 groups (2 db/db mice groups and one wild type mice group). All diabetic and non-diabetic mice were treated with N-Methyl-N-Nitrosourea (MNU) for 20 weeks to induce gastric tumorigenesis. At week 21, one db/db mice group were treated with metformin (5 mg/ml) for 10 weeks and the other 2 groups were treated with saline. Blood samples were collected for testing insulin and insulin-like growth factor (IGF)-1. Stomach tissues were collected for histopathological evaluation and mRNAs analysis. Metformin significantly decreased incidence of MNU-induced gastric dysplasia and cancer in diabetic db/db mice. Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions. The results show that metformin can prevent the risk of gastric cancer in type 2 diabetes and the protective mechanisms may involve in an inhibitory effect of metformin on insulin as well as IGF-1 signals and cancer related pro-inflammatory cytokines.

BACKGROUND Sleep is an important physiological process and beneficial in the removal of brain metabolites and functional recovery. Prior studies have shown that sleep disorders are significant risk factors for Alzheimer's disease (AD). OBJECTIVE The present study was designed to characterize the effect of short-term total sleep deprivation (TSD) on plasma amyloid-β (Aβ) concentrations. METHODS A clinical trial was conducted between March 1, 2016, and April 1, 2016. Twenty volunteers (age 27.3±3.4 years) with normal cognitive function and sleeping habits were recruited from the local population. Participants underwent 24 h of TSD. Periprocedural blood samples were collected to compare the changes of plasma Aβ42, Aβ40, low-density lipoprotein receptor-related protein (sLRP-1), soluble receptors for advanced glycation end products (sRAGE), and serum superoxide dismutase (SOD) and malonaldehyde (MDA). RESULTS TSD increased morning plasma Aβ40 levels by 32.6% (p

Objective. Long noncoding RNAs (lncRNAs) have been reported to play vital roles in non-small-cell lung cancer (NSCLC). Recently, long noncoding RNA Linc00152 has been reported to play important roles in various cancers. In this study, our aim was to investigate its expression pattern and clinical significance and further evaluate its diagnostic value for NSCLC.Methods. The levels of Linc00152 were detected in NSCLC tissues and plasma samples by quantitative real-time PCR (qRT-PCR). Receiver operating characteristic (ROC) curves were depicted to evaluate the diagnostic value.Results. We found that Linc00152 levels were upregulated in both NSCLC tissues and plasma samples. Plasma Linc00152 levels were significantly lower in postoperative samples than in preoperative samples. Besides, high Linc00152 expression was significantly correlated with tumor size (r=0.293,P=0.005) and tumor stage (r=0.324,P=0.011). The ROC curves indicated that plasma Linc00152 has high diagnostic accuracy for NSCLC, and the area under curve (AUC) for NSCLC versus healthy was 0.816 (95% CI: 0.757–0.875). Moreover, we found that the combination of Linc00152 and CEA could provide a more powerful diagnosis efficiency than Linc00152 or CEA alone (AUC = 0.881, 95% CI: 0.836–0.926).Conclusions. Plasma Linc00152 could serve as a promising biomarker for diagnosing and monitoring NSCLC.

Primary cerebral neuroblastoma is a rare malignant tumor encountered most commonly in children. The radiological features of this entity are variable and rarely reported. The diffusion-weighted imaging (DWI) findings have not previously reported. We describe serial DWI and conventional MRI in a case of primary cerebral neuroblastoma to assess the imaging features and the role of DWI for monitoring chemoradiotherapy response.

Capsaicin (CAP), the main ingredient responsible for the hot pungent taste of chilli peppers. This study investigated the effect of CAP on the pharmacokinetics of Cyclosporin A (CyA) in rats and the mechanism of this food-drug interaction. The results indicated that after 7 days of low or middle dose of CAP (0.3 or 1.0 mg/kg), the blood concentration of CyA was not significantly changed compared with that of vehicle-treated rats, whereas the blood concentration of CyA in high dose group (3.0 mg/kg) was significantly increased. The total clearance (CL/F) of CyA was decreased, and the bioavailability was significantly increased to about 1.44-fold of that in vehicle-treated rats after 7 days of high dose CAP treatment. At this time, the P-gp and CYP3A1/2 in the liver and intestine were decreased at both the mRNA and protein levels. These results demonstrated that chronic ingestion of high doses of CAP will increase the bioavailability of CyA to a significant extent in rats and the food-drug interaction between CAP and CyA appears to be due to modulation of P-gp and CYP3A gene expression by CAP, with differential dose-dependence.

