[Clinical effects of percutaneous elastic intramedullary nail assisted by arthrography for the treatment of radial neck fractures in children].

OBJECTIVE: To explore clinical effect of closed reduction percutaneous elastic intramedullary nail assisted by arthrography in the treatment of radial neck fracture in children. METHODS: A retrospective analysis was performed on 23 children with radial neck fracture treated with arthrography assisted closed reduction and percutaneous elastic intramedullary nail internal fixation (arthrography with elastic nail group) from January 2019 to December 2022, including 12 males and 11 females, aged from 2 to 12 years old with an average of (7.36±1.89) years old;According to Judet fracture types, 14 children were type Ⅲ and 9 children were type Ⅳ. In addition, 23 children with radial neck fracture were selected from January 2015 to December 2018 who were treated with closed reduction and percutaneous elastic intramedullary nail fixation (elastic nail group), including 11 males and 12 females, aged from 2 to 14 years old with an average of (7.50±1.91) years old;Judet classification included 15 children were type Ⅲ and 8 children were type Ⅳ. Operative time and intraoperative fluoroscopy times were compared between two groups. Metaizeau evaluation criteria was used to evaluate fracture reduction, and Tibone-Stoltz evaluation criteria was used to evaluate functional recovery of elbow between two groups. RESULTS: Both groups were followed up for 12 to 24 months with an average of (16.56±6.34) months. Operative time and intraoperative fluoroscopy times of elastic nail group were (56.64±19.27) min and (21.13±7.87) times, while those of joint angiography with elastic nail group were (40.33±11.50) min and (12.10±3.52) times;there were difference between two groups (P<0.05). According to Metaizeau evaluation, 11 patients got excellent result, 9 good and 3 fair in joint angiography with elastic nail group, while in elastic nail group, 5 excellent, 13 good, 4 acceptable, and 1 poor;the difference between two groups was statistically significant (P<0.05). According to Tibone-Stoltz criteria, 14 patients got excellent result, 8 good, and 1 fair in joint arthrography with elastic nail group;while in elastic nail group, 12 patients got excellent result, 9 good, 1 fair and 1 poor;there was no significant difference between two groups (P>0.05). CONCLUSION: Compared to percutaneous elastic intramedullary nail fixation, closed reduction assisted by arthrography has advantages of reduced operation time, decreased intraoperative fluoroscopy frequency, and improved fracture reduction. Arthrography enables clear visualization of the anatomical structures of radius, head, neck, bone, and cartilage in children, facilitating comprehensive display of fracture reduction and brachioradial joint alignment. This technique more precisely guides the depth of elastic intramedullary nail implantation in radius neck, thereby enhancing surgical efficiency and success rate.

Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.

Whole-exome sequencing in a cohort of Chinese patients with isolated cervical dystonia.

Background: Dystonia is a kind of movement disorder but its pathophysiological mechanisms are still largely unknown. Recent evidence reveals that genetical defects may play important roles in the pathogenesis of dystonia. Objectives and Methods: -To explore possible causative genes in Chinese dystonia patients, DNA samples from 42 sporadic patients with isolated cervical dystonia were subjected to whole-exome sequencing. Rare deleterious variants associated with dystonia phenotype were screened out and then classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Phenolyzer was used for analyzing the most probable candidates correlated with dystonia phenotype, and SWISS-MODEL server was for predicting the 3D structures of variant proteins. Results: Among 42 patients (17 male and 25 female) recruited, a total of 36 potentially deleterious variants of dystonia-associated genes were found in 30 patients (30/42, 71.4 %). Four disease-causing variants including a pathogenic variant in PLA2G6 (c.797G > C) and three likely pathogenic variants in DCTN1 (c.73C > T), SPR (c.1A > C) and TH (c.56C > G) were found in four patients separately. Other 32 variants were classified as uncertain significance in 26 patients. Phenolyzer prioritized genes TH, PLA2G6 and DCTN1 as the most probable candidates correlated with dystonia phenotype. Although 3D prediction of DCTN1 and PLA2G6 variant proteins detected no obvious structural alterations, the mutation in DCTN1 (c.73C > T:p.Arg25Trp) was closely adjacent to its key functional domain. Conclusion: Our whole-exome sequencing results identified a novel variant in DCTN1 in sporadic Chinese patients with isolated cervical dystonia, which however, needs our further study on its exact role in dystonia pathogenesis.

