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Background: Patients suffered from severe traumatic brain injury (TBI) have twice the risk of developing into neurodegenerative diseases later in their life. Thus, early intervention is needed not only to treat TBI but also to reduce neurodegenerative diseases in the future. Physiological functions of neurons highly depend on mitochondria. Thus, when mitochondrial integrity is compromised by injury, neurons would initiate a cascade of events to maintain homeostasis of mitochondria. However, what protein senses mitochondrial dysfunction and how mitochondrial homeostasis is maintained during regeneration remains unclear. Results: We found that TBI-increased transcription of a mitochondrial protein, phosphoglycerate mutase 5 (PGAM5), during acute phase was via topological remodeling of a novel enhancer-promoter interaction. This up-regulated PGAM5 correlated with mitophagy, whereas presenilins-associated rhomboid-like protein (PARL)-dependent PGAM5 cleavage at a later stage of TBI enhanced mitochondrial transcription factor A (TFAM) expression and mitochondrial mass. To test whether PGAM5 cleavage and TFAM expression were sufficient for functional recovery, mitochondrial oxidative phosphorylation uncoupler carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) was used to uncouple electron transport chain and reduce mitochondrial function. As a result, FCCP triggered PGAM5 cleavage, TFAM expression and recovery of motor function deficits of CCI mice. Conclusions: Findings from this study implicate that PGAM5 may act as a mitochondrial sensor for brain injury to activate its own transcription at acute phase, serving to remove damaged mitochondria through mitophagy. Subsequently, PGAM5 is cleaved by PARL, and TFAM expression is increased for mitochondrial biogenesis at a later stage after TBI. Taken together, this study concludes that timely regulation of PGAM5 expression and its own cleavage are required for neurite re-growth and functional recovery. [ABSTRACT FROM AUTHOR]

Backgroud: Postoperative nausea and vomiting (PONV) is one of the most common complications after total thyroidectomy under general anesthesia. Total intravenous anesthesia (TIVA) has been documented to prevent PONV in patients undergoing total thyroidectomy. Penehyclidine, an anticholinergic agent with an elimination half-life of over 10 h, is widely used as premedication to reduce glandular secretion. This study aimed to explore the preventative effects of penehyclidine with propofol-remifentanil-TIVA to single-TIVA on PONV in patients undergoing total thyroidectomy. Methods: A total of 100 patients scheduled for total thyroidectomy were randomly assigned to either the penehyclidine group (n = 50) or TIVA group (n = 50). Propofol and remifentanil were was used for TIVA in all patients. No patients who received premedication. Patients were administrated with either 5 ml of normal saline or 0.5 mg of penehyclidine soon after anesthesia induction. The incidence of nausea and vomiting, the severity of nausea, the requirement of rescue antiemetics, and adverse effects were investigated during the first 24 h in two time periods (0–2 h and 2–24 h). Results: The overall PONV incidence during the 24 h after surgery was significantly lower in the penehyclidine group compared with the TIVA group (12% vs 36%, P < 0.005). Besides, the incidence of nausea and the incidence of vomiting were significantly lower in the penehyclidine group compared with the TIVA group at 2–24 h after surgery. However, there was no significant difference between the two groups at 0–2 h after surgery. Conclusions: Administration of penehyclidine under TIVA with propofol-remifentanil is more effective for prevention of PONV than TIVA alone, especially 2–24 h after total thyroidectomy. Trial registration: https://www.chictr.org.cn/edit.aspx?pid=132463&htm=4 (Ref: ChiCTR2100050278, the full date of first registration: 25/08/2021). [ABSTRACT FROM AUTHOR]

Store-operated channels (SOCs) are highly selective Ca2+ channels that mediate Ca2+ influx in non-excitable and excitable (i.e., skeletal and cardiac muscle) cells. These channels are triggered by Ca2+ depletion of the endoplasmic reticulum and sarcoplasmic reticulum, independently of inositol 1,4,5-trisphosphate (InsP3), which is involved in cell growth, differentiation, and gene transcription. When the Ca2+ store is depleted, stromal interaction molecule1 (STIM1) as Ca2+ sensor redistributes into discrete puncta near the plasma membrane and activates the protein Ca2+ release activated Ca2+ channel protein 1 (Orai1). Accumulating evidence suggests that SOC is associated with several physiological roles in endothelial dysfunction and vascular smooth muscle proliferation that contribute to the progression of cardiovascular disease. This review mainly elaborates on the contribution of SOC in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in cardiovascular disease. 8M8K4EypuEH95WkhQeH6Ky Video Abstract [ABSTRACT FROM AUTHOR]

