Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear. METHODS: We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored. RESULTS: After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100). CONCLUSIONS: Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).

Vaginal flora during pregnancy and subsequent risk of preterm birth or prelabor rupture of membranes: a nested case-control study from China.

BACKGROUND: The findings of the association of vaginal flora with preterm birth (PTB) or prelabor rupture of membranes (PROM) were conflicts. Moreover, vaginal flora was different by ethnicity and the evidence from China was limited. METHODS: This study was a nested case control study, based on Yiwu birth cohort. We assessed vaginal microbiota in the second or third trimester, using 16S rDNA Amplicon Sequencing and explored the association between the diversity and composition of vaginal flora and PTB or PROM. RESULTS: We finally included 144 pregnant women. In present study, the alpha diversity of TPROM (Term prelabor rupture of membranes) samples was lower than that of full term samples (Chao1 index: P < 0.05). When we further categorized PTB (Preterm birth) into SPB (PTB without PROM) and PPROM (Preterm prelabor rupture of membranes), there was no difference between SPB and full term. In addition, we found that the proportion of PCoA2 in TPROM group was different from that in full term group and preterm group. The difference between groups was significant according to anosim analysis (R = 0.059, P < 0.001). With LEfSe (Linear discriminant analysis Effect Size) analysis, we found that the abundance of Lactobacillus in the vaginal flora of pregnant women with preterm birth was the highest (P = 0.003). CONCLUSION: In Chinese pregnant women, the alpha diversity in TPROM group was significantly lower than that in both PTB and full term group. However, there was no difference between PTB and full term. Lactobacillus was the most abundant in preterm birth group. More studies should be conducted to confirm our findings.

Machine Learning Models of Postoperative Atrial Fibrillation Prediction After Cardiac Surgery.

OBJECTIVES: This study aimed to use machine learning algorithms to build an efficient forecasting model of atrial fibrillation after cardiac surgery, and to compare the predictive performance of machine learning to traditional logistic regression. DESIGN: A retrospective study. SETTING: Second Affiliated Hospital of Zhejiang University School of Medicine. PARTICIPANTS: The study comprised 1,400 patients who underwent valve and/or coronary artery bypass grafting surgery with cardiopulmonary bypass from September 1, 2013 to December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two machine learning approaches (gradient-boosting decision tree and support-vector machine) and logistic regression were used to build predictive models. The performance was compared by the area under the curve (AUC). The clinical practicability was assessed using decision curve analysis. Postoperative atrial fibrillation occurred in 519 patients (37.1%). The AUCs of the support-vector machine, logistic regression, and gradient boosting decision tree were 0.777 (95% CI: 0.772-0.781), 0.767 (95% CI: 0.762-0.772), and 0.765 (95% CI: 0.761-0.770), respectively. As decision curve analysis manifested, these models had achieved appropriate net benefit. CONCLUSION: In the authors' study, the support-vector machine model was the best predictor; it may be an effective tool for predicting atrial fibrillation after cardiac surgery.

Ilizarov method and its combined methods in the treatment of long bone defects of the lower extremity: systematic review and meta-analysis.