Discovery and functional investigation of BMP4 as a new causative gene for human congenital heart disease.

OBJECTIVE: Aggregating evidence highlights the strong genetic basis underpinning congenital heart disease (CHD). Here BMP4 was chosen as a prime candidate gene causative of human CHD predominantly because BMP4 was amply expressed in the embryonic hearts and knockout of Bmp4 in mice led to embryonic demise mainly from multiple cardiovascular developmental malformations. The aim of this retrospective investigation was to discover a novel BMP4 mutation underlying human CHD and explore its functional impact. METHODS: A sequencing examination of BMP4 was implemented in 212 index patients suffering from CHD and 236 unrelated non-CHD individuals as well as the family members available from the proband carrying a discovered BMP4 mutation. The impacts of the discovered CHD-causing mutation on the expression of NKX2-5 and TBX20 induced by BMP4 were measured by employing a dual-luciferase analysis system. RESULTS: A new heterozygous BMP4 mutation, NM_001202.6:c.318T>G;p.(Tyr106*), was found in a female proband affected with familial CHD. Genetic research of the mutation carrier's relatives unveiled that the truncating mutation was in co-segregation with CHD in the pedigree. The nonsense mutation was absent from 236 unrelated non-CHD control persons. Quantitative biologic measurement revealed that Tyr106*-mutant BMP4 failed to induce the expression of NKX2-5 and TBX20, two genes whose expression is lost in CHD. CONCLUSION: The current findings indicate BMP4 as a new gene predisposing to human CHD, allowing for improved prenatal genetic counseling along with personalized treatment of CHD patients.

Revealing the pharmacological mechanisms of nao-an dropping pill in preventing and treating ischemic stroke via the PI3K/Akt/eNOS and Nrf2/HO-1 pathways.

Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen-glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.

Mice harboring the T316N variant in the GABAAR γ2 subunit exhibit sleep-related hypermotor epilepsy phenotypes and hypersynchronization in the thalamocortical pathway.

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by seizures that predominantly occur during sleep. The pathogenesis of these seizures remains unclear. We previously detected rare variants in GABRG2, which encodes the γ2 subunit of γ-aminobutyric acid type A receptor (GABAAR), in patients with SHE and demonstrated that these variants impaired GABAAR function in vitro. However, the mechanisms by which GABRG2 variants contribute to seizure attacks during sleep remain unclear. METHODS: In this study, we designed a knock-in (KI) mouse expressing the mouse Gabrg2 T316N variant, corresponding to human GABRG2 T317N variant, using CRISPR/Cas9. Continuous video-electroencephalogram monitoring and in vivo multichannel electrophysiological recordings were performed to explore seizure susceptibility to pentylenetetrazol (PTZ), alterations in the sleep-wake cycle, spontaneous seizure patterns, and synchronized activity in the motor thalamic nuclei (MoTN) and secondary motor cortex (M2). Circadian variations in the expression of total, membrane-bound, and synaptic GABAAR subunits were also investigated. RESULTS: No obvious changes in gross morphology were detected in Gabrg2T316N/+ mice compared to their wild-type (Gabrg2+/+) littermates. Gabrg2T316N/+ mice share key phenotypes with patients, including sleep fragmentation and spontaneous seizures during sleep. Gabrg2T316N/+ mice showed increased susceptibility to PTZ-induced seizures and higher mortality after seizures. Synchronization of the local field potentials between the MoTN and M2 was abnormally enhanced in Gabrg2T316N/+ mice during light phase, when sleep dominates, accompanied by increased local activities in the MoTN and M2. Interestingly, in Gabrg2+/+ mice, GABAAR γ2 subunits showed a circadian increase on the neuronal membrane and synaptosomes in the transition from dark phase to light phase, which was absent in Gabrg2T316N/+ mice. CONCLUSION: We generated a new SHE mouse model and provided in vivo evidence that rare variants of GABRG2 contribute to seizure attacks during sleep in SHE.

DNA N6-methyladenine methylase N6AMT1 controls neuropathic pain through epigenetically modifying Kcnj16 in dorsal horn neurons.