This study was designed to evaluate the tolerability and pharmacokinetics of biapenem after single and multiple intravenous administrations in healthy Chinese subjects. Subjects were randomly allocated to receive a single 0.15, 0.3, or 0.6 g dose of biapenem. Subjects assigned to the 0.3 g single dose group continued into the multiple-dose phase. Blood samples were collected over 6 h and plasma biapenem concentrations were determined by a validated HPLC method. Tolerability was assessed by monitoring vital signs, laboratory parameters, physical examinations, electrocardiogram, and adverse events collected by non-directive questioning/spontaneous reporting. Pharmacokinetic parameters for biapenem after intravenous administration of a single dose of 0.15, 0.3, or 0.6 g were as follows: Cmax=7.06 (1.30), 15.59 (1.33), and 29.12 (1.22) mg/L; AUC0-6 h=8.95 (1.33), 22.62 (1.25), and 42.05 (1.19) mg · h/L; t1/2=0.97 (0.13), 1.04 (0.08), and 1.12 (0.08) h; CL=15.78 (1.32), 12.91 (1.24), and 13.95 (1.19) L/h; Vd=21.87 (1.25), 19.31 (1.25), and 22.41 (1.23) L, respectively. Pharmacokinetic parameters for biapenem after intravenous administration of multiple 0.3 g doses were as follows: Cmax=18.50 (1.16) mg/L; AUC0-6 h=26.45 (1.15) mg · h/L; t1/2=1.06 (0.15) h; CL=11.06 (1.16) L/h; Vd=16.78 (1.19) L. The incidence of reported AEs was as follows: phlebitis (2/10), nausea (1/10), and diarrhea (1/10). All of the AEs were mild in intensity. The pharmacokinetic properties of biapenem were linear at dose of 0.15-0.6 g. All biapenem doses appeared to be well tolerated.

The purpose of this study is to investigate the changing spectrum and clinicopathologic correlation of biopsy-proven renal diseases in central China. We retrospectively analyzed data of 4931 patients who underwent renal biopsy in ten hospitals between September 1994 and December 2014. Among them, 81.55% were primary glomerular diseases (GD), and 13.02% were secondary GD. IgA nephropathy (IgAN) was the most common primary GD (43.45%), followed by focal glomerulonephritis (16.79%), mesangial proliferative glomerulonephritis (MsPGN, 14.35%), and membranous nephropathy (MN, 13.28%). IgAN was leading primary GD in patients under 60 years old, while MN was the leading one over 60 years old. The most frequent secondary GD was lupus nephritis (LN) (47.35%). The prevalence of IgAN, MN and minimal change disease was found to increase significantly (p

This study aims to analyze the relationship between nutcracker syndrome (NCS) and nutcracker phenomenon (NCP) in glomerular nephritis (GN) of patients with symptom of isolated hematuria. Our observations reveal that patients with combined GN and NCP/NCS have dysmorphic urine red blood cells or mixed-morphological urine red blood cells while patients with NCS only (without GN) contain isomorphic urine red blood cells. Clinical and pathological data of 32 patients with NCP and complicating GN were analyzed. A different group of 17 patients with NCS served as the control. All patients underwent color Doppler ultrasonography. Routine urine examination, red blood cell counts, and phase observations of urinary sediments were performed both before and after exercise. twenty four hour urinary protein and albumin quantities were determined. Twenty-nine patients underwent renal needle biopsy. All 32 patients were diagnosed with NCP. Results of urinary sediment examination of patients were either normal or showed isomorphic hematuria before exercise. Most patients exhibited mixed-morphological or dysmorphic hematuria at different degrees after exercise. Renal pathological findings in 29 patients included multiple types and showed no relevance to urinary examination results. All patients diagnosed with GN complicated by NCP were identified through clinical and laboratory examinations and renal biopsy. NCP may coexist with a glomerular disease. NCS patients with urine red blood cells of mixed morphology or showing dysmorphism after exercise should be noted, with or without the coexistence of GN. Renal needle biopsy must be performed when necessary to avoid adverse effects on the patient’s condition.

