Prognostic stratification of patients with pT4bN0M0 colorectal cancer following multivisceral resection: a multi-institutional case series analysis.

BACKGROUND: Colorectal cancer (CRC) patients with stage pT4b are a complex group as they show differences in tumor-infiltrated organs. Patients with the same stage often exhibit differences in prognosis after multivisceral resection (MVR). Thus far, some important prognostic factors have not been thoroughly investigated. Here, we identified the prognostic factors influencing CRC patients at pT4bN0M0 stage to better stratify the prognostic differences among patients. MATERIALS AND METHODS: A retrospective analysis was conducted on patients diagnosed to have locally advanced CRC and who underwent MVR at three medical institutions from January 2010 to December 2021. The prognostic factors affecting the survival of CRC patients at pT4bN0M0 stage were identified by multivariate Cox proportional hazard models. We then classified the prognosis into different grades on the basis of these independent prognostic factors. RESULTS: We enrolled 690 patients with locally advanced CRC who underwent MVR; of these, 172 patients with pT4bN0M0 were finally included. Patients with digestive system (OS: hazard ratio [HR]=0.441; 95% confidence interval [CI]=0.217-0.900; P=0.024; DFS: HR=0.416; 95% CI=0.218-0.796; P=0.008) or genitourinary system invasion (OS: HR=0.405; 95% CI=0.193-0.851; P=0.017; DFS: HR=0.505; 95% CI=0.267-0.954; P=0.035) exhibited significantly better overall survival (OS) and disease-free survival (DFS) as compared to those with gynecological system invasion, while the OS and DFS were similar between the diggestive system and genitourinary system invasion groups (OS: HR=0.941; 95% CI=0.434-2.042; P=0.878; DFS: HR=1.211; 95% CI=0.611-2.403; P=0.583). Multivariate analysis showed that age (OS: HR=2.121; 95% CI=1.157-3.886; P=0.015; DFS: HR=1.869; 95% CI=1.116-3.131; P=0.017) and type of organs invaded by CRC (OS: HR=3.107; 95% CI=1.121-8.609; P=0.029; DFS: HR=2.827; 95% CI=1.142-6.997; P=0.025) were the independent prognostic factors that influenced the overall survival (OS) and disease-free survival (DFS) of CRC patients with pT4bN0M0 disease. The OS and DFS of patients showing invasion of the gynecological system group were significantly worse (P=0.004 and P=0.003, respectively) than those of patients with invasion of non-gynecological system group. On the basis of the above-mentioned two independent prognostic factors, patients were assigned to high-, medium-, and low-risk groups. Subgroup analysis showed that the OS and DFS of the medium- and high-risk groups were significantly worse (P=0.001 and P=0.001, respectively) than those of the low-risk group. CONCLUSION: Patients with pT4bN0M0 CRC show significant differences in their prognosis. The type of organs invaded by CRC is a valuable indicator for prognostic stratification of CRC patients with pT4bN0M0.

TDP-43 is a potential marker of dopaminergic neuronal damage caused by atrazine exposure.

Atrazine (ATR) is one of the herbicides widely used worldwide. Meanwhile, it is an environmental endocrine disruptor that can cross the blood-brain barrier and cause damage to the endocrine-nervous system, especially by affecting the normal secretion of dopamine (DA). Regrettably, effector markers and cascade response mechanisms in damaged dopaminergic neurons induced by ATR exposure remain elusive. In this paper, we focus on investigating aggregation and position change of transactive response DNA-binding protein-43 (TDP-43) after ATR exposure, and illustrating whether TDP-43 can serve as a potential marker of mitochondrial dysfunction which causes damage to dopaminergic neurons. In our study, we used rat adrenal pheochromocytoma cell line 12 (PC12) to establish an in vitro model of dopaminergic neurons. After PC12 was intervened by ATR, we found reduced DA cycling and DA levels, and that TDP-43 aggregated continuously in the cytoplasm and then translocated to mitochondria. Furthermore, the studies we have performed showed that the translocation can cause mitochondrial dysfunction through activating the unfolded mitochondrial protein response (UPRmt), ultimately causing damage to dopaminergic neuron. The research we have done suggests that TDP-43 can serve as a potential effector marker of dopaminergic neuron damaged caused by ATR exposure.