ABSTRACT: Nerve injury-induced aberrant changes in gene expression in spinal dorsal horn neurons are critical for the genesis of neuropathic pain. N6-methyladenine (m 6 A) modification of DNA represents an additional layer of gene regulation. Here, we report that peripheral nerve injury significantly decreased the level of m 6 A-specific DNA methyltransferase 1 ( N6amt1 ) in dorsal horn neurons. This decrease was attributed, at least partly, to a reduction in transcription factor Nr2f6 . Rescuing the decrease in N6amt1 reversed the loss of m 6 A at the promoter for inwardly rectifying potassium channel subfamily J member 16 ( Kcnj16 ), mitigating the nerve injury-induced upregulation of Kcnj16 expression in the dorsal horn and alleviating neuropathic pain hypersensitivities. Conversely, mimicking the downregulation of N6amt1 in naive mice erased DNA m 6 A at the Kcnj16 promoter, elevated Kcnj16 expression, and led to neuropathic pain-like behaviors. Therefore, decreased N6amt1 caused by NR2F6 is required for neuropathic pain, likely through its regulation of m 6 A-controlled KCNJ16 in dorsal horn neurons, suggesting that DNA m 6 A modification may be a potential new target for analgesic and treatment strategies.

[Combination of acupuncture and medication for dry eye complicated with computer vision syndrome: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy of acupuncture, Chinese medication and combination of acupuncture and medication in the treatment of dry eye complicated with computer vision syndrome (CVS). METHODS: A total of 152 patients with dry eye complicated with CVS were randomly divided into an acupuncture-medication group (38 cases, 1 case was removed), an acupuncture group (38 cases, 1 case dropped off), a Chinese medication group (38 cases, 1 case was removed), and a western medication group (38 cases, 1 case dropped off). In the western medication group, sodium hyaluronate eye drop combined with esculin and digitalis glycosides eye drop were used. In the acupuncture group, acupuncture was applied at bilateral Taiyang (EX-HN 5)， Cuanzhu (BL 2), Fengchi (GB 20), Qimen (LR 14) , and Hegu (LI 4) etc., once a day. In the Chinese medication group, Yiqi Congming decoction formula ganule was given orally, one dose a day. In the acupuncture-medication group, acupuncture combined with Yiqi Congming decoction formula granule were used. All groups were treated for 14 d. The non-invasive first tear film break-up time (NIBUT f), non-invasive average tear film break-up time (NIBUT av), tear meniscus height (TMH), ocular surface disease index (OSDI) score, and CVS symptom score were compared between the patients of each group before and after treatment. RESULTS: After treatment, the NIBUT f, NIBUT av, and TMH were increased compared with those before treatment in the patients of the 4 groups (P<0.01); the NIBUT f and NIBUT av in the acupuncture-medication group and the acupuncture group were higher than those in the Chinese medication group and the western medication group (P<0.05), and the TMH in the acupuncture-medication group and the Chinese medication group were higher than those in the acupuncture group and the western medication group (P<0.05). After treatment, the OSDI scores, the various scores and total scores of CVS (except for head symptom score in the western medication group) were decreased compared with those before treatment in the patients of the 4 groups (P<0.01). The OSDI score, total score, eye symptom score, and body symptom score of CVS in the acupuncture-medication group were lower than those in the acupuncture group, the Chinese medication group, and the western medication group (P<0.01, P<0.05), the head symptom score of the acupuncture-medication group was lower than that in the western medication group (P<0.05), and the CVS physical symptom scores and mental cognitive symptom scores of the acupuncture-medication group and the acupuncture group were lower than those in the Chinese medication group and the western medication group (P<0.05). CONCLUSION: Acupuncture has advantages in improving NIBUT f, NIBUT av, and CVS physical symptoms and cognitive symptoms, and the Chinese medication has advantage in improving TMH. The combination of acupuncture and Chinese medication has better effects compared with monotherapy.

Ability of lactulose breath test results to accurately identify colorectal polyps through the measurement of small intestine bacterial overgrowth.

