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Yong-heng Hou,1,* Wen-cheng Shi,2,* Shu Cai,1,* Hong Liu,3 Zhong Zheng,2 Fu-wei Qi,2 Chang Li,4 Xiao-mei Feng,5,6 Ke Peng,1 Fu-hai Ji1 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Taicang First People’s Hospital, Taicang Affiliated Hospital of Soochow University, Taicang, Jiangsu, People’s Republic of China; 3Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA; 4Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 5Department of Anesthesiology, University of Utah health, Salt Lake City, UT, USA; 6Transitional Residency Program, Intermountain Medical Center, Salt Lake City, UT, USA*These authors contributed equally to this workCorrespondence: Ke Peng; Fu-hai JiDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, People’s Republic of ChinaTel +86-159-6215-5989; +86-512-6797-2352Email pengke0422@163.com; jifuhaisuda@163.comPurpose: Surgical stress promotes tumor metastasis. Interleukin (IL)-17 plays a pivotal role in cancer progression, and high IL-17 expression predicts poor prognosis of non-small-cell lung cancer (NSCLC). Lidocaine may exert tumor-inhibiting effects. We hypothesize that intravenous lidocaine attenuates surgical stress and reduces serum IL-17 levels during video-assisted thoracic surgery (VATS) for NSCLC.Methods: This randomized, double-blind, placebo-controlled trial included 60 early-stage NSCLC patients undergoing VATS, into a lidocaine group (n = 30; intravenous lidocaine bolus 1.0 mg/kg, and 1.0 mg/kg/h until the end of surgery) or a normal saline control group (n = 30). The primary outcome was serum IL-17 level at 24 hours postoperatively. The secondary outcomes included serum IL-17 level at the time of post-anesthesia care unit (PACU) discharge, serum cortisol level at PACU discharge and postoperative 24 hours, pain scores (0– 10) from PACU discharge to 48 hours postoperatively, incidences of postoperative nausea and vomiting, dizziness, and arrhythmia during 0– 48 hours postoperatively, and 30-day mortality. Long-term outcomes included chemotherapy, cancer recurrence, and mortality.Results: The lidocaine group had lower serum IL-17 at 24 hours postoperatively compared with the control group (23.0 ± 5.8 pg/mL vs 27.3 ± 8.2 pg/mL, difference [95% CI] = − 4.3 [− 8.4 to − 0.2] pg/mL; P = 0.038). The lidocaine group also had reduced serum IL-17 (difference [95% CI] = − 4.6 [− 8.7 to − 0.5] pg/mL), serum cortisol (difference [95% CI] = − 37 [− 73 to − 2] ng/mL), and pain scores (difference [95% CI] = − 0.7 [− 1.3 to − 0.1] points) at PACU discharge. During a median follow-up of 10 (IQR, 9– 13) months, 2 patients in the lidocaine group and 6 patients in the control group received chemotherapy, one patient in the control group had cancer recurrence, and no death event occurred.Conclusion: Intravenous lidocaine was associated with reduced serum IL-17 and cortisol following VATS procedures in early-stage NSCLC patients.Trial Registration: ChiCTR2000030629.Keywords: lidocaine, interleukin-17, non-small-cell lung cancer, video-assisted thoracic surgery, surgical stress

Introduction: Elderly patients are at a high risk of postoperative delirium (POD), leading to increased postoperative morbidity and mortality. The use of dexmedetomidine and depth of anaesthesia may influence POD. This study aims to determine the effects of dexmedetomidine infusion versus normal saline placebo during light versus deep anaesthesia on POD among elderly patients undergoing major non-cardiac surgery., Methods and Analysis: This prospective, multicentre, randomised, controlled, factorial trial will be conducted at three tertiary hospitals in Jiangsu, China. We will recruit a total of 420 patients who are at least 60 years old and undergoing major non-cardiac surgery (thoracic, abdominal, urology, orthopaedic and spine surgery) under general anaesthesia. Patients will be randomised (1:1:1:1) to receive one of four anaesthesia regimens: (1) dexmedetomidine and light anaesthesia, (2) dexmedetomidine and deep anaesthesia, (3) placebo and light anaesthesia or (4) placebo and deep anaesthesia. Dexmedetomidine will be infused at 0.5 µg/kg/h throughout surgery, and intraoperative bispectral index target will be 55 for light anaesthesia and 40 for deep anaesthesia. The primary outcome is the occurrence of POD during the first 7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method two times per day. The secondary outcomes include days with POD, type of POD, pain scores at rest and on movement at 24 and 48 hours postoperatively, patient-controlled intravenous fentanyl consumption during 0-24 and 24-48 hours postoperatively, hypotension, bradycardia, postoperative nausea and vomiting, non-delirium complications, length of postoperative hospital stay, 30-day cognitive function and 30-day mortality. Data will be analysed on a modified intention-to-treat basis., Ethics and Dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and each participating centre. The trial results will be published in a peer-reviewed journal., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300073271)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The study objective was to evaluate the primary feasibility of endoscopic submucosal resection (ESD) and endoscopic full-thickness resection (EFTR) via balloon-assisted enteroscopy (BAE) to treat small bowel subepithelial lesions (SELs)., Method: A retrospective case series study was performed. The first fifteen consecutive patients who underwent ESD (n = 10) and EFTR (n = 5) via BAE to remove small bowel SELs from November 2016 to December 2023 were included. The main outcome measures were the technique success rate, operative time and complication rate., Results: This research focused on 15 cases of jejunoileal SELs, four cases of lipomyoma, three cases of ectopic pancreas, two cases of NETs, three cases of benign fibrous tumours and three cases of angioma. The overall technique success rate was 86.7%, with 100% (10/10) and 60% (3/5) for BAE-ESD and BAE-EFTR, respectively, in removing small bowel SELs. Two cases of EFTR failed, as the BAE operation was unsuitable for tumour resection and suture repair of a perforated wound. No serious bleeding or any postoperative complications occurred. The median time of endoscopic resection via BAE for SELs was 44 min (range 22-68 min)., Conclusion: ESD and EFTR via BAE might be alternative choices for treating small SELs in the small bowel, with the advantages of clear and accurate positioning and minimal invasiveness. However, its superiority over surgery still needs to be further investigated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cognitive impairments, which can be caused by neurodegenerative and cerebrovascular disease, represent a growing global health crisis with far-reaching implications for individuals, families, healthcare systems, and economies worldwide. Notably, neurodegenerative-induced cognitive impairment often presents a different pattern and severity compared to cerebrovascular-induced cognitive impairment. With the development of computational technology, machine learning techniques have developed rapidly, which offers a powerful tool in radiomic analysis, allowing a more comprehensive model that can handle high-dimensional, multivariate data compared to the traditional approach. Such models allow the prediction of the disease development, as well as accurately classify disease from overlapping symptoms, therefore facilitating clinical decision making. This review will focus on the application of machine learning-based radiomics on cognitive impairment caused by neurogenerative and cerebrovascular disease. Within the neurodegenerative category, this review primarily focuses on Alzheimer's disease, while also covering other conditions such as Parkinson's disease, Lewy body dementia, and Huntington's disease. In the cerebrovascular category, we concentrate on poststroke cognitive impairment, including ischemic and hemorrhagic stroke, with additional attention given to small vessel disease and moyamoya disease. We also review the specific challenges and limitations when applying machine learning radiomics, and provide our suggestion to overcome those limitations towards the end, and discuss what could be done for future clinical use., Competing Interests: The authors declare they have no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Background: The prevalence of self-injury and suicide is higher than the general population of people living with HIV/AIDS (PLWHA). However, the results reported in existing studies are highly variable in China. The purpose of this systematic review and meta-analysis was to synthesize the currently available high-quality evidence to explore the prevalence and influence factors of self-injury and suicide among PLWHA in China., Method: We retrieve literature written in Chinese and English through databases such as PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, WanFang Database, and CQVIP from inception to 1 September 2022. Sata 16.0 software was used for analysis., Results: A total of 28 studies were included with a sample size of 1,433,971 and had a satisfactory quality score of ≥ 5. The prevalence among PLWHA in China were 30% for suicidal ideation (SI), 5% for suicide attempt (SA), 8% for suicide plan (SP), 7% for attempted suicide (AS), and 3‰ for completed suicide. High stigma (OR = 2.94, 95%CI: 1.90 - 4.57), depression (OR, 3.17; 95%CI, 2.20 - 4.57), anxiety (OR, 3.06; 95%CI, 2.23 - 4.20), low self-esteem (OR, 3.82, 95%CI, 2.22 - 6.57), high HIV related stress (OR, 2.53; 95%CI, 1.36 - 4.72), and unemployment (OR, 2.50; 95%CI, 1.51 - 4.15) are risk factors for SI; high social support (OR, 0.61; 95%CI, 0.44 - 0.84) and spouse infected with HIV (OR, 0.39; 95%CI, 0.21 - 0.74) are protective factors for SI; depression (OR, 1.62; 95%CI, 1.24 - 2.13), high aggression (OR, 4.66; 95%CI, 2.59 - 8.39), and more negative life events (OR, 2.51; 95%CI, 1.47 - 4.29) are risk factors for AS; high level of education (OR, 1.31; 95%CI, 1.21 - 1.43) is risk factor for CS., Conclusion: Figures indicate that approximately one-third of PLWHA had suicidal ideation, and three out of 1,000 completed suicide in China. Positive events are protective factors for self-injury and suicide among PLWHA, while negative events are risk factors. This suggests that psychosocial support and risk assessment should be integrated into the care of PLWHA., (© 2024. The Author(s).)

