Clinical efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for pelvic organ prolapse.

OBJECTIVE: The aim of this study was to analyze the clinical efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for pelvic organ prolapse (POP). PATIENTS AND METHODS: Sixty POP patients admitted to our hospital from January 2020 to December 2021 were picked and divided into Group A (laparoscopic Y-mesh, n = 20), Group B (laparoscopic sacrovaginal fixation, n = 20), and Group C (da Vinci robotic sacral fixation, n = 20). These three groups were compared in terms of the perioperative indexes, such as operation time, intraoperative blood loss, postoperative indwelling catheter days, anal exhaust time, postoperative hospitalization days, etc. The occurrence of short-term and long-term complications in the three groups was compared. The changes of the following index values in the POP quantification system (POP -Q) staging before and 1 year after surgery were recorded and compared among the three groups. It mainly includes the midline of the anterior vaginal wall at 3 cm from the hymenal margin (Aa), the farthest point of the anterior vaginal vault from point Aa (Ba), the farthest point of the ectocervix (C), the location of the posterior vaginal vault or rectal uterine trap (D), the midline of the posterior vaginal wall at 3 cm from the hymenal margin (Ap), and the reflection of the posterior vaginal vault at the farthest point from the Ap point (Bp) values. The changes in Pelvic Floor Distress Inventory-Short Form 20 (PFDI-20) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) were recorded and compared before and 1 year after the operation. RESULTS: The patients in Group C had significantly lower intraoperative bleeding, postoperative indwelling catheter days, anal exhaust time, and postoperative hospitalization days compared with those in Group A and Group B (p < 0.05). There existed no statistical difference in the incidence of short-term and long-term complications between Group B and Group C (p > 0.05), but both were much lower than Group A (p < 0.05). The differences in POP-Q staging, PFDI-20 scale, and PISQ-12 scale were not statistically significant among the three groups before surgery (p > 0.05), and the POP-Q staging Aa, Ba, C, D, Ap, and Bp values, PFDI-20 scale, and PISQ-12 scale were strongly improved in three groups after the surgery (p < 0.05). However, the POP-Q staging, PFDI-20 scale, and PISQ-12 scale among the three groups had no obvious difference after the surgery (p > 0.05). CONCLUSIONS: The efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for POP was comparable to that of laparoscopic Y-mesh treatment and laparoscopic sacral vaginal fixation. However, da Vinci's robotic sacral fixation had the advantages of less intraoperative bleeding and faster postoperative recovery, which helped patients recover quickly and improved their quality of life.

Hysterectomy and risk of osteoarthritis in women: a nationwide nested case-control study.

OBJECTIVE: Hysterectomy is the most common gynaecological surgery, performed mainly for benign uterine pathologies in women. Studies have suggested that hysterectomy is associated with osteoarthritis (OA); however, the association remains controversial. This study aimed to investigate the association between hysterectomy and the risk of OA. METHOD: We performed a population-based nested case-control study using the National Health Insurance programme database from 2000 to 2016 in Taiwan. All medical conditions for each case and control were categorized using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10. A multiple conditional logistic regression model was applied to analyse the adjusted odds ratio (aOR) and 95% confidence interval (CI) for the association between hysterectomy and OA. RESULTS: Our analyses included 16 592 patients with OA and 66 368 matched controls. After adjustment for possible confounders, hysterectomy had a significant association with OA (aOR = 1.19, 95% CI = 1.09-1.30), especially knee OA (aOR = 1.25, 95% CI = 1.13-1.38). Furthermore, women who received oestrogen therapy (ET) alone and patients who underwent hysterectomy without ET showed a greater risk of OA development compared to women who did not receive ET (aOR = 1.14, 95% CI = 1.07-1.23, and aOR = 1.19, 95% CI = 1.08-1.31, respectively). CONCLUSION: Our findings indicate that hysterectomy is associated with OA, especially knee OA. We also found that women who received ET alone and patients who underwent hysterectomy without ET had an increased risk of OA.

Risk factors and psychological condition of pruritus in type 2 diabetes mellitus: a retrospective, propensity score-matched study.