BACKGROUND: Ilizarov method has become one of primary methods for treating bone defects. Currently, there is growing trend in the application of modified Ilizarov methods (e.g., applying unilateral external fixators or with flap tissue) and its combined methods (e.g., Ilizarov method with antibiotic spacer or internal fixation) to manage bone defects. However, there is a lack of studies with systematical evaluation of the clinical effects of these evolving methods. This study aimed to conduct a systematic review and meta-analysis for overall evaluating the clinical effects on long bone defects of lower extremity in Ilizarov methods and its combined methods. METHODS: Studies were identified in three electronic databases (Pubmed, Embase and Cochrane Library) from the earliest indexing year through November 01, 2022, and relevant data were extracted subsequently. The total number of participants, number of participants with bone unions, bone result or functional result, and related complications including pin infection, pin loosening, pain, refracture, limb discrepancy, malalignment, joint stiffness, recurrent infection, and amputation were extracted in this study. Then, union rate (defined as the proportion of patients who achieved bone unions) and specific complication incidence rate (defined as the proportion of patients who experienced specific complication) were pooled estimated respectively. Relative risk (RR) was used for comparing the clinical effects among various Ilizarov technique. RESULTS: Sixty-eight case series studies, 29 comparative studies, and 3 randomized clinical trials were finally included. The union rate of Ilizarov methods was 99.29% (95% CI: 98.67% ~ 99.86%) in tibial defects and 98.81% (95% CI: 98.81% ~ 100.00%) in femoral defects. The union rate of Ilizarov method with antibiotic spacer and intramedullary nail in tibial defects was 99.58% (95% CI: 98.05% ~ 100.00%) and 95.02% (95% CI: 87.28% ~ 100.00%), respectively. Compared to the Ilizarov methods, the union rate of the Ilizarov method with antibiotic spacer in tibial defects increased slightly (RR = 1.02, 95% CI: 1.01 ~ 1.04). Meanwhile, compared to Ilizarov methods, we found lower excellent rate in bone result in Ilizarov method with antibiotic spacer, with the moderate to high heterogeneity. Compared to the Ilizarov method, lower rate of pin infection, higher rate of recurrent infection and amputation were observed in Ilizarov method with intramedullary nail, however, the findings about the comparison of pin infection and recurrent infection between the two groups were presented with high degree of statistical heterogeneity. CONCLUSION: Our study confirmed the reliable treatment of Ilizarov methods and its combined technique on long bone defects, and founded there were significant differences on some complications rate between Ilizarov methods and its combined technique. However, the findings need to be confirmed by further studies.

Estimating the health burden of foodborne gastroenteritis caused by non-typhoidal Salmonella enterica and Vibrio parahaemolyticus in Zhejiang province, China.

As acute gastrointestinal (AGI) disease patients only sometimes seek medical care or submit stool samples for testing, and laboratories cannot detect or identify the pathogen, most cases of foodborne gastroenteritis still need to be identified through public health monitoring. We conducted a population survey and sentinel hospital surveillance to determine the burden of foodborne gastroenteritis caused by non-typhoidal Salmonella enterica (NTS) and Vibrio parahaemolyticus infection, from July 2018 to June 2019 in Zhejiang province, China, and a model for calculating disease burden established. Using the burden of illness pyramid model, we estimated that there were 140.3 cases of NTS infection and 136.2 cases of V. parahaemolyticus infection. We estimated annual incidence per 100,000 population in Zhejiang province as 236 (95% confidence interval [CI] 208-267) and 206 (95% CI 155-232) cases for foodborne NTS and V. parahaemolyticus gastroenteritis, respectively. The results show that AGI caused by these two pathogens constitutes a substantial burden in the Zhejiang population. The health burden of AGI estimations caused by NTS and V. parahaemolyticus in this study can serve as a strategic framework to direct policy and intervention.

Local infiltration of HYR-PB21, a sustained-release formulation of bupivacaine, provides analgesia and reduces opioid requirement after haemorrhoidectomy: a randomised controlled trial.

BACKGROUND: HYR-PB21 is a new sustained-release formulation of bupivacaine indicated for controlling postoperative pain. The objectives of this study were to investigate the analgesic efficacy and safety profile of HYR-PB21 in patients after haemorrhoidectomy. METHODS: This was a multicentre, randomised, double-blind, positive-controlled trial. Patients were assigned randomly to receive a single dose of HYR-PB21 (150 mg or 300 mg) or bupivacaine HCl (75 mg) after surgery for prolapsing haemorrhoids. Postoperative pain was evaluated using a numeric rating scale at rest to calculate a cumulative pain score. Total rescue opioid usage and the proportion of subjects receiving rescue opioid were also assessed. RESULTS: We enrolled 72 patients with haemorrhoidectomy, and 71 patients completed the study. The average cumulative pain score through 72 h after surgery in the 300 mg HYR-PB21 group (87 scores) was lower than in the bupivacaine HCl group (166 scores) in an intention-to-treat analysis (P<0.001). There was a dose-response effect in reducing total opioid usage and the proportion of rescue opioid use between the 150 mg and 300 mg HYR-PB21 groups, with bupivacaine HCl as a reference group. The HYR-PB21 groups did not show more adverse effects than the bupivacaine HCl group. CONCLUSIONS: Local infiltration of a single dose of HYR-PB21 sustained-release bupivacaine had better efficacy in controlling postoperative pain, with similar adverse effects, compared with a single dose of bupivacaine HCl in patients after haemorrhoidectomy. CLINICAL TRIAL REGISTRATION: ChiCTR2000041318 (Chinese Clinical Trial Registry).

