Characteristics and outcomes associated with sarcomere mutations in patients with hypertrophic cardiomyopathy: A systematic review and meta-analysis.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an inherited heart disease that can lead to sudden cardiac death. Impact of genetic testing for the prognosis and treatment of patients with HCM needs to be improved. We conducted a systematic review and meta-analysis to investigate the characteristics and outcomes associated with sarcomere genotypes in index patients with HCM. METHODS: A systematic search was conducted in Medline, Embase, and Cochrane Library up to Dec 31, 2023. Data on clinical characteristics, morphological and imaging features, outcomes and interventions were collected from published studies and pooled using a random-effects meta-analysis. RESULTS: A total of 30 studies with 10,825 HCM index patients were included in the pooled analyses. The frequency of sarcomere genes in HCM patients was 40%. Sarcomere mutations were more frequent in women (p < 0.00001), and were associated with lower body mass index (26.1 ±â€¯4.7 versus 27.5 ±â€¯4.3; p = 0.003) and left ventricular ejection fraction (65.7% ±â€¯10.1% vs. 67.1% ±â€¯8.6%; p = 0.03), less apical hypertrophy (6.5% vs. 20.1%; p < 0.0001) and left ventricular outflow tract obstruction (29.1% vs. 33.2%; p = 0.03), greater left atrial volume index (43.6 ±â€¯21.1 ml/m2 vs. 37.3 ±â€¯13.0 ml/m2; p = 0.02). Higher risks of ventricular tachycardia (23.4% vs. 14.1%; p < 0.00001), syncope (18.3% vs. 10.9%; p = 0.01) and heart failure (17.3% vs. 14.6%; p = 0.002) were also associated with sarcomere mutations. CONCLUSIONS: Sarcomere mutations are more frequent in women, and are associated with worse clinical characteristics and poor outcomes.

Associations between blood inflammatory markers and bone mineral density and strength in the femoral neck: findings from the MIDUS II study.

Chronic and systematic inflammation have been related to increased risks of osteopenia and related fracture. However, studies concerning the association between low-grade inflammation and the bone mineral density (BMD) and strength of the femoral neck are still few and inconsistent. This study aimed to examine the relationships between blood inflammatory biomarkers and BMD and femoral neck strength in an adult-based cohort. We retrospectively analyzed a total of 767 participants included in the Midlife in the United States (MIDUS) study. The blood levels of inflammatory markers, including interleukin-6 (IL6), soluble IL-6 receptor, IL-8, IL-10, TNF-α and C-reactive protein (CRP), in these participants were measured, and their associations with the BMD and strength of the femoral neck were determined. We analyzed these 767 subjects with data concerning the BMD, bending strength index (BSI), compressive strength index (CSI), and impact strength index (ISI) in the femoral neck and inflammatory biomarkers. Importantly, our results suggest that strongly negative associations exist between the blood soluble IL6 receptor levels and the BMD (per SD change, Sß = -0.15; P < 0.001), CSI (per SD change, Sß = -0.07; P = 0.039), BSI (per SD change, Sß = -0.07; P = 0.026), and ISI (per SD change, Sß = -0.12; P < 0.001) in the femoral neck after adjusting for age, gender, smoked cigarettes regularly, number of years drinking, BMI and regular exercise. However, the inflammatory biomarkers, including blood IL-6 (per SD change, Sß = 0.00; P = 0.893), IL-8 (per SD change, Sß = -0.00; P = 0.950), IL-10 (per SD change, Sß = -0.01; P = 0.854), TNF-α (per SD change, Sß = 0.04; P = 0.260) and CRP (per SD change, Sß = 0.05; P = 0.137), were not strongly associated with the BMD in the femoral neck under the same conditions. Similarly, there was no significant difference in the relationships between the inflammatory biomarkers (IL-6, IL-8, IL-10, TNF-α and CRP) and the CSI, BSI, and ISI in the femoral neck. Interestingly, in concomitant inflammation-related chronic diseases, only arthritis affected the soluble IL-6 receptor and the CIS (interaction P = 0.030) and SIS (interaction P = 0.050) in the femoral neck. In this cross-sectional analysis, we only observed that high blood levels of soluble IL-6 receptor were strongly associated with reduced BMD and bone strength in the femoral neck. The independent associations between the other inflammatory indicators, including IL-6, IL-8, IL-10, TNF-α and CRP, and the BMD and femoral neck strength in an adult-based cohort were not significant.

Obesity difference on association blood malondialdehyde level and diastolic hypertension in the elderly population: a cross-sectional analysis.

