The efficacy and safety of high-dose isoniazid-containing therapy for multidrug-resistant tuberculosis: a systematic review and meta-analysis.

Objectives: Accumulating evidence are available on the efficacy of high-dose isoniazid (INH) for multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to perform a systematic review and meta-analysis to compare clinical efficacy and safety outcomes of high-dose INH- containing therapy against other regimes. Methods: We searched the following databases PubMed, Embase, Scopus, Web of Science, CINAHL, the Cochrane Library, and ClinicalTrials.gov. We considered and included any studies comparing treatment success, treatment unsuccess, or adverse events in patients with MDR-TB treated with high-dose INH (>300 mg/day or >5 mg/kg/day). Results: Of a total of 3,749 citations screened, 19 studies were included, accounting for 5,103 subjects, the risk of bias was low in all studies. The pooled treatment success, death, and adverse events of high-dose INH-containing therapy was 76.5% (95% CI: 70.9%-81.8%; I2: 92.03%), 7.1% (95% CI: 5.3%-9.1%; I2: 73.75%), and 61.1% (95% CI: 43.0%-77.8%; I2: 98.23%), respectively. The high-dose INH administration is associated with significantly higher treatment success (RR: 1.13, 95% CI: 1.04-1.22; p < 0.01) and a lower risk of death (RR: 0.45, 95% CI: 0.32-0.63; p < 0.01). However, in terms of other outcomes (such as adverse events, and culture conversion rate), no difference was observed between high-dose INH and other treatment options (all p > 0.05). In addition, no publication bias was observed. Conclusion: In MDR-TB patients, high-dose INH administration is associated with a favorable outcome and acceptable adverse-event profile. Systematic review registration: identifier CRD42023438080.

Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development.

Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1Tg) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.

Oxidation-reduction potential affects medium-chain fatty acid ethyl ester production during wine alcohol fermentation.

The medium-chain fatty acid ethyl esters (MCFAEEs) are a group of important aroma compounds generated during wine production. Wine alcohol fermentation involves several redox processes, which are affected by the oxidation-reduction potential (ORP). However, the mechanism via which ORP regulates MCFAEE production remains unclear. To investigate the effect of ORP on MCFAEE production, wine alcohol fermentation was performed using Saccharomyces cerevisiae under different ORPs. The results demonstrated that the ORPs studied (except for 90 mV) did not significantly affect cell growth, sugar consumption, and ethanol production, while the MCFAEE concentration in the simulated wines can be manipulated by ORP operation. MCFAEE levels increased till 96 h, and then decreased. The maximum MCFAEE level of 1222.97 µg/L was obtained after 96 h at 0 mV, which was 45.32% higher than that of the control. During the increase, higher relative expression of ACC1, FAS1, FAA2 and EEB1, elevated external citric acid flux, and moderate intracellular NADP+/NADPH ratio were observed at 0 mV compared to that at other ORPs. During the decrease, lowest relative expression of POX1 was detected at 0 mV. We showed for the first time the relationship between ORP operation and MCFAEE production in winemaking, which will improve the aroma quality of wine.

St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study.

BACKGROUND: Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan. METHODS: This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect. FINDINGS: 27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2-16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0-1 years were significantly more likely to be infected than children aged 2-5 years (odds ratio [OR] 2·20, 95% CI 1·40-3·44) and children aged 6-12 years (1·53, 1·01-2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28-1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14-0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30-1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 [95% CI 0·24-0·26] to 0·12 [0·10-0·13]) and by 63% among secondary cases (from 0·17 [0·16-0·18] to 0·063 [0·057-0·070]). INTERPRETATION: Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available. FUNDING: National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, US National Institutes of Health, and US National Science Foundation.

ATF6 aggravates acinar cell apoptosis and injury by regulating p53/AIFM2 transcription in Severe Acute Pancreatitis.

