New insights on the association of weight loss with the reduction in carotid intima-media thickness among patients with obesity: an updated systematic review and meta-analysis.

OBJECTIVES: Carotid intima-media thickness (CIMT) is a noninvasive marker of atherosclerosis, a typical pathologic process underlying cardiovascular diseases (CVDs). It is essential to explore the relationships between weight loss and the reduction of CIMT. STUDY DESIGN: This was an updated systematic review and meta-analysis. METHODS: A systematic literature search was conducted to collect relevant clinical trials. The pooled results of meta-analyses were assessed by weighted mean difference (WMD) and the corresponding 95 % confidence interval (95% CI). RESULTS: Thirty-three articles involving 2273 participants were collected in this meta-analysis. Among all participants with obesity, the pooled mean of weight loss was -23.26 kg (95% CI: -27.71 to -18.81), and the pooled mean change of CIMT was -0.06 mm (95% CI: -0.08 to -0.04). Compared with Non-surgical interventions, Surgical ones could lead to much higher weight loss (Pbetween groups < 0.001). A more significant CIMT reduction was identified among Surgical intervention patients than among Non-surgical intervention participants (Pbetween groups < 0.001). CONCLUSIONS: Effective interventions, especially Surgical interventions, could reduce the weight of patients with obesity, followed by the decline of CIMT, which might further disturb atherosclerosis progression and lower CVD risk.

[Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA].

Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

[Epidemiological characteristics of spontaneous subarachnoid hemorrhage cases in Shandong province].

Objective: To investigate the characteristics and trends of spontaneous subarachnoid hemorrhage (SAH) in Shandong province. Methods: In this study, SAH incidence data of residents from 2012 to 2021 were collected from the chronic disease monitoring information management system of Shandong province, including the basic information of outpatient, emergency or inpatient cases and out-of-hospital deaths (name, gender, ID number, address, etc.) and disease diagnosis information (disease diagnosis, date of onset, date of diagnosis, etc.). The crude incidence rate and age-standardized incidence rate were used as indicators to describe the incidence of SAH in different gender, age groups and regions (urban and rural areas). Joinpoint regression was used to analyze the variation of incidence rate and age by year. The rate difference decomposition method was used to estimate the contribution of population aging to the increase of SAH incidence. Global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software. Results: From 2012 to 2021, a total of 11 629 cases of SAH were reported from 19 provincial monitoring sites in Shandong province. Among them, 54.11% (6 293 cases) were female and 91.87% (10 684 cases) were≥45 years old. The reported crude incidence rate increased from 5.26/100 000 to 9.50/100 000, with an average annual increase of 7.75% (Ztrend=7.30, Ptrend<0.001), and the standardized incidence rate also showed an upward trend (Ztrend=3.92, Ptrend=0.004). The crude incidence rate of women was higher than that of men in all years (all P values<0.05), and the standardized incidence rate of women was higher than that of men in all years except in 2012 and 2021 (all P values<0.05). In 2012, the crude incidence and standardized incidence of urban residents were lower than those in rural areas (P<0.05); from 2013 to 2017, the urban incidence was higher than that in rural areas; and after 2018, the rural incidence exceeded the urban incidence again (all P values<0.05). The median age of onset of SAH increased from 61.9 years in 2012 to 67.2 years in 2021. The age of onset of SAH in men was lower than that in women in all years (all P<0.05), and there was no significant difference between urban and rural residents in most years (P>0.05). The incidence of SAH increased with age (Ptrend<0.001), with a low incidence reported in residents aged<45 years and a rapid increase in residents aged≥45 years. According to the seasonal decomposition, the incidence of SAH had three small peaks in January, March to May and October to November. From 2013 to 2021, the contribution of aging population to the increase of crude incidence of SAH increased from 27.86% to 43.68%. The global spatial autocorrelation analysis showed that the incidence of SAH was in an obvious spatial aggregation distribution (Moran's I>0, P<0.05). Local spatial autocorrelation analysis showed that the counties with high incidence were mainly concentrated in Dezhou City in northwest Shandong Province and Heze city in southwest Shandong province. Conclusions: The crude incidence rate of SAH in Shandong province is increasing, with spatial clustering and seasonal clustering. Residents aged 45 years and older, female residents, and rural residents are at high risk of developing SAH, so targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustered areas.