AIMS: Although increased production of malondialdehyde (MDA), an end product of lipid oxidation caused by reactive oxygen species (ROS), has been found be elevated in hypertensive population, whether MDA contributed to a changed risk of hypertension is uncertain. We aimed to investigate whether elevated blood levels of MDA contribute to increased risk of hypertension and obesity has a modified effect on the association in an older Chinese population. METHODS: Data were obtained from 2011 to 2012 of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national cohort of older adults in China. Associations between blood MDA level and systolic and diastolic blood pressure (BP) and risk of hypertension were performed by multivariable linear regression and logistic regression analysis. RESULTS: The results of smooth curve revealed a gradual upward trend on association of blood MDA level with diastolic BP (P < 0.001), but not with systolic BP (P > 0.05). Logistic regression analysis suggested that elevated blood MDA levels were associated with increased risk of diastolic hypertension (OR = 1.079, 95% CI 1.039-1.122, P < 0.001) rather than systolic hypertension (OR = 0.978, 95% CI 0.943-1.015, P = 0.247) after adjustments of related confounding factors were made. Furthermore, we found the significant modification effect of obesity on the association between MDA level and risk of diastolic hypertension evaluated by body mass index (BMI, interaction P = 0.015) and by waist circumference (interaction P = 0.016). CONCLUSION: Our results firstly identified that increased blood MDA levels were associated with elevated risk of diastolic hypertension, rather than systolic hypertension in the non-obese old population.

Whole exome sequencing identifies three novel gene mutations in patients with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis.

BACKGROUND: This study aimed to analyze the genetics and treatments of the patients with the triad of diabetic ketoacidosis (DKA), hypertriglyceridemia, and acute pancreatitis (AP). METHODS: We conducted a retrospective study of six patients with the triad of AP, hypertriglyceridemia, and DKA at our hospital. All patients underwent plasmapheresis as part of their treatment. The clinical characteristics of the patients were obtained from the hospital information system and analyzed. Whole exome sequencing was performed using samples of one patient (case 6) and his family members. RESULTS: The average triglyceride level before plasmapheresis was 3282.17 ± 2975.43 mg/dL (range: 1646-9332 mg/dL). The triglyceride levels dropped by approximately 80% after plasmapheresis. None of the patients developed complications related from plasmapheresis. During follow-up, patients 5 and 6 developed recurrent pancreatitis for several times and showed the formation of pancreatic pseudocysts. We identified three novel heterozygous missense mutations in the family of patient 6, including c.12614C > T (p.Pro4205Leu) in APOB, c.160G > C (p.Glu54Gln) in CILP2, and c.1199C > A (p.Ala400Glu) in PEPD. CONCLUSIONS: Three novel heterozygous missense mutations, including c.12614C > T (p.Pro4205Leu) in APOB, c.160G > C (p.Glu54Gln) in CILP2, and c.1199C > A (p.Ala400Glu) in PEPD were first identified in a patient with the triad of DKA, hypertriglyceridemia, and AP. The combination of plasmapheresis, hydration, and insulin therapy may have the greatest clinical benefits for these patients.

The relationship between Long Noncoding RNA (lncRNA) Small Nucleolar RNA Host Gene 12 (SNHG12) expression in solid malignant tumors and prognosis of tumor patients: A systematic review and meta-analysis.

BACKGROUND: Small nucleolar RNA host gene 12 (SNHG12) has been demonstrated to be a long noncoding RNA (lncRNA) that facilitates the progression of several solid malignant tumors. However, whether the expression level of SNHG12 in solid malignant tumors is associated with patients prognosis have not been investigated. METHODS: We systematically searched PubMed, EMBASE and Cochrane Library from Jan 1, 1950 to Mar 24, 2020 for randomized controlled trials published in English on SNHG12 expression in solid malignant tumors. We used the Newcastle-Ottawa Scale to assess the quality of articles. The HRs and 95%CI that extracted from Kaplan-Meier curves were used to perform the forest plot using a fixed-effects model. The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Thirteen articles containing 821 patients were included in this systematic review and meta-analysis. The result showed that high lncRNA SNHG12 expression is significantly associated with poor overall survival (OS) (HR = 1.94, 95% CI: 1.56-2.41, P < .001) and the studies are lack of statistically significant heterogeneity (P= .878, I = 0.0%). Beggs plot and Eggers test were applied to testify no publication bias existence in these studies. Subgroup analyses were performed and the result showed that TNM stage, lymph node metastasis and tumor type can influence the patients outcome, while there was no significantly correlation between SNHG12 expression and gender. CONCLUSIONS: The systematical review and meta-analysis synthetically analyzed 13 articles including 821 patients with ten types of solid malignant tumors, concluding that higher lncRNA SNHG12 expression is significantly associated with worse clinical prognosis.