OBJECTIVE: Our aim is to characterize patients with pruritus in type 2 diabetes, determine independent risk factors and explore the impact of the psychological condition of these patients. MATERIALS AND METHODS: This is a retrospective study. From October 1, 2020, to September 30, 2021, 944 individuals with T2DM who had medical treatment were identified from the database. Electronic medical record information including patient characteristics, complications, laboratory data, and medication usage was obtained from the database. Propensity score matching, univariate analysis and a multivariable logistic regression model were used in this study. Based on observation, we discussed the psychological impact of pruritus on these patients. RESULTS: There were 97 patients with T2DM who suffered from pruritus. After propensity score matching based on age, gender, and family history of diabetes etc., 97 pairs of subjects were matched. 97 patients were categorized as the Pruritus group and 97 patients as the Non-pruritus group. In univariate analysis, there were 5 variables significantly related to pruritus, including BMI, absolute eosinophils, percentage of eosinophils, diabetic kidney disease, diabetic retinopathy. After multivariable logistic regression, BMI (OR 1.094, 95%CI 1.010-1.185) and diabetic retinopathy (OR 2.440, 95%CI 1.229-4.847) were considered significant. Patients with pruritus in T2DM suffer greatly in psychological condition in many ways. CONCLUSIONS: For patients with pruritus complicated by T2DM, BMI and diabetic retinopathy may be independent risk factors. Mental health problems such as anxiety and depression might exacerbate by pruritus. The intimate partner relationship was also challenged due to the restless sleep caused by their partner. Frequent monitoring of BMI and diabetic retinopathy and psychological assessment may be warranted in these patients.

Evaluation of DNA methylation in matched oral swab and tissue specimens from Chinese patients with oral squamous cell carcinoma.

The DNA methylation statuses of the paired box 1 (PAX1) and zinc finger protein 582 (ZNF582) genes have shown promise in the detection of oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the ability of PAX1 and ZNF582 methylation to distinguish OSCC and the adjacent normal tissue among cancer patients. This study included 67 patients with OSCC. The methylation levels of these two genes were analysed in tissue specimens (lesion site and adjacent normal site) and in oral swabs (lesion site and contralateral normal site). Levels of DNA methylation were higher at lesion sites than at the corresponding normal sites. According to receiver operating characteristics curve analysis, the area under the curve for PAX1 and ZNF582 methylation ranged from 0.73 to 0.82. No significant difference was observed between tissue specimens and oral swabs (PAX1, P= 0.41; ZNF582, P=0.28). For the oral swab, PAX1 methylation was more pronounced in bone invasion (Z=1.988, P= 0.047), and ZNF582 methylation was more pronounced in early-stage (Z=2.354, P= 0.02) and well-differentiated tumours (Z=3.731, P= 0.0002). Hypermethylated PAX1 and ZNF582 are effective biomarkers to distinguish lesion sites and corresponding normal sites in tissue specimens and oral swabs from OSCC patients.

Is chronic obstructive pulmonary disease an independent predictor for adverse outcomes in coronavirus disease 2019 patients?

OBJECTIVE: This study aimed to investigate whether pre-existing chronic obstructive pulmonary disease (COPD) was an independent predictor for adverse outcomes in coronavirus disease 2019 (COVID-19) patients. MATERIALS AND METHODS: We searched electronic databases, including PubMed, Web of Science, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) to screen for eligible articles. A quantitative meta-analysis was performed on the basis of adjusted effect estimates. RESULTS: We observed that COPD was significantly associated with an increased risk of adverse outcomes in COVID-19 patients, which is based on 18 studies with 26,075 cases reporting adjusted effect estimates (pooled effect = 1.53, 95% confidence interval (CI): 1.29-1.8; I2 = 35.4%, random-effects model). CONCLUSIONS: We found that pre-existing COPD was an independent risk factor for predicting the adverse outcomes in COVID-19 patients.

D-dimer is associated with the risk of mortality in Coronavirus Disease 2019 patients.