BACKGROUND: While colorectal polyps are not cancerous, some types of polyps, known as adenomas, can develop into colorectal cancer over time. Polyps can often be found and removed by colonoscopy; however, this is an invasive and expensive test. Thus, there is a need for new methods of screening patients at high risk of developing polyps. AIM: To identify a potential association between colorectal polyps and small intestine bacteria overgrowth (SIBO) or other relevant factors in a patient cohort with lactulose breath test (LBT) results. METHODS: A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology. SIBO was diagnosed by measuring LBT-derived hydrogen (H) and methane (M) levels according to 2017 North American Consensus recommendations. Logistic regression was used to assess the ability of LBT to predict colorectal polyps. Intestinal barrier function damage (IBFD) was determined by blood assays. RESULTS: H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group (41% vs 23%, P < 0.01; 71% vs 59%, P < 0.05, respectively). Within 90 min of lactulose ingestion, the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group (P < 0.01, and P = 0.03, respectively). In 227 patients with SIBO defined by combining H and M values, the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without (15% vs 5%, P < 0.05). In regression analysis with age and gender adjustment, colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO. These models had a sensitivity of ≥ 0.67, a specificity of ≥ 0.64, and an accuracy of ≥ 0.66. CONCLUSION: The current study made key associations among colorectal polyps, SIBO, and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.

GP73 enhances the ox-LDL-induced inflammatory response in THP-1 derived macrophages via affecting NLRP3 inflammasome signaling.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease with its molecular basis incompletely understood. Here, we determined whether the Golgi phosphoprotein 73 (GP73), a novel protein highly related to inflammation and disrupted lipid metabolism, was involved in the development of atherosclerosis. METHODS: Public microarray databases of human vascular samples were analyzed for expression patterns. Apolipoprotein-E-gene-deficient (ApoE-/-) mice (8-week-old) were randomly assigned to either a chow diet group or a high-fat diet group. The levels of serum GP73, lipid profiles and key inflammatory cytokines were determined by ELISA. The aortic root plaque was isolated and used for by Oil Red O staining. PMA-differentiated THP-1 macrophages were transfected with GP73 small interfering RNA (siRNA) or infected with adenovirus expressing GP73, and then stimulated with oxidized low density lipoprotein (ox-LDL). The expressions of pro-inflammatory cytokines and signal pathway key targets were determined by ELISA kit and Western blot respectively. In addition, ichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to measure the intracellular ROS levels. RESULTS: The expressions of GP73 and NLRP3 were substantially upregulated in human atherosclerotic lesions. There were significant linear correlations between GP73 and inflammatory cytokines expressions. High-fat diet-induced atherosclerosis and increased levels of plasma inflammatory mediators (IL-1ß, IL-18, and TNF-α) were observed in ApoE-/- mice. Besides, the expressions of GP73 in the aorta and serum were significantly upregulated and positively correlated with the NLRP3 expression. In the THP-1 derived macrophages, ox-LDL treatment upregulated the expressions of GP73 and NLRP3 proteins and activated the inflammatory responses in a concentration-dependent and time-dependent manner. Silencing of GP73 attenuated the inflammatory response and rescued the decreased migration induced by ox-LDL, inhibiting the NLRP3 inflammasome signaling and the ROS and p-NF-κB activation. CONCLUSIONS: We demonstrated that GP73 promoted the ox-LDL-induced inflammation in macrophages by affecting the NF-κB/NLRP3 inflammasome signaling, and may play a role in atherosclerosis.

Interruption of TRPC6-NFATC1 signaling inhibits NADPH oxidase 4 and VSMCs phenotypic switch in intracranial aneurysm.

Intracranial aneurysm (IA) is a frequent cerebrovascular disorder with unclear pathogenesis. The vascular smooth muscle cells (VSMCs) phenotypic switch is essential for IA formation. It has been reported that Ca2+ overload and excessive reactive oxygen species (ROS) are involved in VSMCs phenotypic switch. The transient receptor potential canonical 6 (TRPC6) and NADPH oxidase 4 (NOX4) are the main pathway to participate in Ca2+ overload and ROS production in VSMCs. Ca2+ overload can activate calcineurin (CN), leading to nuclear factor of activated T cell (NFAT) dephosphorylation to regulate the target gene's transcription. We hypothesized that activation of TRPC6-NFATC1 signaling may upregulate NOX4 and involve in VSMCs phenotypic switch contributing to the progression of IA. Our results showed that the expressions of NOX4, p22phox, p47phox, TRPC6, CN and NFATC1 were significantly increased, and VSMCs underwent a significant phenotypic switch in IA tissue and cellular specimens. The VIVIT (NFATC1 inhibitor) and BI-749327 (TRPC6 inhibitor) treatment reduced the expressions of NOX4, p22phox and p47phox and the production of ROS, and significantly improved VSMCs phenotypic switch in IA rats and cells. Consistent results were obtained from IA Trpc6 knockout (Trpc6-/-) mice. Furthermore, the results also revealed that NFATC1 could regulate NOX4 transcription by binding to its promoter. Our findings reveal that interrupting the TRPC6-NFATC1 signaling inhibits NOX4 and improves VSMCs phenotypic switch in IA, and regulating Ca2+ homeostasis may be an important therapeutic strategy for IA.