Application of Microwave Transmission Sensors for Water Cut Metering under Varying Salinity Conditions: Device, Algorithm and Uncertainty Analysis.

The measurement of water cut in crude oil is an essential procedure in petroleum production and it is desirable to obtain these data through an automatic and real-time method. Microwave sensors can be used for the task, and they are safe, robust and can cover the whole water cut range. However, they are relatively susceptible to the water conductivity and temperature, and the algorithms for addressing these problems are still rare in the literature. In this paper, a microwave transmission sensor that can measure the water cut under varying salinity conditions is proposed, and the algorithm for solving the water cut and salinity simultaneously with the measured amplitude and phase is described in detail. Experiments under different water cut and salinity conditions are conducted, and the results are used to verify the model and algorithm. Finally, a simplified and fast method for uncertainty analysis is proposed and applied to the iteration algorithm under test conditions. It can be concluded that accuracy higher than 95% in the water cut measurements can be expected under the 0~100% water cut range, and an error of about 10% in the water conductivity is achievable under water-continuous flow conditions. The uncertainty analysis shows that the calculated water cut and salinity results are negatively correlated, and the water salinity uncertainty tends to be larger than the water cut uncertainty. When the water salinity is high, the water cut uncertainty tends to be high whereas the water salinity uncertainty tends to be low.

Paraquat induces microglial cause early neuronal synaptic deficits through activation of the classical complement cascade response.

Synapse loss is considered to be an early event in the dysfunction of the central nervous system (CNS), precedes neuronal decline, which is the main pathological change in mild cognitive impairment (MCI). Accumulating evidence has shown that neuronal synapse loss is associated with hyperactivity of microglial phagocytosis. In the CNS, microglia act as macrophages to clear cellular debris and weakened synapses, but the mechanism by which microglia activation leads to phagocytosis disorder remains unclear. Therefore, we treated mice with paraquat (PQ) in intraperitoneal injection to explore the mechanism by which microglia exert immunotoxicity in the CNS and cause neuronal synapse loss. Immunofluorescence results exposed synapses decreased with PQ exposure time, but the staining HE and Nissl showed that neuronal cell bodies were hardly affected. Fluorescence co-localization found that C1q (classical complement cascade initiation factor) was gradually deposited in the postsynaptic membrane of neurons to trigger the cascade reaction, thereby causing the excessive deposition of C3, a key factor of the classical complement cascade, and further induces hyperactivation of microglia, leads to phagocytosis disorder. IHC results demonstrated that the parallel relationship. Therefore, all our preliminary results throw light on the mechanism by which PQ abnormally triggers the immune system to produce immunotoxicity leading to microglial phagocytic dysfunction.

Discovery of new genetic loci for male sexual orientation in Han population.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

A Comparison of Different Schemes of Neoadjuvant Chemotherapy Followed by Concurrent Chemotherapy and Radiotherapy for Locally Advanced Cervical Cancer: A Retrospective Study.