[Analysis of the incidence and mortality of thyroid cancer in Shandong Province from 2012 to 2022 based on the age-period-cohort model].

Objective: To analyze the trend of incidence and mortality of thyroid cancer and estimate its age-period-cohort effect in Shandong Province from 2012 to 2022. Methods: The Joinpoint regression was used to analyze the trend of incidence and mortality of thyroid cancer and calculate the average annual percentage change (AAPC) based on the data on thyroid cancer from 2012 to 2022. The age-period-cohort model was used to analyze the age-effect, time-effect and cohort-effect of thyroid cancer risk in the population aged over 20 years. Results: From 2012 to 2022, the incidence of thyroid cancer in Shandong province showed a significant upward trend, with an AAPC of 21.68% (95%CI: 19.14%-24.27%, P<0.001). The incidence of females was higher than that of males, and the incidence of urban areas was higher than that of rural areas. The trend of thyroid cancer mortality was relatively stable with an AAPC of -3.04% (95%CI:-8.81%-3.09%, P=0.323). The age effect of incidence increased with age before 60 years old and decreased with age after 60 years old. The incidence peaked in the age group of 55-59. The period effect increased with time. The cohort effect showed that the cohort born before 1957 had a downward trend over time, while the cohort born after 1957 had an upward trend. Conclusion: The incidence of thyroid cancer in Shandong shows a rising trend from 2012 to 2022. Age is an important factor affecting the risk of thyroid cancer. The mortality of thyroid cancer remains stable.

Early and intensive Motor Training for people with spinal cord injuries (the SCI-MT Trial): description of the intervention.

STUDY DESIGN: Descriptive. OBJECTIVES: The primary objective is to describe the intervention that will be provided in a large multi-centre randomised controlled trial titled: Early and Intensive Motor Training for people with Spinal Cord Injuries (the SCI-MT Trial). The secondary objective is to describe the strategies that will be used to operationalise and standardise the Motor Training provided to participants while keeping the intervention person-centred. METHODS: The paper focuses on the rationale and principles of Motor Training for people with spinal cord injuries (SCI). The description of the intervention is based on the Template for Intervention Description and Replication (TIDieR) checklist. Specifically, it addresses the following 6 criteria of the TIDieR checklist: why the effectiveness of Motor Training is being examined; what, how, where and when the Motor Training will be administered; and how much Motor Training will be provided. RESULTS: A detailed intervention manual has been developed to help standardise the delivery of the intervention. CONCLUSIONS: This paper describes the details of a complex intervention administered as part of a large randomised controlled trial. It will facilitate the subsequent interpretation of the trial results and enable the intervention to be reproduced in clinical practice and future trials.

[Modified gasless trans-subclavian approach endoscopic lateral neck dissection for treatment of papillary thyroid carcinoma: a series of 31 cases].

Objective: To examine the feasibility of the modified gasless trans-subclavian approach endoscopic thyroidectomy for lateral neck dissection (LND) in papillary thyroid carcinoma (PTC). Methods: The clinical data of 31 patients with PTC who underwent modified gasless trans-subclavian approach endoscopic LND in the Department of Head and Neck Surgery, Run Run Shaw Hospital, from January to October 2022 were retrospectively analyzed. There were 2 males and 29 females, aged (32.6±8.3) years (range: 17 to 55 years). The maximum diameter of the primary thyroid lesion (M(IQR)) was 1.06 (1.16) cm (range: 0.53 to 2.44 cm), and the maximum diameter of the metastatic lymph node was (1.04±0.37) cm (range: 0.44 to 1.88 cm). Operation time, postoperative hospital stay, number of lymph nodes dissected, and postoperative complications were recorded. Outpatient follow-up was conducted until November 30, 2022. Results: All operations were successfully completed with the endoscopy approach without conversion to open surgery. The operation time was 160 (20) minutes (range: 100 to 215 minutes), and the postoperative hospital stay was 4 (2) days (range: 2 to 14 days). The number of lymph nodes obtained by dissection in the central and lateral compartment of the neck was 11 (12) (range: 0 to 37) and 34.7±14.8 (range: 15 to 69), respectively. Temporary hypoparathyroidism occurred in 4 cases and all recovered within 1 month after the operation. One case suffered from recurrent laryngeal nerve injury (continuing followed up to assess whether it is a temporary injury). The complication of LND included 1 case of chylous leakage that was recovered with conservative treatment, 1 case of Horner syndrome returned to normal 3 months after surgery. During follow-up, there was no residual tumor or recurrence. Conclusion: The modified gasless trans-subclavian approach endoscopic LND for PTC is feasible, with a thorough dissection and concealed incision.