Our objective was to achieve the enhanced delivery of vascular endothelial growth factor (VEGF) to ischemically disordered brain through transferrin-coupled liposomes (Tf-PLs) via intravenous administration, and to observe the effect of Tf-VEGF-PLs on ischemic brain neuroprotection and angiogenesis. Cerebral VEGF overexpression was achieved with Tf-PLs by intravenous injection 48 hr after an acute stroke. β-Galactosidase expression was monitored; saline was injected as a control. The success of postischemic gene transduction was confirmed by β-galactosidase staining and by increased VEGF mRNA and protein in ischemic brain. Vascular density, neurological recovery, and ischemic area calculation were performed to evaluate the effect of Tf-VEGF-PLs. The positive expression of β-galactosidase indirectly indicated that VEGF was successfully delivered into brain by Tf-VEGF-PLs. VEGF mRNA in the Tf-VEGF-PL group 24 hr after injection was significantly higher than in the control group (p 0.05). Western blot analysis showed that postischemic Tf-VEGF-PLs resulted in increased VEGF protein levels compared with VEGF-PLs and saline-administered rats (p 0.05) 48 hr after administration. At 21 days after drug injection, we observed a significant decrease in infarct volume and better neurological function in the Tf-VEGF-PL-treated group, compared with the VEGF-PL group. FITC-dextran marking showed increased vascular density in the penumbra of Tf-VEGF-PL-treated hemispheres (245,873.9, number of microvessels per field) compared with that in VEGF-PL-treated hemispheres (139,801.3) or saline-treated hemispheres (102,175.5) (p 0.05). The remainder of the cerebral blood flow after ischemia in the Tf-VEGF-PL group was significantly more than in the control groups (0.35 vs. 0.29, 0.21; p 0.05). We conclude that the VEGF gene can be delivered noninvasively into the brain by Tf-VEGF-PLs. Postischemic treatment with Tf-VEGF-PLs effectively promoted neuroprotection and vascular regeneration in the chronic stage of cerebral infarction.

Background: Cefotetan disodium for injection is a semisynthetic cephamycin antibiotic that exerts its bactericidal effects by inhibition of cell-wall synthesis. Despite being widely used in the treatment of various infections, little information is available on the pharmacokinetic properties of cefotetan disodium in Chinese subjects. Objectives: This study evaluated the pharmacokinetics of single and multiple intravenous doses of a generic formulation of cefotetan disodium in healthy Chinese volunteers. The effect of sex on the pharmacokinetics of cefotetan disodium was evaluated as a secondary objective. Methods: In this open-label, dose-escalating study, subjects were randomized to receive a single dose of cefotetan disodium 0.5, 1.0, or 2.0 g administered as a 1-hour intravenous infusion. Those allocated to the 1.0-g dose continued into the multiple-dose phase, in which they received 1.0 g BID for 7 consecutive days. During the single-dose phase, blood samples were col- lected at regular intervals from 0 to 15 hours after drug administration and were analyzed using a validated HPLC method. During the multiple-dose phase, blood samples were obtained before drug administration on days 5, 6, and 7 to determine the C min at steady state; on day 7, blood samples were also collected from 0 to 15 hours after drug administration. Tolerability was assessed based on physical examinations, vital signs, laboratory tests (hematology, biochemistry, hepatic and renal function, and urinalysis), and subject interviews. Results: Three groups, each consisting of 5 men and 5 women, were enrolled in the single-dose phase. The mean (SD) age of subjects was 23.2 (2.2) years (range, 19–30 years). Their mean weight was 57.0 (6.3) kg (range, 46.4–72.0 kg), and their mean height was 1.66 (0.08) m (range, 1.48–1.81 m). After intravenous administration of single doses of 0.5, 1.0, and 2.0 g, the cefotetan disodium C max was 35.01 (6.98), 76.67 (10.52), and 154.33 (27.17) mg/L, respectively; the AUC 0−15h was 145.35 (18.36), 307.45 (33.07), and 746.09 (103.07) mg · h/L; the AUC 0−∞ was 171.51 (20.61), 347.25 (44.20), and 843.84 (131.13) mg · h/L; the t 1/2 was 5.80 (1.29), 4.91 (1.15), and 5.04 (1.26) hours; the CL was 2.96 (0.41), 2.92 (0.39), and 2.42 (0.39) L/h; and the V d was 24.55 (5.19), 20.37 (3.66), and 17.30 (3.52) L. After administration of multiple doses, the cefotetan disodium C max,ss was 80.53 (10.04) mg/L; the C mix,ss was 11.00 (4.04) mg/L; the AUC ss was 347.92 (50.04) mg · h/L; the steady-state plasma concentration was 28.99 (4.17) mg/L; the t 1/2 was 6.24 (2.52) hours; the CL was 2.32 (0.64) L/h; and the Vd was 19.19 (4.58) L. No significant differences in pharmacokinetic parameters were noted by sex in the multipledose phase. Cefotetan disodium appeared to be well tolerated. Conclusions: In these healthy Chinese subjects, the cefotetan disodium AUC and C max increased in a doseproportional manner, whereas the t 1/2 was independent of dose. The pharmacokinetic properties of cefotetan disodium were linear at doses of 0.5 to 2.0 g. After multiple doses, the pharmacokinetic parameters of cefotetan disodium were consistent with those after single doses. At the doses studied, cefotetan disodium appeared to be well tolerated in these healthy volunteers.