PURPOSE: To examine the clinical significance of unoperated cervical cancer patients treated with different neoadjuvant chemotherapy (NACT) schemes followed by concurrent chemotherapy and radiotherapy (CCRT). METHODS: This retrospective analysis included women with locally advanced cervical cancer treated with NACT-CCRT between September 2011 and September 2014. Neoadjuvant chemotherapy included paclitaxel plus cisplatin (TP group; 62 patients) or paclitaxel plus loplatin (TL group; 58 patients), which were administered three weekly, and cisplatin or loplatin, which were administered weekly for synchronous chemotherapy. External beam radiation therapy (50.4-56.35 Gy/28 f, 180-215 cGy/f, 5 f/w) was followed by intracavitary brachytherapy (5 Gy per fraction, mostly 5 fractions, Ir192 based). RESULTS: One hundred twenty women were included in the analysis. The complete/partial response rate was 99.2% after treatment. The one-year, three-year, and five-year survival rates were 99.2%, 82.5%, and 70.8%, respectively. In the TP and TL groups, the three-year and five-year survival rates were 85.5% vs 77.6% and 75.8% vs 65.5%, respectively, with no significant difference. The 5-year overall survival (OS) rates between patients with stage IIB and stage IIIB disease were not significantly different (69.2% vs 64.7%). In the TP group, grade 3 or 4 digestive reactions were more frequent than those in the TL group. Leukopenia, neutropenia, and thrombocytopenia were more common in the TL group. No significant difference was found in anemia, radiation enteritis, radiation proctitis, or radiation cystitis between the groups. CONCLUSION: Lobaplatin may be used as an alternative drug for patients with severe digestive system reactions or contraindications to cisplatin, but hematological toxicity must be considered, particularly in dose-intensive schemes. Neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy (NACT-CCRT) warrants further prospective study in cervical cancer patients with a wide range of tumor invasion (eg, mass size ≥5 cm or stage IIIB).

[Pharmacoeconomic evaluation of Suhuang Zhike Capsules using Markov model for inpatients with acute exacerbation of chronic obstructive pulmonary disease].

To evaluate the economics of Suhuang Zhike Capsules in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) for inpatients. Based on the published clinical research data, cost-utility analysis was used in this study to evaluate the pharmacoeconomics of Suhuang Zhike Capsules in treatment of AECOPD inpatients from the perspective of medical insu-rance. The test group was treated with Suhuang Zhike Capsules combined with conventional Western medicine, and the control group was treated with conventional Western medicine alone. Treeage software was used to construct a pharmacoeconomic model and perform simulation analysis. The results showed that the cost and output of Suhuang Zhike Capsules combined with the conventional Western medicine were 60 010.18 yuan and 1.92 quality adjusted life year(QALYs), respectively in the simulated 3 years of disease treatment. The cost and output of the conventional Western medicine were 96 730.60 yuan and 1.90 QALYs respectively. Suhuang Zhike Capsules combined with conventional Western medicine required lower cost but achieved higher output, showing cost-utility advantages, so this drug combination was a plan with pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is believed that as compared with the conventional Western medicine, Suhuang Zhike Capsules combined with conventional Western medicine have lower cost and higher output for the treatment of AECOPD inpatients, and it is a treatment plan with pharmacoeconomic advantages.

[Meta-analysis of efficacy and safety of Shexiang Tongxin Dripping Pills combined with conventional therapy of coronary heart disease].

The aim of the research was to evaluate the efficacy and safety associated with Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD). We searched 8 electronic databases up to November 2020, including PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP and SinoMed. Eligible studies were clinical trials of Shexiang Tongxin Dropping Pills combined with conventional therapy used in the treatment of coronary heart disease(CHD). The Meta-analysis was performed using STATA 15 software. A total of 21 RCTs(n=2 186) were shortlisted for the Meta-analysis. The results of efficacy evaluation showed that the total effective rate of Shexiang Tongxin Dropping Pills combined with conventional therapy was higher than that of conventional therapy of coronary heart disease(RR=1.20, 95%CI[1.15, 1.26], Z=8.63, P<0.001). Furthermore, Shexiang Tongxin Dripping Pills combined with conventional therapy had better effect on electrocardiogram efficacy(RR=1.24, 95%CI[1.16, 1.34], Z=5.98, P<0.001) and the number of angina attacks(SMD=-2.30, 95%CI[-3.47,-1.14], Z=3.88, P<0.001), the duration of angina attack(SMD=-2.31, 95%CI[-3.07,-1.55], Z=5.97, P<0.001), with lower levels of LDL-C(SMD=-0.73, 95%CI[-1.32,-0.14], Z=2.42, P=0.016), TC(SMD=-1.16, 95%CI[-1.35,-0.96], Z=11.56, P<0.001) and TG(SMD=-0.87, 95%CI[-1.06,-0.68], Z=8.97, P<0.001), and higher levels of HDL-C(SMD=0.87, 95%CI[0.02, 1.71], Z=2.00, P=0.045). The results of safety evaluation showed that the incidence of adverse reactions of Shexiang Tongxin Dropping Pills combined with conventional therapy was lower than that of conventional therapy of coronary heart disease(RR=0.45, 95%CI[0.22, 0.91], Z=2.23, P=0.026). There were significant differences in the above outcome indexes between the two groups. After the Harbord method test, the total effective rate outcome index has publication bias, but the sensitivity analysis of the cut-and-fill method suggested that the result was stable. In general, limited by the quantity and quality of included literature, more high-quality studies are needed to further verify the conclusions of this study.