Autonomous drone hunter operating by deep learning and all-onboard computations in GPS-denied environments.

This paper proposes a UAV platform that autonomously detects, hunts, and takes down other small UAVs in GPS-denied environments. The platform detects, tracks, and follows another drone within its sensor range using a pre-trained machine learning model. We collect and generate a 58,647-image dataset and use it to train a Tiny YOLO detection algorithm. This algorithm combined with a simple visual-servoing approach was validated on a physical platform. Our platform was able to successfully track and follow a target drone at an estimated speed of 1.5 m/s. Performance was limited by the detection algorithm's 77% accuracy in cluttered environments and the frame rate of eight frames per second along with the field of view of the camera.

The Ubiquitin-like Protein FAT10 Stabilizes eEF1A1 Expression to Promote Tumor Proliferation in a Complex Manner.

Human HLA-F adjacent transcript 10 (FAT10) is the only ubiquitin-like protein that can directly target substrates for degradation by proteasomes, but it can also stabilize the expression of certain substrates by antagonizing ubiquitination, through mechanisms as yet uncharacterized. In this study, we show how FAT10 stabilizes the translation elongation factor eEF1A1, which contributes to cancer cell proliferation. FAT10 overexpression increased expression of eEF1A1, which was sufficient to promote proliferation of cancer cells. Mechanistic investigations revealed that FAT10 competed with ubiquitin (Ub) for binding to the same lysines on eEF1A1 to form either FAT10-eEF1A1 or Ub-eEF1A1 complexes, respectively, such that FAT10 overexpression decreased Ub-eEF1A1 levels and increased FAT10-eEF1A1 levels. Overall, our work establishes a novel mechanism through which FAT10 stabilizes its substrates, advancing understanding of the biological function of FAT10 and its role in cancer. Cancer Res; 76(16); 4897-907. ©2016 AACR.

[Meta-analysis of pylorus-preserving pancreaticoduodenectomy in the treatment of periampullary adenocarcinoma].

OBJECTIVE: To evaluate the efficacy and safety of pylorus-preserving pancreatico-duodenectomy(PPPD) in the treatment of periampullary adenocarcinoma by using Meta-analysis. METHODS: From January 1, 1980 to November 8, 2013, the articles of randomized controlled trials (RCTs) about PPPD versus PD in the treatment of periampullary adenocarcinoma were collected from Cochrane Libriary, Embase, PubMed, Ovid, Web of science and CBM etc. The methodological quality of the included studies was evaluated according to Cochrane system review valuator handbook of risk of bias standards. Meta-analysis was performed by RevMan 5.2 software. RESULTS: Seven RCTs were enrolled in the meta-analysis. Compared to PD group, PPPD group was associated with significantly less intraoperative blood loss (MD=-200.10, 95% CI:-400.66 to 0.46, P=0.05), shorter operation time (MD=-46.55, 95% CI:-91.02 to -2.07, P=0.04), and less postoperative blood transfusion (MD=-0.89, 95% CI:-1.59 to -0.19, P=0.01). There were no significant differences between the PPPD and PD group in pancreatic fistula, biliary fistula, intestinal fistula, abdominal abscess, postoperative bleeding, wound infection, relaparotomy, mortality and survival rate(all P>0.05). CONCLUSIONS: PPPD in the treatment of the periampullary adenocarcinoma is safe and effective with similar survival of PD surgery. PPPD can reduce operative time, intraoperative blood loss, transfusion and does not increase the surgery complications as compared to PD.

Overexpression of HOXB9 promotes metastasis and indicates poor prognosis in colon cancer.

OBJECTIVE: Homeobox B9 (HOXB9) is proposed to be involved in tumor angiogenesis and metastasis. We investigated the role of HOXB9 in the progression of colon cancer. METHODS: HOXB9 expression was investigated by immunohistochemically and Western blotting in 128 colon cancer patients and the results were analyzed statistically associated with clinicopathological data and survival of the patients. The effect of HOXB9 on cell invasion and metastases abilities were analyzed in vitro and in vivo. RESULTS: HOXB9 is overexpressed in colon cancer tissues and significantly correlated with metastasis and poor survival of patients (P<0.05, respectively). Additionally, high levels of expression of HOXB9 were observed in metastatic lymph nodes. The down-regulation of HOXB9 expression can inhibit the migration and invasive ability of colon cancer cells, while exogenous expression of HOXB9 in colon cancer cells enhanced cell migration and invasiveness. Moreover, stable knockdown of HOXB9 reduced the liver and lung metastasis of colon cancer in vivo. CONCLUSIONS: HOXB9 may play an important role in the invasion and metastasis of colon cancer cells and may be a useful biomarker for metastasis and prognostic of colon cancer.