Association of hypertensive disorders of pregnancy with infant growth in the first 36 months of life.

To investigate the association of chronic hypertension, gestational hypertension, and preeclampsia diseases with infant growth in the first 36 months of life, we conducted a retrospective birth cohort of 31,734 children born in Zhoushan Maternal and Child Care Hospital between January 2001 and May 2018. Birthweight, gestational age, and infant growth (weight, height, weight/height-for-age Z score, the weight gain during childhood) were the main outcomes. The associations of chronic hypertension, gestational hypertension, and preeclampsia diseases with birth outcomes and infant growth at children's age of 3, 6, 12, 18, and 24 months were analyzed by multivariable regression models. Gestational hypertension, preeclampsia diseases, and chronic hypertension were significantly associated with lower birthweight and shorter gestational age. Both gestational hypertension and preeclampsia diseases were respectively inversely associated with weight, weight-for-age Z score, height, and height-for-age Z score of children in the whole sample and sub-sample data analysis from birth to the age of 36 months, although correction for birthweight rendered the associations nonsignificant. No significant association of gestational hypertension, preeclampsia diseases, and chronic hypertension with weight gain was found. Conclusion: The inverse associations of gestational hypertension and preeclampsia diseases with infant growth in early childhood were mainly mediated by the effect of gestational hypertension and preeclampsia diseases on lower birthweight. What is Known: • Hypertensive disorders of pregnancy are associated with increased risk of adverse birth outcomes. What is New: • Both gestational hypertension and preeclampsia were respectively inversely associated with physical development of offspring from birth to the age of 36 months. • Lower birthweight might be the mediator of the inverse associations of gestational hypertension and preeclampsia diseases with infant growth in early childhood.

Global trends in total fertility rate and its relation to national wealth, life expectancy and female education.

OBJECTIVES: Along with the development of the times and progress of the society, the total fertility rate (TFR) markedly changed in each country. Therefore, it is critical to describe the trend of TFR and explore its influencing factors. However, previous studies did not consider the time lag and cumulative effect in the associations between the influencing factors and TFR. Thus, our study aimed to analyze the associations from a new dimension. METHODS: The study was employed using national-level data from the World Bank and United Nations Development Programme. Distributed lag non-linear models with 5-year lag were used to examine the independent associations between the relevant factors and TFR. RESULTS: The cumulative exposure-TFR curves were inverted U-shaped for log gross domestic product (GDP) per capita and life expectancy at birth, while the cumulative exposure-response curves were approximately linear for female expected years of schooling and human development index (HDI). However, it is worth noting that in the developed regions, TFR increased slightly with the high level of GDP per capita, female expected years of schooling and HDI. CONCLUSIONS: Nowadays, with the growth of GDP per capita, life expectancy at birth, female expected years of schooling and HDI, TFR are on a drastic downward trend in most regions. Besides, with the development of society, when levels of the factors continued to increase, TFR also showed a slight rebound. Therefore, governments, especially those in developing countries, should take measures to stimulate fertility and deal with a series of problems caused by declining TFR.

Descriptive study of foodborne disease using disease monitoring data in Zhejiang Province, China, 2016-2020.