Background: There is no curative therapy for severe acute pancreatitis (SAP) due to poor understanding of its molecular mechanisms. Endoplasmic reticulum (ER) stress is involved in SAP and increased expression of ATF6 has been detected in SAP patients. Here, we aimed to investigate the role of ATF6 in a preclinical SAP mouse model and characterize its regulatory mechanism. Methods: Pancreatic tissues of healthy and SAP patients were collected during surgery. Humanized PRSS1 transgenic mice were treated with caerulein to mimic the SAP development, which was crossed to an ATF6 knockout mouse line, and pancreatic tissues from the resulting pups were screened by proteomics. Adenovirus-mediated delivery to the pancreas of SAP mice was used for shRNA-based knockdown or overexpression. The potential functions and mechanisms of ATF6 were clarified by immunofluorescence, immunoelectron microscopy, Western blotting, qRT-PCR, ChIP-qPCR and luciferase reporter assay. Results: Increased expression of ATF6 was associated with elevated apoptosis, ER and mitochondrial disorder in pancreatic tissues from SAP patients and PRSS1 mice. Knockout of ATF6 in SAP mice attenuated acinar injury, apoptosis and ER disorder. AIFM2, known as a p53 target gene, was identified as a downstream regulatory partner of ATF6, whose expression was increased in SAP. Functionally, AIFM2 could reestablish the pathological disorder in SAP tissues in the absence of ATF6. p53 expression was also increased in SAP mice, which was downregulated by ATF6 knockout. p53 knockout significantly suppressed acinar apoptosis and injury in SAP model. Mechanistically, ATF6 promoted AIFM2 transcription by binding to p53 and AIFM2 promoters. Conclusion: These results reveal that ATF6/p53/AIFM2 pathway plays a critical role in acinar apoptosis during SAP progression, highlighting novel therapeutic target molecules for SAP.

SARS-CoV-2 detection in patients with influenza-like illness.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei Province, China in late December 2019. We re-analysed 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020 and found that 9 of the 640 throat swabs were positive for SARS-CoV-2 RNA by quantitative PCR, suggesting community transmission of SARS-CoV2 in Wuhan in early January 2020.

[Effect of hypnosis on pain and fear in the acupuncture subjects].

OBJECTIVE: To observe the effect of hypnosis on pain and fear in the healthy acupuncture subjects. METHODS: A total of 52 healthy subjects were randomized into an observation group and a control group, 26 cases in each one. In the observation group, the subjects received the first-time acupuncture under hypnosis. After wakened up and 30 min later, the subjects received the second-time acupuncture under clear consciousness condition. In the control group, the subjects received the first-time acupuncture under clear consciousness condition, 30 min later, received the second-time acupuncture under hypnosis. Likert scale was adopted to investigate the relaxation, pain sensation and the willingness in the subjects at the normal condition before acupuncture, after the first-time and the second-time acupuncture of the two groups separately. Using Boeran electronic blood pressure monitor, the pulse and blood pressure were measured in the subjects at the normal condition and after the first-time acupuncture of the two groups. RESULTS: Compared with the normal condition, the relaxation degree was increased, the pain sensation decreased and the willingness enhanced after acupuncture either after hypnosis or after wakened-up in the observation group (P<0.001). The difference was not significant in each index between acupuncture after hypnosis and acupuncture after wakened-up in the observation group (P>0.05). In the control group, compared with the normal condition, after the first-time acupuncture (acupuncture in clear consciousness), the relaxation degree was decreased, pain was alleviated and the willingness was increased when acupuncture was exerted once again (P<0.001, P<0.05); compared with the normal condition, after the second-time acupuncture (acupuncture after hypnosis), pain was alleviated and the willingness increased (P<0.001), but the difference in relaxation was not significant (P>0.05); compared with the first-time acupuncture, the relaxation degree was increased, pain alleviated and willingness enhanced after the second-time acupuncture (acupuncture after hypnosis) (P<0.05, P<0.001). Compared with the control group after the first-time acupuncture (acupuncture in clear consciousness), the relaxation degree and willingness were increased and the pain sensation was reduced in the observation group during acupuncture either after hypnosis or after wakened-up (P<0.001). Compared with the control group the second-time acupuncture (during acupuncture after hypnosis), the relaxation degree was increased and pain sensation reduced in the observation group during acupuncture either after hypnosis or after wakened-up (P<0.01, P<0.001), but the difference was not significant in willingness (P>0.05). In the control group, compared with the normal condition, the pulse was faster, both the diastolic pressure and systolic pressure were increased after the first-time acupuncture (P<0.05, P<0.01). In the observation group, compared with the normal condition, the pulse was getting slow and blood pressure was reduced after the first-time (acupuncture under hypnosis, P<0.01). Compared with the first-time acupuncture in the control group, pulse was getting slow and blood pressure was reduced in the observation group after acupuncture under hypnosis (P<0.001). CONCLUSION: During acupuncture, with hypnosis combined, the fear alleviates, pain reduces and the willingness of acupuncture increases in the subjects.

Phosphotungstic acid immobilized nanofibers-Nafion composite membrane with low vanadium permeability and high selectivity for vanadium redox flow battery.