Study Design: A meta-analysis., Objective: This study aimed to analyze the incidence of spontaneous resorption of lumbar disk herniation (LDH) after conservative treatment., Summary of Background Data: The resorption of intervertebral disks has been more frequently reported, but there is a lack of reference to the probability of resorption., Methods: We strictly refer to the standard established in the PRISMA (Preferred Reporting Items for a Systematic Review and Meta-analysis) statement, comprehensively searched electronic databases using the terms related to the spontaneous resorption of LDH. Two reviewers independently evaluated the potential studies, extracted, and analyzed the enrolled data., Results: Thirty-one studies with 2233 patients who received conservative treatment were included for this analysis. We found that the pooled overall incidence of disk resorption was 70.39%, 87.77% for disk sequestration, 66.91% for disk extrusion, 37.53% for disk protrusion, and 13.33% for disk bugle, respectively. The resorption incidence in of 25%≤ reduction of disk herniation (RDH) 50%, RDH≥50%, and RDH=100% were 40.19%, 43.62, and 36.89%. The resorption incidence was 66.98% in Japan, 61.66% in the United States, 83.52% in Korea, 60.68% in China, 78.30% in the UK, 56.70% in Italy, and 83.68% in Turkey, respectively. Subgroup analysis showed that there was no significant difference in resorption incidence among prospective, retrospective studies and randomized controlled trials ( P =0.77), and there was no significant difference in evaluation method among qualitative and quantitative studies ( P =0.05)., Conclusions: The existing evidence shows that the overall resorption incidence of LDH was 70.39%, the resorption incidence of ruptured LDH is higher than that of contained LDH. There are significant differences in the resorption incidence among countries. The resorption process mainly occurred within 6 months of conservative treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This study focuses on recent advances in proteomics and provides an up-to-date use of this technology in identifying cardiovascular disease (CVD) biomarkers. A total of eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang, Vip, Sinomed, and CNKI) were searched and five were used for integrative analysis of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR) and 1 secondary indicator area under the curve (AUC). This systematic review and integrative analysis summarized potential biomarkers previously identified by proteomics. The integrative analysis suggested that proteomics technology had high clinical value in CVD diagnosis. The findings provided new possible directions for the prevention or diagnosis of CVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Frailty, type 2 diabetes (T2D) and dyslipidemia are highly prevalent in middle-aged and elderly populations. However, evidence on the longitudinal association of frailty with T2D and dyslipidemia is limited. The aim of our study was to explore the cross-sectional and longitudinal effects of frailty levels on T2D and dyslipidemia in combination with phenotypic frailty and frailty index (FI)., Materials and Methods: Multivariate logistic regression model was used to explore the association of frailty status with T2D and dyslipidemia. Area under curve (AUC) of the receiver operating characteristic curve (ROC) to estimate the predictive values of phenotypic frailty and frailty index for T2D and dyslipidemia. In addition, depressive symptom was used as a mediating variable to examine whether it mediates the association between frailty and T2D or dyslipidemia., Results: 10,203 and 9587 participants were chosen for the longitudinal association analysis of frailty with T2D and dyslipidemia. Frailty was associated with T2D (phenotypic frailty: OR=1.50, 95 %CI=1.03, 2.17; FI: OR=1.17, 95 %CI=1.08, 1.26) and dyslipidemia (phenotypic frailty: OR=1.56, 95 %CI=1.16, 2.10; FI: OR=1.17, 95 %CI=1.10, 1.25). Phenotypic frailty and frailty index significantly improved the risk discrimination of T2D and dyslipidemia (p<0.05). Depressive symptoms played a mediating role in the association between frailty and long-term T2D or dyslipidemia (p<0.05)., Conclusion: Frailty had adverse effects on type 2 diabetes and dyslipidemia, with depressive symptoms acting as the mediator., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway., Methods: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR., Results: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01)., Conclusions: EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Intervertebral disc degeneration (IDD) is a main contributor to low back pain. Oxidative stress, which is highly associated with the progression of IDD, increases senescence of nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens the differentiation ability of NPMSCs in degenerated intervertebral discs (IVDs). Quercetin (Que) has been demonstrated to reduce oxidative stress in diverse degenerative diseases., Aim: To investigate the role of Que in oxidative stress-induced NPMSC damage and to elucidate the underlying mechanism., Methods: In vitro , NPMSCs were isolated from rat tails. Senescence-associated β-galactosidase (SA-β-Gal) staining, cell cycle, reactive oxygen species (ROS), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and western blot analyses were used to evaluated the protective effects of Que. Meanwhile the relationship between miR-34a-5p and Sirtuins 1 (SIRT1) was evaluated by dual-luciferase reporter assay. To explore whether Que modulates tert-butyl hydroperoxide (TBHP)-induced senescence of NPMSCs via the miR-34a-5p/SIRT1 pathway, we used adenovirus vectors to overexpress and downregulate the expression of miR-34a-5p and used SIRT1 siRNA to knockdown SIRT1 expression. In vivo, a puncture-induced rat IDD model was constructed, and X rays and histological analysis were used to assess whether Que could alleviate IDD in vivo ., Results: We found that TBHP can cause NPMSCs senescence changes, such as reduced cell proliferation ability, increased SA-β-Gal activity, cell cycle arrest, the accumulation of ROS, and increased expression of senescence-related proteins. While abovementioned senescence indicators were significantly alleviated by Que treatment. Que decreased the expression levels of senescence-related proteins (p16, p21, and p53) and senescence-associated secreted phenotype (SASP), including IL-1β, IL-6, and MMP-13, and it increased the expression of SIRT1. In addition, the protective effects of Que on cell senescence were partially reversed by miR-34a-5p overexpression and SIRT1 knockdown. In vivo , X-ray, and histological analyses indicated that Que alleviated IDD in a puncture-induced rat model., Conclusion: In summary, the present study provides evidence that Que reduces oxidative stress-induced senescence of NPMSCs via the miR-34a/SIRT1 signaling pathway, suggesting that Que may be a potential agent for the treatment of IDD., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article. Figures 12A and 13 were created using Figdraw (www.figdraw.com)., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Study Design: A systematic review and meta-analysis., Objective: To evaluate the safety and efficacy of local steroid application (LSA) on dysphagia after anterior cervical discectomy and fusion (ACDF)., Summary of Background Data: Dysphagia is one of the most common adverse events in the early postoperative period of ACDF. LSA is reported as an effective method to reduce the swelling of soft tissues, thereby decreasing the incidence of dysphagia. However, the safety and efficacy of LSA on dysphagia after ACDF need to be systematically reviewed and analyzed., Methods: A comprehensive literature search was carried out in the database PubMed, Web of Science, EMBASE, Clinical key, Cochrane library, and Wiley Online Library to screen papers that report LSA in ACDF surgery. The Cochrane Collaboration tool and a methodological index for nonrandomized studies were used for the assessment of study quality. Data were analyzed with the Review Manager 5.3 software., Results: A total of 10 studies were included. The results revealed no significant differences between the steroid group and the control group in ACDF regarding postoperative drainage, estimated blood loss, and neck disability index score ( P > 0.05). LSA significantly alleviates visual analog scale score for neck pain (or odynophagia) ( P < 0.05), reduces the length of hospital stay (weighted mean difference, -1.00 (-1.05 to -0.95); P < 0.001), and mitigates dysphagia rate and prevertebral soft-tissue swelling in the early postoperative period ( P < 0.05). There seemed to be no significant increase in the complication rate and steroid-related adverse events in the steroid group compared with the control group ( P < 0.05)., Conclusions: LSA shows advantages in reducing the length of hospital stay, decreasing dysphagia rate, and mitigating prevertebral soft-tissue swelling in the early postoperative period of ACDF. Further large-scale studies are urgently required for the development of a standard protocol for LSA and further analysis of potential delay complications., Competing Interests: J.w.W. and P.z.S. contributed equally to this work and share the first authorship. The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Spinal cord injury is an intricate process involving a series of multi-temporal and multi-component pathological events, among which inflammatory response is the core. Thus, it is crucial to find a way to prevent the damaging effects of the inflammatory response. The research has found that Treg cells can suppress the activation, proliferation, and effector functions of many parenchymal cells by multiple mechanisms. This review discusses how Treg cells regulate the inflammatory cells to promote spinal cord recovery. These parenchymal cells include macrophages/microglia, oligodendrocytes, astrocytes, and others. In addition, we discuss the adverse role of Treg cells, the status of treatment, and the prospects of cell-based therapies after spinal cord injury. In conclusion, this review provides an overview of the regulatory role of Treg cells in spinal cord injury. We hope to offer new insights into the treatment of spinal cord injury., (© 2023. The Author(s).)