Background: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic inherited disease caused by mutations of the autoimmune regulator gene (AIRE). The three major components of this syndrome are chronic mucocutaneous candidiasis, hypoparathyroidism and adrenocortical insufficiency. Case presentation: We report a 20-year-old male who was clinically diagnosed with APS-1 at the age of 15. He was admitted to our department this time for suffering from polyuria and polydipsia for 6 months and was finally diagnosed with diabetes insipidus. Whole-exome sequencing (WES) revealed a novel compound heterozygous mutation of the AIRE gene —the c.239 T > G (p.Val80Gly) variant on one allele and the copy number variant (CNV) of 21q22.3(chr21:45,670,150–45,706,528)*1 on the other. Conclusions: This case suggests that diabetes insipidus is a rare component of APS-1 and expands the variety of mutations on AIRE gene. [ABSTRACT FROM AUTHOR]

Background: Studies assessing the efficacy of pioglitazone solely for primary stroke prevention in Asian patients with type 2 diabetes mellitus (DM) and present multiple cardiovascular (CV) risk factors are rare. Thus, we aimed to assess the effect of pioglitazone on primary stroke prevention in Asian patients with type 2 DM without established CV diseases but with risk factors for CV diseases. Methods: Between 2000 and 2012, we enrolled patients aged ≥ 18 years, who were newly diagnosed with type 2 diabetes and had at least one of the following CV risk factors: hypertension and hyperlipidemia. Patients with a history of stroke and those using insulin or glucagon-like peptide-1 agonist for more than 3 months were excluded. Patients were divided into the pioglitazone and non-pioglitazone groups based on their receipt of pioglitazone during the follow-up period. Propensity-score matching (1:1) was used to balance the distribution of the baseline characteristics and medications. Follow-up was terminated upon ischemic stroke development, withdrawal from the insurance system, or on December 31, 2013, whichever occurred first. The overall incidence of new-onset ischemic stroke in the two groups was subsequently compared. The subgroup analyses of ischemic stroke were conducted using different baseline features. Additionally, the effect of pioglitazone exposure dose on the occurrence of ischemic stroke was evaluated. Chi square test, Student's t-test, competing risk regression models, Kaplan–Meier method, and log-rank test were some of the statistical tests conducted. Results: A total of 13 078 patients were included in the pioglitazone and non-pioglitazone groups. Compared with patients who did not receive pioglitazone, those administered pioglitazone had a lower risk of developing ischemic stroke (adjusted hazard ratio: 0.78; 95% confidence interval: 0.62–0.95). The subgroup analyses defined by different baseline features did not reveal significant alterations in the observed effect of pioglitazone. Moreover, a significant decreasing trend in ischemic stroke risk with an increase in pioglitazone dose (p-value for trend = 0.04) was observed. Conclusion: Pioglitazone use decreased the risk of new-onset ischemic stroke in Asian patients with type 2 DM and CV risk factors. Trial registration number CMUH104-REC2-115-CR4 [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyse the genomic alteration profiles and immune characteristics of a cohort of Chinese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and immunotherapy as well as their prognostic significance. Methods: PD-L1 expression and clinicopathological information were obtained from 98 cervical cancer patients. Differences in PD-L1 expression and gene mutations between squamous cell carcinoma (SCC) and adenocarcinoma (AC) were analysed by the chi-square test or Fisher's exact test. Differences in gene mutations between our cohort and The Cancer Genome Atlas (TCGA) cohort were tested by Fisher's exact test. Logistic regression was used to analyse factors influencing TMB-high. Results: Positive PD-L1 expression was significantly higher in cervical SCC than in cervical AC (87% vs. 39%, p < 0.001). Frequently mutated genes in cervical cancer included the PIK3CA, KMT2D, and KMT2C genes, among others. PIK3CA gene mutation rates were significantly higher in SCC than in AC (p = 0.004). The TERT gene mutation rate was significantly higher in our cohort than in the TCGA cohort (12% vs. 1%, p < 0.001). The independent predictors of high TMB were KMT2C and LRP1B gene mutations (p < 0.05). We also found that PTEN mutations were associated with worse survival (median PFS, 12.16 vs. 21.75 months, p = 0.0024). Conclusion: Cervical SCC and AC have different molecular profiles and immune characteristics, suggesting that targeted treatments for SCC and AC patients may improve clinical outcomes. KMT2C and LRP1B gene mutations are independent predictors of TMB-high status in cervical cancer. We also proposed the prognostic value of PTEN mutations. [ABSTRACT FROM AUTHOR]

Background: This study aims to provide 14-year nationwide epidemiology data to evaluate the incidence ratio of APS in Taiwan and the condition of comorbidities by analyzing the National Health Insurance Research Database. Methods: Nineteen thousand one hundred sixty-three patients newly diagnosed as having APS during the 2000–2013 period and 76,652 controls (with similar distributions of age and sex) were analyzed. Results: The incidence of APS increased from 4.87 to 6.49 per 10,000 person-years in the Taiwan population during 2000–2013. The incidence of APS increased with age after 20 years old, especially in the female population, and it rose rapidly after age over 60 years old. In addition, APS cohorts presented a higher proportion of diabetes mellitus, hypertension, hyperlipidemia, stroke, heart failure, atrial fibrillation, myocardial infarction, PAOD, chronic kidney disease, COPD, deep vein thrombosis, pulmonary embolism, SLE, rheumatoid arthritis, Sjogren's syndrome, and polymyositis. Conclusions: Our study indicated an increasing trend in APS incidence among the Taiwanese population and a relationship between APS and potential comorbidities. This large national study found that the APS risk is heavily influenced by sex and age. Thus, the distinctive sex and age patterns might be constructive given exploring potential causal mechanisms. Furthermore, our findings indicate that clinicians should have a heightened awareness of the probability of APS, especially in women in certain age groups presenting with symptoms of APS. [ABSTRACT FROM AUTHOR]