BACKGROUND: This study aimed to identify the epidemiology, seasonality, aetiology and clinical characteristics of sporadic foodborne diseases in Zhejiang province during 2016-2020. METHODS: Descriptive statistical methods were used to analyze the data from surveillance network established by the Zhejiang Provincial Center for Disease Control and Prevention. There were 31 designated hospitals in all 11 cities which were selected using probability proportionate to size sampling method. RESULTS: During the study period, the surveillance system received 75,124 cases with 4826 (6.42%) hospitalizations from 31 hospitals. The most common cause was Norovirus, 6120 cases (42.56%), followed by Salmonella, 3351 cases (23.30%). A significant seasonal trend was observed for the V. parahaemolyticus, with the highest rates over the summer period, peaking in August, 1171 cases (38.75%), a similar trend was also observed with Salmonella and Diarrheagenic E. coli. Norovirus infections showed the highest rate in November (904, 14.77%) and March (660,10.78%), the lowest in August, 215 cases (3.51%). Patients between 19 ~ 40 years were more likely to infected by Norovirus, V. parahaemolyticus and Diarrheagenic E. coli, patients below 1 year were the highest among patients with Salmonella infection, 881 cases (26.3%). The Norovirus, V. parahaemolyticus and Diarrheagenic E. coli infection with the highest positive detection rates among the workers were observed. The largest number cases of food categories were from aquatic product infection. The private home was the most common exposure setting. CONCLUSION: Our study highlighted the necessity for conducting an active, comprehensive surveillance for pathogens in all age groups, to monitor the changing dynamics in the epidemiology and aetiology of foodborne diseases to guide policies that would reduce related illnesses.

Construction of a new complete growth reference for urban Chinese children.

BACKGROUND: Growth chart is a valuable clinical tool to monitor the growth and nutritional status of children. A growth chart widely used in China is based on the merged data sets of national surveys in 2005. We aimed to establish an up-to-date, complete growth curve for urban Chinese children and adolescents with a full range of ages. METHODS: Using data collected in a large-scale, cross-sectional study (Prevalence and Risk factors for Obesity and Diabetes in Youth (PRODY), 2017-2019), we analyzed 201,098 urban children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations. Sex-specific percentiles of height-for-age and weight-for-age were constructed by Generalized Additive Models for Location Scale and Shape (GAMLSS) model. We also compared the median values of height-for-age or weight-for-age between our growth chart and the established growth reference using Welch-Satterthwaite T-Test. RESULTS: Consistent with the established growth reference, we observed that the P50 percentile of height-for-age reached plateaus at the age of 15 years (172 cm) and 14 years (160 cm) for boys and girls, respectively. In addition, boys aged 10 ~ 14 years and girls aged 10 ~ 12 years exhibited the most dramatic weight difference compared to those of other age groups (19.5 kg and 10.3 kg, respectively). However, our growth chart had higher median values of weight-for-age and height-for-age than the established growth reference with mean increases in weight-for-age of 1.36 kg and 1.17 kg for boys and girls, respectively, and in height-for-age of 2.9 cm and 2.6 cm for boys and girls, respectively. CONCLUSIONS: Our updated growth chart can serve as a reliable reference to assess the growth and nutritional status in urban Chinese children throughout the entire childhood.

Prophylactic efficacy on periprosthetic bone loss in calcar region after total hip arthroplasty of antiosteoporotic drugs: a network meta-analysis of randomised controlled studies.