[Cancer survival during 2012-2018 in cancer registries of Shandong Province].

Objective: To analyze the 5-year cancer relative survival rate in cancer registries of Shandong Province during 2012-2018. Methods: 399 072 new cancer cases were collected in 23 cancer registries in Shandong Province during 2012-2018. All malignant tumors (C00-C97, D45-D47), benign central nervous system tumors (D32-D33), and central nervous system tumors (D42-D43) were registered according to the 10th revision of international classification of diseases (ICD). The survival of cancer patients was obtained by passive and active follow-up. The follow-up date was December 31, 2020. The diagnostic years were divided into three periods: 2012-2014, 2015-2017 and 2018-2020. The 5-year cancer survival rates were calculated by cohort approach, period analysis and hybrid approach, and the survival status of different sex, urban and rural areas, cancer species and age groups were analyzed. Results: The age of 399 072 new cancer cases was (63.5±13.7) years old, with 57.77% (230 538 cases) about male and 32.89% (131 247 cases) from urban. During 2012-2014, 2015-2017 and 2018-2020, the 5-year cancer survival rates in Shandong Province were 32.3%, 34.7% and 40.2%, respectively. In 2018-2020, the first five cancers with survival rates were thyroid cancer (86.0%), breast cancer (78.2%), testicular cancer (75.7%), bladder cancer (70.3%) and uterine cancer (69.2%), and the last five cancers with survival rates were pancreatic cancer (15.5%), liver cancer (16.8%), gallbladder cancer (19.6%), bone cancer (22.7%) and lung cancer (24.4%). The 5-year survival rate for cancer of women (47.8%) was higher than that of men (33.8%), and the rate of urban areas (45.7%) was higher than that of rural areas (37.3%) during 2018-2020. The first five cancers in men were thyroid (87.1%), testicular (75.7%), bladder (70.9%), kidney (65.6%) and prostate (62.8%) cancers, and the last five cancers were pancreatic (14.3%), liver (16.8%), gallbladder (18.2%), bone (19.9%) and lung (21.7%) cancers. The first five cancers in women were thyroid (85.5%), breast (78.0%), uterine (69.2%), bladder (68.8%) and kidney (66.8%) cancers, and the last five cancers were liver (17.2%), pancreatic (17.2%), gallbladder (22.0%), bone (27.2%) and lung (29.1%) cancers. Conclusion: The 5-year cancer survival rate in Shandong Province was on the rise from 2012 to 2018, and the survival rates of different cancers were different.

[Intraseasonal variation of the association between cold temperature and mortality risk in Shandong Province].