High hospital occupancy degrades emergency department performance by increasing wait times, decreasing patient satisfaction, and increasing patient morbidity and mortality. Late discharges contribute to high hospital occupancy by increasing emergency department (ED) patient length of stay (LOS). We share our experience with increasing and sustaining early discharges at a 650-bed academic medical center in the United States. Our process improvement project followed the Institute of Medicine Model for Improvement of successive Plan‒Do‒Study‒Act cycles. We implemented multiple iterative interventions over 41 months. As a result, the proportion of discharge orders before 10 am increased from 8.7% at baseline to 22.2% (p < 0.001), and the proportion of discharges by noon (DBN) increased from 9.5% to 26.8% (p < 0.001). There was no increase in balancing metrics because of our interventions. RA-LOS (Risk Adjusted Length Of Stay) decreased from 1.16 to 1.09 (p = 0.01), RA-Mortality decreased from 0.65 to 0.61 (p = 0.62) and RA-Readmissions decreased from 0.92 to 0.74 (p < 0.001). Our study provides a roadmap to large academic facilities to increase and sustain the proportion of patients discharged by noon without negatively impacting LOS, 30-day readmissions, and mortality. Continuous performance evaluation, adaptability to changing resources, multidisciplinary engagement, and institutional buy-in were crucial drivers of our success. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare cardiovascular risks among participants with T2DM with and without subsequent HTN and participants with HTN with and without subsequent T2DM.Methods: From January 1, 2000, to December 31, 2018, we identified 16,236 matched pairs of T2DM participants with and without HTN (T2DM cohorts), 53,509 pairs of HTN participants with and without T2DM (HTN cohorts), and 21,158 pairs of comorbid HTN and T2DM participants with T2DM history or HTN history (comorbid cohorts) from Taiwan's National Health Insurance Research Database. Cox proportional-hazard models were used to calculate the risk of cardiovascular disease.Results: The mean follow-up time of this study was 6.75 years. Mean incident rates of coronary artery disease for T2DM cohorts, HTN cohorts, and comorbid cohorts were 16.80, 23.18, and 31.53 per 1000 person-years, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [95% CIs]) for incident coronary artery disease, stroke, and heart failure in T2DM participants with versus without HTN were 2.22 (2.07-2.37), 1.19 (1.16-1.23), and 0.92 (0.82-1.02), respectively; the adjusted HRs for HTN participants with versus without T2DM were 1.69 (1.55-1.84), 1.25 (1.21-1.30), and 0.98 (0.93-1.05), respectively; the adjusted HRs for comorbid T2DM and HTN participants with previous T2DM versus previous HTN were 2.78 (2.37-3.27), 1.20 (1.13-1.28), and 0.95 (0.88-1.03), respectively.Conclusions: This nationwide cohort study demonstrated that both T2DM with subsequent HTN and HTN with subsequent diabetes were associated with higher cardiovascular disease risks. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects between computer-assisted and traditional cannulated screw internal fixation on treating femoral neck fracture. Methods: The search was conducted in Embase, Pubmed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Database from the beginning to August 2020. RevMan5.4 software, which was provided by the International Cochrane Group, was used for the meta-analysis comparing the differences in operation time, intraoperative bleeding volume, fluoroscopy frequency, fracture healing time, total drilling times, Harris score, fracture healing rate, and femoral head necrosis rate between computer-assisted and traditional methods groups. Results: A total of 1028 patients were included in 16 studies. Primary outcome indicators: Compared with the traditional method group, the computer-assisted group had less operative time (2RCTs, P < 0.00001; 8 non-RCTs, P = 0.009; Overall, P < 0.00001), intraoperative bleeding (1 RCTs, P < 0.00001; 9non-RCTs, P < 0.00001; Overall, P < 0.00001), femoral head necrosis rate (1 RCT, P = 0.11;7 non-RCTs, P = 0.09; Overall, P = 0.02) and higher Harris scores (1 RCT, P < 0.0001; 9 non-RCTs, P = 0.0002; Overall, P < 0.0001), and there were no significant differences in fracture healing rate between the two groups (5 non-RCTs, P = 0.17). Secondary outcomes indicators: The computer-assisted group had a lower frequency of intraoperative fluoroscopy and total number of drills compared with the traditional method group, while there was no significant difference in fracture healing time. Conclusion: Compared with the traditional hollow screw internal fixation on the treatment of femoral neck fracture, computer-assisted percutaneous cannulated screw fixation can shorten the operation time and improve the operation efficiency and reduce the X-ray injury of medical staff and help patients obtain a better prognosis. Therefore, computer-assisted percutaneous cannulated screw fixation is a better choice for the treatment of femoral neck fracture. Study registration PROSPERO registration number CRD42020214493. [ABSTRACT FROM AUTHOR]