Targeting efficacy of spironolactone in patients with heart failure with preserved ejection fraction: the TOPCAT study.

AIMS: We aimed to explore the heterogeneous treatment effects (HTEs) for spironolactone treatment in patients with Heart failure with preserved ejection fraction (HFpEF) and examine the efficacy and safety of spironolactone medication, ensuring a better individualized therapy. METHODS AND RESULTS: We used the causal forest algorithm to discover the heterogeneous treatment effects (HTEs) from patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Cox regressions were performed to assess the hazard ratios (HRs) of spironolactone medication for cardiovascular death and drug discontinuation in each group. The causal forest model revealed three representative covariates and participants were partitioned into four subgroups which were Group 1 (baseline BMI ≤ 31.71 kg/m2 and baseline ALP ≤ 80 U/L, n = 759); Group 2 (BMI ≤ 31.71 kg/m2 and ALP > 80 U/L, n = 1088); Group 3 (BMI > 31.71 kg/m2 , and WBC ≤ 6.6 cells/µL, n = 633); Group 4 (BMI > 31.71 kg/m2 and WBC > 6.6 cells/µL, n = 832), respectively. In the four subgroups, spironolactone therapy reduced the risk of cardiovascular death in high-risk group (Group 4) with both high BMI and WBC count (HR: 0.76; 95% CI 0.58 to 0.99; P = 0.045) but increased the risk in low-risk group (Group 1) with both low BMI and ALP (HR: 1.45; 95% CI 1.02 to 2.07; P = 0.041; P for interaction = 0.020) but showed similar risk of drug discontinuation (P for interaction = 0.498). CONCLUSION: Our study manifested the HTEs of spironolactone in patients with HFpEF. Spironolactone treatment in HFpEF patients is feasible and effective in patients with high BMI and WBC while harmful in patients with low BMI and ALP. Machine learning model could be meaningful for improved categorization of patients with HFpEF, ensuring a better individualized therapy in the clinical setting.

Ionic Chiral Ferrocene Doped Cholesteric Liquid Crystal with Electronically Tunable Reflective Bandwidth performance.

Cholesteric liquid crystals (CLC) were widely used in optical devices as one-dimensional photonic crystals. However, their reflective bands cannot be adjusted, which limits their wide application in many fields. In this paper, a series of ionic chiral ferrocene derivatives (CD-Fc+) as dopants were designed and prepared, and their doping into negative liquid crystal matrix was investigated to develop cholesteric response liquid crystal composites with electrically tunable reflective bands. The effects of electric field frequency, voltage, retention time of voltage and molecular structure on the broadening of reflection bandwidth were investigated in detail.

Long-term efficacy and safety of cap-assisted endoscopic sclerotherapy with long injection needle for internal hemorrhoids.

BACKGROUND: Hemorrhoids are a common anal condition and can afflict an individual at any age. Epidemiological survey results in China show that the prevalence of anorectal diseases is as high as 50.1% among which 98.08% of patients have hemorrhoid symptoms. AIM: To assess long-term efficacy and safety of cap-assisted endoscopic sclerotherapy (CAES) with long injection needle for internal hemorrhoids. METHODS: This study was retrospective. Data from patients with symptomatic internal hemorrhoids treated with CAES using endoscopic long injection needle from April 2016 to December 2019 were collected. Patients were telephoned and followed at two time points, December 2020 and 2021, to evaluate the improvements in symptoms, complications, recurrence, and satisfaction. RESULTS: Two hundreds and one patients with internal hemorrhoids underwent CAES with the long needle. The first median follow-up was performed 33 mo post-operatively. Symptoms improved in 87.5% of patients after the first CAES. Efficacy did not decrease with treatment time extension. Fifty-four patients underwent colonoscopy after the first CAES treatment of which 21 underwent CAES again, and 4 underwent hemorrhoidectomy. At the first follow-up, 62.7% of patients had both improved hemorrhoid grades and symptoms, and 27.4% had a significant improvement in both parameters. At the second follow-up, 61.7% of the patients showed satisfactory improvement in their hemorrhoid grade and symptoms when compared with pre-surgery values. 90% of patients reported CAES was painless, and 85% were satisfied/very satisfied with CAES treatment outcomes. CONCLUSION: The present study based on the largest sample size reported the long-term follow-up of the treatment for internal hemorrhoid with the CAES using endoscopic long injection needle. Our findings demonstrate that CAES should be a micro-invasive endoscopic technology yields satisfactory long-term efficacy and safety.