Programmed cell death 1 (PD-1) has been reported to have a genetic association in several autoimmune diseases. The aim of this study was to investigate the association of PD-1 polymorphisms and haplotypes with ankylosing spondylitis (AS) in Chinese Han population. In a case-control association study, three single-nucleotide polymorphisms (SNP), PD-1.3 G/A, PD-1.5 C/T and PD-1.9 T/C, were genotyped in 216 AS patients and 264 healthy controls using polymerase chain reaction-restriction fragment length polymorphism assay. All genotype distributions in the patients and in the controls were in Hardy-Weinberg equilibrium. The associations of genotypes and alleles with AS were analyzed. The genotype distributions of PD-1.9 were significantly different between the patients with AS and the controls (P = 0.025). The frequencies of TC genotype and T allele of PD-1.9 were higher in the patients than those in the controls (P = 0.026 and 0.004). No association for PD-1.5 in AS was found, and PD-1.3 was non-polymorphic in Chinese Han population. Moreover, the frequency of the CT haplotype (PD-1.5 C/T, PD-1.9 T/C) was significantly higher in AS patients than the controls (21.6 vs. 13.9%, P = 0.002). The CC haplotype was more common in the controls than in the patients (57.1 vs. 44.6%, P = 0.000). The results support a genetic association between the PD-1 polymorphism and susceptibility to AS in Chinese Han population.

The objective of this study was to explore the relationships between varicocele-related spermatogenesis dysfunction and the expression of leptin and leptin receptors. In rats with experimental varicocele, the function of spermatogenesis, the expression of leptin and leptin receptors in testes were analysed; and in patients with varicocele-related male infertility, serum and seminal plasma levels of leptin, gonadal hormones and semen parameters were evaluated. In the testes of rats, leptin was expressed in seminiferous tubules and intersitium, leptin receptor was predominantly expressed in interstitium. The expression of leptin and its receptor in the testis of rats was not related to the weight of rat, but was inversely related to the weight of testis (r = -0.408, p = 0.009 and r = -0.433, p = 0.005, respectively), the Johnsen scores (r = -0.916, p = 0.000 and r = -0.863, p = 0.000, respectively), the seminiferous tubules diameter (r = -0.853, p = 0.000 and r = -0.870, p = 0.000, respectively) and the thickness of seminiferous epithelium (r = -0.929, p = 0.000 and r = -0.948, p = 0.000, respectively). In varicocele patients (N = 40), the sperm concentration and motility were significantly lower (p = 0.000) than those in the control group (N = 25), and the leptin level in seminal plasma was significantly higher (p = 0.000) than that in the control group. The leptin in serum and seminal plasma was positively related (r = 0.223, p = 0.002). The seminal plasma leptin level was inversely related to sperm concentration (r = -0.632, p = 0.000) and motility (r = -0.635, p = 0.000). There was no significant relation between serum leptin and seminal parameters and between leptin and gonadal hormone values. The dysfunction of spermatogenesis in varicocele-related infertile male is associated with increase in leptin and leptin receptors. Leptin may have local effects on the function of testis and spermatogenesis.