Background: Liver function is routinely assessed in clinical practice as liver function tests provide sensitive indicators of hepatocellular injury. However, the prognostic value of enzymes that indicate hepatic injury has never been systematically investigated in lymphoma, including diffuse large B-cell lymphoma (DLBCL).Methods: This study examined the prognostic value of baseline aspartic transaminase (AST) in DLBCL patients. The association between AST and clinical features was analyzed in 179 DLBCL patients treated from 2006 to 2016. All enrolled patients were treated with R-CHOP or R-CHOP-like chemotherapy. Log-rank test, univariable analysis, and subgroup analysis were performed to evaluate the impact of AST on survival.Results: AST 33.3 U/L was considered to be the optimal threshold value for predicting prognosis. A higher AST level was associated with advanced stage (P = 0.001), poorer performance status (P = 0.014), elevated lactate dehydrogenase level (P <  0.0001), presence of B symptoms (P = 0.001), high-risk International Prognostic Index (IPI, IPI 3-5) (P = 0.002), non-germinal center B-cell subtypes (P = 0.038), hepatitis B virus surface antigen positivity (P = 0.045) and more extra nodal involvement (ENI, ENI ≥ 2) (P = 0.027). Patients with a higher AST level had a shorter overall survival (OS) (2-year OS rate, 53.6% vs. 83.6%, P <  0.001). Subgroup analysis indicated that higher AST levels have poorer prognostic values in patients without B symptoms and LDH positive groups.Conclusion: A pretreatment AST level is associated with OS in DLBCL patients treated with R-CHOP or similar chemotherapy regimens. A high pretreatment AST level might be a reliable prognostic factor for predicting a dismal outcome in DLBCL patients. Serum AST levels may be investigated for use as an easily determinable, inexpensive biomarker for risk assessment in patients with DLBCL. [ABSTRACT FROM AUTHOR]

Background: Macroautophagy (hereafter autophagy) is a tightly regulated process that delivers cellular components to lysosomes for degradation. Damage-regulated autophagy modulator 1 (DRAM1) induces autophagy and is necessary for p53-mediated apoptosis. However, the signalling pathways regulated by DRAM1 are not fully understood. Methods: HEK293T cells were transfected with FLAG-DRAM1 plasmid. Autophagic proteins (LC3 and p62), phosphorylated p53 and the phosphorylated proteins of the class I PI3K-Akt-mTOR-ribosomal protein S6 (rpS6) signalling pathway were detected with Western blot analysis. Cellular distribution of DRAM1 was determined with immunostaining. DRAM1 was knocked down in HEK293T cells using siRNA oligos which is confirmed by quantitative RT-PCR. Cells were serum starved for 18 h after overexpression or knockdown of DRAM1 to decrease the rpS6 activity to the basal level, and then the cells were stimulated with insulin growth factor, epidermal growth factor or serum. rpS6 phosphorylation and rpS6 were detected with Western blotting. Similarly, after overexpression or knockdown of DRAM1, phosphorylation of IGF-1Rβ and IGF-1R were examined with Western blotting. Cell viability was determined with CCK-8 assay and colony formation assay. Finally, human cancer cells Hela, SW480, and HCT116 were transfected with the FLAG-DRAM1 plasmid and phosphorylated rpS6 and rpS6 were detected with Western blot analysis. Results: DRAM1 induced autophagy and inhibited rpS6 phosphorylation in an mTORC1-dependent manner in HEK293T cells. DRAM1 didn't affect the phosphorylated and total levels of p53. Furthermore, DRAM1 inhibited the activation of the PI3K-Akt pathway stimulated with growth factors or serum. DRAM1 was localized at the plasma membrane and regulate the phosphorylation of IGF-1 receptor. DRAM1 decreased cell viability and colony numbers upon serum starvation. Additionally, DRAM1 inhibited rpS6 phosphorylation in several human cancer cells. Conclusions: Here we provided evidence that DRAM1 inhibited rpS6 phosphorylation in multiple cell types. DRAM1 inhibited the phosphorylation of Akt and the activation of Akt-rpS6 pathway stimulated with growth factors and serum. Furthermore, DRAM1 regulated the activation of IGF-1 receptor. Thus, our results identify that the class I PI3K-Akt-rpS6 pathway is regulated by DRAM1 and may provide new insight into the potential role of DRAM1 in human cancers. [ABSTRACT FROM AUTHOR]