[Pharmacoeconomic evaluation of Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment for coronary heart disease by Markov model].

This research was to evaluate the economics of Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD) in Chinese medical environment. From the perspective of medical insurance, a Markov model was established in this study based on the results of Meta-analysis comparing the effectiveness and safety of Shexiang Tongxin Dripping Pills combined with conventional treatment and conventional treatment alone. The experimental group was treated with She-xiang Tongxin Dropping Pills combined with conventional Western medicine treatment, while the control group was treated with conventional Western medicine treatment alone. The cost-utility analysis and sensitivity analysis were performed for the two regimens using Treeage pro. After 30 cycles of model simulation, according to the results of Markov model, the total cost and health output were CNY 237 795.73 and 16.36 QALYs(the quality adjusted life years, QALYs), respectively for Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment, CNY 247 396.55 and 16.36 QALYs respectively for the conventional Western medicine treatment alone. Compared with the conventional treatment alone, the Shexiang Tongxin Dropping Pills combined with conventional treatment had lower long-term cost and higher health output, with advantages of cost-utility and pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is considered that compared with the conventional Western medicine alone, Shexiang Tongxin Dropping Pill combined with conventional Western medicine is a treatment regimen with pharmacoeconomic advantages for the treatment of CHD.

Transjugular intrahepatic portosystemic shunt through left branch versus right branch of portal vein: a meta-analysis.

PURPOSE: To compare the clinical outcomes between patients that underwent transjugular intrahepatic portosystemic shunt (TIPS) via the left and right portal veins (PVs). MATERIALS AND METHODS: All relevant studies in the Pubmed, Embase, and Cochrane Library databases published as of June 2020 were identified by searching, after which RevMan v5.3 was used to conduct the present meta-analysis. Relevant endpoint data were extracted from each study, related to postoperative hepatic encephalopathy (HE) rates, TIPS dysfunction, re-bleeding, and mortality. RESULTS: A total of eight studies were identified as being relevant for inclusion in this meta-analysis. These studies included 2592 total patients suffering from liver cirrhosis that underwent TIPS treatment via the left (n = 1500) or right (n = 1092) PVs. Rates of postoperative HE were significantly lower in the left PV group relative to the right PV group (5.7% vs. 18.1%, OR 0.19; P < 0.00001), as were rates of TIPS dysfunction (8.1% vs. 16.5%, OR 0.41; P < 0.00001). In contrast, the rates of re-bleeding did not differ significantly between these groups (12.0% vs. 14.9%, OR 0.76; P = 0.11), nor did mortality rates (30.9% vs. 31.0%, OR 0.85, P = 0.22). We did not detect any significant heterogeneity among included studies for any analyzed endpoints, nor was any risk of publication bias pertaining to these studies detected through the use of funnel plots. CONCLUSIONS: TIPS conducted via the left PV was associated with decreased rates of postoperative HE and TIPS dysfunction relative to TIPS conducted via the right PV.

The Impact of the COVID-19 Pandemic on Pediatric Clinical Practice in Wenzhou, China: A Retrospective Study.