This study aims to investigate the association between D-dimer and the risk of mortality in coronavirus disease 2019 (COVID-19) patients using a meta-analysis. We found that the D-dimer levels in non-survival patients were significantly higher than those in survival patients (SMD = 0.91, 95% CI = 0.79 to 1.03). In conclusion, the elevated D-dimer levels were associated with an increased risk of mortality in COVID-19 patients.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

Experimental study on synergistic effect of HIFU treatment of tumors using Bifidobacterium bound with cationic phase-change nanoparticles.

OBJECTIVE: Anaerobic bacteria can enter the solid tumor in the hypoxic region to colonize and proliferate. Aggregation of nanoparticles in the tumor area can enhance molecular imaging and therapy. It is hypothesized that the combination of the two could possibly achieve better imaging and tumor treatment. This study presents a biocompatible bacteria-based system that can deliver cationic phase-change nanoparticles (CPNs) into solid tumor to achieve enhanced imaging and treatment integration. MATERIALS AND METHODS: Cationic phase-change nanoparticles (CPNs) and Bifidobacterium longum (BF) were mixed to determine the best binding rate and were placed in an agar phantom for ultrasonography. BF-CPNs complex adhesion to breast cancer cells was observed by laser confocal microscopy. In vivo, BF-CPNs and control groups were injected into tumors in breast cancer nude mouse models. Nanoparticles distribution was observed by ultrasound and in vivo fluorescence imaging. HIFU ablation was performed after injection. Gross and histological changes were compared and synergy was evaluated. RESULTS: Bifidobacterium longum (BF) and CPNs were combined by electrostatic adsorption. The BF-CPNs particles could increase the deposition of energy after liquid-gas phase-change during High Intensity Focused Ultrasound (HIFU) irradiation of tumor. CONCLUSIONS: This study shows a valid method in diagnosis and therapy integration for providing stronger imaging, longer retention time, and more effective tumor treatment.

Outcome of patients with chlorpyrifos intoxication.

INTRODUCTION: There is a paucity of literature analyzing outcome of chlorpyrifos intoxication. METHODS: A total of 40 patients with chlorpyrifos intoxication were seen at Chang Gung Memorial Hospital between 2008 and 2017. Patients were stratified into two subgroups according to their prognosis, as good (n = 12) or poor (n = 28). Good prognosis group were defined as patients who survived without serious complications, and poor prognosis group included patients who died and survived after development of severe complications. Demographic, clinical, laboratory, and mortality data were obtained for analysis. RESULTS: Patients aged 53.8 ± 16.3 years and most were male (80.0%). All patients (100.0%) developed acute cholinergic crisis such as emesis (45.0%), respiratory failure (42.5%), tachycardia (30.0%), kidney injury (22.5%), and seizure (7.5%). Intermediate syndrome developed in 12.5% of patients, but none had delayed neuropathy (0%). The poor prognosis group suffered higher incidences of respiratory failure (p = 0.011), kidney injury (p = 0.026), and prolonged corrected QT interval (p = 0.000), and they had higher blood urea nitrogen level (p = 0.041), lower Glasgow coma scale score (p = 0.011), and lower monocyte count (p = 0.023) than good prognosis group. All patients were treated with atropine and pralidoxime therapy, but six patients (15.0%) still died of intoxication. In a multivariate logistic regression model, blood urea nitrogen was a significant risk factor for poor prognosis (odds ratio: 1.375, 95% confidence interval: 1.001-1.889, p = 0.049). Nevertheless, no mortality risk factor could be identified. CONCLUSION: The mortality rate of patients with chlorpyrifos intoxication was 15.0%. Furthermore, acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 12.5%, and 0% of patients, respectively.

A common variant rs2272804 in the 5'UTR of RIBC2 inhibits downstream gene expression by creating an upstream open reading frame.