The study tested the hypothesis that transplantation of human neurotrophin-3 (hNT-3) over-expressing neural stem cells (NSCs) into rat striatum after a severe focal ischemia would promote functional recovery. Rat NSCs, transduced by Flag-tagged hNT-3 gene mediated by lentiviral vector (LV), were transplanted into the striatum ipsilateral to the injury of adult rats 7 days after 2-h occlusion of the middle cerebral artery (MCAO). From 3 days to 2 weeks after transplantation, the modified cells (NSCs-hNT3, as defined by Flag immunofluorencence staining) that survived the transplantation procedures could secrete significantly higher levels of neurotrophin-3 protein in the graft sites than controls (P

Aim: To promote the provision of reproductive health services to young people by exploring the attitudes and perceptions of university students in Shanghai, China, toward reproductive health. Methods: From July 2004 to May 2006, 5 243 students from 14 universities in Shanghai took part in our survey. Topics covered the demands of reproductive health-care services, attitudes towards and experience with sex, exposure to pornographic material, and knowledge on sexual health and sexually transmitted infections (STIs)/AIDS. Results: Of the 5 067 students who provided valid answer sheets, 50.05% were female and 49.95% were male, 14.86% were medical students, and 85.14% had non-medical backgrounds. A total of 38.4% of respondents had received reproductive health education previously. The majority of students supported school-based reproductive health education, and also acquired information about sex predominantly from books, schoolmates, and the Internet. Premarital sexual behavior was opposed by 17.7% of survey participants, and 37.5% could identify all the three types of STIs listed in the questionnaire. Although 83.7% knew how HIV is transmitted, only 55.7% knew when to use a condom and 57.8% knew that the use of condoms could reduce the risk of HIV infection. Conclusion: The reproductive health service is lagging behind current attitudes and demands of university students. Although students' attitudes towards sexual matters are liberal, their knowledge about reproductive health and STIs/AIDS is still limited. It is therefore necessary to provide effective and confidential reproductive health services to young people.

Patatin-like phospholipase domain-containing 3 (PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism, and has been reported to be significantly associated with liver fat content. Various studies have established a strong link between the 148 isoleucine to methionine protein variant (I148M) of PNPLA3 and liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, detailed demographic and ethnic characteristics of the I148M variant and its role in the development of nonalcoholic fatty liver fibrosis have not been fully elucidated. The present review summarizes the current knowledge on the association between the PNPLA3 I148M variant and NAFLD, and especially its role in the development of nonalcoholic fatty liver fibrosis. First, we analyze the impact of demographic and ethnic characteristics of the PNPLA3 I148M variant and the presence of metabolic syndrome on the association between PNPLA3 I148M and NAFLD. Then, we explore the role of the PNPLA3 I148M in the development of nonalcoholic fatty liver fibrosis, and hypothesize the underlying mechanisms by speculating a pro-fibrogenic network. Finally, we briefly highlight future research that may elucidate the specific mechanisms of the PNPLA3 I148M variant in fibrogenesis, which, in turn, provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.

Background Soluble urokinase receptor (suPAR) may be involved in the pathological mechanisms of focal segmental glomerulosclerosis (FSGS) changes. However, it remains unclear whether suPAR is correlated with the FSGS-like lesions in IgA nephropathy (IgAN). Methods We measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed. Results We found that the plasma suPAR levels were significantly correlated with age and renal function by both univariate and multivariate analysis in our IgAN patient cohort. Female had higher plasma suPAR levels and no significant correlation was observed between plasma suPAR levels and 24-h urine protein and highly sensitive C-reaction protein with multivariate analysis. In our cohort, sixty of these IgAN patients could be diagnosed with a type of FSGS lesions. The plasma suPAR levels were higher in the IgAN patients with FSGS lesions than in the IgAN patients without FSGS lesions by univariate (P < 0.0001) and multivariate (P < 0.001) analysis adjusting for other predictor variables, which might be helpful to differentiate the pathological changes with and without FSGS lesions. And the optimal cutoff value was 1806 pg/ml in this study. The plasma suPAR concentrations were also associated with the degree of tubular atrophy/interstitial fibrosis in both univariate and multivariate analysis. In multivariate analysis, the plasma suPAR levels were correlated with the percentage of crescents, not global sclerosis and arterial lesions. Conclusions Our study suggested that the plasma suPAR levels were associated with age, gender, renal function, the degree of tubular atrophy/interstitial fibrosis and the percentage of crescent formation. The plasma suPAR might be a potential predictor for the presence of FSGS pathological lesions in Chinese patients with IgAN.