Introduction: The COVID-19 pandemic has affected all aspects of life worldwide. The aim of the present study was to review and describe and acknowledge the impact of COVID-19 on the pediatric health care system at a pediatric tertiary hospital in Wenzhou. Methods: A retrospective study was conducted at Yuying Children's Hospital of Wenzhou Medical University, a public pediatric tertiary hospital in Southern Zhejiang Province that specializes in pediatrics. The data regarding the primary diagnosis of patients were extracted from the electronic medical records system of the hospital. Data for outpatients and inpatients treated at the pediatric department were analyzed in the time frame of 22 weeks since the beginning of the pandemic (from December 30, 2019 to June 2, 2020) and compared with data from the same period in 2019. Results: The total number of outpatient cases in the previous 22 weeks of the year declined from 560,620 in 2019 to 247,030 in 2020, and inpatient cases decreased from 14,177 to 7,555. This negative trend settled by week 6 and 7 and subsequently approached the 2019 numbers. The most noticeable decrease in the number of cases was observed in children of preschool age. Moreover, the number of weekly visits decreased at the beginning of the epidemic, reached the lowest value during the lockdown period, and recovered after the lockdown. Conclusion: Based on the results of this study, clinical practice in a pediatric department in Wenzhou was substantially affected by the epidemic and measures such as physical distancing and increased personal hygiene, particularly in preschool-age children. An understanding of the trends and impacts of the pandemic on pediatric patients and health systems will facilitate better preparation of pediatricians in the future.

Clinical effect of Zoledronic Acid in the treatment of Senile Osteoporosis.

OBJECTIVE: To investigate the clinical efficacy of zoledronic acid in the treatment of senile osteoporosis. METHODS: One hundred and six cases of senile osteoporosis who visited to our hospital from August 2017 to December 2018 for treatment were selected and randomly divided into a control group and an observation group. The control group was treated with conventional therapy, while the observation group was treated with zoledronic acid in addition to the treatment of the control group. Bone mineral density, pain degree, therapeutic effect and adverse reactions of the two groups were compared. RESULTS: The total effective rate of the observation group was 96.67%, higher than 80.00% of the control group (P<0.05); the bone mineral density of lumbar vertebrae, femoral neck and Ward' area in the two groups increased after 6 months of treatment, and the bone mineral density of the observation group increased more than that of the control group (P<0.05); the pain degree of the observation group was lower than that of the control group after 6 months of treatment, and the difference was significant (P<0.05). There was no significant difference in the occurrence of adverse reactions between the two groups (P>0.05). CONCLUSION: Zoledronic acid is helpful to alleviate clinical symptoms, reduce the degree of bone pain, and promote the increase of bone mass, and has high safety in the treatment of senile osteoporosis, which is worth promotion.

Experimental studies on the effect of ultrasonic treatment and hydrogen donors on residual oil characteristics.

Residual oil, the residue after the distillation of crude oil, imposes deleterious effects on refinery due to its high viscosity and asphaltene content. In this context, ultrasonic technology has been widely applied in refining processes given its high efficiency and minimal environmental impacts. To guide the selection of operation parameters, in this work, we probed the effect of treatment duration, power, and hydrogen donor on the characteristics of residual oil under ultrasonic treatments. Underlying mechanisms of ultrasonic treatments, in the absence and presence of hydrogen donors, were verified through systematically analyzing viscosity, component conversion, molecular weight, hydrogen distribution, and functional groups of residual oil. While viscosity reductions under low-power density treatment are caused by colloidal system disaggregation, high-power density treatment can bring in both chemical bond cleavage and colloidal system disaggregation. In addition, adding hydrogen donor can effectively prevent radical recombination, and thus increases the yield of saturate. These results provide fundamental understandings on the effects of ultrasonic treatments.

Genetic analysis and molecular detection of resistance to chlorpyrifos mediated by the A216S substitution in acetylcholinesterase-1 in the plant bug Apolygus lucorum.