Objective: To explore the intraseasonal variation in mortality risk from cold temperature exposure in Shandong Province. Methods: Mortality data in Shandong province from 2013 to 2018 were collected from the cause of death surveillance system of Shandong Center for Disease Control and Prevention. The basic information mainly included the date of death, age, gender, education level, cause of death, home address, etc. The daily meteorological data from China Meteorological Data Network mainly included the grid coordinate data of 0.01°×0.01° latitude and longitude, such as daily average temperature (℃) and daily average relative humidity (%). The cold season was from November to February. The first two months were the early cold season and the last two months were the late cold season. The extreme cold temperature was defined as the 10th percentile of the temperature range of cold season. Time-stratified case crossover design with distributed lag non-linear model analyzed the association between temperature and mortality and the association between extreme low temperature and mortality in different lag days in the cold season, and compared the intraseasonal differences between early (November-December) and late (January-February) cold season. Results: The temperature ranged from -17.3 ℃ to 18.6 ℃ in Shandong Province during the cold season from 2013 to 2018, and the P10 (extreme low temperature) was -13.7 ℃. The average daily temperature in the early cold season was (3.63±4.66) ℃. The temperature in the late cold season was (-0.09±3.70) ℃. The average daily relative humidity was (63.89±14.75) % in the early cold season and (62.27±14.19) % in the late cold season. This study included 1 473 300 deaths in the cold season in Shandong Province between 2013 and 2018. There were 824 601 (55.97%) males and 349 824 (23.75%) cases aged<65 years. There were 803 691 (54.55%) deaths due to circulatory diseases and 140 415 (9.53%) deaths due to respiratory diseases. The results of DLNM showed that the cumulative OR of extreme low temperature in the four months of cold season was 1.74 (95%CI: 1.63, 1.86) with the optimal temperature of 18.6 ℃ as the reference. The cumulative OR values of early and late cold season were 1.50 (95%CI: 1.32, 1.71) and 2.56 (95%CI: 2.12, 3.09), respectively (P<0.001). The lag effect lasted for 12 d. Conclusion: There is an intraseasonal variation of the association between cold temperature and mortality risk in Shandong Province. The mortality risk related to cold temperature in the late cold season is higher than that in the early cold season.

[Spatio-temporal trend of female breast cancer mortality in Shandong Province from 1970 to 2013].

The mortality of female breast cancer in Shandong Province has increased since the 1970. The differential decomposition analysis found that the slight decline in the crude mortality of breast cancer among women was entirely due to non-demographic factors during the 1970-1990, and the significant increase in the crude mortality was due to a combination of demographic and non-demographic factors since the 1990. The contribution rate of demographic factor has gradually increased from 53.5% in 2004-2005 to 59.5% in 2011-2013, while that of non-demographic factor has decreased from 46.5% to 40.5%. The women aged 45-64 years old were the major population of female breast cancer deaths, accounting for 40%-60% of total breast cancer deaths in different times, and then the mortality in female aged 55-64 years old increased rapidly, with increases of 52.12%, 115.19% and 29.01% in 2011-2013 over the 1970-1974, 1990-1992 and 2004-2005, respectively (Z=-7.342,P<0.001). Compared with 1970-1974, the age-standardized mortality rate of rural women increased by 41.86% in 2011-2013 (Z=-17.933, P<0.001), and that of urban women increased by 18.62% in 2011-2013 (Z=-25.642, P<0.001). The age-standardized mortality rate of breast cancer in urban women was higher than that in rural women in different times (all P<0.05). The spatial scan analysis found that eastern Shandong Province was found to be a sustained high-risk area for death, and other high-risk areas were transferred from north to southwest of Shandong between 1970 and 2013.

[Mortality level and tendency of road traffic injury in Shandong Province from 2012 to 2020].

Objective: To analyze the mortality level and tendency of road traffic injury in Shandong province from 2012 to 2020. Methods: Based on the data of road traffic deaths from the cause of death registration system in Shandong province from 2012 to 2020, the mortality rates of road traffic injury were calculated by sex, age, area, and injury type. The mortality was standardized based on the age structure of the Chinese population in the sixth Population Census in 2010. The annual percent change (APC) and average annual percent change (AAPC) of the mortalities and the standarized mortalities were calculated by using Joinpoint regression model, and the trends were also examined. Results: In 2020, the crude mortality of road traffic injury in Shandong Province was 15.58/100 000, and the standardized mortality was 12.90/100 000. From 2012 to 2020, the standardized mortality of road traffic injury in Shandong province showed a downward trend with AAPC of -5.4%. The standardized mortality of middle-south mountain areas, male and children aged 0-14 years in Shandong showed a significantly decreasing trend with AAPC of -6.8%, -6.1% and -6.0%, respectively. The standardized mortality of people aged 65 years and over did not decrease significantly, but the number of deaths increased significantly by 50.96% in 2020 (5 780 cases), compared with those in 2012 (3 829 cases). The standardized mortality of pedestrian and motorcyclists decreased significantly with AAPC of -7.5% and -6.7%, respectively. There was no significant change in the standardized mortality among people who rode motor vehicles or bicycles. Conclusion: From 2012 to 2020, the standardized mortality of road traffic injury in Shandong Province showed an obvious downward trend, but the standardized mortality of people aged 65 years and over did not decrease significantly. In the future, it is still necessary to take government-led, multi-sectoral collaboration, with a focus on comprehensive preventive measures, to further reduce road traffic injury mortality.

