[A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma].

Objective: To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma. Methods: This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People's Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method. Results: Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95%CI:93.4% to 100%) and 90.7%(95%CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95%CI:83.0% to 99.8%) and 71.3%(95%CI:58.7% to 86.5%). Conclusions: The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

The effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease.

AIMS: To assess the effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease (COPD). BACKGROUND: A few recent studies have shown that unsupervised home-based pulmonary rehabilitation can improve the clinical outcome of patients with COPD. More studies are needed to prove its benefits. DESIGN: This study used a quasi-experimental design. METHODS: Seventy-two admitted COPD patients were assigned to experimental group or control group through purposeful sampling. Data were collected from March 2016 to November 2017 in the Thoracic Intensive Care Unit of a Medical Center in Taiwan. The Medical Research Council dyspnea scale, the COPD Self-Efficacy Scale and the Clinical COPD Questionnaire were measured before education and at the first, second and third months after discharge. RESULTS: The Medical Research Council dyspnea scale and COPD Self-Efficacy Scale results in the experimental group were significantly improved compared with the control group in the third month after discharge. The Clinical COPD Questionnaire score continued to improve in both groups in the third month after discharge, and there was no difference between the two groups. CONCLUSION: A short-term unsupervised home-based pulmonary rehabilitation with self- management program had significant benefits for patients with COPD. The long-term effects need to be confirmed.

A Randomized Trial of Endometrial Scratching before In Vitro Fertilization.

BACKGROUND: Endometrial scratching (with the use of a pipelle biopsy) is a technique proposed to facilitate embryo implantation and increase the probability of pregnancy in women undergoing in vitro fertilization (IVF). METHODS: We conducted a pragmatic, multicenter, open-label, randomized, controlled trial. Eligible women were undergoing IVF (fresh-embryo or frozen-embryo transfer), with no recent exposure to disruptive intrauterine instrumentation (e.g., hysteroscopy). Participants were randomly assigned in a 1:1 ratio to either endometrial scratching (by pipelle biopsy between day 3 of the cycle preceding the embryo-transfer cycle and day 3 of the embryo-transfer cycle) or no intervention. The primary outcome was live birth. RESULTS: A total of 1364 women underwent randomization. The frequency of live birth was 180 of 690 women (26.1%) in the endometrial-scratch group and 176 of 674 women (26.1%) in the control group (adjusted odds ratio, 1.00; 95% confidence interval, 0.78 to 1.27). There were no significant between-group differences in the rates of ongoing pregnancy, clinical pregnancy, multiple pregnancy, ectopic pregnancy, or miscarriage. The median score for pain from endometrial scratching (on a scale of 0 to 10, with higher scores indicating worse pain) was 3.5 (interquartile range, 1.9 to 6.0). CONCLUSIONS: Endometrial scratching did not result in a higher rate of live birth than no intervention among women undergoing IVF. (Funded by the University of Auckland and others; PIP Australian New Zealand Clinical Trials Registry number, ACTRN12614000626662 .).

[Application of deep learning neural network in pathological image classification of non-inflammatory aortic membrane degeneration].

Objective: To investigate the value of deep learning in classifying non-inflammatory aortic membrane degeneration. Methods: Eighty-nine cases of non-inflammatory aortic media degeneration diagnosed from January to June 2018 were collected at Beijing Anzhen Hospital, Capital Medical University, China and scanned into digital sections. 1 627 hematoxylin and eosin stained photomicrographs were extracted. Combined with the ResNet18-based deep convolution neural network model, 4-category classification of pathological images were performed to diagnose the non-inflammatory aortic lesion. Results: The prediction model of artificial intelligence assisted diagnosis had the best accuracy, sensitivity and precision in identifying lesions with smooth muscle cell nuclei loss, which were 99.39%, 98.36% and 98.36%, respectively. The classification accuracy of elastic fiber fragmentation and/or loss lesions was 98.08%, while that of intralamellar mucoid extracellular matrix accumulation lesions was 96.93%. The overall accuracy of the classification model was 96.32%, and the area under the curve was 0.982. Conclusions: The accuracy of deep learning neural network model in the 4-category classification of non-inflammatory aortic lesionsis confirmed based on digital photomicrographs. This method can effectively improve the diagnostic efficiency of pathologists.