Intervertebral disc (IVD) degeneration is the common cause of lumbar degenerative diseases, causing severe social and economic burden. The process of IVD degeneration involves a complex of pathologic changes on both extracellular matrix degradation and resident cell apoptosis. In recent years, there is increasing evidence that macrophages play vital roles during the damage and repair process of IVD degeneration. Nevertheless, the interactions between macrophages and IVD are not well understood, even if the IVD has long been regarded as the immune privileged site. Therefore, this review mainly focuses on the progress and obstacles of studies investigating the blood supply, immune response and especially macrophages during the IVD degeneration process., (Copyright © 2022 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: The mechanisms underlying M2 macrophage polarization induced by nucleus pulposus (NP) cells are unclear. The effects that M2-polarized macrophages have on NP cells are also controversial., Methods: Transcriptome sequencing was performed to detect the gene change profiles between NP cells from ruptured intervertebral disc (IVD) and normal IVD. The main difference on biological activities between the two cell groups were analyzed by GO analysis and KEGG analysis. Virus transduction, flow cytometry, immunofluorescence, RT-PCR, western blot, CCK-8, TUNEL staining, and AO/EB staining were performed to explore the interactions between NP cells and RAW264.7 macrophages. Statistics were performed using SPSS26., Results: 801 upregulated and 276 downregulated genes were identified in NP cells from ruptured IVD in mouse models. According to GO and KEGG analysis, we found that the differentially expressed genes (DEG) were dominantly enriched in inflammatory response, extracellular matrix degradation, blood vessel morphogenesis, immune effector process, ossification, chemokine signaling pathway, macrophage activation, etc. CX3CL1 was one of the top 20% DEG, and we confirmed that both NP tissue and cells expressed remarkably higher level of CX3CL1 in mouse models ( p < 0.001 ∗ ). Besides, we further revealed that both the recombinant CX3CL1 and NP cells remarkably induced M2 polarization of RAW264.7 ( p < 0.001 ∗ ), respectively, while this effect was significantly reversed by si-CX3CL1 or JMS-17-2 ( p < 0.001 ∗ ). Furthermore, we found that M2 macrophages significantly decreased the apoptosis rate ( p < 0.001 ∗ ) and the catabolic gene levels ( p < 0.001 ∗ ) of NP cells, while increased the viability, proliferation as well as the anabolic gene levels of NP cells ( p < 0.01 ∗ )., Conclusions: Via regulating CX3CL1/CX3CR1 pathway, NP cells can induce the M2 macrophage polarization. M2 polarized macrophages can further promote NP cell viability, proliferation, and anabolism, while inhibit NP cell apoptosis and catabolism., Competing Interests: No conflict of interest needs to be declared in this study., (Copyright © 2023 Xiao-Tao Wu et al.)

Background: Posterior approach pedicle screw fixation without fusion is widely used in the treatment of neurologically intact type A3 thoracolumbar fractures., Objective: To analyze the influence of the facet joint (FJ) angle on FJ degeneration following posterior approach pedicle screw fixation without fusion in neurologically intact type A3 thoracolumbar fractures., Methods: Fifty-eight patients who underwent pedicle screw fixation via the traditional posterior approach (n= 28) or the Wiltse approach (n= 30) were enrolled. A CT scan was performed before fixation and before fixation removal (Within 1.5 to 2 years after fixation) to evaluate the FJs parameters, including FJ inclination (FJI), FJ tropism (FJT), FJ violation, and FJ degeneration grade (FJDG), of three fixed segments and the adjacent segment below the fixed segments., Results: There was no significant difference in FJ violation rate, FJDG deterioration, or FJ angle between the two groups (P> 0.05). FJDG deterioration showed a weak positive correlation with FJI and FJT before fixation, and the angular change in FJI (P< 0.05); and FJT before fixation and the angular change in FJI were risk factors for FJDG deterioration (P< 0.01)., Conclusion: The Wiltse approach did not increase the rate of FJDG deterioration and FJs angle changes. However, the FJT before fixation and the angular change in FJI were risk factors for FJDG deterioration.