[Gasless submental-transoral combined appoach endoscopic thyroidectomy for papillary thyroid carcinoma: a series of 41 cases].

Objective: To examine the safety and feasibility of gasless submental-transoral combined appoach endoscopic thyroidectomy for papillary thyroid carcinoma (PTC). Methods: A retrospective analysis of the clinical data of 41 patients with PTC who underwent the gasless submental-transoral combined appoach endoscopic thyroidectomy at the Department of Head and Neck Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from November 2020 to April 2021. There were 5 males and 36 females with the age of (35.0±8.7) years (range: 19 to 58 years). A horizontal incision with a length of 2.0 cm is made under the chin as an observation hole, a 10 mm Trocar and a self-developed retractor are inserted, and two 5 mm longitudinal incisions are made on the labial side in the vestibule of the oral cavity as an operation hole, each inserting a 5 mm Trocar, the operation direction is from the cranial side to the caudal side. The sensation of the lower lip and chin was measured on the first day and one month postoperative. The operation time, hospital stay, the number of lymph nodes dissected and postoperative complications were recorded. Results: Surgical procedures in all cases were successfully completed under endoscopic approach without transfering to open surgery. The operation time was (99±34) minutes (range: 50 to 180 minutes) and the postoperative hospital stay was (3.4±2.2) days (range: 2 to 16 days). The maximum diameter of PTC was (7.6±5.8) mm (range: 2 to 30 mm), and the number of lymph nodes of the central compartment dissection was 6(5) (M(IQR)) (range: 1 to 25). The duration of follow-up is 1 month after operation, and the follow-up method is adopted in outpatient clinic. Postoperation complications included 2 cases of transient hypoparathyroidism, One case of recurrent laryngeal nerve injury (continue to follow up to assess whether it is a temporary injury). Postoperative minor chyle leak, seroma, and local redness and swelling in 1 case each were cured after conservative treatment. 1 case of transient minor numbness of the lower lip was observed. No permanent hypoparathyroidism, postoperative bleeding and numbness of the chin was observed. Conclusion: The gasless submental-transoral combined appoach endoscopic thyroidectomy is a feasible approach in selected PTC patients and has clinical application value.

[Analysis of suicide ideation and its influencing factors among nursing staff of different grades in different hospitals during their career].

Objective: To analyze the prevalence and related factors of suicide ideation among nurses in different levels of hospitals in Shandong Province, and to analyze the relationship between them. Methods: From June to July 2020, 1644 nurses in Shandong Province were surveyed by multi-stage stratified cluster sampling. The suicidal ideation of nurses was investigated by suicidal ideation screening. Social support and mental health were measured by the perceived social support scale (pass) and kessler10 scale respectively. The simple coping style scale (SCSQ) was used to evaluate the coping styles of the subjects when they encountered problems. Logistic regression was used to analyze the influencing factors of suicidal ideation, Amos software was used to establish the path model of suicidal ideation related factors, and the maximum likelihood estimation was used to test the path model coefficient. Results: The incidence of suicidal ideation among nurses in secondary hospitals during their career was 8.44%, and that in tertiary hospitals was 11.66%. There was no significant difference in suicidal ideation among nurses at all levels in secondary hospitals (P>0.05) . The main factors related to suicidal ideation were unmarried and others (OR=0.362, 95%CI=0.155, 0.844, P=0.019) , social support (OR=1.084, 95% CI=1.059, 1.109, P=0.000) and mental health status (OR=0.921, 95% CI=0.890, 0.953, P=0.000) . The suicide ideation of skilled nurses in tertiary hospitals was higher than that of other levels (P<0.05) . The related factors of suicide ideation mainly included unmarried and others (OR=0.369, 95% CI=0.214, 0.636, P=0.000) , night shift (OR=1.889, 95%CI=10.57, 3.377, P=0.032) , general self-rated social status (OR=2.377, 95%CI=1.031, 5.483, P=0.042) , physical disease (OR=2.747, 95%CI=1.601, 4.714) , P=0.000) , Social support (OR=0.960, 95%CI=1.042, 1.077, P=0.000) and mental health status (OR=0.942, 95%CI=0.922, 0.963, P=0.000) . Social support and mental health have a direct effect on suicidal ideation. Self-assessment of social status, social support and physical disease can affect suicidal ideation by affecting mental health. Conclusion: It is necessary to pay more attention to the mental health status of nurses at different levels in different hospitals during their career, improve their social support level, and improve their cognition of the practice environment.