Management of patients with diabetes and heart failure with reduced ejection fraction: An international comparison.

AIMS: To compare the management of patients with diabetes and heart failure with reduced ejection fraction (HFrEF) in the United States and Asia to understand variations in treatment patterns across different healthcare systems. MATERIALS AND METHODS: Our cohort included patients with diabetes and HFrEF (ejection fraction <40%) from a US-based registry of adults with diabetes (2013-2016, electronic health records) and a multi-national Asian registry of adults with heart failure (2010-2016, prospective registry). Asian countries were categorized as high income (HI) or low income (LI), according to the United Nations classification. Rates of use of guideline-directed medical therapies (determined through review of active medication lists) were compared across regions. RESULTS: Patients with diabetes and HFrEF in the United States (n = 28 877) were older, had higher body mass indices, and were more likely to have coronary disease than those in Asia (n = 2235). Compared with US patients, the use of guideline-directed medical therapy for HFrEF was lower in patients in LI Asian countries (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers: patients in the United States, 77% vs. patients in HI Asian countries, 76% vs patients in LI Asian countries, 69%; ß-blockers: patients in the United States, 91% vs. patients in HI Asian countries, 87% vs. patients in LI Asian countries, 69%; P < 0.001 for both). Insulin was used more commonly in the United States (44% vs. 24% vs. 25%, respectively; P < 0.001), whereas sulphonylureas were more often prescribed in Asian countries (42% vs. 52% vs. 54%; respectively, P < 0.001). Thiazolidinediones were prescribed in 6% of US patients compared with <1% of patients in Asia. The use of newer diabetes medications was <5% in all. CONCLUSION: In both the United States and Asia, opportunities for improvement in the use of evidence-based therapies exist for patients with both diabetes and HFrEF. Effective tools to guide medication choices for these complex, high-risk patients could have substantial impact on quality and outcomes.

[Analysis of 113 cases with mucinous cystic neoplasms in a single institutional study].

OBJECTIVE: To describe the clinicopathological characteristics and prognostic factors of mucinous cystic neoplasm(MCN). METHODS: One hundred and thirteen patients with MCN comfirmed by histological examination admitted in People's Liberation Army General Hospital from January 1994 to June 2015 were analyzed, including 21 male and 92 female patients with mean age of (50.2±14.5) years. Forty-eight patients had incidental discovery of their cystic neoplasm for another reason, 65 patients were symptomatic, and abdominal pain or distension was main clinical symptom. Among 113 patients with MCN, 75 cases were MCN with dysplasia, and 38 cases were MCN with invasive carcinoma. Wilcoxon test and χ(2) test, et al were used to analyzed the data, respectively. RESULTS: MCN was mostly located in body and tail of pancreas.Sex, mean age, clinical symptom, tumor size, and CA19-9 showed significant difference between MCN with dysplasia and MCN with invasive carcinoma (all P<0.05). The presence of a solid component (χ(2)=32.460, P=0.000)and main pancreatic duct dilation(χ(2)= 5.729, P=0.022) were significantly associated with malignancy. Fifty-eight patients with dysplasia were followed up, only one patient occurred tumor recurrence. Thirty-one patients with malignancy were followed up, among which there were 22 patients dead, 1-, 3-, 5-year survival of MCN with malignancy was 76.9%, 56.5%, 36.6%, respectively. Lymphatic metastasis and tumor recurrence were important prognostic factors of MCN with malignancy(both P<0.05). CONCLUSIONS: MCN is most affected by old female with no specific symptom, most tumors are located at the body and tail of the pancreas.MCN with dysplasia have excellent prognosis underwent surgery. Even with complete resection, the long-term survival of MCN with malignancy is not satisfied.

EMG-guided salpingopharyngeus Botox injection for palatal myoclonus.

Palatal myoclonus (PM) is a rare neurological disorder characterized by involuntary movements of the soft palate musculature causing objective clicking tinnitus. Two forms are recognized as distinct clinical entities, with poorly understood pathogenesis: essential and symptomatic PM. The intrusive nature of the tinnitus prompts patients to seek medical advice. Conventional medical treatments with anxiolytics, antidepressants, and anticonvulsants have limited efficacy in these patients. In this case report, electromyography-guided injection of botulinum toxin type A (Botox; Allergan, Irvine, CA, USA) to the involved salpingopharyngeus and tensor veli palatini yielded satisfactory results with minimal temporary adverse effects.