OBJECTIVE: The RIB43A domain with coiled-coils 2 (RIBC2) encodes an uncharacterized vertebrate protein exhibiting similarity with Chlamydomonas protofilament ribbon proteins, required for ciliary motility. To date, no functional variants capable of triggering a change in the expression of RIBC2 have been reported. PATIENTS AND METHODS: The genotypes of rs2272804 in 30 individuals were identified with Sanger sequencing to estimate allele frequencies. Dual-Luciferase and mutagenesis assays were carried out to investigate the impact of rs2272804 on transcriptional and translational levels. The microarray data of 7 types of cancer were obtained from the Gene Expression Omnibus (GEO) to explore the role of rs2272804 in those diseases. RESULTS: In this study, we identified a common variant in the 5'UTR of RIBC2, rs2272804, which can create an upstream open reading frame (uORF) in the 5'UTR significantly inhibiting the expression of its host gene. Using Dual-Luciferase constructs, we found that this variant leads to an 85% reduction in translational efficiency, but only a 20% decrease was observed at the transcriptional level. In terms of population studies, mRNA levels of RIBC2 varied according to their rs2272804 genotypes. The "A" allele homozygotes, which created a uORF, showed the lowest transcriptional levels while the transcriptional activity of the "C" allele homozygotes without an uORF was the highest, consistent with the in-vitro studies. Furthermore, we explored its role in 7 types of cancer and identified RIBC2 as a significantly differentially expressed gene (DEG) in breast cancer (BRCA), ovarian serous cystadenocarcinoma (OV), and kidney renal clear cell carcinoma (KIRC). Finally, we showed that the overexpression of RIBC2 enhanced the expression of TRIM37 and down-regulated TRAF2. TRIM37 is a member of the tripartite motif (TRIM) family involved in developmental patterning and oncogenesis while TRAF2 is associated with the signal transduction from members of the TNF receptor superfamily. CONCLUSIONS: Our reports identified a common variant that exerts a dramatic impact on expression efficiency and provides further functional insight into RIBC2.

Diagnostic value of ultrasound elastography for differentiation of benign and malignant axillary lymph nodes: a meta-analysis.

AIM: To investigate the diagnostic value of ultrasound elastography (UE) for benign and malignant axillary lymph nodes. MATERIALS AND METHODS: A literature search was conducted from PubMed, Cochrane EMBASE, and Medline. Fourteen studies including 1,186 patients with 1,411 lymph nodes were enrolled. Overall, diagnostic descriptive statistics included pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) with corresponding 95% confidence intervals (95% CIs) were generated by random effect model. Subgroup analyses were performed in (real-time elastography [RTE] versus shear wave elastography [SWE]) and (conventional ultrasound versus combination of traditional ultrasound and elastography). Meta-regression was used to explore potential sources of heterogeneity. RESULTS: The overall pooled sensitivity, specificity, and AUC of UE was 0.79 (95% CI: 0.71-0.86), 0.90 (95% CI: 0.83-0.95), and 0.91 (95% CI: 0.88-0.93), respectively. In the subgroup analysis of the two UE techniques, the pooled sensitivity, specificity, and AUC of SWE was higher than that of RTE (sensitivity: 0.82>0.77; specificity: 0.91>0.89; AUC: 0.94>0.89). The pooled diagnostic value of ultrasound combined with UE were significantly improving compared with traditional ultrasound (sensitivity: 0.87>0.82, specificity: 0.83>0.78, and AUC: 0.91>0.87). No independent heterogeneous factor was found in meta-regression. CONCLUSION: The results indicate that UE was an effective technique for identifying malignant axillary lymph nodes due to its high diagnostic efficiency, which can provide useful information for surgical procedure selection.

Long non-coding RNA FTX alleviates hypoxia/reoxygenation-induced cardiomyocyte injury via miR-410-3p/Fmr1 axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) are involved in the development of myocardial ischemia/reperfusion (I/R) injury. In this study, we aimed to investigate the roles and underlying mechanisms of five prime to Xist (FTX) in myocardial I/R injury using cardiomyocyte hypoxia/reoxygenation (H/R) model. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine the expression of FTX, microRNA-410-3p (miR-410-3p) and fragile X mental retardation 1 (Fmr1) mRNA. Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis were employed to evaluate cell proliferation and apoptosis, respectively. Western blot assay was conducted to examine the protein levels of apoptosis-associated factors and Fmr1. Specific kits were used to detect the levels of oxidative stress-associated factors. Dual-luciferase reporter assay was performed to verify the association between miR-410-3p and FTX or Fmr1. RESULTS: FTX was reduced in myocardial I/R injury patients' serum and H/R-stimulated H9c2 cells. FTX overexpression relieved cell damage caused by H/R treatment through inducing cell proliferation and repressing cell apoptosis and oxidative stress in H9c2 cells. FTX was a sponge for miR-410-3p and the impact of FTX overexpression on H/R-induced cell injury was abolished by miR-410-3p elevation in H9c2 cells. Fmr1 was identified as a target of miR-410-3p and Fmr1 knockdown reversed the effect on H/R-induced cell damage mediated by miR-410-3p inhibition in H9c2 cells. Moreover, FTX positively regulated Fmr1 expression through sponging miR-410-3p in H9c2 cells. CONCLUSIONS: FTX regulated H/R-induced cardiomyocyte damage by upregulating Fmr1 via sponging miR-410-3p.