OBJECTIVES: The aim of this study was to evaluate the effect of antiosteoporotic drugs on preventing periprosthetic bone loss in calcar 6 and 12 months after total hip arthroplasty. METHODS: The network meta-analysis was conducted guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. A systematic literature search was conducted and 21 studies that enrolled a total of 955 patients with 9 antiosteoporotic drugs met the inclusion criteria. Network meta-analysis and conventional meta-analysis were carried out for calculating standard mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the bone mineral density (BMD) in calcar (Gruen zone 7) as well as bone turnover markers (BTMs) including bone-specific alkaline phosphatase (BSAP) and collagen type I cross-linked N telopeptide (NTX) at 6 and 12 months between different antiosteoporotic drugs. RESULTS: At 6 months after total hip arthroplasty, zoledronate (SUCRA=86.4%), risedronate (SUCRA=51.3%) and etidronate (SUCRA=44.5%) were effective in retaining BMD in calcar; zoledronate was significantly more effective than etidronate (SMD=0.65, 95% CI 0.03 to 1.27). Teriparatide (SUCRA=84.5%), denosumab (SUCRA=82.5%), zoledronate (SUCRA=69.2%), alendronate+alfacalcidol (SUCRA=66.2%) and etidronate (SUCRA=51.5%) were the top five drugs in retaining BMD in calcar at 12 months after total hip arthroplasty and the efficacy were comparable. After simultaneously excluding studies in which the prosthesis were cement and the drug dosages as well as treatment durations were inconsistent with those in treating osteoporosis, the above results were robust with the exception that alendronate showed significant efficacy compared with placebo (SMD=1.22, 95% CI 0.46 to 1.99) and was comparable with those effective drugs at 12 months. Long-term residual effect was corroborated only in etidronate, alendronate and zoledronate from previous studies. BTMs were significantly decreased as early as 6 months (SMD of BSAP -0.49, 95% CI -0.84 to -0.13; SMD of NTX -0.93, 95% CI -1.21 to -0.64) and sustained until 12 months (SMD of BSAP -0.27, 95% CI -0.50 to -0.03; SMD of NTX -0.84, 95% CI -1.11 to -0.56) during the prophylaxis. CONCLUSIONS: Antiosteoporotic drugs showed prophylactic efficacy on periprosthetic bone loss after total hip arthroplasty in calcar, the effectiveness varied. Zoledronate was the best recommendation due to its optimal efficacy both within 6 and 12 months as well as its residual effect in the long term. BTMs could be used as indicators for monitoring through the treatment. More head-to-head clinical trials are needed to confirm those findings.

Association of nausea and vomiting of pregnancy with infant growth in the first 24 months of life.

PURPOSE: We aimed to investigate the association of maternal nausea and vomiting during pregnancy (NVP) with infant growth in the first 24 months of life and compare the effect of fetal gender. METHODS: This prospective cohort study was conducted in Zhoushan Maternal and Child Health Hospital, Zhejiang, from 2011 to 2018. 1942 pairs of singleton newborns and their mothers were selected as participants. Main outcomes were gestational weight gain (GWG), birth outcomes (birthweight and gestational age) and infant growth [weight, height, weight/height-for-age Z score (WAZ/HAZ), the weight gain during childhood]. The associations of NVP with birth outcomes and infant growth at children's age of 1, 3, 6, 12, 18, and 24 months were analyzed by multivariable regression models. RESULTS: Of the 1942 women, 1395 had NVP at first trimester (T1) and among them, 210 still experienced NVP at second trimester (T2). Compared with women without NVP, women experienced severe NVP at T1 were related with lower total GWG. Mild and moderate NVP at T1 were negatively associated with lower birthweight among women with male infants. Female infants exposed to maternal NVP at T1, especially for severe degree, were showed greater weight, WAZ, height, HAZ, and weight gain after 1 year old (at age of 12, 18, 24 months). No association between maternal NVP and infant growth was observed among male infants. CONCLUSION: Exposure to NVP at T1 was, respectively, associated with lower GWG. Favorable influence of NVP at T1 on infant growth was observed among female offspring.

Changing patterns of prenatal depression and anxiety status in different trimesters and modified form of Zung scales for pregnant women.

