Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis.

Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.

Shape Memory Polyurethane Composite With Fast Response to Near-Infrared Light Based on Tannic Acid-Iron and Dynamic Phenol-Carbamate Network.

Intelligent materials derived from green and renewable bio-based materials garner widespread attention recently. Herein, shape memory polyurethane composite (PUTA/Fe) with fast response to near-infrared (NIR) light is successfully prepared by introducing Fe3+ into the tannic acid-based polyurethane (PUTA) matrix through coordination between Fe3+ and tannic acid. The results show that the excellent NIR light response ability is due to the even distribution of Fe3+ filler with good photo-thermal conversion ability. With the increase of Fe3+ content, the NIR light response shape recovery rate of PUTA/Fe composite films is significantly improved, and the shape recovery time is reduced from over 60 s to 40 s. In addition, the mechanical properties of PUTA/Fe composite film are also improved. Importantly, owing to the dynamic phenol-carbamate network within the polymer matrix, the PUTA/Fe composite film can reshape its permanent shape through topological rearrangement and show its good NIR light response shape memory performance. Therefore, PUTA/Fe composites with high content of bio-based material (TA content of 15.1-19.4%) demonstrate the shape memory characteristics of fast response to NIR light; so, it will have great potential in the application of new intelligent materials including efficient and environmentally friendly smart photothermal responder.

Knowledge of Alzheimer's disease and associated factors among adults in Zhuhai, China: a cross-sectional analysis.

BACKGROUND: This study aimed to assess the public knowledge regarding Alzheimer's Disease (AD) in Zhuhai, China, focusing on identifying knowledge gaps and the influence of demographic and health factors. METHODS: A cross-sectional study was conducted in Zhuhai, China, from October to November 2022. A total of 1986 residents from 18 communities were selected employing stratified multi-stage equi-proportional sampling. Questionnaires covering general information and the Alzheimer's Disease Knowledge Scale (ADKS) were investigated face-to-face. Ordinal multiclass logistic regression was applied to assess the relationship between AD awareness and demographic and health characteristics. RESULTS: The average ADKS score was 18.5 (SD = 3.36) in Zhuhai. The lowest awareness rates were observed in the "Symptoms" and "Caregiving" subdomains of ADKS, with rates of 51.01% and 43.78%, respectively. The correct rates for the 30 ADKS questions ranged from 16.62 to 92.6%, showing a bimodal pattern with clusters around 80% and 20%. Women (OR = 1.203, 95% CI: 1.009-1.435), individuals aged 60 years or older (OR = 2.073, 95% CI: 1.467-2.932), those living in urban areas (OR = 1.361, 95% CI: 1.117-1.662), higher average monthly household income per capita (OR = 1.641, 95% CI: 1.297-2.082), and without any neurological or mental disorders (OR = 1.810, 95% CI: 1.323-2.478) were more likely to have higher levels of awareness about Alzheimer's disease. CONCLUSIONS: Adults in Zhuhai show a limited knowledge of AD, particularly in the 'Symptoms' and 'Caregiving' subdomains. Upcoming health campaigns must focus on bridging the knowledge gaps in different subdomains of AD, especially among subgroups with lower awareness, as identified in our study.

Long non-coding RNA FKSG29 regulates oxidative stress and endothelial dysfunction in obstructive sleep apnea.

Altered expressions of pro-/anti-oxidant genes are known to regulate the pathophysiology of obstructive sleep apnea (OSA).We aim to explore the role of a novel long non-coding (lnc) RNA FKSG29 in the development of intermittent hypoxia with re-oxygenation (IHR)-induced endothelial dysfunction in OSA. Gene expression levels of key pro-/anti-oxidant genes, vasoactive genes, and the FKSG29 were measured in peripheral blood mononuclear cells from 12 subjects with primary snoring (PS) and 36 OSA patients. Human monocytic THP-1 cells and human umbilical vein endothelial cells (HUVEC) were used for gene knockout and double luciferase under IHR exposure. Gene expression levels of the FKSG29 lncRNA, NOX2, NOX5, and VEGFA genes were increased in OSA patients versus PS subjects, while SOD2 and VEGFB gene expressions were decreased. Subgroup analysis showed that gene expression of the miR-23a-3p, an endogenous competitive microRNA of the FKSG29, was decreased in sleep-disordered breathing patients with hypertension versus those without hypertension. In vitro IHR experiments showed that knock-down of the FKSG29 reversed IHR-induced ROS overt production, early apoptosis, up-regulations of the HIF1A/HIF2A/NOX2/NOX4/NOX5/VEGFA/VEGFB genes, and down-regulations of the VEGFB/SOD2 genes, while the protective effects of FKSG29 knock-down were abolished by miR-23a-3p knock-down. Dual-luciferase reporter assays confirmed that FKSG29 was a sponge of miR-23a-3p, which regulated IL6R directly. Immunofluorescence stain further demonstrated that FKSGH29 knock-down decreased IHR-induced uptake of oxidized low density lipoprotein and reversed IHR-induced IL6R/STAT3/GATA6/ICAM1/VCAM1 up-regulations. The findings indicate that the combined RNA interference may be a novel therapy for OSA-related endothelial dysfunction via regulating pro-/anti-oxidant imbalance or targeting miR-23a-IL6R-ICAM1/VCAM1 signaling.