Background: Vacuolar protein sorting-associated protein 4B (VPS4B) is a member of the ATP enzyme AAA protein family, and is mainly involved in protein degradation and cell membrane fusion. Recently, a dominant mutation in this gene was identified in human dentin dysplasia type I (DD-I). Herein, we report the generation of Vps4b knockout (Vps4b KO) mice; however, the homozygous Vps4b KO mutation was embryonic lethal at the early stages of embryo development, and we therefore report the results of heterozygous mutant mice. Results: Mice heterozygous for Vps4b did not develop tooth defects replicating human DD-I. Immunohistochemistry showed that gene KO was successful, as there was decreased expression of Vps4b in heterozygous mice; hematoxylin and eosin (H&E) staining also showed that the width of the pre-dentin zone was increased in heterozygous mice, although the arrangement of the odontoblasts was not significantly different from wild-type (WT) mice. However, H&E staining showed no obvious abnormalities in the bones of heterozygous mice. Moreover, stereomicroscopic and X-ray radiography results indicated no abnormal manifestations in teeth or bones. Furthermore, statistical analysis of the volume and density of dentin and enamel, as well as skeletal analysis, including the volume and separation of trabecular bone analyzed by micro-CT, all showed no differences between Vps4b heterozygotes and WT mice. In addition, there also were no significant differences in bone or cartilage mineralization as evaluated by Alcian blue–Alizarin red staining. Conclusions: The heterozygous Vps4b KO mice do not develop tooth defects that replicate human DD-I and this is likely to be due to differences in tooth development between the two species. Consequently, further studies are needed to determine whether mice are an appropriate animal model for human tooth diseases. [ABSTRACT FROM AUTHOR]

Background: Spontaneous intracerebral hemorrhage (ICH) is a condition associated with high mortality and morbidity. Survivors may require prolonged intubation with mechanical ventilation (MV). The aim of this study was to analyze the predictors of extubation failure and prolonged MV in patients who undergo surgical evacuation. Methods: This retrospective study was conducted on adult patients with ICH who underwent MV for at least 48 h and survived > 14 days after surgery. The demographics, clinical characteristics, laboratory tests, and Glasgow Coma Scale score were analyzed. Results: A total of 134 patients with ICH were included in the study. The average age of the patients was 60.34 ± 15.59 years, and 79.9% (n = 107) were extubated after satisfying the weaning parameters. Extubation failure occurred in 11.2% (n = 12) and prolonged MV in 48.5% (n = 65) patients. Multivariable regression analysis revealed that a white blood cell count > 10,000/mm3 at the time of extubation was an independent predictor of reintubation. Meanwhile, age and initial Glasgow Coma Scale scores were predictors of prolonged MV. Conclusions: This study provided the first comprehensive characterization and analysis of the predictors of extubation failure and prolonged MV in patients with ICH after surgery. Knowledge of potential predictors is essential to improve the strategies for early initiation of adequate treatment and prognosis assessment in the early stages of the disease. [ABSTRACT FROM AUTHOR]

Background: The outcomes of mitral valve replacement (MVR) in pediatrics especially in the patients weighing less than 10 kg are not always favorable. This study aimed to measure long-term outcomes of MVR in our institution.Methods: Nine young children weighing less than 10 kg underwent MVR with mechanical prostheses were enrolled in this retrospectively study. Kaplan-Meier survival analysis was used for the prediction of freedom from death and adverse events. Chi-square test was performed to compare outcomes for patients with different ratios of mechanical prosthesis size and body weight. Fourteen related literatures were also reviewed to support our study.Results: All patients received bileaflet mechanical prostheses replacement. The surgical technique varied among the patients with prostheses implanted in the intra-annular (n = 5), supra-annular (n = 1), or with a Dacron conduit segment in the supra-annular position (n = 3). The valve size/weight ratio ranged from 2.11 to 5.00. There were two early death and one late death post-operation. The mean follow-up period was 80.67 ± 63.37 months, the transvalvular gradient was 10.5 ± 1.76 mmHg (range 8 to 12) and the peak gradient of LVOT was 5.00 ± 0.64 mmHg. One (11.1%) patient underwent an immediate revision MVR after initial MVR due to the periprosthetic leak. No patients required surgical reintervention or permanent pacemaker placement during long-term follow-up.Conclusions: The tailored surgical strategy utilized for MVR in infants resulted in reliable valve function and excellent survival. Although revision is inevitable due to somatic growth, the bileaflet mechanical prostheses displayed appropriate durability. [ABSTRACT FROM AUTHOR]

Background: Postoperative nausea and vomiting (PONV) is one of the most frequent complications following strabismus surgery. Penehyclidine, an anticholinergic agent, is widely used as premedication. This study investigated the effect of preoperative penehyclidine on PONV in patients undergoing strabismus surgery. Methods: In this prospective, randomized, double-blind study, patients scheduled for strabismus surgery under general anesthesia were randomly assigned to either penehyclidine (n = 114) or normal saline (n = 104) group. Penehyclidine was administrated immediately after anesthesia induction, and normal saline was substituted as control. PONV was investigated from 0 to 48 h after surgery. Intraoperative oculocardiac reflex (OCR) was also recorded. Results: Compared with normal saline, penehyclidine significantly reduced PONV incidence (30.7% vs. 54.8%, P < 0.01) and mitigated PONV severity as indicated by severity scoring (P < 0.01). Compared with normal saline, penehyclidine also significantly reduced OCR incidence (57.9% vs. 77.9%, P < 0.01) and mitigated OCR severity, as indicated by the requirement for atropine rescue (77.3% vs. 90.1%, P < 0.05) and the maximum decrease of heart rate during OCR (23.1 ± 9.4 bpm vs. 27.3 ± 12.4 bpm, P < 0.05). The recovery course did not differ between groups. Conclusions: Penehyclidine administrated after anesthesia induction significantly reduced the incidence of PONV and alleviated intraoperative OCR in patients undergoing strabismus surgery. Trial registration: ClinicalTrials.gov (NCT04054479). Retrospectively registered August 13, 2019. [ABSTRACT FROM AUTHOR]