With the recent development of minimally invasive techniques, minimally invasive posterior cervical foraminotomy (MIS-PCF) has become increasingly popular as a minimally invasive method to treat cervical radiculopathy. However, there are still controversies about whether MIS-PCF is superior to anterior cervical discectomy and fusion (ACDF). The purpose of this study is to evaluate the therapeutic effects of MIS-PCF and ACDF on unilateral cervical radiculopathy without myelopathy. We searched PubMed, Embase, the Cochrane Library, and Scopus comprehensively using the terms related to MIS-PCF. Two reviewers independently evaluated the potential studies, and extracted and analyzed the data of operation time, hospital stay, neck disability index (NDI) score, visual analog scale for neck pain (VAS-neck) and arm pain (VAS-arm) scores, reoperation rate, and complications. Seven studies with 1175 patients were included. The study population was 53.5% male, with a mean age of 48.9. MIS-PCF presented a significantly shorter postoperative hospitalization time compared to ACDF, while the operation time, complication/reoperation rate, and VAS-arm, VAS-neck, and NDI scores were comparable between the two cohorts. In North America, the average cost of MIS-PCF is lower than ACDF. Thus, we suggest that MIS-PCF is an alternative to ACDF for selected patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The purpose of this study is to evaluate the change patterns of leg numbness (LN) after lumbar decompression surgery (LDS), and to find the predictive factors that affect the recovery of numbness., Methods: Patients who underwent LDS in our institution between August 2020 and July 2021 were prospectively enrolled in this study, and were followed by a 12-month follow-up. The degree of LN, leg pain (LP) and the disability were assessed using the visual analog scale (VAS) and oswestry disability index (ODI)., Results: A total of 314 patients finished the 12-month follow-up. The preoperative mean VAS-LN score was 3.49 ± 2.44, which decreased to 1.91 ± 1.30 at 3 months, to 1.29 ± 0.97 at 6 months and to 1.26 ± 0.96 at 12 months after surgery. The preoperative mean VAS-LP score was 6.05 ± 1.30, which decreased to 2.00 ± 0.86 at 3 months, to 1.02 ± 0.80 at 6 months, and to 0.49 ± 0.71 at 12 months after surgery. The preoperative mean ODI score was 27.90 ± 7.08, which decreased to 9.73 ± 3.09 at 3 months, to 6.72 ± 2.98 at 6 months, and to 4.57 ± 2.76 at 12 months after surgery. Via multivariate logistic regression analysis, only preoperative VAS-LN score (p < 0.001*) was identified as a significantly independent predictive factor for residual LN after operation., Conclusion: Clinically significant improvement in LN was observed in the majority of patients within 6 months after LDS, and the improvement of VAS-LN was slower than the VAS-LP. High pre-operative VAS-LN score can independently predict the presence of residual LN after surgery at 12-month follow up., (© 2022. The Author(s).)

Objective: Cluster classification based on m6A methylation regulators and construct prognostic evaluation model. Methods: Utilizing consensus cluster to classify the liver cancer samples form TCGA based on the expression of 13 m6A methylation regulators, and verify the function and prognostic significance of the clustered subtypes. Marker genes were further screened to construct a risk prediction model for evaluating the prognosis of liver cancer patients. Results: The two clustered subtypes based on m6A methylation regulators showed significant differences in the prognosis value of liver cancer patients ( P =0.048), and 38 prognostic markers related to m6A methylation in liver cancer were screened from the subgroup with poor prognosis. Two m6A regulatory genes, YTHDF1 and YTHDF2, are proved with adverse prognosis by univariate cox analysis ( P <0.05, Hazard ratio>1). We used Lasso regression method to build risk assessment model and effectively predicted the prognosis status of liver cancer patients within 4 years (4-year AUC=0.685, 3-year AUC=0.669). Moreover, the assessment model was validated in another dataset of Asia liver cancer patients. Conclusion: The study provided ideas for studying m6A methylation in liver cancer, and the risk prediction model can be used to evaluate the short-term prognosis of liver cancer patients.

Background: The mechanisms underlying myocardial ischemia/reperfusion (I/R) injury are not fully understood. This study aims to explore key candidate genes and potential therapeutic targets for treatment of myocardial I/R injury. Methods: The transcriptional profiles of ventricular myocardium during cardiac arrest, ischemia, and reperfusion were obtained from the Gene Expression Omnibus database. Based on the transcriptional data of GSE6381, functional pathway and process enrichment analyses, protein-protein interaction network, and gene set enrichment analyses were conducted. In the animal experiments, we established the myocardial I/R injury model in mice. We validated the mRNA and protein expression of the key genes using the qPCR and western blots. We further assessed the expression and localization of CCL21 and its receptors using immunofluorescence staining experiments. Results: The microarray analyses identified five key genes ( CCL21 , XCR1 , CXCL13 , EDN1 , and CASR ). Myocardial I/R process in mice resulted in significant myocardial infraction, histological damage, and myocardial apoptosis. The results of qPCR and western blots showed that the expression of CCL21 and CXCL13 were increased following myocardial I/R injury in mice. Furthermore, the immunofluorescence staining results revealed that the expression of GPR174/CCR7 (CCL21 receptors), but not CXCR5 (CXCL13 receptor), was elevated following myocardial I/R injury. Moreover, the activated CCL21-GPR174/CCR7 signaling was located on the cardiac fibroblasts of the myocardium with I/R injury. Conclusion: This study revealed several key factors underlying myocardial I/R injury. Of these, the activation of CCL21-GPR174/CCR7 signaling on cardiac fibroblasts was highlighted, which provides potential therapeutic targets for cardioprotection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Meng, Zhang, Hu, Chen, Long, Liu, Feng, Ji and Peng.)

Background: Opioid-free anesthesia (OFA) may improve postoperative outcomes by reducing opioid-related adverse effects. This study aims to evaluate the effects of OFA on postoperative nausea and vomiting (PONV), postoperative pain, and 30-day outcomes after thyroid and parathyroid surgery., Methods: This two-center, randomized, double-blind, controlled trial will include 400 adult patients scheduled for thyroid and parathyroid surgery. Patients will be randomly assigned, 1:1 and stratified by sex and site, to an OFA group (esketamine, lidocaine, and dexmedetomidine) or a control group (opioid-based anesthesia with sufentanil). All patients will receive propofol-based total intravenous anesthesia and PONV prophylaxis with dexamethasone and ondansetron. The primary outcome is the incidence of PONV (defined as experiencing any event of nausea, retching, or vomiting) during the first 48 h postoperatively. The secondary outcomes include the severity of PONV, antiemetic rescue therapy, pain scores at rest and while coughing, need for rescue analgesia, perioperative adverse effects related to anesthetics or analgesics (hypotension, bradycardia, hypertension, tachycardia, desaturation, dizziness, headache, hallucination, and nightmare), time to extubation, length of post-anesthesia care unit stay, length of postoperative hospital stay, patient satisfaction, and a composite of 30-day major adverse events (myocardial infarction, cardiac arrest, cerebrovascular accident, coma, acute renal failure, pulmonary embolism, sepsis, septic shock, deep neck space infection, reintubation, reoperation, blood transfusion, failure to wean off ventilator, and death). Analyses will be performed in the modified intention-to-treat population., Discussion: We hypothesize that our OFA regimen reduces PONV after thyroid and parathyroid surgery. We will also investigate whether OFA leads to improvements in postoperative pain and major adverse events. Our results will offer evidence for optimizing anesthesia regimens in patients who undergo thyroid and parathyroid surgical procedures., Clinical Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR2200059656., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Long, Sun, Zhu, Feng, Liu, Ji and Peng.)