Effects of Dexmedetomidine on Systemic Inflammation and Postoperative Complications in Laparoscopic Pancreaticoduodenectomy: A Double-blind Randomized Controlled Trial.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) may induce intense inflammatory response which might be related to the patient's outcomes. Clinical dexmedetomidine (DEX) has been widely used for opioid-sparing anesthesia and satisfactory sedation. The objective of this study was to investigate the influence of DEX on inflammatory response and postoperative complications in LPD. METHODS: Ninety-nine patients undergoing LPD were randomly assigned to two groups: normal saline (NS) and DEX. The primary outcome was the neutrophil-to-lymphocyte ratio (NLR) differences postoperatively within 48 h. Secondary outcomes were postoperative complications, the length of postoperative hospital stay and the incidence of ICU admission. Other outcomes included anesthetics consumption and intraoperative vital signs. RESULTS: NLR at postoperative day 2 to baseline ratio decreased significantly in the DEX group (P = 0.032). Less major complications were observed in the DEX group such as pancreatic fistula, delayed gastric emptying and intra-abdominal infection (NS vs. DEX, 21.7% vs. 13.6%, P = 0.315; 10.9% vs. 2.3%, P = 0.226; 17.4% vs. 11.4%, P = 0.416, respectively) though there were no statistical differences. Three patients were transferred to the ICU after surgery in the NS group, while there was none in the DEX group (P = 0.242). The median postoperative hospital stay between groups were similar (P = 0.313). Both intraoperative propofol and opioids were less in the DEX group (P < 0.05). CONCLUSIONS: Intraoperative DEX reduced the early postoperative inflammatory response in LPD. It also reduced the use of narcotics that may related to reduced major complications, which need additional research further.

Production of all-male non-transgenic zebrafish by conditional primordial germ cell ablation.

Many fish species exhibit remarkable sexual dimorphism, with males possessing numerous advantageous traits for commercial production by aquaculture such as faster growth rate, more efficient food energy utilization for muscle development, and better breeding performance. Several studies have shown that a decrease in the number of primordial germ cells (PGCs) during early development leads predominantly to male progeny. In this study, we developed a method to obtain all-male zebrafish (Danio rerio) by targeted PGC ablation using the nitroreductase/metronidazole (NTR/Mtz) system. Embryos generated by female heterozygous Tg(nanos3:nfsB-mCherry-nanos3 3'UTR) and male wild-types (WTs) were treated with vehicle or Mtz. Compared to vehicle-treated controls, 5.0 and 10.0 mM Mtz treatment for 24 h significantly reduced the number of PGCs and yielded an exclusively male phenotype in adulthood. The gonads of offspring treated with 5.0 mM Mtz exhibited relatively normal morphology and histological characteristics. Furthermore, these males were able to chase females, spawn, and produce viable offspring, while about 20.0% of males treated with 10.0 mM Mtz were unable to produce viable offspring. The 5.0 mM Mtz treatment protocol may thus be suitable for large-scale production of fertile male offspring. Moreover, about half of these males were WT as evidenced by the absence of nfsB gene expression. It may thus be possible to breed an all-male WT fish population by Mtz-mediated PGC ablation.

Transposon-based identification of genes involved in the rimocidin biosynthesis in Streptomyces rimosus M527.