[Increased muscle mass increases risks of intervertebral disc degeneration: a two-sample Mendelian randomization study].

OBJECTIVE: To investigate the causal relationship between sarcopenia (SP) and intervertebral disc degeneration (IVDD) using two-sample Mendelian randomization analysis. METHODS: Genome-wide association study (GWAS) databases of SP (lean body mass, right and left hand grip strength) and IVDD were obtained. The single nucleotide polymorphisms (SNPs) strongly associated with exposure were obtained as an instrumental variable. After conservatively removing two confounders (smoking and sedentary life style), the causal relationship between SP and IVDD was assessed using Mendelian randomization analyses through the inverse variance weighting (IVW), weighted median (WM) and MR-Egger methods. The consistency and accuracy of the results were verified by MR-PRESSO, double validation, negative control, heterogeneity and diversity tests. RESULTS: A total of 570 SNPs associated with lean muscle mass, 97 with strong right hand grip strength, and 79 with strong left hand grip strength were included in the analysis. The results showed that lean muscle mass had a significant positive correlation with IVDD (IVW: OR=1.139, 95% CI: 1.076-1.204, P=6.619e-6) and right hand grip strength had a possible positive correlation with IVDD. After reanalysis in MR-PRESSO and selection of a new IVDD database, the results remained largely consistent with the previous results. CONCLUSION: Increased muscle mass may increase the risk of intervertebral disc degeneration.

[Study on completion and academic thought of Dou Ke Jian(The Key of Smallpox)].

Dou Ke Jian(The Key of Smallpox) was written by Zhu Xun in the late Ming dynasty,collated and published by Zhu Fengtai in the Qing dynasty.It was rarely studied in China ,but have a far-reaching influence in Japan.By comparing with other works about smallpox and refering to the Japanese Ikeda family's Doukejian Huitong, Doukejian Siheng, Doukejian Shanzhengbuzhu completed on the basis of Dou Ke Jian,this paper systematically reviews the author's life, compilation and publication background, main content, academic characteristics and value, and influence on later generations.The views advocated in this book, such as "toxin hidden in the spleen meridians, attaching importance to qi and blood", "distinguishing between the exterior and interior, deficiency and excess, and take the lips and tongue as the key" have important reference value for the treatment of infectious diseases in later generations.

Performance of rural health clinics: an examination of efficiency and Medicare beneficiary outcomes.

INTRODUCTION: In 2011, some 3800 Rural Health Clinics (RHCs) delivered primary care in underserved rural areas throughout the USA. To date, little research has been conducted to identify the variability in RHC performance. In an effort to address the knowledge gaps, a national, longitudinal study was conducted of a panel of 3565 RHCs. The goals of the study were to determine: (1) the relationship between two aspects of performance: efficiency and effectiveness; and (2) the factors that influence variation in RHC performance. METHODS: A non-experimental study of RHC performance was conducted using 2 years of secondary data from multiple sources. A study panel of RHCs was formed. This panel was composed of all RHCs continuously in operation during the period 2006-2007. The study panel was divided into two subsets - one for the provider-based clinics; another for the independent clinics. The individual RHC was the unit of analysis throughout the study. Descriptive statistics were calculated for each subset. Bivariate analyses was conducted of the relationships between the clinic characteristics and the performance outcome measures, as well as the interrelationships between various clinic characteristics using χ², t-tests, Cramer's V, Pearson correlation, and Spearman correlation statistics. Next, using covariance structure analysis, the interrelationships were examined among the context (community or demographic factors), design (organizational structure and other mediating factors), and performance (efficiency and effectiveness) of RHCs. Three hypotheses were tested: (1) the effectiveness of RHCs is positively influenced by efficiency; (2) there is a reciprocal relationship between RHC efficiency and effectiveness; and (3) large RHCs are more efficient than small RHCs. RESULTS: To test the hypotheses that effectiveness of RHCs is positively influenced by efficiency and that there is a reciprocal relationship between efficiency and effectiveness, two covariance structure models were developed and revised: one for independent and one for provider-based RHCs. However, the revised models were not supported by the data. To test the hypothesis that large RHCs are more efficient than small ones, two additional efficiency-based structural equation models were constructed (one for independent RHCs and another for provider-based RHCs). Both of these models were supported by the data (independent model: χ² = 13.8, df = 8, p = 0.088, relative χ² = 1.723, adjusted goodness of fit index [AGFI] = .981, root mean square error of approximation [RMSEA] = .034; provider-based model: χ² = 19.011, df = 8, p = 0.015, relative χ² = 2.376, AGFI = .978, RMSEA = .043). CONCLUSION: This study examined the relationship between efficiency and effectiveness of RHCs. In addition, it identified several factors that influence the variation in RHC performance. The study has implications for optimizing RHC performance, providing quality services to rural populations, and enhancing the value of RHC data. The present is a critical time in the history of RHCs as they transition to meet the goals and expectations of the US health system reform. Additional research is needed to quantify and trend RHCs' contribution to the rural health delivery system in order to optimize their service to rural populations.

Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain:systematic review.

BACKGROUND: Intranasal diamorphine is a potential treatment for breakthrough pain but few paediatric data are available to assist dose estimation. AIM: To determine an intranasal diamorphine dose in children through an understanding of pharmacokinetics. DESIGN: A systematic review of the literature was undertaken to seek diamorphine pharmacokinetic parameters in neonates, children and adults. Parenteral and enteral diamorphine bioavailability were reviewed with respect to formation of the major metabolite, morphine. Clinical data quantifying equianalgesic effects of diamorphine and morphine were reviewed. REVIEW SOURCES: PubMed (1960-2020); EMBASE (1980-2020); IPA (1973-2020) and original human research studies that reported diacetylmorphine and metabolite after any dose or route of administration. RESULTS: The systematic review identified 19 studies: 16 in adults and 1 in children and 2 neonatal reports. Details of study participants were extracted. Age ranged from premature neonates to 67 years and weight 1.4-88 kg. Intranasal diamorphine bioavailability was predicted as 50%. The equianalgesic intravenous conversion ratio of morphine:diamorphine was 2:1. There was heterogeneity between pharmacokinetic parameter estimates attributed to routes of administration, lack of size standardisation, methodology and pharmacokinetic analysis. Estimates of the pharmacokinetic parameters clearance and volume of distribution were reduced in neonates. There were insufficient paediatric data to characterise clearance or volume maturation of either diamorphine or its metabolites. CONCLUSIONS: We estimate equianalgesic ratios of intravenous morphine:diamorphine 2:1, intravenous morphine:intranasal diamorphine 1:1 and oral morphine:intranasal diamorphine of 1:3. These ratios are based on adult literature, but are reasonable for deciding on an initial dose of 0.1 mg/kg in children 4-13 years.

Gestational diabetes: development of an early risk prediction tool to facilitate opportunities for prevention.

BACKGROUND AND AIM: In the setting of advancing maternal age, escalating obesity and increasing Gestational Diabetes Mellitus (GDM) rates, we aimed to develop a novel risk prediction tool to identify high-risk women in early pregnancy, specifically to facilitate targeted antenatal prevention of GDM. METHODS: In this retrospective, observational study, first-trimester data collected routinely by midwifery staff in 4276 women attending a large tertiary hospital in 2007/2008 was analysed to examine predictive factors for GDM. GDM was diagnosed with a 28-week oral glucose tolerance test. The data set included a derivation group (n=2880, from 2007 deliveries) and a validation group (n = 1396, from 2008). Multivariate analysis generated a scoring system. RESULTS: GDM was significantly correlated with a number of factors: past history of GDM, increasing maternal age and body mass index, Asian descent and family history of diabetes. Validation group clinical scores achieved a sensitivity of 61.3% and specificity of 71.4% for differentiating women according to their risk of developing GDM. CONCLUSIONS: Risk factors for GDM are easily identified at the first-trimester midwifery hospital booking visit. A risk prediction tool, derived from risk factors in early pregnancy, identifies women at high risk of GDM. This represents a novel approach to facilitate targeted early intervention with the potential to prevent development of, or ameliorate, GDM.