BACKGROUND: We described the changing patterns of depression and anxiety status in different trimesters among Chinese pregnant women, and identified the modified form of SDS/SAS for pregnant women and assessed its reliability and validity. METHODS: Changing patterns of depression/ anxiety status in different trimesters were described. The modified form of SDS/SAS was identified for pregnant women. Cohen's Kappa to measure agreement with SDS/SAS, and the ROC analysis was performed to assess its validity. RESULTS: The SDS score in 1st trimester was higher than 2nd and 3rd trimester; there was no significant difference between SDS score in 2nd and 3rd trimester. Modified form of SDS evaluated the depression; the areas under the curve (AUC) in testing group were up to 0.988, 0.989 and 0.992 for 1st, 2nd and 3rd trimester, respectively. Modified form of SAS evaluated the anxiety, the AUC in testing group were up to 0.987, 0.985, 0.987 for 1st, 2nd and 3rd trimester, respectively. CONCLUSION: Pregnant women had higher severity of depression and anxiety status in 1st trimester than that in 2nd and 3rd trimester. The modified form of SDS/SAS may be more brief and suitable to assess the depression and anxiety status in pregnant women.KEY POINTSPregnant women had a higher severity of depression and anxiety status in the 1st trimester than that in the 2nd and 3rd trimester.The present study suggests that prenatal depression and anxiety status are prevalent in Chinese pregnant women.Prevention or treatments focus on high-score items of SDS and SAS would be beneficial for rectifying prenatal depression and anxiety.

Uric acid fluctuation had no effect on renal function among gout patients.

BACKGROUND AND AIMS: To investigate the effects of serum uric acid (SUA) level and its fluctuation on renal dysfunction in gout patients. METHODS AND RESULTS: Data on gout patients was collected from Huzhou city electronic medical record system data sharing platform, and information about relevant diagnoses, prescriptions, biochemical indexes and imaging characteristics was extracted. The gout patients with baseline normal renal function were enrolled in this analysis, and the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 was defined as renal dysfunction. The generalized estimating equation and Cox regression analysis were used. A total of 1009 patients with gout were enrolled. Compared with the reference group (normal baseline SUA with endpoint SUA to be < 6 mg/dL), endpoint SUA ≥ 10 mg/dL was associated with an increased risk of renal dysfunction (baseline normal SUA group: HR [95% CI] = 3.28 [1.21, 8.91]; baseline high SUA group: HR [95% CI] = 3.01 [1.43, 6.35]). Subgroup analysis of 771 SUA stable gout patients demonstrated that SUA levels at 8-10 (excluding 10), and ≥10 mg/dL were significantly associated with an increased risk for renal dysfunction, with HR [95%CI] to be 1.99 [1.05, 3.77], and 2.98 [1.38, 6.43], respectively. CONCLUSION: Regardless of the baseline SUA level, SUA >10 mg/dL was a significant risk factor for renal dysfunction. SUA between 6 and 10 mg/dL was a potential risk factor for renal dysfunction. No significant correlation of SUA fluctuation and renal function was found.

Intravenous thrombolysis with 0.9 mg/kg alteplase for acute ischaemic stroke: a network meta-analysis of treatment delay.

OBJECTIVES: The aim of this study was to evaluate the effect of alteplase in intravenous thrombolysis of acute ischaemic stroke (AIS) regarding the different time windows of treatment (<3 hours, 3-4.5 hours, >4.5 hours). METHODS: A systematic literature search was conducted from PubMed, Cochrane Library and Embase. 12 clinical randomised controlled trials with 3402 patients with AIS met the inclusion criteria. The primary, secondary and tertiary outcomes were modified Rankin Scale (mRS) scores 0-1, mortality at 90th day after treatment and symptomatic intracerebral haemorrhage within 36 hours, respectively. Network meta-analysis and conventional meta-analysis were carried out for calculating odds ratio (OR), the surface under cumulative ranking curve (SUCRA) and the probabilities of being the best. RESULTS: For mRS, alteplase regardless of time delay was significantly more effective than placebo (OR 1.33-2.17). However, alteplase used within 3 hours after AIS occurrence (SUCRA=98.3%) was significantly more effective (OR=1.64) than that at 3-4.5 hours (SUCRA=43%) and showed the trend of priority (OR=1.47) compared with that beyond 4.5 hours (SUCRA=58%). For the mortality, compared with placebo (SUCRA=64.7%), alteplase within 3 hours was similar to that of 3-4.5 hours whereas alteplase beyond 4.5 hours (SUCRA=7.3%) showed the trend of significantly increasing 85% mortality. For the tertiary outcome, alteplase within 3 hours (SUCRA=19.0%) was comparable with placebo (SUCRA=99.9%) whereas alteplase beyond 3 hours significantly increased (OR 5.89-6.67) the symptomatic intracerebral haemorrhage. CONCLUSIONS: Alteplase within 3 hours should be recommended as the best treatment delay for its best efficacy among all the intervention and equivalent safety compared with placebo. Alteplase beyond 3 hours was less effective compared with that within 3 hours and increased the risk of mortality on 3 months as well as symptomatic intracerebral haemorrhage at 36 hours. More head-to-head clinical trials are needed to confirm those findings.