The transposon mutagenesis strategy has been employed to generate random insertion mutants and analyze the correlation between genes and secondary metabolites in the genus Streptomyces. In this study, our primary objective was to identify an unknown gene involved in rimocidin biosynthesis and elucidate its role in rimocidin production in Streptomyces rimosus M527. To achieve this, we established a random mutant library of S. rimosus M527 using a Tn5 transposon-mediated random mutagenesis strategy. Among the 137 isolated mutants, M527-G10 and M527-W5 exhibited the most significant variations in antagonistic activity against the plant pathogenic fungus Fusarium oxysporum f. sp. cucumerinum. Specifically, M527-G10 displayed a 72.93% reduction, while M527-W5 showed a 49.8% increase in rimocidin production compared to the wild-type (WT) strain S. rimosus M527. Subsequently, we employed a plasmid rescue strategy to identify the insertion loci of the transposon in the genomes of mutants M527-G10 and M527-W5, revealing a response regulator transcription factor (rrt) and a hypothetical protein (hyp), respectively. The roles of rrt and hyp in rimocidin biosynthesis were determined through gene deletion, overexpression in the WT strain, and complemented expression in the transposon mutants. Notably, the gene-deletion mutants M527-ΔRRT and M527-ΔHYP exhibited similar behavior in rimocidin production compared to the corresponding transposon mutants M527-G10 and M527-W5, suggesting that transposon insertions in genes rrt and hyp led to alterations in rimocidin production. Furthermore, both gene deletion and overexpression of rrt and hyp had no discernible effects on cell growth. These results reveal that genes rrt and hyp have positive and negative impacts on rimocidin production in S. rimosus M527, respectively.

Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury.

BACKGROUND: Peripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus result in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first-order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain. METHODS: The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC glutamatergic neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling. RESULTS: Increased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC glutamatergic neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6. CONCLUSIONS: The descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain.

Early versus the traditional start of oral intake following esophagectomy for esophageal cancer: a systematic review and meta-analysis.

BACKGROUND: Nil by mouth is considered the standard of care during the first days following esophagectomy. However, with the routine implementation of enhanced recovery after surgery, early oral intake is more likely to be the preferred mode of nutrition following esophagectomy. The present study aims to evaluate the safety and effectiveness of early oral intake following esophagectomy for esophageal cancer. METHODS: Comprehensive literature searches were conducted using PubMed, Web of Science, Embase, and Cochrane Library. Weighted mean differences (WMD) and odds ratios (OR) with 95% confidence intervals (CI) were calculated as the effect sizes for continuous and dichotomous variables, respectively. RESULTS: Fourteen studies with a total of 1947 patients were included. Length of hospital stay (WMD = - 3.94, CI: - 4.98 to - 2.90; P < 0.001), the time to first flatus (WMD = - 1.13, CI: - 1.25 to - 1.01; P < 0.001) and defecation (WMD = - 1.26, CI: - 1.82 to - 0.71; P < 0.001) favored the early oral intake group. There was no statistically significant difference in mortality (OR = 1.23, CI: 0.45 to 3.36; P = 0.69). Early oral intake also did not increase the risk of pneumonia and overall postoperative complications. CONCLUSIONS: Current evidence indicates early oral intake following esophagectomy seems to be safe and effective. It may be the preferred mode of nutrition following esophagectomy. However, more high-quality studies are still needed to further validate this conclusion.

Esophagectomy versus definitive chemoradiotherapy as initial treatment for clinical stage I esophageal cancer: a systematic review and meta-analysis.

BACKGROUND: Esophagectomy and definitive chemoradiotherapy are commonly used in the treatment of stage I esophageal cancer (EC). The present study aims to compare the efficacy and safety of esophagectomy and definitive chemoradiotherapy as the initial treatment for clinical stage I EC. METHODS: This study was registered with the International Prospective Register of Systematic Reviews (CRD42020197203). Relevant studies were identified through PubMed, Web of Science, EMBASE, and Cochrane Library from database inception to June 30, 2020. Hazard ratio (HR) with 95% confidence intervals (CI) was employed to compare overall survival (OS) and progression-free survival (PFS). Odds ratio (OR) with 95% CI was employed to compare treatment-related death, complications, and tumor recurrence. RESULTS: A total of 13 non-randomized controlled studies involving 3,346 patients were included. Compared with definitive chemoradiotherapy, esophagectomy showed an improved OS (HR 0.69, 95% CI 0.55-0.86; P < 0.001), PFS (HR 0.47, 95% CI 0.33-0.67; P < 0.001), and a lower risk of tumor recurrence (OR 0.43, 95% CI 0.30-0.61; P < 0.001). There was no significant difference in the incidence of complications (OR 1.11, 95% CI 0.75-1.65; P = 0.60) and treatment-related death (OR 1.15, 95% CI 0.31-4.30; P = 0.84) between the two treatments. CONCLUSIONS: Current evidence shows esophagectomy has superior survival benefits as the initial treatment for clinical stage I EC. It is still the preferred choice for patients with clinical stage I EC. However, future high-quality randomized controlled trials are needed to validate this conclusion.