Risk factors for gestational diabetes mellitus: implications for the application of screening guidelines.

BACKGROUND: Recent evidence has shown the importance of ensuring that all pregnancies with gestational diabetes mellitus (GDM) are identified and managed appropriately. However, there remains a lack of consensus as to how to best identify these women. AIM: To review risk profiles of women with GDM and to evaluate international GDM screening recommendations. METHODS: A retrospective observational study was carried out at a tertiary referral hospital (Monash Medical Centre, Victoria). Data of singleton pregnancies in women (without pre-existing diabetes mellitus) giving birth in 2007 from the Birthing Outcomes System were analysed and the performance of the British National Institute for Health and Clinical Excellence (NICE), the American Diabetes Association (ADA) and the Australasian Diabetes in Pregnancy Society (ADIPS) GDM selective screening guidelines were evaluated. Predictors of GDM were identified with logistic regression, and sensitivity and specificity of international screening guidelines were calculated. RESULTS: The strongest independent risk factors for GDM were a past history of GDM (OR = 10.7; 95% CI: 5.4-21.1), maternal age ≥40 years (OR 7.0; 95% CI 2.9-17.2) and BMI ≥35 kg/m(2) (OR 6.1; 95% CI 3.0-12.1). The sensitivity and specificity of the NICE, ADA and ADIPS guidelines were 92.7% and 32.4%, 100% and 3.9% and 98.6% and 13.7%, respectively. CONCLUSIONS: Increasing age and BMI and previous GDM were the most significant risk factors for GDM. Current selective screening guidelines have high sensitivity but low specificity and offer little over universal screening.

[Chronic radiation-induced rectal injury after adjuvant radiotherapy for pelvic malignant tumors: report based on a phase 3 randomized clinical trial].

Objective: Radiotherapy is one of the standard treatments for pelvic malignant tumors. However, researches associated with intestinal radiation injury and the quality of life (QoL) of patients receiving radiotherapy were lacking in the past. This study aims to analyze the occurrence of radiation-induced rectal injury after adjuvant radiotherapy for pelvic malignant tumors and call for more attention on this issne. Methods: A retrospectively observational study was conducted. Case data of cervical cancer patients from the database of STARS phase 3 randomized clinical trial (NCT00806117) in Sun Yat-sen University Cancer Center were analyzed. A total of 848 cervical cancer patients who received adjuvant radiation following hysterectomy and pelvic lymphadenectomy in Sun Yat-sen University Cancer Center from February 2008 to August 2015 were recruited. The pelvic radiation dosage was 1.8 Gy/day or 2.0 Gy/day, five times every week, and the total dosage was 40-50 Gy. Among 848 patients, 563 patients received radiation six weeks after surgery, of whom 282 received adjuvant radiation alone and 281 received concurrent chemoradiotherapy (weekly cisplatin); other 285 patients received sequential chemoradiotherapy (paclitaxel and cisplatin). Acute adverse events, chronic radiation damage of rectum, and QoL were collected and analyed. The digestive tract symptoms and QoL were evaluated based on EORTC QLQ-C30 questionnaires at one week after surgery (M0), during adjuvant therapy period (M1), and at 12 months and 24 months after the completion of treatments (M12 and M24), respectively. Higher scores in the functional catalog and overall quality of life indicated better quality of life, while higher scores in the symptom catalog indicated severe symptoms and worse QoL. Chronic radiation rectal injury was defined as digestive symptoms that were not improved within three months after radiotherapy. Grading standard of acute adverse events and chronic radiation rectal injury was according to the gastrointestinal part of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE Version 4.0). Results: The mean total radiation dosage of 848 patients was (47.8±4.6) Gy. During adjuvant therapy, the common symptoms of acute intestinal dysfunction were nausea (46.0%, 390/848), vomiting (33.8%, 287/848), constipation (16.3%, 138/848) and abdominal pain (10.3%, 87/848). At M12 and M24, the number of 0 QLQ-C30 questionnaires collected was 346 and 250, respectively. QLQ-C30 questionnaires showed that the scores of nausea or vomiting, appetite decrease, diarrhea, constipation, etc. were improved obviously at M12 or M24 compared with those at M0 or during M1 (all P<0.05). As the extension of the follow-up time, the score of the overall QoL of patients gradually increased [M0: 59.7 (0.0-100.0); M1: 63.1 (0.0-100.0); M12: 75.2 (0.0-100.0); M24: 94.1 (20.0-120.0); H=253.800, P<0.001]. Twelve months after the completion of treatments, the incidence of chronic radiation rectal injury was 9.8% (34/346), mainly presenting as abdominal pain, constipation, stool blood, diarrhea, mostly at level 1 to 2 toxicity (33/34, 97.1%). One patient (0.3%) developed frequent diarrhea (>8 times/d), which was level 3 toxicity. Twenty-four months after all treatments, the incidence of chronic radiation rectal injury was 9.6% (24/250), which was not decreased significantly compared to that in the previous period (χ(2)=0.008, P=0.927). The symotoms of one patient with level 3 toxicity was not relieved. Conclusions: The common symptoms of patients with pelvic maligant tumors during postoperative adjuvant radiotherapy include nausea, vomiting, constipation, abdominal pain and diarrhea. These symptoms are alleviated obviously at 12 and 24 months after adjuvant radiotherapy, and the QoL is significantly improved. However, a few patients may develop chronic radiation rectal injury which is not improved for years or even decades, and deserves attention in clinical practice.