Chronic stress as well as major depressive disorders is associated with cortisol metabolism. Two enzymes modulate cortisol (F) and cortisone (E) interconversion: 11β-hydroxysteroid dehydrogenase type 1 and type 2 (11β-HSD1 and 11β-HSD2). Furthermore, F and E were inactivated by 5α and 5β reductases to their tetrahydro-metabolites: tetrahydrocortisol (THF), allo-tetrahydrocortisol (5α-THF) and tetrahydrocortisone (THE). To better understand depression a LC-MS/MS method for simultaneous determination of F, E THF, 5α-THF and THE in human urine has been developed and validated. The quantification range was 0.1-160 ng mL(-1) for F and E, and 0.2-160 ng mL(-1) for the tetrahydro-metabolites, with >86.1% recovery for all analytes. The nocturnal urine concentrations of F, E and tetrahydro-metabolites in 12 apparently healthy male adult volunteers and 12 drug-free male patients (age range, 20-50 years) with a diagnosis of depression were analyzed. A series of significant changes in glucocorticoid metabolism can be detected: F/E ratios and (THF+5α-THF)/THE ratios as well as F and THF concentrations were significantly higher in depression patients than in healthy subjects (p

1. Capsaicin (CAP) is the primary pungent principle in peppers and an inhibitor of CYP3A subfamily and P-gp.2. Pitavastatin is mainly metabolized via glucuronidation and metabolism by hepatic CYPs is minimal. Pitavastatin is taken up by Oatp1b2 (encoded by Slco1b2) in rat.3. The pharmacokinetics results showed that AUC and Cmax in the group pre-treated with 3 mg/kg/d CAP were increased by 1.2 fold and 1.6 fold; AUC and Cmax in the group pre-treated with 8 mg/kg/d CAP were increased by 2.1 fold (p

The developed muscle activity imaging approach (MAI) was validated with surface EMG and intramuscular EMG signals simultaneously acquired from the biceps of a healthy male subject. 128 unipolar channels were employed for surface EMG measurement and one bipolar channel was employed for simultaneous intramuscular EMG measurement for the validation purpose. Ultrasound scans were also specifically performed to localize the location of the wire electrode inserted into the biceps. The surface EMG measurements, after noise filtering and signal decomposition, were used to reconstruct the internal muscle activities for the biceps by using the MAI approach. The locations of the reconstructed muscle activities were compared against the location of the wire electrode in the biceps identified from ultrasound images. Results demonstrate the feasibility and validity of the MAI approach in imaging internal muscle activities from multi-channel surface EMG recordings.

To discuss the feasibility of using free tissue flap for simultaneous tongue reconstruction after tongue cancer resection.Radial forearm flaps and anterolateral thigh flaps were used for simultaneous reconstruction of different defects after tongue cancer resection in 47 cases. The functional evaluation was assessed during the follow-up period of 3 months to 9 years.Only one flap failed,giving a success rate of 97.7%. The 36 patient available for postoperative follow-up were all able to communicate in basic languages and eat normally. Among them, normal speech was found in 34, while slurred speech was found in two. 31 patients could eat normal diet ,while eight could eat soft diet and two could eat liquid diet.Simultaneous tongue reconstruction with free tissue flap is a reliable method with high successful rate. Flaps selection based on different tongue defects is the key point to achieve good functional and cosmetic results for the reconstruction tongue.

Background The recombinant human parathyroid hormone (1–34) (rhPTH[1-34]) teriparatide is the first anabolic agent approved by the US Food and Drug Administration for the treatment of osteoporosis in men and women. This study was conducted to provide support for marketing authorization of an agent biosimilar to teriparatide in China. Objective The main aim of the present study was to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic parameters of rhPTH(1–34) after single and multiple subcutaneous doses in healthy Chinese subjects. Methods Two open-label, randomized, single-center, dose-escalation studies were performed. In study 1, subjects were randomized to receive a single dose of rhPTH(1–34) (10, 20, 30, 40, 50, or 60 μg) or a multiple dose of rhPTH(1–34) (10 and 20 μg once daily for 7 consecutive days) to determine the safety profile and tolerability, as reflected by the incidence, intensity, and seriousness of the observed adverse events. In study 2, a single dose of rhPTH(1–34) (10, 20, or 40 μg) and a multiple dose of rhPTH(1–34) (20 μg) were administrated subcutaneously to investigate the pharmacokinetic and pharmacodynamic parameters. Results Forty-two subjects completed study 1, and 30 subjects completed study 2. rhPTH(1–34) was well tolerated during the investigated single (10–60 μg) and multiple (10–20 μg once daily for 7 consecutive days) dose ranges. The most generally reported adverse events were erythema at the injection site and gastrointestinal reactions. After single and multiple subcutaneous administration of rhPTH(1–34), the drug was rapidly absorbed, with a T max of 20 to 30 minutes, and rapidly cleared from the plasma, with a t ½ of 47.2 to 60.6 minutes. The mean C max , AUC 0–t , and AUC 0–∞ increased in proportion to the doses, whereas the t ½ , total clearance, and T max values were independent of the administered dose. No significant differences in pharmacokinetic parameters were noted by sex except for T max in the 10-μg and 20-μg single-dose groups. Compared with the baseline levels, no significant changes or dose-related significant effects were observed in serum calcium and phosphate levels. Conclusions All rhPTH(1–34) doses appeared to be well tolerated in the population studied. Linear pharmacokinetic characteristics were displayed in the dose range studied. Chinese ClinicalTrials.gov identifier: ChiCTR-ONC-12002874.