Curcumin Ameliorates the Experimental Diabetic Peripheral Neuropathy through Promotion of NGF Expression in Rats.

Increasing evidence suggested that inhibiting the apoptosis of Schwann cells (SCs) and promoting nerve growth factor (NGF) expression in sciatic nerves play key roles in preventing the onset of diabetic peripheral neuropathy (DPN). Curcumin, a primary bioactive substance in turmeric with multiple characteristics, has been shown to have many therapeutic effects in a variety of diseases. However, curcumin is poorly studied in the DPN models. We aimed to explore the therapeutic benefits and underlying mechanism of curcumin in high fat/sugar diets joint streptozotocin (STZ)-induced DPN rat models. Sprague-Dawley (SD) rats were divided into five groups (6 rats per group), control group, DPN group, Curcumin groups (50, 100, and 150 mg/kg). Curcumin was administered intragastrically once per day for 4 continuous weeks. Body weight (BW) and fasting blood glucose (FBG) were monitored in all groups. The mechanical withdraw threshold (MWT) was measured. We also assessed neuropathic change by testing nerve conductance velocity (NCV) in sciatic nerves. TEM was applied to observe the sciatic nerves ultrastructure. The SCs apoptosis in sciatic nerves was stained using TUNEL kit. NGF contents in sciatic nerves and serum were detected using western blotting and ELISA analysis. The results showed curcumin had no obvious effect on the BW and FBG change. Curcumin (100 and 150 mg/kg) attenuated the MWT, NCV, and sciatic nerves ultrastructure in DPN rats. Curcumin (50, 100 and 150 mg/kg) reduced SCs apoptosis in sciatic nerves. In addition, curcumin at 150 mg/kg had the best efficacy in increasing protein expression of NGF in sciatic nerves and serum NGF level. Our work demonstrated that curcumin has neuroprotective effects for the treatment of DPN.

NLRP3-Mediated Piezo1 Upregulation in ACC Inhibitory Parvalbumin-Expressing Interneurons Is Involved in Pain Processing after Peripheral Nerve Injury.

The anterior cingulate cortex (ACC) is particularly critical for pain information processing. Peripheral nerve injury triggers neuronal hyper-excitability in the ACC and mediates descending facilitation to the spinal dorsal horn. The mechanically gated ion channel Piezo1 is involved in the transmission of pain information in the peripheral nervous system. However, the pain-processing role of Piezo1 in the brain is unknown. In this work, we found that spared (sciatic) nerve injury (SNI) increased Piezo1 protein levels in inhibitory parvalbumin (PV)-expressing interneurons (PV-INs) but not in glutaminergic CaMKⅡ+ neurons, in the bilateral ACC. A reduction in the number of PV-INs but not in the number of CaMKⅡ+ neurons and a significant reduction in inhibitory synaptic terminals was observed in the SNI chronic pain model. Further, observation of morphological changes in the microglia in the ACC showed their activated amoeba-like transformation, with a reduction in process length and an increase in cell body area. Combined with the encapsulation of Piezo1-positive neurons by Iba1+ microglia, the loss of PV-INs after SNI might result from phagocytosis by the microglia. In cellular experiments, administration of recombinant rat TNF-α (rrTNF) to the BV2 cell culture or ACC neuron primary culture elevated the protein levels of Piezo1 and NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3). The administration of the NLRP3 inhibitor MCC950 in these cells blocked the rrTNF-induced expression of caspase-1 and interleukin-1ß (key downstream factors of the activated NLRP3 inflammasome) in vitro and reversed the SNI-induced Piezo1 overexpression in the ACC and alleviated SNI-induced allodynia in vivo. These results suggest that NLRP3 may be the key factor in causing Piezo1 upregulation in SNI, promoting an imbalance between ACC excitation and inhibition by inducing the microglial phagocytosis of PV-INs and, thereby, facilitating spinal pain transmission.

Subxiphoid versus intercostal video-assisted thoracic surgery for lung resection: a meta-analysis.