The green plant bug Apolygus lucorum is a major pest of Bacillus thuringiensis cotton in China. Previously, we reported that chlorpyrifos resistance in a laboratory-selected strain of A. lucorum (BZ-R) is associated with the homozygosis of an allele in the ace-1 gene encoding an alanine to serine substitution at position 216 of acetylcholinesterase-1. Here we describe the results of crosses between the resistant BZ-R strain (41-fold to chlorpyrifos) and the unselected susceptible BZ-S strain homozygous for the wild type alanine allele at position 216. Resistance to chlorpyrifos was inherited as a semi-dominant trait mainly controlled by a single autosomal gene and co-segregates strongly but not completely with the serine substitution in ace-1. Synergism bioassays and enzyme assays showed that minor contributions to resistance are also made by enhanced cytochrome P450 and carboxylesterase activities. A survey of 25 field populations from five Chinese provinces showed strong positive correlations between 50% lethal concentration against chlorpyrifos and S216 allele and genotype frequencies, although the most tolerant populations still only show 40%-50% S216 allele frequencies. The results above provide important information for designing effective resistance monitoring and management strategies for A. lucorum in China.

Methacrylic acid/butyl acrylate onto feruloylated bagasse xylan: Graft copolymerization and biological activity.

In this paper, feruloylated bagasse xylan (FBX) was synthesized with a method based on homogeneous catalytic esterification of bagasse xylan (BX) with ferulic acid (FA) in the presence of triethylamine as a catalyst, and it was further grafted with methacrylic acid (MAA) and butyl acrylate (BA) to synthesize FBX-g-MAA/BA grafted copolymer by using ammonium persulfate as initiator and N,N-methylene acrylamide as cross-linker. The effects of reaction variables including reaction time, temperature and reactant concentration on the esterification and graft reactions were investigated carefully by conducting orthogonal tests. A maximum degree of substitution (DS) of 1.76 for the esterification and a maximum graft ratio (GR) of 31% can be achieved by performing the reaction at optimized reaction parameters. The molecular docking was further performed to study the binding mode of the final product into the active site of human Caprin-2 C1q domain (4OUM, cause gastric cancer protein), liver cancer protein (1UV0) and lung cancer protein (3B9S). The software generated results were in satisfactory agreement with the evaluated biological activity. The anticancer performances of BX, FBX and FBX-g-MAA/BA copolymer were investigated by using a 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) method. The results indicated that the inhibition ratio of FBX-g-MAA/BA copolymer on BEL-7407 (liver cancer cells) can reach 25.28% ±â€¯4.01%, which is two times higher than that of BX.

Trichostatin A promotes GLI1 degradation and P21 expression in multiple myeloma cells.

BACKGROUND: Histone deacetylase inhibitors are promising drugs for the future application in cancer therapy. Trichostatin A (TSA), a histone deacetylase inhibitor, exhibits effective antitumor effects in various cancers. However, the effects and underlying mechanisms of TSA on multiple myeloma (MM) are not fully investigated. METHODS: In the present study, RPMI8226 and MM.1S cells treated with TSA were used for cell proliferation, cell cycle, and survival examinations, then the localization and post transcriptional modification of GLI1 protein as well as the target gene P21 were analyzed using immunofluorescence, immunoprecipitation, western blots and qPCR, respectively. RESULTS: TSA exerted a time and dose-dependent cytotoxicity on MM cell lines, and suppressed the proliferation of MM cells and induced an upregulation of p21 protein accompanied by a decreased expression of cyclin D1. TSA treatment led to a downregulation of GLI1, and the nuclear accumulation of GLI1 was also inhibited. As a result of hedgehog inhibition, the expression of MYC and SURVIVIN was greatly weakened after TSA treatment. Furthermore, TSA accelerated GLI1 degradation in a proteasome-dependent manner. Additionally, p21 induction also contributed to GLI1 downregulation via reducing the transcription of GLI in mRNA level. Rescue experiments verified that exogenous expression of GLI1 alleviated MM cell apoptosis induced by TSA. CONCLUSION: These results indicated that TSA represses MM cell growth and induces cell apoptosis. The inhibition of hedgehog signaling is an important mechanism accounting for the cytotoxic effects of TSA.

The expression and role of lncRNA AX800134 in hepatitis B virus-related hepatocellular carcinoma.