Dental follicle cell differentiation towards periodontal ligament-like tissue in a self-assembly three-dimensional organoid model.

Periodontitis remains an unsolved oral disease, prevalent worldwide and resulting in tooth loss due to dysfunction of the periodontal ligament (PDL), a tissue connecting the tooth root with the alveolar bone. A scaffold-free three-dimensional (3D) organoid model for in vitro tenogenesis/ligamentogeneis has already been described. As PDL tissue naturally arises from the dental follicle, the aim of this study was to investigate the ligamentogenic differentiation potential of dental follicle cells (DFCs) in vitro by employing this 3D model. Human primary DFCs were compared, in both two- and three-dimensions, to a previously published PDL- hTERT cell line. The 3D organoids were evaluated by haematoxylin and eosin, 4',6-diamidino-2-phenylindole and F-actin staining combined with detailed histomorphometric analyses of cell-row structure, angular deviation and cell density. Furthermore, the expression of 48 tendon/ligament- and multilineage-related genes was evaluated using quantitative polymerase chain reaction, followed by immunofluorescent analyses of collagen 1 and 3. The results showed that both cell types were successful in the formation of scaffold-free 3D organoids. DFC organoids were comparable to PDL-hTERT in terms of cell density; however, DFCs exhibited superior organoid morphology, cell-row organisation (p < 0.0001) and angular deviation (p < 0.0001). Interestingly, in 2 dimensions as well as in 3D, DFCs showed significantly higher levels of several ligament- related genes compared to the PDL-hTERT cell line. In conclusion, DFCs exhibited great potential to form PDL-like 3D organoids in vitro suggesting that this strategy can be further developed for functional PDL engineering.

Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial.

OBJECTIVE: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. DESIGN: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). SETTING: Twenty-eight UK NHS early pregnancy units. SAMPLE: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage. METHODS: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. MAIN OUTCOME MEASURES: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs). RESULTS: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. CONCLUSIONS: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. TWEETABLE ABSTRACT: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages.

Perspectives of pregnant and breastfeeding women on longitudinal clinical studies that require non-invasive biospecimen collection - a qualitative study.

BACKGROUND: Investigation of the microbiome during early life has stimulated an increasing number of cohort studies in pregnant and breastfeeding women that require non-invasive biospecimen collection. The objective of this study was to explore pregnant and breastfeeding women's perspectives on longitudinal clinical studies that require non-invasive biospecimen collection and how they relate to study logistics and research participation. METHODS: We completed in-depth semi-structured interviews with 40 women who were either pregnant (n = 20) or breastfeeding (n = 20) to identify their understanding of longitudinal clinical research, the motivations and barriers to their participation in such research, and their preferences for providing non-invasive biospecimen samples. RESULTS: Perspectives on research participation were focused on breastfeeding and perinatal education. Participants cited direct benefits of research participation that included flexible childcare, lactation support, and incentives and compensation. Healthcare providers, physician offices, and social media were cited as credible sources and channels for recruitment. Participants viewed lengthy study visits and child protection as the primary barriers to research participation. The barriers to biospecimen collection were centered on stool sampling, inadequate instructions, and drop-off convenience. CONCLUSION: Women in this study were interested in participating in clinical studies that require non-invasive biospecimen collection, and motivations to participate center on breastfeeding and the potential to make a scientific contribution that helps others. Effectively recruiting pregnant or breastfeeding participants for longitudinal microbiome studies requires protocols that account for participant interests and consideration for their time.