Simultaneous determination of 31 endocrine disrupting chemicals in fish plasma by solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry.

Solid phase extraction combined with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of 31 endocrine-disrupting chemicals in fish plasma. The strong anion exchange/primary-secondary amine cartridge and the mixed cation exchange cartridge were used in tandem instead of using a single mixed cation exchange cartridge for sample purification. Suitable eluents were selected for each of the two cartridges: 4.5% ammonia/acetonitrile solution for cartridges in tandem and acetone:n-hexane (V:V = 3:7) for the strong anion exchange/primary-secondary amine cartridge alone. With this optimized Solid phase extraction method, the recoveries of 31 endocrine disrupting chemicals were between 43.0% and 131.3%, the method detection limits were 0.45 to 1.35 ng/ml, and the limits of quantitation were 1.50-4.50 ng/ml. The innovative pretreatment method that connects two cartridges in tandem is well positioned to mitigate the matrix effects of fish plasma, thereby improving the accuracy of multiclass endocrine-disrupting chemicals determination. The significance of this method is to facilitate the application of the fish plasma model for the environmental risk assessment of endocrine-disrupting chemicals.

Rare variants in GABRG2 associated with sleep-related hypermotor epilepsy.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome. The underlying pathophysiology is presumed to be closely related with disruption of GABAergic neurotransmission, which is mainly medicated by γ-aminobutyric acid type A receptor (GABAAR). Thus, it is reasonable to assume that rare GABAAR variants might contribute to the pathogenesis of SHE. To test this hypothesis, we performed next-generation sequencing in 58 SHE patients and analyzed the functional effects of the identified variants in both neuronal and non-neuronal cells using a combination of electrophysiology recordings, western blot, flow cytometry, and confocal microscopy. In our study, we detected three rare variants (NM_198904.2: c.269C > T, p.T90M; NM_198904.2: c.950C > A, p.T317N and NM_198903.2: c.649C > T, p.Q217X) in GABRG2 (MIM:137,164, encoding GABAAR γ2 subunit) in three unrelated patients. Two of the three rare variants were transmitted unaffected maternally (T90M) or unaffected paternally (Q217X), whereas the T317N variant arose de novo. The mother of proband carrying the T90M variant was unaffected and being mosaicism for this variant. Functional analysis showed that T90M and T317N variants decreased GABA-evoked current amplitudes by diverse mechanisms including impaired surface expression, endoplasmic reticulum retention, and channel gating defects. And Q217X variant reduced synaptic clustering and distribution of GABAAR. While a causal role of these variants cannot be established directly from these results, the functional assessment together with the genetic sequencing suggests that these rare GABRG2 variants may constitute genetic risk factors for SHE. Our study further expands the GABRG2 phenotypic spectrum and supports the view that GABAergic neurotransmission participates in the epileptogenesis of SHE.

CIDEC: A Potential Factor in Diabetic Vascular Inflammation.

Cell death-inducing DFF45-like effector C (CIDEC) is involved in diet-induced adipose inflammation. Whether CIDEC plays a role in diabetic vascular inflammation remains unclear. A type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated its characteristics by metabolic tests, Western blot analysis of CIDEC and C1q/tumor necrosis factor-related protein-3 (CTRP3) expression, and histopathological analysis of aortic tissues. The diabetic group exhibited elevated CIDEC expression, aortic inflammation, and remodeling. To further investigate the role of CIDEC in the pathogenesis of aortic inflammation, gene silencing was used. With CIDEC gene silencing, CTRP3 expression was restored, accompanied with amelioration of insulin resistance, aortic inflammation, and remodeling in diabetic rats. Thus, the silencing of CIDEC is potent in mediating the reversal of aortic inflammation and remodeling, indicating that CIDEC may be a potential therapeutic target for vascular complications in diabetes.

Cell death-inducing DFFA-like effector C/CIDEC gene silencing alleviates diabetic cardiomyopathy via upregulating AMPKa phosphorylation.