Chronic infection with hepatitis B virus (HBV) is one of most important risk factors for the development of hepatocellular carcinoma (HCC). Several long non-coding RNAs (lncRNAs) have been shown to be involved in the etiology of HBV-related HCC. AX800134 is one recently identified lncRNA associated with HCC. In this study, we validated the upregulated expression of AX800134 in HBV-positive HCC compared with HBV-negative HCC. Furthermore, we found that HBV X protein (HBx) directly triggered AX800134 expression in human hepatoma HepG2 cells. Pro-inflammatory cytokine TNFα also induced AX800134 upregulation in HBx-expressing HepG2 cells, which could be reversed by reactive oxygen species (ROS) scavenger pyrrolidine dithiocarbamate (PDTC). Additionally, silencing AX800134 with siRNA interference remarkably inhibited the growth and invasion of HBx-expressing HepG2 cells. AX800134 antagonism also enhanced spontaneous apoptosis of HepG2 cells under serum deprivation condition. Therefore, our results indicate that highly expressed AX800134 acts as an oncogenic factor in HCC, and its upregulation is related with the viral product HBx and chronic inflammation.

An analysis on HIV/AIDS epidemiological characteristics of people aged 15~24 years in Shaoxing / 预防医学

Objective To learn the epidemiological characteristics of HIV/AIDS cases aged 15-24 years in Shaoxing for making targeted prevention and control measures among young people. Methods To analyze the HIV/AIDS cases' distribution, route of transmission and reported route according to the cases which were reported 2003-2016 and aged 15-24 years. Results There were 325 cases had been reported. The epidemic had spread outward to each county, and transient population was accounted for 64.00%, and the ratio of male to female was 2.46:1. Career was widely dispersed, and farmers/migrant workers accounted for 31.08% , and students accounted for 10.15% . Homosexual transmission accounted for 41.29% , and heterosexual transmission accounted for 51.08% . The cases that were locality census register/high school education or above/unmarried adolescent, and professional for business services and student's homosexual transmission ratio was higher than that of heterosexual transmission. Voluntary counseling and testing was the major detection route which accounted for 16.9%. Conclusion The results showed that the male who aged 15-24 years was the most susceptible population. It is necessary to carry out effective measures to prevent and control HIV/AIDS transmission among young people, especially MSM and out-of-school youth.

Paeonol protects endotoxin-induced acute kidney injury: potential mechanism of inhibiting TLR4-NF-κB signal pathway.

STUDY DESIGN AND METHODS: In order to determine the therapeutic effect and mechanism of paeonol on acute kidney injury induced by endotoxin, an acute kidney injury model was established by intraperitoneal administration of lipopolysaccharide in mice in vivo and on LPS-induced dendritic cells in vitro. Renal tissues were used for histologic examination. Concentrations of blood urea nitrogen and serum creatinine were detected, inflammatory cytokines were determined by ELISA. The relative proteins' expression of TLR4-NF-κB signal pathway was assessed by Western blot, the localization and expression of phospho-NF-κB p65 in kidney was monitored by immunohistochemistry. RESULTS: Treatment of paeonol successfully cuts histopathological scores and dilutes the concentrations of blood urea nitrogen and serum creatinine as index of renal injury severity. In addition, paeonol reduces pro-inflammatory cytokines and increases anti-inflammatory cytokines stimulated by LPS in a dose-dependent manner. Paeonol also inhibits the expression of phosphorylated NF-κB p65, IκBα and IKKß, and restrains NF-κB p65 DNA-binding activity. Paeonol treatment also attenuates the effects of LPS on dendritic cells, with significant inhibition of pro-inflammatory cytokines release, then TLR4 expression and NF-κB signal pathway have been suppressed. CONCLUSIONS: These results indicated that paeonol has protective effects on endotoxin-induced kidney injury. The mechanisms underlying such effects are associated with its successfully attenuate inflammatory and suppresses TLR4 and NF-κB signal pathway. Therefore, paeonol has great potential to be a novel and natural product agent for treating AKI or septic-AKI.