Importance: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown., Objective: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant., Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population., Interventions: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine., Main Outcomes and Measures: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30., Results: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit., Conclusions and Relevance: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

Background: Same-day esophagogastroduodenoscopy and colonoscopy procedures under sedation have been increasingly performed. This study aims to assess the effects of esketamine combined with ciprofol (a novel anesthetic/sedative agent) or propofol on respiratory and hemodynamic adverse events in patients undergoing same-day bidirectional endoscopy. Methods: This is a prospective, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. A total of 180 adult patients scheduled for same-day bidirectional endoscopy under sedation will be randomized, in a 1:1:1:1 ratio, to receive 1 of 4 sedation regimens: 1) ciprofol and esketamine, 2) propofol and esketamine, 3) ciprofol and normal saline placebo, or 4) propofol and normal saline placebo. The primary outcome is a composite of desaturation [peripheral oxygen saturation (SpO 2 ) < 95%] and hypotension [mean blood pressure (MBP) < 65 mmHg or decrease in MBP ≥20% of baseline] during the sedation and in the recovery room. Secondary outcomes include episodes of desaturation, severe desaturation (SpO 2 < 90%), hypotension, severe hypotension (decrease in MBP ≥30% of baseline), bradycardia, postoperative nausea and vomiting, dizziness or headache, hallucination or nightmare, injection pain, pain scores and fatigue scores, endoscopist satisfaction, and patient satisfaction. Data will be analyzed on the modified intention-to-treat basis. Discussion: We hypothesize that esketamine as an adjuvant to ciprofol or propofol sedation would improve cardiorespiratory stability. In addition, the potential interactions between interventions will be explored using the factorial design. The results of this trial will provide evidence for daily practice of sedation regimens for same-day bidirectional endoscopy. Clinical Trial Registration: Chinese Clinical Trials Registry, Identifier ChiCTR2100052523., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Long, Feng, Ding, Feng, Liu, Ji and Peng.)

Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. The local environment of the degenerated intervertebral disc (IVD) increases oxidative stress and apoptosis of endogenous nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens its ability of endogenous repair ability in degenerated IVDs. A suitable concentration of 1 α ,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) has been certified to reduce oxidative stress and cell apoptosis. The current study investigated the protective effect and potential mechanism of 1,25(OH) 2 D 3 against oxidative stress-induced damage to NPMSCs. The present results showed that 1,25(OH) 2 D 3 showed a significant protective effect on NPMSCs at a concentration of 10 -10  M for 24 h. Protective effects of 1,25(OH) 2 D 3 were also exhibited against H 2 O 2 -induced NPMSC senescence, mitochondrial dysfunction, and reduced mitochondrial membrane potential. The Annexin V/PI apoptosis detection assay, TUNEL assay, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction assay showed that pretreatment with 1,25(OH) 2 D 3 could alleviate H 2 O 2 -induced NPMSC apoptosis, including the apoptosis rate and the expression of proapoptotic-related (Caspase-3 and Bax) and antiapoptotic-related (Bcl-2) proteins. The intracellular expression of p-Akt increased after pretreatment with 1,25(OH) 2 D 3 . However, these protective effects of 1,25(OH) 2 D 3 were significantly decreased after the PI3K/Akt pathway was inhibited by the LY294002 treatment. In vivo , X-ray, MRI, and histological analyses showed that 1,25(OH) 2 D 3 treatment relieved the degree of IVDD in Sprague-Dawley rat disc puncture models. In summary, 1,25(OH) 2 D 3 efficiently attenuated oxidative stress-induced NPMSC apoptosis and mitochondrial dysfunction via PI3K/Akt pathway and is a promising candidate treatment for the repair of IVDD., Competing Interests: The authors declare no conflict of interest regarding the publication of this paper., (Copyright © 2022 Jun-wu Wang et al.)

Glial cells play an important role in signal transduction, energy metabolism, extracellular ion homeostasis and neuroprotection of the central nervous system. However, few studies have explained the potential effects of exosomes from glial cells on central nervous system health and disease. In this study, the genes expressed in exosomes from astrocytes and microglia were identified by deep RNA sequencing. Kyoto Encyclopedia of Genes and Genomes analysis indicated that several pathways in these exosomes are responsible for promoting neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. Gene ontology analysis showed that extracellular exosome, mitochondrion and growth factor activity were enriched in exosomes from the unique astrocyte group, while extracellular exosome and mitochondrion were enriched in exosomes from the unique microglia group. Next, combined with the screening of hub genes, the protein-protein interaction network analysis showed that exosomes from astrocytes influence neurodegenerative diseases through metabolic balance and ubiquitin-dependent protein balance, whereas exosomes from microglia influence neurodegenerative diseases through immune inflammation and oxidative stress. Although there were differences in RNA expression between exosomes from astrocytes and microglia, the groups were related by the hub genes, ubiquitin B and heat shock protein family A (Hsp70) member 8. Ubiquitin B appeared to be involved in pleiotropic regulatory functions, including immune regulation, inflammation inhibition, protein catabolism, intracellular protein transport, exosomes and oxidative stress. The results revealed the clinical significance of exosomes from glia in neurodegenerative diseases. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. S20180102-152) on January 2, 2018., Competing Interests: None

Background: Results from previous studies evaluating the effects of remote ischemic preconditioning (RIPC) on morbidity and mortality after cardiac surgery are inconsistent. This meta-analysis of randomized controlled trials (RCTs) aims to determine whether RIPC improves cardiac and renal outcomes in adults undergoing cardiac surgery., Methods: PubMed, EMBASE, and Cochrane Library were comprehensively searched to identify RCTs comparing RIPC with control in cardiac surgery. The coprimary outcomes were the incidence of postoperative myocardial infarction (MI) and the incidence of postoperative acute kidney injury (AKI). Meta-analyses were performed using a random-effect model. Subgroup analyses were conducted according to volatile only anesthesia versus propofol anesthesia with or without volatiles, high-risk patients versus non-high-risk patients, and Acute Kidney Injury Network (AKIN) or Kidney Disease Improving Global Outcomes (KDIGO) criteria versus other criteria for AKI diagnosis., Results: A total of 79 RCTs with 10,814 patients were included. While the incidence of postoperative MI did not differ between the RIPC and control groups (8.2% vs 9.7%; risk ratio [RR] = 0.87, 95% confidence interval [CI], 0.76-1.01, P = .07, I2 = 0%), RIPC significantly reduced the incidence of postoperative AKI (22% vs 24.4%; RR = 0.86, 95% CI, 0.77-0.97, P = .01, I2 = 34%). The subgroup analyses showed that RIPC was associated with a reduced incidence of MI in non-high-risk patients, and that RIPC was associated with a reduced incidence of AKI in volatile only anesthesia, in non-high-risk patients, and in the studies using AKIN or KDIGO criteria for AKI diagnosis., Conclusions: This meta-analysis demonstrates that RIPC reduces the incidence of AKI after cardiac surgery. This renoprotective effect of RIPC is mainly evident during volatile only anesthesia, in non-high-risk patients, and when AKIN or KDIGO criteria used for AKI diagnosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P <0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue( t =1.262, P =0.025),whereas the expression of H19 showed an opposite trend( t =1.285, P =0.005).The expression levels of CASC2 in QBC939( t =8.114, P =0.015)and HuH-28( t =9.202, P =0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE( t =-10.244, P <0.001),QBC939( t =-10.476, P <0.001),HuH-28( t =-19.798, P <0.001),and HuCCT1( t =-16.193, P =0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation( χ 2 =6.222, P =0.022)and lymph node metastasis( χ 2 =5.455, P =0.020),and that of lncRNA H19 with pathological differentiation( χ 2 =1.174, P =0.029)and tumor size( χ 2 =-0.507, P =0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.