Nonmyeloablative allogeneic stem cell transplantation for nasopharyngeal carcinoma.

We present a case of a patient with metastatic nasopharyngeal carcinoma who failed two lines of palliative combination chemotherapy and was treated with allogeneic nonmyeloablative stem cell transplantation (NST). This patient achieved a durable tumor response, dramatic relief of his symptoms, and elimination of tumor in his bone marrow-an effect likely achieved via a graft-versus-tumor response. Although NST has been explored previously in solid tumors, such as renal cell carcinoma and breast cancer, it has not been widely explored in nasopharyngeal carcinoma. We also present data from a flow cytometric immune analysis and cytokine enzyme-linked immunosorbent assay analysis in the pre- and post-NST period.

Identification and characterization of differentially expressed lncRNA in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental pollutant and also a strong teratogen for cleft palate (CP). But up to now, the underlying molecular mechanisms of TCDD-induced CP are largely unknown. More recently, accumulating evidences are revealing important roles of long noncoding RNAs (lncRNAs) in all kinds of diseases including CP. However, the role and molecular mechanism of lncRNAs in TCDD-induced CP are still largely unexplored. Thus, identification of differentially expressed lncRNA (DEL) might help figuring out the mechanism of CP induced by TCDD. In this study, a CP offspring model of C57BL/6 female mice was generated by TCDD (64 µg/kg body weight) induce on embryo day 10 (E10). The incidence rate of CP was 100% in the TCDD group (105) after cervical dislocation on E16. Then, the high-throughput RNA sequencing (RNA-seq) was established to search a comprehensive profile of the lncRNAs. In addition, a coexpression network of lncRNA and messenger RNA (mRNA) was performed to discern potential mechanism. The result showed that 26,246 novel lncRNAs and 9635 known lncRNAs were screened out, and 413 lncRNA transcripts and 65 mRNA transcripts were identified as being significantly different between the CP group and control group. Notably, we found that there are seven lncRNAs that can target Smad1 and Smad5, which are key molecules of bone morphogenetic protein (BMP) signaling pathway, which suggested that they may be concerned with BMP signaling in TCDD-induced CP. In addition, some lncRNAs targeted the important molecules of Hippo and Wnt signaling pathways. These results suggested that characteristic lncRNA alterations may play a critical role in TCDD-induced CP, which provided a theoretical basis for further research.

Ethnic differences in quality of life and its association with survival in patients with heart failure.