Application of virome capture sequencing in shellfish sold at retail level in Singapore.

During the period from late 2019 to early 2020, we performed a foodborne virus detection from shellfish collected in Singapore at retail level. Multiple human enteric viruses were included as our targets including human noroviruses (NoVs) GI and GII, hepatitis A virus, hepatitis E virus and rotavirus. Out of the 60 shellfish samples, 23 (38·3%) were detected to be positive by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) with human enteric viruses. Six samples were selected to proceed with virome capture sequencing with positive control samples spiked with serially diluted NoV GII clinical samples in oyster extract. As a result, the natural sample with comparable Ct values (34·0-35·0) of the spiked sample as detected by RT-qPCR generated much lower read counts (>7-log2 cumulative sum scaling difference) and genome coverage (406 nt. vs 3715 nt.), suggesting that the RT-qPCR positive signals detected from the shellfish samples collected at the retail market were likely from degraded RNA derived from inactive virus particles.

[Analysis of the trend and spatial clustering of gastric cancer deaths in Shandong Province from 1970 to 2013].

Objective: To investigate the distribution characteristics and trends of mortality and spatial aggregation of gastric cancer in Shandong Province from 1970 to 2013. Methods: The mortality data of gastric cancer from 1970 to 1974, 1990 to 1992 and 2004 to 2005 were collected from the first, second and third retrospective sampling survey of causes of death in Shandong Province, respectively. The mortality data of gastric cancer from 2011 to 2013 were collected from the all-cause surveillance data of Shandong Province. The crude mortality rate and age-standardized mortality rate were used to describe the death level of gastric cancer. The age-standardized mortality rate of Shandong Province was calculated based on Segi's world standard population, and the age-standardized mortality rate of counties (cities and districts) was calculated based on the Chinese population in 1964.The factors influencing the difference of gastric cancer mortality in different periods were decomposed by using the method of differential decomposition of mortality, and the contributions of population and non-population factors in different periods were estimated.Using ArcGIS 10.2 software, the death level of gastric cancer in different counties (cities and districts) in Shandong province from 1970 to 1974 and 2011 to 2013 were visualized. DeoDa 1.12 software was used for global and local spatial autocorrelation analysis. Results: The crude death rate and age-standardized death rate of gastric cancer in Shandong province increased firstly and then decreased during 1970-2013, and the crude death rate of gastric cancer increased from 18.33/100 000 in 1970-1974 to 28.51/100 000 in 2011-2013. Segi's age-standardized mortality rate for gastric cancer decreased from 20.94 per 100 000 in 1970-1974 to 18.17 per 100 000 in 2011-2013.From 1990 to 1992, from 2004 to 2005 and from 2011 to 2013, the contribution value of non-population factors to the increase of crude gc mortality was 95.59%, 48.45% and -20.57%, respectively, showing a continuous downward trend. The Moran's I index of crude mortality of gastric cancer in Shandong province from 1970 to 1974 and from 2011 to 2013 were 0.77 and 0.57, respectively, and the Moran's I index of age-normalized mortality was 0.75 and 0.44, respectively. Local autocorrelation analysis showed that there were 31 and 19 high aged-mortality areas of gastric cancer in 1970-1974 and 2011-2013 respectively, and 7 overlapping counties (cities and districts), 6 of which were located in Jiaodong area. Conclusion: The crude mortality and age-standardized mortality of gastric cancer in Shandong province increased first and then decreased from 1970 to 2013, and the distribution of gastric cancer mortality had obvious spatial aggregation and changed with time.

Factors associated with Scrub Typhus infection: A case-control study from Luhe, China.