A novel composite vanadium-blocking proton exchange membrane for vanadium redox flow battery (VRB) was designed and constructed by immobilizing phosphotungstic acid (PWA) on Nano Kevlar Fibers (NKFs) via a solution-casting method. The proton/vanadium selectivity of the composite membrane is greatly improved by incorporating the complex formed by NKFs and PWA into the Nafion matrix. Simple tuning of the complex doping quantity results in different composite membranes with superior vanadium barrier properties (namely, a minimum vanadium permeability of 2.46 × 10-7 cm2 min-1). This coupled with proton conductivities reaching 0.061 S cm-1 at room temperature indicates a proton/vanadium selectivity of 2.48 × 105 S min cm-3, which is 6.3 times higher than that of recast Nafion (0.34 × 105 S min cm-3). When tested in a VRB, the performance of the single cell assembled with the composite membrane greatly outperforms that with recast Nafion at current densities ranging from 40 to 100 mA cm-2.

Application of a combined model with seasonal autoregressive integrated moving average and support vector regression in forecasting hand-foot-mouth disease incidence in Wuhan, China.

Hand-foot-mouth disease (HFMD) is a serious public health problem with increasing cases and substantial financial burden in China, especially in Wuhan city. Hence, there is an urgent need to construct a model to predict the incidence of HFMD that could make the prevention and control of this disease more effective.The incidence data of HFMD of Wuhan city from January 2009 to December 2016 were used to fit a combined model with seasonal autoregressive integrated moving average (SARIMA) model and support vector regression (SVR) model. Then, the SARIMA-SVR hybrid model was constructed. Subsequently, the fitted SARIMA-SVR hybrid model was applied to obtain the fitted HFMD incidence from 2009 to 2016. Finally, the fitted SARIMA-SVR hybrid model was used to forecast the incidence of HFMD of the year 2017. To assess the validity of the model, the mean square error (MSE) and mean absolute percentage error (MAPE) between the actual values and predicted values of HFMD incidence (2017) were calculated.From 2009 to 2017, a total of 107636 HFMD cases were reported in Wuhan City, Hubei Province, and the male-to-female ratio is 1.60:1. The age group of 0 to 5 years old accounts for 95.06% of all reported cases and scattered children made up the large proportion (accounted for 56.65%). There were 2 epidemic peaks, from April to July and September to December, respectively, with an emphasis on the former. High-prevalence areas mainly emerge in Dongxihu District, Jiangxia District, and Hongshan District. SARIMA (1,0,1)(0,0,2)[12] is the optimal model given with a minimum Akaike information criterion (AIC) (700.71), then SVR model was constructed by using the optimum parameter (C = 100000, =0.00001, =0.01). The forecasted incidences of single SARIMA model and SARIMA-SVR hybrid model from January to December 2017 match the actual data well. The single SARIMA model shows poor performance with large MSE and MAPE values in comparison to SARIMA-SVR hybrid model.The SARIMA-SVR hybrid model in this study showed that accurate forecasting of the HFMD incidence is possible. It is a potential decision supportive tool for controlling HFMD in Wuhan, China.

Gefitinib plus Fuzheng Kang'ai Formula () in Patients with Advanced Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. METHODS: A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed. RESULTS: No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05). CONCLUSION: Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.

Application of seasonal auto-regressive integrated moving average model in forecasting the incidence of hand-foot-mouth disease in Wuhan, China.

Outbreaks of hand-foot-mouth disease (HFMD) have occurred many times and caused serious health burden in China since 2008. Application of modern information technology to prediction and early response can be helpful for efficient HFMD prevention and control. A seasonal auto-regressive integrated moving average (ARIMA) model for time series analysis was designed in this study. Eighty-four-month (from January 2009 to December 2015) retrospective data obtained from the Chinese Information System for Disease Prevention and Control were subjected to ARIMA modeling. The coefficient of determination (R 2), normalized Bayesian Information Criterion (BIC) and Q-test P value were used to evaluate the goodness-of-fit of constructed models. Subsequently, the best-fitted ARIMA model was applied to predict the expected incidence of HFMD from January 2016 to December 2016. The best-fitted seasonal ARIMA model was identified as (1,0,1)(0,1,1)12, with the largest coefficient of determination (R 2=0.743) and lowest normalized BIC (BIC=3.645) value. The residuals of the model also showed non-significant autocorrelations (P Box-Ljung (Q)=0.299). The predictions by the optimum ARIMA model adequately captured the pattern in the data and exhibited two peaks of activity over the forecast interval, including a major peak during April to June, and again a light peak for September to November. The ARIMA model proposed in this study can forecast HFMD incidence trend effectively, which could provide useful support for future HFMD prevention and control in the study area. Besides, further observations should be added continually into the modeling data set, and parameters of the models should be adjusted accordingly.