Changes in cellular Ca2+ and Na+ regulation during the progression towards heart failure in the guinea pig.

KEY POINTS: During compensated hypertrophy in vivo fractional shortening (FS) remains constant until heart failure (HF) develops, when FS decreases from 70% to 39%. Compensated hypertrophy is accompanied by an increase in INa,late and a decrease in Na+ ,K+ -ATPase current. These changes persist as HF develops. SR Ca2+ content increases during compensated hypertrophy then decreases in HF. In healthy cells, increases in SR Ca2+ content and Ca2+ transients can be achieved by the same amount of inhibition of the Na+ ,K+ -ATPase as measured in the diseased cells. SERCA function remains constant during compensated hypertrophy then decreases in HF, when there is also an increase in spark frequency and spark-mediated Ca2+ leak. We suggest an increase in INa,late and a decrease in Na+ ,K+ -ATPase current and function alters the balance of Ca2+ flux mediated by the Na+ /Ca2+ exchange that limits early contractile impairment. ABSTRACT: We followed changes in cardiac myocyte Ca2+ and Na+ regulation from the formation of compensated hypertrophy (CH) until signs of heart failure (HF) are apparent using a trans-aortic pressure overload (TAC) model. In this model, in vivo fractional shortening (FS) remained constant despite HW:BW ratio increasing by 39% (CH) until HF developed 150 days post-TAC when FS decreased from 70% to 39%. Using live and fixed fluorescence imaging and electrophysiological techniques, we found an increase in INa,late from -0.34 to -0.59 A F-1 and a decrease in Na+ ,K+ -ATPase current from 1.09 A F-1 to 0.54 A F-1 during CH. These changes persisted as HF developed (INa,late increased to -0.82 A F-1 and Na+ ,K+ -ATPase current decreased to 0.51 A F-1 ). Sarcoplasmic reticulum (SR) Ca2+ content increased during CH then decreased in HF (from 32 to 15 µm l-1 ) potentially supporting the maintenance of FS in the whole heart and Ca2+ transients in single myocytes during the former stage. We showed using glycoside blockade in healthy myocytes that increases in SR Ca2+ content and Ca2+ transients can be driven by the same amount of inhibition of the Na+ ,K+ -ATPase as measured in the diseased cells. SERCA function remains constant in CH but decreases (τ for SERCA-mediated Ca2+ removal changed from 6.3 to 3.0 s-1 ) in HF. In HF there was an increase in spark frequency and spark-mediated Ca2+ leak. We suggest an increase in INa,late and a decrease in Na+ ,K+ -ATPase current and function alters the balance of Ca2+ flux mediated by the Na+ /Ca2+ exchange that limits early contractile impairment.

CircRNA UBAP2 promotes the progression of ovarian cancer by sponging microRNA-144.