Cell death-inducing DFFA-like effector C (CIDEC) is responsible for metabolic disturbance and insulin resistance, which are considered to be important triggers in the development of diabetic cardiomyopathy (DCM). To investigate whether CIDEC plays a critical role in DCM, DCM rat model was induced by a high-fat diet and a single injection of low-dose streptozotocin (27.5 mg/kg). DCM rats showed severe metabolic disturbance, insulin resistance, myocardial hypertrophy, interstitial fibrosis, ectopic lipid deposition, inflammation and cardiac dysfunction, accompanied by CIDEC elevation. With CIDEC gene silencing, the above pathophysiological characteristics were significantly ameliorated accompanied by significant improvements in cardiac function in DCM rats. Enhanced AMP-activated protein kinase (AMPK) α activation was involved in the underlying pathophysiological molecular mechanisms. To further explore the underlying mechanisms that CIDEC facilitated collagen syntheses in vitro, insulin-resistant cardiac fibroblast (CF) model was induced by high glucose (15.5 mmol/L) and high insulin (104  µU/mL). We observed that insulin-resistant stimulation dramatically raised CIDEC expression and promoted CIDEC nuclear translocation in CFs. Meanwhile, AMPKα2 was observed to distribute almost completely inside CF nucleus. The results further proved that CIDEC biochemically interacted and co-localized with AMPKα2 rather than AMPKα1 in CF nucleus, which provided a novel mechanism of CIDEC in promoting collagen syntheses. This study suggested that CIDEC gene silencing alleviates DCM via AMPKα signaling both in vivo and in vitro, implicating CIDEC may be a promising target for treatment of human DCM.

Prolonged flushing and locking interval for totally implantable vascular access device: A systematic review and meta-analysis.

The objective of this systematic review is to evaluate the safety ad feasibility of the totally implantable vascular access devices (TIVADs) flushed more than 4 weeks. We searched the following electronic databases from the date their build-up to February 2020: PubMed, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL. The final selection resulted in 14 trials fulfilling the inclusion criteria and being included in our review. A pooled frequency of port-related late complications with longer flushing intervals (>4 weeks) was 8.0%, and the pooled frequency of occlusions, infections, and mechanical complications was 5.0%, 2.0%, and 3.0%, respectively. Then, we compared the frequency of port-related complications between standard and longer flushing intervals. There were no differences between the group's changes in the frequency of total late complications, occlusions, infections, and mechanical complications. This systematic review and meta-analysis demonstrates that longer flushing intervals for ports are safe. However, more prospective, power appropriated randomized trials are needed to explore the specific flushing time for ports.

[Ozone Pollution, Nitrogen Addition, and Drought Stress Interact to Affect Non-structural Carbohydrates in the Leaves and Fine Roots of Poplar].

Ground-level ozone (O3) pollution frequently co-occurs with drought and nitrogen (N) deposition during the growing season. It is important to understand how the carbon dynamics of plants respond to O3 pollution in drier and N-enriched environments. Here we present the patterns of non-structural carbohydrates and its components (soluble sugar and starch) in the leaves and fine roots in poplar clone 546 (Populus deltoides cv. '55/56'×P. deltoides cv. 'Imperial') for one growing season at two O3 concentrations (control, charcoal-filtered air, and elevated O3, non-filtered air+40 nmol·mol-1 of O3), two watering regimes (well-watered and reduced watering at 40% of well-watered irrigation), and two soil nitrogen addition treatments[no addition and the addition of 50 kg·(hm2·a)-1]. The results showed that O3 stress significantly increased the content of soluble sugar in leaves and starch in fine roots but decreased the content of starch and total non-structural carbohydrate (NSC) in leaves. Drought stress significantly reduced the content of starch and total NSC in leaves but increased the contents of soluble sugar and total NSC in fine roots. Nitrogen addition had no significant effect on NSC and its components in leaves and fine roots. NSC and its components in leaves and fine roots were positively correlated with photosynthetic rate and biomass. With an increase in the number of environmental stress factors, NSC in leaves showed a significant downward trend while NSC in fine roots showed a significant upward trend. The study demonstrates that environmental stress can promote the transformation of starch into soluble sugars in plant leaves and the transfer of NSC from leaves to roots for storage, which may be a coping strategy for plants exposed to environmental stress.