Background: Fertility awareness and menses prediction are important for improving fecundability and health management. Previous studies have used physiological parameters, such as basal body temperature (BBT) and heart rate (HR), to predict the fertile window and menses. However, their accuracy is far from satisfactory. Additionally, few researchers have examined irregular menstruators. Thus, we aimed to develop fertile window and menstruation prediction algorithms for both regular and irregular menstruators. Methods: This was a prospective observational cohort study conducted at the International Peace Maternity and Child Health Hospital in Shanghai, China. Participants were recruited from August 2020 to November 2020 and followed up for at least four menstrual cycles. Participants used an ear thermometer to assess BBT and wore the Huawei Band 5 to record HR. Ovarian ultrasound and serum hormone levels were used to determine the ovulation day. Menstruation was self-reported by women. We used linear mixed models to assess changes in physiological parameters and developed probability function estimation models to predict the fertile window and menses with machine learning. Results: We included data from 305 and 77 qualified cycles with confirmed ovulations from 89 regular menstruators and 25 irregular menstruators, respectively. For regular menstruators, BBT and HR were significantly higher during fertile phase than follicular phase and peaked in the luteal phase (all P < 0.001). The physiological parameters of irregular menstruators followed a similar trend. Based on BBT and HR, we developed algorithms that predicted the fertile window with an accuracy of 87.46%, sensitivity of 69.30%, specificity of 92.00%, and AUC of 0.8993 and menses with an accuracy of 89.60%, sensitivity of 70.70%, and specificity of 94.30%, and AUC of 0.7849 among regular menstruators. For irregular menstruators, the accuracy, sensitivity, specificity and AUC were 72.51%, 21.00%, 82.90%, and 0.5808 respectively, for fertile window prediction and 75.90%, 36.30%, 84.40%, and 0.6759 for menses prediction. Conclusions: By combining BBT and HR recorded by the Huawei Band 5, our algorithms achieved relatively ideal performance for predicting the fertile window and menses among regular menstruators. For irregular menstruators, the algorithms showed potential feasibility but still need further investigation. Trial registration: ChiCTR2000036556. Registered 24 August 2020. [ABSTRACT FROM AUTHOR]

Background: The role of consolidative chemotherapy (CCT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. We aimed to compare the overall survival (OS) of those treated with vs without CCT via a population based approach.Methods: Eligible LA-ESCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between those with vs without CCT. We also evaluated the OS in supplementary analyses via alternative approaches.Results: Our primary analysis consisted of 368 patients in whom covariates were well balanced after PS weighting. The HR of death when CCT was compared to without was 0.67 (95% confidence interval 0.52-0.86, P = 0.002). The HR of IECM was 0.66 (P = 0.04). The HR of OS remained similarly in favor of CCT in supplementary analyses.Conclusions: We found that CCT was associated with significantly improved OS for LA-ESCC patients treated with dCCRT. Randomized controlled trials were needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Background: An increasing number of studies have shown that dysregulated miR-589-3p is associated with multiple diseases. However, the role of miR-589-3p in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. This study aimed to explore the biological function and potential molecular mechanism of miR-589-3p in osteogenic differentiation of PDLSCs. Methods: GSE159508 was downloaded from Gene Expression Omibus (GEO, http://www.ncbi.nlm.nih.gov/geo/). Differentially expressed miRNAs between osteogenic induction PDLSCs versus non-induction PDLSCs were obtained by R software. miR-589-3p mimic and miR-589-3p inhibitor and corresponding negative control were obtained and to identify the role of miR-589-3p in osteogenic differentiation of PDLSCs. ALP staining and ARS were used to evaluate ALP activity and mineralization, respectively. The targeted binding relationship between miR-589-3p and ATF1 was predicted and verified by target prediction analysis and dual-luciferase assay. Furthermore, the functional mechanism based on miR-589-3p and ATF1 in osteogenic differentiation of PDLSCs was further investigated through rescue experiments. Results: According to the cut-off criteria with log 2 FC > 1.0 and P < 0.05, 514 differentially expressed miRNAs were identified between osteogenic induction and non-induction PDLSCs, including 309 upregulated miRNAs and 205 downregulated miRNAs. Compared with control PDLSCs, miR-589-3p expression level was notably increased in PDLSCs that underwent osteogenic induction. The overexpression of miR-589-3p promoted the cell viability of PDLSCs, while the low expression of miR-589-3p had the opposite effect. The dual luciferase reporter assay verified that ATF1 was proved to be a direct target of miR-589-3p in PDLSCs. And overexpressed miR-589-3p reduced the expression of ATF1. Overexpression of miR-589-3p enhanced the osteogenic capacity of PDLSCs, as demonstrated by increases in ALP activity, matrix mineralization, and RUNX2, OCN and OSX expression. In addition, the rescue experiments confirmed that overexpressed ATF1 restored the effects of overexpressed miR-589-3p on cell proliferation and osteogenic differentiation of PDLSCs. Conclusion: miR-589-3p could down-regulate the expression of ATF1, thereby promote the proliferation and osteogenic differentiation of PDLSCs. This finding may provide a new therapeutic target for molecular therapy of periodontitis. [ABSTRACT FROM AUTHOR]