OBJECTIVE: This study aims to elucidate the regulatory effect of circular RNA UBAP2 (circUBAP2) on the progression of ovarian cancer (OC). PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expressions of circUBAP2, microRNA-144 and CHD2 in OC tissues and adjacent normal tissues. The correlation between the expression levels of circUBAP2 and microRNA-144 with pathological parameters of OC patients was analyzed. Subcellular distribution of circUBAP2 was detected by chromatin fractionation assay. After overexpression of circUBAP2 in OC cells, changes in proliferative and migratory abilities were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. In addition, the Dual-Luciferase reporter gene assay was used to verify the binding of circUBAP2 and microRNA-144, and the binding of CHD2 to microRNA-144. RESULTS: QRT-PCR results showed that circUBAP2 was highly expressed in OC tissues, and its expression was negatively correlated with TMN stage and five-year survival of OC patients. CircUBAP2 was mainly distributed in the cytoplasm. Overexpression of circUBAP2 significantly promoted the proliferative and migratory abilities of OC cells. The Dual-Luciferase reporter gene assay demonstrated that circUBAP2 could bind to microRNA-144. Meanwhile, circUBAP2 negatively regulated microRNA-144 expression in OC cells. Besides, the promotive effects of circUBAP2 on the proliferation and migration of OC cells were reversed by microRNA-144 overexpression. MicroRNA-144 was lowly expressed in OC tissues, which was negatively correlated with TNM stage of OC patients. The Dual-Luciferase reporter gene assay confirmed the binding condition between CHD2 and microRNA-144. CHD2 expression was negatively regulated by microRNA-144 in OC cells. Moreover, CHD2 could bind to microRNA-144 and partially inhibited its activity, thereby promoting the proliferative and migratory abilities of OC cells. CONCLUSIONS: CircUBAP2 promotes the progression of ovarian cancer by adsorbing microRNA-144.

Long noncoding RNA LSINCT5 is upregulated and promotes the progression of esophageal squamous cell carcinoma.

OBJECTIVE: Long stress-induced noncoding transcripts 5 (LSINCT5) has been reported to be upregulated in several human cancers and related to poor prognosis. However, its involvement in esophageal squamous cell carcinoma (ESCC) remains largely unknown. We aim to evaluate the expression and putative role of LSINCT5 on the progression of ESCC. MATERIALS AND METHODS: LSINCT5 expression was first examined in the ESCC cell lines using RT-qPCR, and the next-generation RNA-Seq technology was employed to analyze and functionally annotate the differential gene expression before and after LSINCT5 knockdown in ESCC was made. Based on the functional annotation results, the effects of LSINCT5 knockdown on cell growth, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were assessed in the ESCC cell lines. Finally, the expression and clinicopathological significance of LSINCT5 in ESCC and corresponding nontumor tissues were further explored using RT-qPCR. RESULTS: The RT-qPCR results showed that LSINCT5 expression was significantly upregulated in the ESCC cell lines. The differential gene expression analysis by next-generation RNA-Seq showed that 138 genes were up-regulated, and 227 genes were downregulated after LSINCT5 was knocked down in the ECA 109 cells. In addition, the functional annotation revealed that the differentially expressed genes were mainly functionally involved in tight junctions, ECM-receptor interactions, and MAPK signaling pathway. Further in vitro studies indicated that the knockdown of LSINCT5 significantly suppressed proliferation, migration, invasion, and EMT in ESCC cells. Finally, a comparative study of paired ESCC and corresponding nontumor tissues showed that LSINCT5 was upregulated in the ESCC tissues, and the increased LSINCT5 expression was related to late clinical stages, large tumor sizes, and lymph node metastasis. CONCLUSIONS: The results indicate that LSINCT5 is upregulated in ESCC and may act as an oncogene promoting the progression of ESCC.

The HINTEGRA total ankle arthroplasty: functional outcomes and implant survivorship in 210 osteoarthritic ankles at a mean of 6.4 years.

AIMS: The purpose of this study was to determine the functional outcome and implant survivorship of mobile-bearing total ankle arthroplasty (TAA) performed by a single surgeon. PATIENTS AND METHODS: We reviewed 205 consecutive patients (210 ankles) who had undergone mobile-bearing TAA (205 patients) for osteoarthritis of the ankle between January 2005 and December 2015. Their mean follow-up was 6.4 years (2.0 to 13.4). Functional outcome was assessed using the Ankle Osteoarthritis Scale, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, 36-Item Short-Form Health Survey (SF-36) score, visual analogue scale, and range of movement. Implant survivorship and complications were also evaluated. RESULTS: There were significant improvements in all functional outcome categories between the preoperative and final follow-up assessments (p < 0.001). Patients showed marked improvement in clinical outcomes in terms of pain, function, and quality of life. The overall implant survivorship was 91.7% at a mean follow-up of 6.4 years. In all, 33 major complications were identified with a 15.7% rate, resulting in 12 prosthesis failures (5.7%). Periprosthetic osteolysis (19 cases; 9.0%) was the most frequent complication. CONCLUSION: Mobile-bearing TAA resulted in improved functional outcomes, a low major complication rate, and excellent implant survivorship at a mean follow-up of 6.4 years. Cite this article: Bone Joint J 2019;101-B:695-701.