Early childhood caries and related risk factors: A cross-sectional study of children in Zhejiang Province, China.

OBJECTIVES: This work aims to exploring the risk factors related to ECC by investigating oral health status, related behaviours and habits of children and their parent's knowledge regarding oral hygiene. METHOD: A total of 2700 children aged 3-5 years and their parents from Zhejiang province were examined. Chi-square test or U test was used to analyse the difference of caries incidence among different groups. Logistic multiple factor stepwise regression model was used to analyse the risk factors influencing ECC prevalence. RESULTS: ECC prevalence rate in these children was 70.7%. The mean decayed missing filled teeth(dmft) scores were 4.33. Through analysis of logistic multiple factor stepwise regression model, risk factors related to the prevalence of ECC in children include: older age, region (coastal or mountainous area), higher frequency of bedtime dessert consumption and poor care of children's oral health by parents. In the questionnaire, 5 of 14 questions showed parents' poor oral knowledge or awareness. CONCLUSION: The prevalence rate of ECC in children aged 3-5 in this study was high and associated with older age, region (coastal or mountainous area), higher frequency of bedtime dessert consumption and poor care of children's oral health. Parents need to strengthen their understanding and action of dental caries.

Association of trimester-specific gestational weight gain with birth weight and fetal growth in a large community-based population.

BACKGROUND: Previous studies showed that the association of gestational weight gain (GWG) with fetal birthweight and offspring developmental growth was unclear. The aim of this study is to investigate the respective effect of 1 kg of GWG during three trimesters on birthweight and offspring growth from birth to 3 years of age. METHODS: We extracted the decoded information from the Maternal and Child Health Information Management System of Zhoushan Maternal and Child Health Hospital in Zhejiang, China from October 2001 to March 2015, and used multiple linear and logistic regression models. RESULTS: This study included 20,232 women with a full-term singleton birth and 15,557 newborns who took regular health check-ups. Compared to that in the 2nd and 3rd trimester, 1 kg GWG increasing in the 1st trimester had the strongest positive association with higher birthweight, body weight, and height from 1 to 36 months. Their associations with BMI after birth were similar among the three trimesters. In addition, some positive dose-response effects found between quartiles of GWG in the 1st trimester and offspring body weight, as well as BMI. The 1 kg GWG in 1st trimester played the strongest role in contributing to birth weight and benefiting to body growth among children aged up to 3 years. CONCLUSION: The 1 kg GWG in 1st trimester contributed more to birth weight and body development from birth to 3 years compared to the 2nd and 3rd trimesters. The possible beneficial effects of GWG in the 1st trimester on birthweight and offspring development in under/normal weight mothers are found.

Does fibrosis have an impact on survival of patients with hepatocellular carcinoma: evidence from the SEER database?