For some infectious diseases such as mumps, HBV, there is evidence showing that vaccinated individuals always lose their immunity at different rates depending on the inoculation time. In this paper, we propose an age-structured epidemic model using a step function to describe the rate at which vaccinated individuals lose immunity and reduce the age-structured epidemic model to the delay differential model. For the age-structured model, we consider the positivity, boundedness, and compactness of the semiflow and study global stability of equilibria by constructing appropriate Lyapunov functionals. Moreover, for the reduced delay differential equation model, we study the existence of the endemic equilibrium and prove the global stability of equilibria. Finally, some numerical simulations are provided to support our theoretical results and a brief discussion is given., (© The Editorial Office of AMAS & Springer-Verlag GmbH Germany 2022.)

Study Design: A systematic review and meta-analysis., Objectives: To evaluate clinical and radiographic outcomes, and perioperative complications of oblique lateral interbody fusion (OLIF) for adult spinal deformity (ASD)., Methods: We performed a systematic review and meta-analysis of related studies reporting outcomes of OLIF for ASD. The clinical outcomes were assessed by visual analogue scale (VAS) and Oswestry Disability Index (ODI). The radiographic parameters were evaluated by sagittal vertical axis (SVA), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence-lumbar lordosis (PI-LL), Cobb angle and fusion rate. A random effects model and 95% confidence intervals (CI) were performed to investigate the results., Results: A total of 16 studies involving 519 patients were included in the present study. The mean difference of VAS-back score, VAS-leg score and ODI score before and after surgery was 5.1, 5.0 and 32.3 respectively. The mean correction of LL was 20.6°, with an average of 6.9° per level and the mean correction of Cobb was 16.4°, with an average of 4.7° per level. The mean correction of SVA, PT, SS, TK and PI-LL was 59.3 mm, 11.7°, 6.9°, 9.4° and 20.6° respectively. The mean fusion rate was 94.1%. The incidence of intraoperative and postoperative complications was 4.9% and 29.6% respectively., Conclusions: OLIF is an effective and safe surgery method in the treatment of mild or moderate ASD and it has advantages in less intraoperative blood loss and lower perioperative complications.

Background: In degenerative intervertebral disc (IVD), an unfavorable IVD environment leads to increased senescence of nucleus pulposus (NP)-derived mesenchymal stem cells (NPMSCs) and the inability to complete the differentiation from NPMSCs to NP cells, leading to further aggravation of IVD degeneration (IDD). Urolithin A (UA) has been proven to have obvious effects in delaying cell senescence and resisting oxidative stress., Aim: To explore whether UA can alleviate NPMSCs senescence and to elucidate the underlying mechanism., Methods: In vitro , we harvested NPMSCs from rat tails, and divided NPMSCs into four groups: the control group, H 2 O 2 group, H 2 O 2 + UA group, and H 2 O 2 + UA + SR-18292 group. Senescence-associated β-Galactosidase (SA-β-Gal) activity, cell cycle, cell proliferation ability, and the expression of senescence-related and silent information regulator of transcription 1/PPAR gamma coactivator-1α (SIRT1/ PGC-1α) pathway-related proteins and mRNA were used to evaluate the protective effects of UA. In vivo , an animal model of IDD was constructed, and X-rays, magnetic resonance imaging, and histological analysis were used to assess whether UA could alleviate IDD in vivo ., Results: We found that H 2 O 2 can cause NPMSCs senescence changes, such as cell cycle arrest, reduced cell proliferation ability, increased SA-β-Gal activity, and increased expression of senescence-related proteins and mRNA. After UA pretreatment, the abovementioned senescence indicators were significantly alleviated. To further demonstrate the mechanism of UA, we evaluated the mitochondrial membrane potential and the SIRT1/PGC-1α pathway that regulates mitochondrial function. UA protected mitochondrial function and delayed NPMSCs senescence by activating the SIRT1/PGC-1α pathway. In vivo , we found that UA treatment alleviated an animal model of IDD by assessing the disc height index, Pfirrmann grade and the histological score., Conclusion: In summary, UA could activate the SIRT1/PGC-1α signaling pathway to protect mitochondrial function and alleviate cell senescence and IDD in vivo and vitro ., Competing Interests: Conflict-of-interest statement: The authors have no relevant financial or non-financial interests to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Study Objective: To determine the effect of dexmedetomidine on acute kidney injury (AKI) following endovascular aortic repair (EVAR) for Stanford type B aortic dissection (TBAD)., Design: Randomized, double-blind, placebo-controlled, pilot study., Setting: University Hospital., Patients: 102 TBAD patients undergoing EVAR procedures were enrolled. Patients with dissection involving aortic arch or renal artery were excluded., Interventions: Patients were randomly assigned, in a 1:1 ratio, to a dexmedetomidine group (intravenous dexmedetomidine 0.4 μg/kg/h immediately after anesthesia induction and 0.1 μg/kg/h after extubation, which was maintained until 24 h) or a normal saline control group., Measurements: The primary outcome was the incidence of AKI within the first two days after surgery, based on the Acute Kidney Injury Network (AKIN) criteria. The secondary outcomes included serum cystatin C and estimated glomerular filtration rate on postoperative days 1, 2, and 7, and in-hospital need for renal replacement therapy (RRT). Long-term outcomes included RRT and all-cause mortality., Main Results: Ninety-eight patients completed the study (dexmedetomidine, n = 48; control, n = 50). AKIN stage 1 AKI occurred in 3/48 (6.3%) patients receiving dexmedetomidine, compared with 11/50 (22%) patients receiving normal saline (odds ratio = 0.24, 95% CI: 0.07 to 0.89, P = 0.041). This difference remained significant after adjusting for baseline covariates (adjusted odds ratio = 0.21, 95% CI: 0.05 to 0.84; P = 0.028). Dexmedetomidine led to a lower serum cystatin C on postoperative day 1 (median [IQR] mg/L: 1.31 [1.02-1.72] vs. 1.58 [1.28-1.96]). There were no between-group differences in other secondary or long-term outcomes. During the follow-up (median = 28.4 months), 1 patient in the dexmedetomidine group and 3 patients in the control group required RRT., Conclusions: Dexmedetomidine reduced the incidence of AKI in TBAD patients after EVAR procedures. The long-term benefits of dexmedetomidine in this patient population warrant further investigation., Trial Registration: ChiCTR-IPR-15006372., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Patients undergoing major laparoscopic surgery often experience significant pain and postoperative nausea and vomiting (PONV). Deep neuromuscular block (NMB) improves surgical conditions and facilitates the application of low intra-abdominal pressure (IAP), which may be beneficial for these patients. This study is designed to determine the effects of deep NMB combined with low IAP, as compared to moderate NMB combined with standard IAP, on patients' nociceptive recovery after major laparoscopic gastrointestinal surgery., Study Design and Methods: This single-center randomized controlled trial will include 220 patients scheduled for major laparoscopic gastrointestinal surgery (lasts for ≥ 90 minutes). Patients will be randomly assigned, with a 1:1 ratio, into a deep NMB + low IAP group (train of four = 0, post-tetanic count = 1-3, IAP = 8 mmHg) and a moderate NMB + standard IAP group (train of four = 1-3, IAP = 12 mmHg). If the surgical workspace is inadequate, the surgeons can request a step increase of 1 mmHg in IAP during 3-min intervals. The upper limit of IAP will be set at 15 mmHg. Postoperative recovery will be assessed using the postoperative quality recovery scale (PQRS). The primary outcome of this trial is the PQRS nociceptive recovery (including pain and PONV) at postoperative day (POD) 1. The secondary outcomes include recovery in other PQRS domains at POD 1, and recovery in all PQRS domains in a post-anesthesia care unit, at POD 3 in the surgical wards, at hospital discharge, and at postoperative 30 days. For the sample size estimation, 110 patients in each group (220 in total) would be needed to detect an absolute increase rate of 20% in the PQRS nociceptive domain in the deep NMB + low IAP group at POD 1., Discussion: This study investigates the effects of deep NMB combined with low IAP on postoperative PQRS nociceptive recovery in patients undergoing major laparoscopic gastrointestinal surgery. We expect that this deep NMB + low IAP strategy would improve postoperative pain and PONV following major laparoscopic gastrointestinal surgery., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Long et al.)