Background: Ischemic heart diseases is one of the leading causes of death worldwide. Although revascularization timely is an effective therapeutic intervention to salvage the ischemic myocardium, reperfusion itself causes additional myocardial injury called ischemia/reperfusion (I/R) injury. Bone marrow-derived mesenchymal stem cells (MSCs) is one of the promising cells to alleviate ischemic myocardial injury. However, this cell therapy is limited by poor MSCs survival after transplantation. Here, we investigated whether sevoflurane preconditioning could promote MSCs to attenuate myocardial I/R injury via transient receptor potential canonical channel 6 (TRPC6)-induced angiogenesis. Methods: The anti-apoptotic effect of sevoflurane preconditioning on MSCs was determined by Annexin V-FITC/propidium iodide staining. TRPC6, hypoxia-inducible factor-1α (HIF-1α), Chemokine receptor 4 (CXCR4) and vascular endothelial growth factor (VEGF) protein expressions and VEGF release from MSCs were determined after hypoxia and reoxygenation (H/R). Small interfering RNA (siRNA) was used to knock down TRPC6 gene expression in MSCs. The angiogenesis of human umbilical vein endothelial cells (HUVECs) co-cultured with MSCs was determined by Matrigel tube formation. Myocardial I/R mouse model was induced by occluding left anterior descending coronary artery for 30 min and then reperfusion. MSCs or sevoflurane preconditioned MSCs were injected around the ligature border zone 5 min before reperfusion. Left ventricle systolic function, infarction size, serum LDH, cTnI and inflammatory cytokines were determined after reperfusion. Results: Sevoflurane preconditioning up-regulated TRPC6, HIF-1α, CXCR4 and VEGF expressions in MSCs and VEGF release from MSCs under H/R, which were reversed by knockdown of TRPC6 gene using siRNA in MSCs. Furthermore, sevoflurane preconditioning promoted the angiogenic and anti-inflammatory effect of HUVECs co-cultured with MSCs. Sevoflurane preconditioned MSCs improved left ventricle systolic function and alleviated myocardial infarction and inflammation in mice subjected to I/R insult. Conclusion: The current findings reveal that sevoflurane preconditioned MSCs boost angiogenesis in HUVECs subjected to H/R insult and attenuate myocardial I/R injury, which may be mediated by TRPC6 up-regulated HIF-1α, CXCR4 and VEGF. [ABSTRACT FROM AUTHOR]

Background: LncRNA prostate cancer-associated transcript 6 (PCAT6) has been reported to be dysregulated in several cancers and is associated with tumor progression. Here, we have performed a meta-analysis to assess the general prognostic role of PCAT6 in malignancies. Methods: Four public databases (Embase, Pubmed, Web of Science, Cochrane Library) were used to identify eligible studies, then data was extracted and associations between prognostic indicators and clinical characteristics were combined to estimate hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Publication bias was measured using the Begg's test, and the stability of the combined results was measured using sensitivity analysis. Subsequently, results were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the National Genomics Data Center (NGDC). Results: Ten studies were considered eligible for inclusion. In total, 937 patients and eight types of cancer were included. Our results revealed that overexpression of PCAT6 was significantly associated with a shorter OS (HR = 1.82; 95% CI, [1.40, 2.38]; P < 0.0001) and progression-free survival (PFS) (HR = 1.66; 95% CI, [1.22, 2.25]; P < 0.0001) in cancer patients, and that PCAT6 overexpression was significantly associated with individual tumor clinicopathological parameters, including TNM stage (OR = 0.29; 95% CI, [0.09, 0.94]; P = 0.04), gender (OR = 1.84; 95% CI, [1.31, 2.59]; P = 0.0005), and whether the tumor was metastatic (OR = 5.02; 95% CI, [1.36, 18.57]; P = 0.02). However, PCAT6 overexpression was not correlated with patient age and tumor differentiation. PCAT6 expression was significantly up-regulated in four types of cancer, which was validated using the GEPIA cohort. Combining OS and disease-free survival (DFS) of these four types of cancer revealed a shorter OS and DFS in patients with PCAT6 overexpression. PCAT6 expression in various types of cancer was also validated in NGDC. A total of eight cancers were analyzed and PCAT6 was highly expressed in all eight cancers. Further functional predictions suggest that PCAT6 is correlated with tumor prognosis, and that PCAT6 may be useful as a new tumor-specific marker. Conclusions: LncRNA PCAT6 is highly expressed in multiple cancer types and its upregulation was significantly associated with patient prognosis and poorer clinical features, thereby suggesting that PCAT6 may be a novel prognostic factor in multiple cancer types. [ABSTRACT FROM AUTHOR]