To study the relationship between the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene and hereditary susceptibility to non-alcoholic fatty liver disease (NAFLD) by detecting single nucleotide polymorphisms (SNPs).Peripheral blood DNA from 315 patients diagnosed with NAFLD (including the spectrum of simple steatosis (SS) and non-alcoholic steatosis (NASH)) and 336 control subjects was used to determine the PNPLA3 genotype by polymerase chain reaction (PCR) and direct sequencing. The relationship of SNPs and NAFLD-related markers of liver function were assessed by correlation analysis.The SNP rs738409 was identified in more of the NAFLD patients (allele variant frequencies: NAFLD, 65.40%; NASH: 71.87%; SS, 56.47%) than in the controls (33.18%). Case-control analysis revealed that carriers of the 148GG genotype were at 3.81-fold (95% CI: 3.03 ~ 4.79) higher risk of developing NAFLD and at 1.97-fold (95% CI: 1.41 ~ 2.75) higher risk of progressing from SS to NASH, compared with non-carriers. rs738409 was also found to be associated with serum levels of alanine aminotransferase (ALT) and y-glutamyltransferase (y-GT) (both P less than 0.05). Carriers of the 148GG genotype had significantly higher body mass index, ALT, and fasting insulin than carriers of the 148CC genotype (all P less than 0.05), and significantly higher level of serum HDL than carriers of either the 148CC genotype or the 148GC genotype (both P less than 0.05).Polymorphisms in the PNPLA3 gene may play an important role in mediating susceptibility to developing NAFLD in the Chinese population. The rs738409 polymorphism, in particular, is related to development and progression of NAFLD and may play a role in the contribution of PNPLA3 to NAFLD pathogenesis.

To investigate the association between two polymorphisms of apolipoprotein C3 (APOC3) and risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese Han population.Genotypes for rs2854116 and rs2854117 in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) in 390 patients with NAFLD and 409 control subjects were determined by sequencing and polymerase chain reaction analysis. Serum lipid profiles were determined using biochemical methods, and an index of insulin resistance (IR, HOMA-IR), serum APOC3 concentrations and total antioxidant status (TAS) were also assessed.No significant differences in genotype and allele frequencies of rs2854116 and rs2854117 were found between the NAFLD population and the controls (P0.05). The OR for the association between -455C and -482T allele carriers and the risk of NAFLD were 1.06 (95%CI: 0.72-1.57, P0.05) and 1.00 (95%CI: 0.68-1.48, P0.05), respectively. The variant carriers did not have a significantly increased risk of NAFLD or elevated clinical and biochemical parameters such as APOC3 concentrations, IR (1.42 ± 0.43 vs 1.48 ± 0.52, P0.05), liver enzymes and TAS (13.94 ± 2.01 vs 14.38 ± 1.92, P0.05) compared with the controls. Moreover, the results were similar when testing was carried out independent of the genetic variation in PNPLA3.The two polymorphisms of the APOC3 gene are not associated with a risk of NAFLD, or with lipid profiles, IR and oxidative stress in the Chinese Han population.

To explore the expression of CCAAT/enhancer binding protein beta (CEBPB) in gastric carcinoma tissues and its association with clinicopathological features and prognosis.CEBPB protein expression level was detected by immunohistochemistry method in resected gastric carcinomas and adjacent gastric mucosa tissues (n=81), and its association with clinicopathological features and prognosis was analyzed.The immunohistochemical staining of CEBPB was predominantly in the nucleus with some cytoplasmic staining. As a result, 16% (13/81) of the gastric carcinomas were stained positively, whereas there was hardly positive expression in adjacent gastric mucosa tissues. There was a significant association between the expression of CEBPB and distant metastasis on univariate analysis (P0.05). The median survival time in patients with positive CEBPB expression was significantly lower than those with negative CEBPB expression (19.4 months vs. 45.2 months, P=0.024). Multivariable analysis showed that CEBPB was independently associated with prognosis (HR=2.544, 95%CI:1.154-5.610, P=0.021).Up-regulation of CEBPB suggests poor prognosis in patients with gastric cancer.