Purpose: Urethral pain syndrome is a chronic condition characterized by disturbing feeling or server pain sensed at the urethra without specific treatment. This double-center, two-arm controlled trial aimed to explore the efficacy of electrical pudendal nerve stimulation (EPNS) versus intravesical instillation (II) of heparin and alkalinized lidocaine for urethral pain syndrome (UPS)., Methods: Eighty eligible patients took three sessions of EPNS, or 1 session of II per week, for 6 consecutive weeks. The primary end point was the change of pelvic pain and urgency/frequency symptom (PUF) score from baseline to week 6. Secondary outcome measures included changes of visual analogue scale (VAS) score and three sub-score extracted from PUF score., Results: The enrolled participants were all included in the intention-to-treat analyses, and baseline characteristics between the two groups were well balanced. The post-treatment PUF score decreased by 10.0 (7.00, 16.50) in the EPNS group, and by 7.0 (3.00, 10.00) in the II group. At the closure of treatment, the medians of changes in symptom score, bother score, pain-related score and VAS score were 6.50 (4.25, 10.00), 4.00 (2.00, 6.00), 6.00 (5.00, 8.00),4.50 (2.25, 6.00), respectively, in the EPNS group, and 4.00 (2.00, 7.00), 3.00 (1.00, 3.00), 3.00 (2.00, 6.00), 2.00 (1.00, 4.00), respectively, in the II group. All the between-group differences were statistically significant., Conclusion: Compared with the II, the EPNS results in superior pain control and better relief of lower urinary tract symptoms, and deserves further attention., Trial Registration: ClinicalTrials.gov (NCT03671993)., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Postoperative ileus is common after abdominal surgery, and small clinical studies have reported that intraoperative administration of dexmedetomidine may be associated with improvements in postoperative gastrointestinal function. However, findings have been inconsistent and study samples have been small. Further examination of the effects of intraoperative dexmedetomidine on postoperative gastrointestinal function is needed., Objective: To evaluate the effects of intraoperative intravenous dexmedetomidine vs placebo on postoperative gastrointestinal function among older patients undergoing abdominal surgery., Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at the First Affiliated Hospital of Anhui Medical University in Hefei, China (lead site), and 12 other tertiary hospitals in Anhui Province, China. A total of 808 participants aged 60 years or older who were scheduled to receive abdominal surgery with an expected surgical duration of 1 to 6 hours were enrolled. The study was conducted from August 21, 2018, to December 9, 2019., Interventions: Dexmedetomidine infusion (a loading dose of 0.5 μg/kg over 15 minutes followed by a maintenance dose of 0.2 μg/kg per hour) or placebo infusion (normal saline) during surgery., Main Outcomes and Measures: The primary outcome was time to first flatus. Secondary outcomes were postoperative gastrointestinal function measured by the I-FEED (intake, feeling nauseated, emesis, physical examination, and duration of symptoms) scoring system, time to first feces, time to first oral feeding, incidence of delirium, pain scores, sleep quality, postoperative nausea and vomiting, hospital costs, and hospital length of stay., Results: Among 808 patients enrolled, 404 were randomized to receive intraoperative dexmedetomidine, and 404 were randomized to receive placebo. In total, 133 patients (60 in the dexmedetomidine group and 73 in the placebo group) were excluded because of protocol deviations, and 675 patients (344 in the dexmedetomidine group and 331 in the placebo group; mean [SD] age, 70.2 [6.1] years; 445 men [65.9%]) were included in the per-protocol analysis. The dexmedetomidine group had a significantly shorter time to first flatus (median, 65 hours [IQR, 48-78 hours] vs 78 hours [62-93 hours], respectively; P < .001), time to first feces (median, 85 hours [IQR, 68-115 hours] vs 98 hours [IQR, 74-121 hours]; P = .001), and hospital length of stay (median, 13 days [IQR, 10-17 days] vs 15 days [IQR, 11-18 days]; P = .005) than the control group. Postoperative gastrointestinal function (as measured by the I-FEED score) and delirium incidence were similar in the dexmedetomidine and control groups (eg, 248 patients [72.1%] vs 254 patients [76.7%], respectively, had I-FEED scores indicating normal postoperative gastrointestinal function; 18 patients [5.2%] vs 12 patients [3.6%] had delirium on postoperative day 3)., Conclusions and Relevance: In this randomized clinical trial, the administration of intraoperative dexmedetomidine reduced the time to first flatus, time to first feces, and length of stay after abdominal surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative recovery of gastrointestinal function among older adults., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800017232.

Based on the migratory phenomenon of the puffer and the cone-shaped structures on its skin, the effects of spinal height and tilt angle on the drag reduction characteristics is presented by numerical simulation in this paper. The results show that the trend of total drag reduction efficiency changes from slow growth to a remarkable decline, while the viscous drag reduction efficiency changes from an obvious increase to steady growth. The total and viscous drag reduction efficiencies are 19.5% and 31.8%, respectively. In addition, with the increase in tilt angle, the total drag reduction efficiency decreases gradually; the viscous drag reduction efficiency first increases and then decreases, finally tending to be stable; and the total and viscous drag reduction efficiency reaches 20.7% and 26.7%, respectively. The flow field results indicate that the pressure drag mainly originates at the front row of the spines and that the total pressure drag can be effectively controlled by reducing the former pressure drag. With the increase in low-speed fluid and the reduction in the near-wall fluid velocity gradient, the viscous drag can be weakened. Nevertheless, the drag reduction effect is achieved only when the decrement of viscous drag is greater than the increment of pressure drag. This work can serve as a theoretical basis for optimizing the structure and distribution parameters of spines on bionic non-smooth surfaces.