Background: Sepsis may be accompanied by acute respiratory distress syndrome (ARDS) in patients admitted to intensive care units (ICUs). It is essential to identify prognostic biomarkers in patients with sepsis and ARDS.Objective: Determine whether changes in the level of serum fibroblast growth factor 21 (FGF21) can predict the 28-day mortality of ICU patients with sepsis and ARDS.Methods: Consecutive sepsis patients were divided into two groups (Sepsis + ARDS and Sepsis-only), and the Sepsis + ARDS group was further classified as survivors or non-survivors. Demographic data and comorbidities were recorded. The Sequential Organ Failure Assessment (SOFA) score and serum levels of cytokines and other biomarkers were recorded 3 times after admission. Multiple Cox proportional hazards regression was used to identify risk factors associated with 28-day mortality in the Sepsis + ARDS group. Multivariate receiver operating characteristic curve analysis was used to assess the different predictive value of FGF21 and SOFA.Results: The Sepsis + ARDS group had a greater baseline SOFA score and serum levels of cytokines and other biomarkers than the Sepsis-only group; the serum level of FGF21 was almost twofold greater in the Sepsis + ARDS group (P < 0.05). Non-survivors in the Sepsis + ARDS group had an almost fourfold greater level of FGF21 than survivors in this group (P < 0.05). The serum level of FGF21 persistently increased from the baseline to the peak of shock and death in the non-survivors, but persistently decreased in survivors (P < 0.05). Changes in the serum FGF21 level between different time points were independent risk factors for mortality. No statistical difference was observed between the AUC of FGF21 and SOFA at baseline.  CONCLUSION: A large increase of serum FGF21 level from baseline is associated with 28-day mortality in ICU patients with sepsis and ARDS. [ABSTRACT FROM AUTHOR]

Background: Insulin is highly recommended for diabetes management in persons with liver cirrhosis. However, few studies have evaluated its long-term effects in these persons. We conducted this study to compare the risks of mortality, liver-related complications, and cardiovascular events in persons with type 2 diabetes mellitus (T2DM) and compensated liver cirrhosis.Methods: From January 1, 2000, to December 31, 2012, we selected 2047 insulin users and 4094 propensity score-matched nonusers from Taiwan's National Health Insurance Research Database. Cox proportional hazard models were used to assess the risks of outcomes.Results: The mean follow-up time was 5.84 years. The death rate during the follow-up period was 5.28 and 4.07 per 100 person-years for insulin users and nonusers, respectively. In insulin users, the hazard ratios and 95% confidence intervals (CIs) of all-cause mortality, hepatocellular carcinoma, decompensated cirrhosis, hepatic failure, major cardiovascular events, and hypoglycemia were 1.31 (1.18-1.45), 1.18 (1.05-1.34), 1.53 (1.35-1.72), 1.26 (1.42-1.86), 1.41 (1.23-1.62), and 3.33 (2.45-4.53), respectively.Conclusions: This retrospective cohort study indicated that among persons with T2DM and compensated liver cirrhosis, insulin users were associated with higher risks of death, liver-related complications, cardiovascular events, and hypoglycemia compared with insulin nonusers. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood.Methods: Four hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE.Results: Microbial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed.Conclusion: Altogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism. [ABSTRACT FROM AUTHOR]

Objectives: The availability of matched sequencing data for the same sample across different sequencing platforms is a necessity for validation and effective comparison of sequencing platforms. A commonly sequenced sample is the lab-adapted MG1655 strain of Escherichia coli; however, this strain is not fully representative of more complex and dynamic genomes of pathogenic E. coli strains. Data description: We present six new sequencing data sets for another E. coli strain, UTI89, which is an extraintestinal pathogenic strain isolated from a patient suffering from a urinary tract infection. We now provide matched whole genome sequencing data generated using the PacBio RSII, Oxford Nanopore MinION R9.4, Ion Torrent, ABI SOLiD, and Illumina NextSeq sequencers. Together with other publically available datasets, UTI89 has a nearly complete suite of data generated on most second- and third-generation sequencers. These data can be used as an additional validation set for new sequencing technologies and analytical methods. More than being another E. coli strain, however, UTI89 is pathogenic, with a 10% larger genome, additional pathogenicity islands, and a large plasmid, features that are common among other naturally occurring and disease-causing E. coli isolates. These data therefore provide a more medically relevant test set for development of algorithms. [ABSTRACT FROM AUTHOR]