Effect of microRNA-409 on the pathogenesis of polycystic ovary syndrome.

OBJECTIVE: To explore the expression level of microRNA-409 in PCOS (polycystic ovary syndrome) rats, as well as its potential effects on fertility of PCOS rats and phenotypes of offspring rats. MATERIALS AND METHODS: PCOS model in rats was established by Letasazole administration. Follicular development of rats was evaluated by the percentages of the cystic follicle (FC) and corpus luteum (CL) of all follicles. The enzyme-linked immunosorbent assay (ELISA) was conducted to detect serum levels of hormones in rats, including LH, LH/FSH, T, INS, FSH, and E2. Subsequently, PCOS rats received a subcapsular injection of microRNA-409 mimics. The expression level of microRNA-409 in ovary was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Serum levels of LH, LH/FSH, T, INS, FSH, and E2 in PCOS rats with microRNA-409 overexpression were accessed by enzyme-linked immunosorbent assay (ELISA) as well. PCOS rats were mated with male rats for recording pregnancy rate. At 6-week-old of offspring, they were sacrificed for detecting microRNA-409 level, percentages of FC and CL, as well as serum levels of hormones. RESULTS: PCOS rats showed irregular estrous cycle and they were mainly in the anestrum. Rats in the control group were in a regular estrous cycle. A higher percentage of FC and a lower percentage of CL were seen in PCOS rats compared with those of controls. ELISA data revealed higher serum levels of LH, LH/FSH, and T in PCOS rats compared with those of controls. However, levels of FSH and E2 were lower in PCOS rats. Although INS level increased in PCOS rats, we did not observe a significant difference in INS level between PCOS rats and control rats. MicroRNA-409 was lowly expressed in ovaries of PCOS rats than those of controls. After injection of microRNA-409 mimics into rat ovary, microRNA-409 expression remarkably upregulated than those PCOS rats without injection. Rats in PCOS+microRNA-409 mimics group showed the largest body weight compared with those in the PCOS group and control group. PCOS rats showed a lower pregnancy rate than those of controls, which was markedly increased after administration of microRNA-409 mimics. Rats in PCOS+microRNA-409 mimics group presented lower levels of LH, LH/FSH, T, and INS, but higher levels of FSH and E2 than those in PCOS group. CONCLUSIONS: MicroRNA-409 is lowly expressed in the ovary of PCOS rats. Overexpression of microRNA-409 could improve hormone levels and pregnancy rate in PCOS rats, as well as affect clinical phenotypes of their offspring.

Long non-coding RNA HULC promotes proliferation and osteogenic differentiation of bone mesenchymal stem cells via down-regulation of miR-195.

OBJECTIVE: LncRNAs HULC has been reported to be important regulators in the development of various human diseases. However, the role of HULC in bone mesenchymal stem cells (BMSCs) remains unclear. The present study aimed to explore the regulatory effect of HULC on proliferation and osteogenic differentiation of BMSCs and the underlying mechanism. MATERIALS AND METHODS: The expression of HULC and miR-195 in BMSCs were altered by transfection and measured by qRT-PCR. Cell viability was measured by the CCK-8 assay. Osteogenic differentiation of BMSCs was determined by evaluation of osteogenic markers (Ocn, ALP, Runx2, and Col-1) expression levels using Western blot and qRT-PCR. Furthermore, Western blot was performed to assess the expression of proliferation-related factors, Wnt/ß-catenin and p38MAPK pathway-related factors. RESULTS: HULC overexpression significantly increased cell viability, down-regulated p21 expression but up-regulated CyclinD1 expression, and promoted the levels of osteogenic markers. However, the complete opposite effect was observed in HULC knockdown. Notably, miR-195 expression was negatively regulated by HULC and miR-195 exerted a reversed effect of HULC on BMSCs. Moreover, miR-195 mediated the regulatory effect of HULC on BMSCs proliferation and osteogenic differentiation, as miR-195 mimic abolished the effect of HULC overexpression on BMSCs. We also found that HULC overexpression enhanced the activation of Wnt/ß-catenin and p38MAPK pathway through down-regulating miR-195. CONCLUSIONS: We revealed that HULC promoted proliferation and osteogenic differentiation of BMSCs. The potential mechanism might be involved in its negative regulation on miR-195 and enhanced activation of Wnt/ß-catenin and p38MAPK pathway.