INTRODUCTION: Scrub typhus (ST) is an acute febrile infection and remains a significant health problem globally. This study aimed to determine the factors associated with ST infection in Luhe District, China. MATERIAL AND METHODS: The case-control study was conducted among 116 cases identified through passive surveillance systems over three years.The control subjects were 232 living in the same village for more than six months without any history of ST infection were selected by matching to the age (within 5-years) and identified through active surveillance. Statistical analyses were performed using SPSS v. 25.0 for Windows (IBM SPSS, Chicago, IL, USA). RESULTS: The mean age of confirmed persons was 58.1(SD=10.15) years, while control subjects were 56.14 (11.57).There is no significant difference in gender, age, education, and occupations between case and control. Farmers had the most significant number of cases among occupational groups. The three factors that were significantly associated with an increased odds of having ST infection are bundling or moving waste straw (OR: 1.94, 95%CI; 0.99,381), morning exercise in the park or field (OR: 4.74 95%CI; 1.19, 18.95), and working as labourer in the vegetable field (OR:1.02, 95%CI:1.02,3.19). CONCLUSIONS: Our findings suggested establishing a prevention and control strategy for these groups to lower ST development risk.

[Study of portal venous pressure gradient to predict high-hepatic encephalopathy-risk population post TIPS].

Transjugular intrahepatic portosystemic shunt (TIPS) can effectively reduce the portal venous pressure and relieve the clinical complications related to portal hypertension. However, hepatic encephalopathy (HE) is still the main complication post TIPS. Studies have shown that patients over 65 years old with liver function reserve in Child-Pugh grade C are the high-HE-risk group post TIPS, and early TIPS treatment can benefit the survival of these high-risk patients. In this study, TIPS was used to treat 60 cases aged > 65 years old and liver function reserve in Child-Pugh grade C (decompensated liver cirrhosis) with esophagogastric variceal bleeding. The clinical results of 1-year was observed and the porto systemic gradient (PSG) was evaluated. The relationship between the incidence of HE and the PSG of patients with and without HE were compared to evaluate the effect of PSG on the incidence of HE.

[The effect of booster dose vaccination 21- to 32-years after primary vaccination with hepatitis B vaccine in the population born from 1986 to 1996 in Zhengding County of Hebei Province].

Objective: Aanalysis the effect of booster one dose of hepatitis B vaccine after 21-32 years of primary immunization in Zhengding Country of Hebei Province. Methods: A total of 322 participants who were born between 1986 and 1996, received a full course of primary vaccination with plasma-derived hepatitis B vaccine (HepB), had no experience with booster vaccination, were HBsAg, anti-HBcnegative, had anti-HBs<10 mIU/ml, completed the booster and had laboratory results were enrolled between August 2017 to February 2018. A simple random method was uesd to randomly assigned 322 subjects to two groups, receiving a booster dose of HepB derived from either Saccharomyces cerevisiae ï¼»HepB (SC), (151 cases)ï¼½ or Chinese hamster ovary-derived HepB ï¼»HepB (CHO), (171 cases)ï¼½, the dose was 20 µg. Blood samples were collected 30 days after boosting and quantitatively tested for the geometric mean concentration (GMC) of anti-HBs to assess immunological effect. The related influencing factors of GMC and seroconversion rates of anti-HBs were analyzed by multiple linear regression and multivariate logistic regression models. Results: The 266 subjects (82.61%) had anti-HBs≥ 10 mIU/ml, and GMC was (131.63±12.94) mIU/ml.The seroconversion rates of anti-HBs in the anti-HBs<2.5 mIU/ml group and 2.5-10 mIU/ml group were 74.54% (161 cases) and 99.06% (105 cases), respectively (P<0.001).The seroconversion rates of anti-HBs after one dose of HepB (CHO) was higher than that of one dose of HepB (SC), the seroconversion rates were 87.13% (149 cases) and 77.48% (117 cases), respectively (P=0.023). Participants boostered with HepB (CHO) was the factor influencing the effect of strengthening immunization compared with boostered with HepB (SC), and OR (95%CI) was 1.91 (1.02-3.56) (P=0.042).Compared with anti-HBs<2.5 mIU/ml, prebooster anti-HBs was between 2.5 mIU/ml and 10 mIU/ml was the related factor of seroconversion rates of anti-HBs after booster immunization, and OR (95%CI) was 36.15 (4.91-266.02) (P<0.001). Conclusion: Participants boostered withone dose of HepB had a good immune response. Pre-booster anti-HBs concentration and a variety of vaccine were related factors of immune response.