A Molecular Signature of Two Long Non-Coding RNAs in Peripheral Blood Predicts Acute Renal Allograft Rejection.

BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.

A BAP1 Mutation-specific MicroRNA Signature Predicts Clinical Outcomes in Clear Cell Renal Cell Carcinoma Patients with Wild-type BAP1.

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.

Application of Seasonal Auto-regressive Integrated Moving Average Model in Forecasting the Incidence of Hand-foot-mouth Disease in Wuhan, China / 华中科技大学学报（医学）（英德文版）

Outbreaks of hand-foot-mouth disease (HFMD) have occurred many times and caused serious health burden in China since 2008.Application of modem information technology to prediction and early response can be helpful for efficient HFMD prevention and control.A seasonal auto-regressive integrated moving average (ARIMA) model for time series analysis was designed in this study.Eighty-four-month (from January 2009 to December 2015) retrospective data obtained from the Chinese Information System for Disease Prevention and Control were subjected to ARIMA modeling.The coefficient of determination (R2),normalized Bayesian Information Criterion (BIC) and Q-test P value were used to evaluate the goodness-of-fit of constructed models.Subsequently,the best-fitted ARIMA model was applied to predict the expected incidence of HFMD from January 2016 to December 2016.The best-fitted seasonal ARIMA model was identified as (1,0,1)(0,1,1)12,with the largest coefficient of determination (R2=0.743) and lowest normalized BIC (BIC=3.645) value.The residuals of the model also showed non-significant autocorrelations (PBox-Ljung (Q)=0.299).The predictions by the optimum ARIMA model adequately captured the pattern in the data and exhibited two peaks of activity over the forecast interval,including a major peak during April to June,and again a light peak for September to November.The ARIMA model proposed in this study can forecast HFMD incidence trend effectively,which could provide useful support for future HFMD prevention and control in the study area.Besides,further observations should be added continually into the modeling data set,and parameters of the models should be adjusted accordingly.

Development and Validation of a Risk Score for Prediction of Acute Kidney Injury in Patients With Acute Decompensated Heart Failure: A Prospective Cohort Study in China.

BACKGROUND: Although several risk factors for acute kidney injury (AKI) have been identified, early detection of AKI in acute decompensated heart failure patients remains a challenge. The aim of this study was to develop and validate a risk score for early prediction of AKI in acute decompensated heart failure patients. METHODS AND RESULTS: A total of 676 consecutive acute decompensated heart failure participants were prospectively enrolled from 6 regional central hospitals. Data from 507 participants were analyzed. Participants from 4 of the 6 hospitals (n=321) were used to develop a risk score and conduct internal validation. External validation of the developed risk score was conducted in participants from the other 2 hospitals (n=186). Sequential logistic regression was used to develop and validate the risk score. The c statistic and calibration plot were used to assess the discrimination and calibration of the proposed risk score. The overall occurrence of AKI was 33.1% (168/507). The risk score, ranging from 0 to 55, demonstrated good discriminative power with an optimism-corrected c statistic of 0.859. Similar results were obtained from external validation with c statistic of 0.847 (95% CI 0.819-0.927). The risk score had good calibration with no apparent over- or under-prediction observed from calibration plots. CONCLUSIONS: The novel risk score is a simple and accurate tool that can help clinicians assess the risk of AKI in acute decompensated heart failure patients, which in turn helps them plan and initiate the most appropriate disease management for patients in time.

Overexpression of ST3Gal-I promotes migration and invasion of HCCLM3 in vitro and poor prognosis in human hepatocellular carcinoma.