Impact of weight-related advice from healthcare professionals on body mass index of patients in the USA.

OBJECTIVES: Healthcare professionals (HCPs) can help promote healthy eating and active living in patients. This study assessed the effects of weight-related advice from HCPs on change in body mass index (BMI) of patients in the USA. STUDY DESIGN: A 1-year follow-up study of 20,002 adults who participated in a nationally representative survey between 2004 and 2008. METHODS: Using the 2004-2008 Medical Expenditure Panel Survey data, 1-year BMI and weight status changes were compared between patients who did and did not report receiving advice on exercise or on restricted intake of fat and cholesterol from their HCPs. RESULTS: Patients who received weight-related advice had a greater increase in BMI compared with those who did not receive weight-related advice. Stratified by the baseline weight status of patients (i.e. normal weight, overweight or obese), adverse direction of BMI change was only significantly associated with advice on exercise. Patients who received advice to exercise more were more likely to move to a higher weight status than remaining at the same weight status, compared with patients who did not receive advice to exercise more. CONCLUSION: This study did not find that weight-related advice from HCPs had a positive impact on BMI loss in patients. On the contrary, patients who reported receiving weight-related advice from HCPs had worse weight outcomes 1 year later than patients who did not report receiving weight-related advice. Further research is warranted to elucidate the role of weight-related advice from HCPs on lifestyle change and obesity prevention and control.

What happens after no contralateral exploration in total extraperitoneal (TEP) herniorrhaphy of clinical unilateral inguinal hernias?

BACKGROUND: While performing unilateral TEP herniorrhaphy, controversy still exists about whether to do contralateral exploration or not. Routine contralateral exploration has been proposed to prevent metachronous contralateral hernias by the repair of incidental contralateral occult hernias. Some surgeons have even proposed to do prophylactic bilateral TEP herniorrhaphy for unilateral hernia patients. To evaluate the appropriateness of not doing contralateral exploration in unilateral TEP herniorrhaphy, we reviewed our experiences under our practice of no contralateral exploration and we also reviewed other published literature. METHODS: A total of 305 patients who underwent 313 TEP herniorrhaphies for inguinal hernias by a single surgeon during August 2012-July 2016 at Chia-Yi Christian Hospital were enrolled in this retrospective study. Demographic, perioperative and follow-up data were obtained for analysis and review. RESULTS: Of the 305 patients, 261 patients had unilateral TEP herniorrhaphy and 44 patients had bilateral TEP herniorrhaphy. The mean operation time for the unilateral TEP herniorrhaphy group was 59.8 min, and for the bilateral TEP herniorrhaphy group it was 85.2 min (p < 0.001). Seven of 261 (2.7%) patients had metachronous contralateral hernia after unilateral TEP herniorrhaphy. There were no statistically significant differences in any of the outcome variables when comparing the sequential and simultaneous primary bilateral TEP herniorrhaphies. CONCLUSIONS: Without routine contralateral exploration, the incidence of metachronous contralateral hernia was 2.7% (7/261) in unilateral hernia patients. This is acceptable as metachronous hernia also occurred in 3.2% of patients with negative contralateral exploration according to our literature review. Sequential and simultaneous bilateral primary TEP herniorrhaphy outcomes were similar. We conclude that no exploration for the other groin is a justified decision for unilateral inguinal hernia patients.