INTRODUCTION: To systematically evaluate the safety and advantages of subxiphoid approach video-assisted thoracic surgery (SA-VATS) compared with intercostal approach video-assisted thoracic surgery (IA-VATS) for lung resection, we conducted a meta-analysis of the current literature. MATERIAL AND METHODS: The literature search was conducted in PubMed, Web of Science, Cochrane Library, Embase, and China National Knowledge Infrastructure. RevMan 5.3 software was used to perform this meta-analysis. RESULTS: Eleven studies involving 934 patients were included. Compared with patients in the IA-VATS group, those in the SA-VATS group had lower pain scores on the day of the operation and at 24 h, 48 h and 72 h after the operation (p < .001) and suffered from less postoperative paraesthesia at the first, third and sixth months after the operation (p < .001). Moreover, there was no statistically significant difference between the two groups regarding postoperative complications, intraoperative blood loss, length of hospital stay, drainage amount, or chest tube duration. However, SA-VATS had a longer operative time (p < .001). CONCLUSIONS: SA-VATS is a safe surgical technique and has superior postoperative outcomes over IA-VATS for lung resection in terms of acute postoperative pain and chronic postoperative paraesthesia.

A Meta-analysis of Jejunostomy Versus Nasoenteral Tube for Enteral Nutrition Following Esophagectomy.

BACKGROUND: Postoperative nutritional therapy is of paramount importance for patients undergoing esophagectomy. The jejunostomy and nasoenteral tube are the popular routes for nutritional therapy. However, which one is the preferred route is unclear. This study aims to analyze the differences in safety and efficacy of the two routes for nutritional therapy. MATERIALS AND METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE (till September 17, 2020) were searched. The primary outcome was postoperative pneumonia. Secondary outcomes were the length of hospital stays (LOS), bowel obstruction, catheter dislocation, anastomotic leakage, overall postoperative complications, and postoperative albumin. Weighted mean differences (WMD) and odds ratios (OR) were calculated for statistical analysis. RESULTS: Ten studies involving a total of 1,531 patients in the jejunostomy group and 1,375 patients in the nasoenteral tube group were included. Compared with patients in the nasoenteral tube group, those in the jejunostomy group had a lower incidence of postoperative pneumonia (OR = 0.68, P < 0.001), shorter LOS (WMD = -0.85, P < 0.001), and lower risk of catheter dislocation (OR = 0.15, P = 0.001). There were no significant differences in the incidence of anastomotic leakage (OR = 0.84, P = 0.43), overall postoperative complications (OR = 0.87, P = 0.59), and postoperative albumin (WMD = -0.40, P = 0.24). However, patients in the jejunostomy group had a higher risk of bowel obstruction (OR = 8.42, P = 0.002). CONCLUSIONS: Jejunostomy for enteral nutrition showed superior outcomes in terms of postoperative pneumonia, LOS, and catheter dislocation. Jejunostomy may be the preferred enteral nutritional route following esophagectomy.

Predicting readmission and death after hospital discharge: a comparison of conventional frailty measurement with an electronic health record-based score.

BACKGROUND: frailty measurement may identify patients at risk of decline after hospital discharge, but many measures require specialist review and/or additional testing. OBJECTIVE: to compare validated frailty tools with routine electronic health record (EHR) data at hospital discharge, for associations with readmission or death. DESIGN: observational cohort study. SETTING: hospital ward. SUBJECTS: consented cardiology inpatients ≥70 years old within 24 hours of discharge. METHODS: patients underwent Fried, Short Physical Performance Battery (SPPB), PRISMA-7 and Clinical Frailty Scale (CFS) assessments. An EHR risk score was derived from the proportion of 31 possible frailty markers present. Electronic follow-up was completed for a primary outcome of 90-day readmission or death. Secondary outcomes were mortality and days alive at home ('home time') at 12 months. RESULTS: in total, 186 patients were included (79 ± 6 years old, 64% males). The primary outcome occurred in 55 (30%) patients. Fried (hazard ratio [HR] 1.47 per standard deviation [SD] increase, 95% confidence interval [CI] 1.18-1.81, P < 0.001), CFS (HR 1.24 per SD increase, 95% CI 1.01-1.51, P = 0.04) and EHR risk scores (HR 1.35 per SD increase, 95% CI 1.02-1.78, P = 0.04) were independently associated with the primary outcome after adjustment for age, sex and co-morbidity, but the SPPB and PRISMA-7 were not. The EHR risk score was independently associated with mortality and home time at 12 months. CONCLUSIONS: frailty measurement at hospital discharge identifies patients at risk of poorer outcomes. An EHR-based risk score appeared equivalent to validated frailty tools and may be automated to screen patients at scale, but this requires further validation.

Is it necessary to routinely perform feeding jejunostomy at the time of esophagectomy? A systematic review and meta-analysis.