Whether right ventricular outfow tract septum (RVOTS) pacing is superior to right ventricular apex (RVA) pacing with respect to left ventricular synchrony, cardiac function, and remodelling in the elderly with normal left ventricular ejection fraction (LVEF), is still unknown.To assess the impact of RVOTS vs. RVA pacing on the cardiac performance of the elderly with normal LVEF during a long-term observation.From 2007 to 2010, 65 patients with standard pacing indications for permanent pacing were recruited and randomised to receive RVA (32 patients) or RVOTS pacing (33 patients). Over a median 28 months' follow-up, available data was summarised, including New York Heart Association (NYHA) functional class, echocardiographic and pacing parameters, axis, QRS duration and plasma B-type natriuretic peptide (BNP) level. Then these values were compared between the RVA group and the RVOTS group, as well as between pacemaker pre- and post-implantation in the RVA group and in the RVOTS group, respectively.There were no significant differences in baseline characteristics between the RVA group and the RVOTS group. The median pacing durations did not differ significantly between the groups (31.5 months in the RVA group vs. 28 months in the RVOTS group, p = 0.728). Compared to the baseline values, LVEF decreased with RVA pacing (from 59.5 ± 6.21 to 54.22 ± 8.73, p = 0.001), but LVEF did not markedly vary in the RVOTS group (57.82 ± 6.06 and 56.94 ± 5.54, p = 0.152). The number of patients with moderate tricuspid valve regurgitation remarkably increased in the RVA group, from six (18.75%) patients to 10 (31.3%) patients, preoperatively to postoperatively (p = 0.046), but this change was not statistically significant in the RVOTS group. Compared to the RVOTS group, NYHA functional class had a deteriorated tendency in the RVA group (p = 0.071). After the implantation, the increase of median BNP level was observed in the RVA group (35 pg/mL at preimplantation and 50 pg/mL at the end of follow-up, p = 0.007); No significant change was obtained in the RVOTS group (36.4 pg/mL at pre-implantation vs. 38 pg/ml at the end of follow-up, p = 0.102). Compared to the RVA pacing group, the mean QRS width narrowed substantially in the RVOTS pacing group (from 143.56 ± 12.90 to 105.52 ± 15.21, p = 0.000). In terms of the end diastolic and systolic diameters of the left ventricular, there were no statistical variations observed during the follow-up.Permanent RVA pacing in elderly patients with normal LVEF led to left ventricular systolic function deterioration denoted by lower LVEF and higher BNP level. When compared to RVA pacing, RVOTS pacing had no remarkable benefit in terms of preventing cardiac remodelling.

To investigate the clinical value of tumor markers CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of patients with gastric cancer.One hundred and sixty gastric cancer patients who had received treatment from 2002 to 2007 at the Beijing Cancer Hospital were retrospectively analyzed. Blood samples were taken from patients upon admission to the hospital, and CEA, CA19-9, CA72-4, CA242 levels were detected. Statistical analysis was performed to identify the clinical value of these tumor markers in diagnosis and prognosis.On initial diagnosis, the positive rates of CEA, CA19-9, CA72-4 and CA242 were 37.7%, 26.7%, 37.6% and 21.3%, respectively, and the positive rate of combined detection was 62.9%. CEA was more frequently positive in patients with lymph node metastasis (P=0.029); CA72-4 was more frequently positive in patients with vascular involvement and advanced stage (P=0.039, P=0.011). Multivaraite analysis showed that CA72-4 was an independent prognostic factor (P=0.012). Patients with positive CA72-4 carried a 2.147-fold increased risk of death than those with negative CA72-4. Kaplan-Meier analysis showed that patients with positive CA19-9 or positive CA72-4 had worse survival than those with negative CA19-9 or CA72-4 (P=0.006, P=0.002).Tumor markers including CEA, CA19-9, CA72-4 and CA242 have clinical significance and prognostic value in patients with gastric cancer. Combined detection of four tumor markers can increase the positive rate. CA72-4 is an independent prognostic factor. CA19-9 and CA72-4 are associated with the prognosis of patients with gastric cancer.