BACKGROUND: Optimizing quality of life (QoL) is a key priority in the management of heart failure (HF). HYPOTHESIS: To investigate ethnic differences in QoL and its association with 1-year survival among patients with HF. METHODS: A prospective nationwide cohort (n = 1070, mean age: 62 years, 24.5% women) of Chinese (62.3%), Malay (26.7%) and Indian (10.9%) ethnicities from Singapore, QoL was assessed using the Minnesota Living with HF Questionnaire (MLHFQ) at baseline and 6 months. Patients were followed for all-cause mortality. RESULTS: At baseline, Chinese had a lower (better) mean MLHFQ total score (29.1 ± 21.6) vs Malays (38.5 ± 23.9) and Indians (41.7 ± 24.5); P < .001. NYHA class was the strongest independent predictor of MLHFQ scores (12.7 increment for class III/IV vs I/II; P < .001). After multivariable adjustment (including NT-proBNP levels, medications), ethnicity remained an independent predictor of QoL (P < .001). Crude 1-year mortality in the overall cohort was 16.5%. A 10-point increase of the physical component (of MLHFQ) was associated with a hazard (HR 1.22, 95% 1.03-1.43) of 1-year mortality (P = .018) in the overall cohort. An interaction between MLHFQ and ethnicity was found (P = .019), where poor MLHFQ score (per 10-point increase) predicted higher adjusted mortality only in Chinese (total score: HR 1.18 [95% CI 1.07-1.30]; physical: HR 1.44 [95% CI 1.17-1.75]; emotional score: HR 1.45 [95% CI 1.05-2.00]). CONCLUSIONS: Ethnicity is an independent determinant of QoL in HF. Despite better baseline QoL in Chinese, QoL was more strongly related to survival in Chinese vs Malays and Indians. These findings have implications for HF trials that use patient-reported outcomes as endpoints.

TNF receptors differentially signal and are differentially expressed and regulated in the human heart.

Tumor necrosis factor (TNF) utilizes two receptors, TNFR1 and 2, to initiate target cell responses. We assessed expression of TNF, TNFRs and downstream kinases in cardiac allografts, and compared TNF responses in heart organ cultures from wild-type ((WT)C57BL/6), TNFR1-knockout ((KO)), TNFR2(KO), TNFR1/2(KO) mice. In nonrejecting human heart TNFR1 was strongly expressed coincidentally with inactive apoptosis signal-regulating kinase-1 (ASK1) in cardiomyocytes (CM) and vascular endothelial cells (VEC). TNFR2 was expressed only in VEC. Low levels of TNF localized to microvessels. Rejecting cardiac allografts showed increased TNF in microvessels, diminished TNFR1, activation of ASK1, upregulated TNFR2 co-expressed with activated endothelial/epithelial tyrosine kinase (Etk), increased apoptosis and cell cycle entry in CM. Neither TNFR was expressed significantly by cardiac fibroblasts. In (WT)C57BL/6 myocardium, TNF activated both ASK1 and Etk, and increased both apoptosis and cell cycle entry. TNF-treated TNFR1(KO) myocardium showed little ASK1 activation and apoptosis but increased Etk activation and cell cycle entry, while TNFR2(KO) myocardium showed little Etk activation and cell cycle entry but increased ASK1 activation and apoptosis. These observations demonstrate independent regulation and differential functions of TNFRs in myocardium, consistent with TNFR1-mediated cell death and TNFR2-mediated repair.

Prevalence and risk factors of ocular trauma in an urban south-east Asian population: the Singapore Malay Eye Study.

PURPOSE: To describe the prevalence and risk factors of ocular trauma in an urban Asian population. METHODS: A population-based survey of 3280 (78.7% response rate) Malay people aged 40-80 years residing in Singapore was conducted in 2004-2006. Interviewer-administered questionnaire was used to ascertain a history of ocular trauma, defined as any eye injury requiring medical attention from a doctor. RESULTS: Of the 3264 participants, 149 (5.0%, 95% confidence intervals [CI] 4.1-6.0%) reported a history of ocular trauma. Of those, 30.2% had trauma from a blunt object, 33.6% from a sharp object, and 22.1% from chemical burns. After adjusting for age and sex, men had a higher prevalence of ocular trauma than women (8.3% vs. 2.1%, age-adjusted odds ratio [OR] 4.7, CI 3.1-7.1), and younger persons had a higher risk of ocular trauma (per year increase in age, OR 0.98, CI 0.96-0.99). Consumption of alcohol was associated with higher likelihood of having ocular injury (OR 4.3, CI 2.2-8.4). CONCLUSIONS: One in 20 persons in this urban south-east Asian population had a history of ocular trauma. Younger persons, men and consumption of alcohol were risk factors for ocular trauma.