PURPOSE: Excessive ST3Gal-I levels predict a poor outcome for patients with several types of tumors. This study aims to investigate the role of ST3Gal-I in determining the invasive and metastatic potential of human hepatocellular carcinoma (HCC) and clinical prognosis for patients with HCC. METHODS: We compared the expression of ST3Gal-I in various HCC cell lines and in 20 pairs of tumor and peritumor tissue samples using Western blot analysis. Changes in the degree of invasiveness and migration were determined before and after small interfering RNA-induced knockdown of ST3Gal-I using a Transwell matrigel invasion assay and scratch wound assay. The correlation between ST3Gal-I expression and prognosis was determined in a large HCC patient cohort (n=273). RESULTS: ST3Gal-I expression was higher in metastatic HCCLM3 cells and tumor tissue compared with normal adjacent tissue. Following the ST3Gal-I knockdown, the invasiveness and migration of HCCLM3 cells were markedly reduced. ST3Gal-I expression in HCC correlated closely with tumor thrombus (P<0.001), tumor size (>5.0 cm, P=0.032), tumor node metastasis stages II-III (P=0.002), and Barcelona Clinic Liver Cancer stages B-C (P<0.001). Cox regression analysis demonstrated that ST3Gal-I is an independent predictor of prognosis in patients with HCC, and related to disease-free survival (hazard ratio =1.464, P=0.037) and overall survival (hazard ratio =1.662, P=0.012). CONCLUSION: ST3Gal-I might contribute to the invasiveness and metastatic nature of HCC and, thus, could be an independent predictor of recurrence and a suitable pharmaceutical target in patients with HCC.

[Combination of Jianpi Liqi Yiliu Formula with Cytokine-induced Killer Cell Treatment for Advanced Hepatocellular Carcinoma].

OBJECTIVE: To evaluate the clinical efficacy of Jianpi Liqi Yiliu Formula (JLYF) combined with cytokine-induced killer (CIK) cells for treating patients with advanced hepatocellular carcinoma (HCC). METHODS: Between January 2011 and January 2014, 60 advanced HCC patients were enrolled in this study, who were assigned to the treatment group and the control group according to their willingness for taking JLYF, 30 cases in each group. All patients received CIK cell treatment: 1 x 109-3 x 109 each time, by intravenous dripping from the 1st day to the 3rd day, once per day. Besides, patients in the treatment group took JLYF decoction, while those in the control group took Chinese medical decoction by syndrome typing. All patients received treatment of at least two cycles. The time to progression (TTP) , overall survival (OS), disease control rate (DCR), performance status scale (PS), Child-Pugh scale, and adverse reactions were observed, and subgroup analyzed. RESULTS: To May 31, 2014, all patients reached the clinical endpoint. TTP was 3.5 months (95% Cl: 3.30-4.10) in the treatment group, better than that (2.5 months, 95% CI: 2.32-2.68) of the control group (P < 0.05). DCR was 36.7% in the treatment group and 30.0% in the control group (P > 0.05). OS was 5.2 months (95% CI: 4.53-5.87) in the treatment group and 4.6 months (95% CI: 4.06-5.14) in the control group (P > 0.05). The PS scale was 1.60 ± 0.10 after treatment, lower than that (1.80 ± 0.09) before treatment in the treatment group (P < 0.05). When the PS scale was 0-2 or Child-Pugh scale was class A, TTP was longer in the treatment group than in the control group (P < 0.05). No adverse reaction occurred in the two groups during the treatment course. CONCLUSIONS: The combination of JLYF with ClK cell treatment could prolong advanced HCC patients' TTP, improve PS scale, as compared with syndrome typed Chinese medical decoction treatment group. Besides, when the PS scale was 0-2 or Child-Pugh scale was class A, it was a better treatment program for advanced HCC patients.

Dynamics of Rodent and Rodent-borne Disease during Construction of the Three Gorges Reservoir from 1997 to 2012.

OBJECTIVE: To investigate the impact of impoundment and active public health interventions on rodent populations and rodent-borne diseases in the Three Gorges reservoir region from 1997 to 2012. METHODS: Surveillance data from 1997 to 2012 were extracted from the Public Health Surveillance System of The Three Gorges established in 1997. Temporal changes in the incidences of hemorrhagic fever with renal syndrome (HFRS) and leptospirosis, rodent density, pathogen-carrying rates, and their correlations were analyzed. RESULTS: The average indoor and outdoor rodent densities decreased overall from 1997 to 2012. The average densities decreased by 47.72% (from 4.38% to 2.29%) and 39.68% (from 4.41% to 2.66%), respectively, after impoundment (2003-2012) compared with before impoundment (1997-2002). The average annual incidence rates of HFRS and leptospirosis were 0.29/100,000 and 0.52/100,000, respectively, and decreased by 85.74% (from 0.68/100,000 to 0.10/100,000) and 95.73% (from 1.47/100,000 to 0.065/100,000), respectively, after impoundment compared with before impoundment. Incidences of HFRS and leptospirosis appear to be positively correlated with rodent density in the reservoir area. CONCLUSION: This study demonstrated that rodent density and incidences of rodent-borne diseases decreased and were maintained at low levels during construction of the Three Gorges dam. Measures that reduce rodent population densities could be effective in controlling rodent-borne diseases during large-scale hydraulic engineering construction.