BACKGROUND: Liver fibrosis is involved in hepatocellular carcinoma (HCC), but its effect on the survival of patients with HCC remains controversial. This study aims to explore whether the severity of liver fibrosis has an impact on HCC overall survival (OS) and disease-specific survival (DSS) in Surveilance, Epidemiology, and End-Results (SEER) database. METHODS: A total of 11,783 HCC patients diagnosed between 2004 and 2014 from SEER database were enrolled. Cox proportional hazard regression models were used to estimate crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for fibrosis group associated with survival. Decision curve analysis (DCA) was also performed to compare the effect of fibrosis with other clinicopathological characteristics for survival outcome. RESULTS: Patients with high fibrosis score (5-6) had a greater proportion than those with low fibrosis score (0-4) (80.3% vs. 19.7%). Fibrosis score was an independent prognostic factor for OS (HR = 1.09, 95%CI: 1.02-1.16), but not for DSS (HR = 1.05, 95%CI: 0.98-1.13) by multivariate Cox proportional hazard models. Additionally, there was no significant effect of liver fibrosis on OS and DSS with stratification of TNM stage and therapy. Findings of DCA showed that fibrosis was less associated with survival outcome in comparison with other tumor characteristics. CONCLUSIONS: The effect of fibrosis on HCC survival was less important than that of other clinicopathological characteristics (like TNM stage or tumor size).

The relationship of dietary diversity score with depression and anxiety among prenatal and post-partum women.

AIM: The objective of the study is to explore the relationship between the dietary diversity score (DDS) and anxiety and depression of perinatal women. METHODS: The Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and the dietary recall questionnaire were used to measure the status of depression, anxiety and dietary diversity at T1 (first trimester), T2 (second trimester), T3 (third trimester) and T4 (post-partum). The association of dietary diversity and food groups with depression and anxiety status were estimated by linear and logistic regression models. RESULTS: The prevalence of depression and anxiety status were the highest at T1, which were 35.58% and 22.57%, respectively. Cross-sectional and longitudinal association of DDS with SDS and SAS was estimated by ordinary or multilevel linear or logistic model. In the cross-sectional analysis, high dietary status (>6) was negatively associated with depression status [T1: OR (95% CI) = 0.56 (0.46, 0.69); T2: 0.55 (0.36, 0.84); T3: 0.45 (0.31, 0.65); T4: 0.58 (0.34, 0.99)] and anxiety status [T1: OR (95% CI) = 0.70 (0.56, 0.88); T2: 0.42 (0.27, 0.65)]. In the longitudinal analysis, it was demonstrated that the DDS level was negatively associated with SDS [ß(se) = -0.99 (0.09), P = <0.0001] and SAS scores [ß(se) = -0.37 (0.08), P = <0.0001] throughout pregnancy. There was a negative relationship between some food groups and SDS or SAS scores at different periods. CONCLUSION: A negative relationship between DDS and depression as well as anxiety was found among prenatal and post-partum women.

Prevalence and relevant factors of anxiety and depression among pregnant women in a cohort study from south-east China.

OBJECTIVE: To describe the prevalence rate of prenatal anxiety and depression among pregnant women in a prospective cohort study and to explore the relevant factors of anxiety and depression during each trimester. METHODS: Pregnant women were recruited into the Zhoushan Pregnant Women Cohort at Zhoushan Maternal and Child Care Hospital from September 2011 to March 2015. A self-made questionnaire was used to collect information about social demography, reproductive history, physical activity, and life behaviour at the first, second and third trimester, respectively. The Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) were used to assess anxiety and depression status at each trimester, respectively. Prevalence rates of prenatal anxiety and depression at each trimester were described. RESULTS: The prevalence of anxiety status was 22.7%, 17.4% and 20.8% in the first, second and third trimester, respectively. The corresponding prevalence rate of depression status was 35.7%, 24.0% and 26.1%, respectively. Furthermore, women with a lower education level (junior high school or below) and a more physical occupation had higher prevalence of anxiety and depression status. CONCLUSIONS: The prevalence of prenatal anxiety and depression status was very common during pregnancy among pregnant women. Lower educational level and more physical occupations were associated with higher prevalence of anxiety and depression status.