[Effects of two surgical techniques for vocal cord cyst].

OBJECTIVE: To compare the effectiveness of vocal cord cyst excision with electronic laryngoscope (EL) and self-retaining laryngoscope (SRM). METHOD: Nightly-two patients, diagnosed as vocal cord cyst with strobolaryngoscope or electronic laryngoscope, were randomly divided into two groups. One group was 48 cases treated with electronic laryngoscope and another group was 44 cases treated with self-retaining laryngoscope. Electronic laryngoscopy examination and voice function assessments were performed to all patients, preoperatively and postoperatively at one week, three months and six months. RESULT: One failed cases under SRM, difficult exposure of glottic portion, were treated under EL. The recurrence rate of the two groups was of no statistical significance in three months after operation. Voice function assessment of the two groups was of no statistical significance at one week, three months and six months after operation. CONCLUSION: The operation under electronic laryngoscope is a minimal invasive procedure to the laryngeal mucosa. Electronic laryngoscope had advantages such as clear view, accurate operation. Furthermore, it can be used for those that could not be treated under self-retaining laryngoscope.

[Glottic measurement and vocal evaluation after three surgical techniques in the treatment of bilateral vocal cord paralysis].

OBJECTIVE: To evaluate postoperative glottic area and vocal quality of three various surgical techniques for treating bilateral vocal cord paralysis, including laser arytenoidectomy (Group A, 24 cases), reinnervation of the posterior cricoarytenoid muscle by phrenic nerve (Group B, 9 cases) and arytenoidectomy accompanying lateral cordopexy by extralaryngeal approach (Woodman's procedure, Group C, 13 cases). METHODS: 46 cases suffered from bilateral recurrent laryngeal nerve injury were included in our study. The pre-postoperative glottic measurement and vocal acoustic parameters were analyzed. RESULTS: The decannulated cases in group A and group B and group C were 22, 8, 13 respectively. The post-operative mean maximal glottic area was (47.2 +/- 7.4) mm2, (78.3 +/- 16.0) mm2, (48.1 +/- 6.5) mm2 respectively. Group B cases glottic area was larger than that of group A and group C (t value were 4.46 and 3.85, P value were 0.000 and 0.001). No significant difference was found between group A and group C (t = 1.68, P = 0.101). After surgery, in group A, 17 cases voice quality was the same compared with that of before surgery, and 7 cases voice quality had become worse; In group B, the voice quality had become better in 5 cases, completely recovered in 1 case, and had not change in 3 cases; In group C, the voice quality had become deteriorated in 10 cases and no change in 3 cases. And in group B, ipsilateral diaphragm paralysis in 9 cases after surgery, whose vital capacity and forced vital capacity had decreased to 72%-84%, 76%-84% of that before the surgery respectively; and the diaphragm mobility had recovered by 35%-76% respectively, while vital capacity and forced vital capacity had become 93%-97%, 91%-98% of that before the surgery. In Group B, all cases' pulmonary function was normal half a year postoperatively. CONCLUSIONS: Reinnervation of the posterior cricoarytenoid muscle by phrenic nerve seems to be best procedure with better post-operative voice and larger glottic area. Although the sufficient airway for decannulation can be acquired in Group A and Group C, but most of patients in Group A had pre-operative vocal level and badly abnormal in Group C.

[Intratumor bleomycin-A5 injection under electrolaryngoscope for treatment of large laryngopharyngeal and laryngeal hemangioma].

OBJECTIVE: To study the therapeutic effect of bleomycin-A5 injection under eletrolaryngoscope for treatment of large laryngopharyngeal and laryngeal hemangioma. METHODS: Intratumor bleomycin-A5 injection under eletrolaryngoscope was performed in 18 cases of large laryngopharyngeal and laryngeal hemangioma with surface anaesthesia, for totally 7 to 14 (mean 10.2) injections in each case. RESULTS: Twelve patients were cured and 6 showed obvious improvement. Follow-up of the patients for over one year found no recurrence of the hemangioma. CONCLUSION: Bleomycin-A5 injection is a minimal invasive procedure for treatment of large laryngopharyngeal and laryngeal hemangioma, causing less pain and better preserving the laryngeal function without the necessity of tracheotomy.