Feeding jejunostomy (FJ) is a routine procedure at the time of esophagectomy in some centers. With the widespread popularization of enhanced recovery after surgery, the necessity of FJ has been increasingly questioned. This study aims to analyze the differences in safety and effectiveness between with (FJ group) or without (no-FJ group) performing FJ at the time of esophagectomy. PubMed, Embase, Web of Science, and Cochrane Library were comprehensively searched for relevant studies, including randomized controlled trials and cohort studies. The primary outcome was the length of hospital stay (LOS). Secondary outcomes were overall postoperative complications, postoperative pneumonia, intestinal obstruction, and weight loss at 3 and 6 months after esophagectomy. Weighted mean differences (WMD) and odds ratios (OR) were calculated for statistical analysis. About 12 studies comprising 2,173 patients were included. The FJ group had a longer LOS (WMD = 2.05, P = 0.01) and a higher incidence of intestinal obstruction (OR = 11.67, P < 0.001) than the no-FJ group. The incidence of overall postoperative complications (OR = 1.24, P = 0.31) and postoperative pneumonia (OR = 1.43, P = 0.13) were not significantly different, nor the weight loss at 3 months (WMD = 0.58, P = 0.24) and 6 months (P > 0.05) after esophagectomy. Current evidence suggests that routinely performing FJ at the time of esophagectomy appears not to generate better postoperative outcomes. FJ may need to be performed selectively rather than routinely. More studies are required to further verify.

Haplotype-based association of two SNPs in miR-423 with unexplained recurrent pregnancy loss in a Chinese Han population.

MicroRNAs (miRNAs) regulate diverse cellular processes such as cell differentiation, proliferation and apoptosis. Mutation in miRNAs results in various pathological conditions such as inflammation, viral infections, neurodegeneration, and autoimmunity. We have evaluated the association of miR-423 rs6505162C>A and rs8067576 A>T among patients with recurrent pregnancy loss (RPL) and controls from North China. Our study found that one SNP rs6505162C>A in miR-423 coding region was associated with the increase risk of humanunexplained RPL (URPL), but no differences were found in another SNP rs8067576 A>T. However, in two-locus haplotype analysis, miR-423-CC/TT haplotype was associated with an increased risk of URPL. The level of mature miR-423 was obviously down-regulated in cells transfected with miR-423-CC/TT haplotype. miR-423-CC/TT haplotype inhibited HTR-8/SVneo cells proliferation and migration and promoted cells apoptosis. Further experiments identified that mesoderm development candidate 1 (MESDC1) was a functionally relevant target of miR-423, and its expression was reversely regulated by miR-423. More importantly, dual-luciferase assay indicated miR-423-CC/TT haplotype decreasing miR-423 expression, could up-regulate MESDC1 expression. Collectively, our data suggest that miR-423-CC/TT haplotype in pre-miR-423 may aggravate the risk of developing URPL by influencing the level of mature miR-423 and its target gene MESDC1.

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling.

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes-including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4-were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

Telomere length and type 2 diabetes: Mendelian randomization study and polygenic risk score analysis.

Recent epidemiological studies suggest an association between shorter telomere length and higher risk for type 2 diabetes (T2D). However, results from observational studies are susceptible to confounding and reverse causation, and it is not clear whether there is a causal association between telomere length and T2D. Using Mendelian randomization (MR) and polygenic risk score (PRS) approaches, we had evaluated the causal effect of telomere length on T2D in the Chinese Han population. Using 8 telomere-length associated genetic variants as instrumental variables, an analysis of genetically predicted telomere length and T2D risk was performed in the MR study based on data from a T2D genome-wide association study (GWAS) in 2632 individuals (1318 cases and 1314 controls). We also applied a PRS approach to investigate the causal relationship using Chinese GWAS data. The inverse-variance weighted, MR-Egger regression, simple median, and weighted median methods yielded no evidence of association between genetically predicted longer telomere length and risk of T2D (OR = 0.78, 95% CI: 0.36 ~ 1.68, P = 0.522; OR = 0.23, 95% CI: 0.01 ~ 7.64, P = 0.412; OR = 0.60, 95% CI: 0.28 ~ 1.28, P = 0.185; OR = 0.64, 95% CI: 0.31 ~ 1.33,P = 0.233; respectively). Further, PRS analysis did not produce consistent genetic overlap between telomere length and T2D. Accordingly, this study found no evidence supporting a causal association between telomere length and T2D. Further studies with larger cohorts could yield more reliable results and conclusions.