Background: Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery., Methods: This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 μg kg -1 min -1 was initiated before or immediately after cardiopulmonary bypass and lasted for < 24 h. The primary outcome was 5-year survival after cardiac surgery. The propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting approaches were used to minimise bias. Survival analyses were performed with Cox proportional-hazard models., Results: The median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P<0.001), and after adjustment with PSM (HR=0.63; 95% CI, 0.45-0.89; P=0.009), IPTW (HR=0.70; 95% CI, 0.51-0.95; P=0.023), or overlap weighting (HR=0.67; 95% CI, 0.51-0.89; P=0.006). The 5-yr mortality rate after cardiac surgery was 13% and 20% in the dexmedetomidine and non-dexmedetomidine groups, respectively (PSM adjusted odds ratio=0.61; 95% CI, 0.42-0.89; P=0.010)., Conclusion: Perioperative dexmedetomidine infusion was associated with improved 5-yr survival in patients undergoing cardiac surgery., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

The changes in near-surface soil freeze-thaw cycles (FTCs) are crucial to understanding the related hydrological and biological processes in terrestrial ecosystems under a changing climate. However, long-term dynamics of soil FTCs at the hemisphere scale and the underlying mechanisms are not well understood. In this study, the spatiotemporal patterns and main driving factors of soil FTCs across the Northern Hemisphere (NH) during 1979-2017 were analyzed using multisource data fusion and attribution approaches. Our results showed that the duration and the annual mean area of frozen soil in the NH decreased significantly at rates of 0.13 ± 0.04 days/year and 4.9 × 10 4 km 2 /year, respectively, over the past 40 years. These were mainly because the date of frozen soil onset was significantly delayed by 0.1 ± 0.02 days/year, while the end of freezing and onset of thawing were substantially advanced by 0.21 ± 0.02 and 0.15 ± 0.03 days/year, respectively. Moreover, the interannual FTC changes were more drastic in Eurasia than in North America, especially at mid-latitudes (30°-45° N) and in Arctic regions (>75° N). More importantly, our results highlighted that near-surface air temperature ( T a ) and snowpack are the main driving factors of the spatiotemporal variations in soil FTCs. Furthermore, our results suggested that the long-term dynamics of soil FTCs at the hemisphere scale should be considered in terrestrial biosphere models to reduce uncertainties in future simulations., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Graft versus host disease (GVHD) is a common complication and the leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Pharmacological immunosuppression used in GVHD prophylaxis and treatment lacks specificity and can increase the likelihood of infection and relapse. Regulatory T lymphocytes (Tregs) play a vital role in restraining excessive immune responses and inducing peripheral immune tolerance. In particular, clinical trials have demonstrated that Tregs can prevent and treat GVHD, without increasing the risk of relapse and infection. Hence, adoptive transfer of Tregs to control GVHD using their immunosuppressive properties represents a promising therapeutic approach. To optimally apply Tregs for control of GVHD, a thorough understanding of their biology is necessary. In this review, we describe the biological characteristics of Tregs, including how the stability of FOXP3 expression can be maintained. We will also discuss the mechanisms underlying Tregs-mediated modulation of GVHD and approaches to effectively increase Tregs' numbers. Finally, we will examine the developing trends in the use of Tregs for clinical therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guo, Su, Wang, Han, Feng and Jiang.)

Background: Endoplasmic reticulum stress (ERS)-mediated myocardial inflammation and apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has been used clinically with sedative, analgesic, and anti-inflammatory properties. This study aimed to determine the effects of dexmedetomidine pretreatment on inflammation, apoptosis, and the expression of ERS signaling during myocardial I/R injury., Methods: Rats underwent myocardial ischemia for 30 min and reperfusion for 6 h, and H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury (OGD for 12 h and reoxygenation for 3 h). Dexmedetomidine was administered prior to myocardial ischemia in rats or ODG in cardiomyocytes. In addition, the α2-adrenergic receptor antagonist (yohimbine) or the PERK activator (CCT020312) was given prior to dexmedetomidine treatment., Results: Dexmedetomidine pretreatment decreased serum levels of cardiac troponin I, reduced myocardial infarct size, alleviated histological structure damage, and improved left ventricular function following myocardial I/R injury in rats. In addition, dexmedetomidine pretreatment increased cell viability and reduced cytotoxicity following OGD/R injury in cardiomyocytes. Mechanistically, the cardioprotection offered by dexmedetomidine was mediated via the inhibition of inflammation and apoptosis through downregulating the expression of the ERS signaling pathway, including glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6). Conversely, the protective effects of dexmedetomidine were diminished by blocking the α2 adrenergic receptors with yohimbine or promoting PERK phosphorylation with CCT020312., Conclusion: Dexmedetomidine pretreatment protects the hearts against I/R injury via inhibiting inflammation and apoptosis through downregulation of the ERS signaling pathway. Future clinical studies are needed to confirm the cardioprotective effects of dexmedetomidine in patients at risk of myocardial I/R injury., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Yang et al.)

Background: Older hypertensive adults are at increased risk for postoperative morbidity and mortality. As first line antihypertensive drug therapy, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have many beneficial effects. However, the use of ACEIs/ARBs in the perioperative period remains controversial. This study aims to determine the effects of withholding vs. continuing ACEIs/ARBs before non-cardiac surgery on perioperative hypotension and postoperative outcomes in older patients. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, a total of 2036 patients aged 60-80 years undergoing non-cardiac surgical procedures will be randomly assigned, in a 1:1 ratio, to receive oral ACEIs/ARBs (the ACEIs/ARBs continued group) or inactive placebos (the ACEIs/ARBs withheld group) on the morning of surgery. For both groups, the ACEIs/ARBs will be continued from the first postoperative day. The primary outcome measure is the incidence of perioperative hypotensive events, defined as mean blood pressure (MBP) < 65 mmHg or ≥30% reduction in MBP from baseline during surgery and in a post-anesthesia care unit. The secondary outcomes include duration of perioperative hypotension, intraoperative use of fluids and vasopressors, hypotensive events within postoperative 3 days, and perioperative neurocognitive disorders, major adverse cardiocerebral events (a composite outcome of stroke, coma, myocardial infarction, heart block, and cardiac arrest), and mortality within 30 days after surgery. Discussion: The results of this trial will offer an evidence-based perioperative ACEIs/ARBs therapy for older hypertensive adults undergoing non-cardiac surgery. Study Registration: This study is approved by the Medical Ethics Committee of The First Affiliated Hospital of Soochow University (Approval No. 2020-077-1) and by the institutional ethics review board of each participating center. This protocol is registered at the Chinese Clinical Trials Registry (ChiCTR2000039376)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Zhu, Long, Liu, Shan, Feng, Peng and Ji.)

Whether allicin can suppress the angiogenesis via inhibiting the activity of vascular endothelial cells (VECs) in preventing epidural hypertrophic scars remains unknown. VECs were treated by allicin at a gradient of concentrations. Cell activity was measured by CCK-8 assay, scratch assay and flow cytometry. Reverse-transcription PCR and Western Blot were used to measure the expression levels of relevant genes and proteins. After treated with allicin at concentrations of 0, 25, 50 and 100 mg/L, the viability of VECs significantly decreased at 24 h (p < 0.001*) and 48 h (p < 0.001*), and migration rate significantly decreased in scratch assay (p = 0.017*) and in Transwell assay (p = 0.021*). As the concentrations of allicin increased, the apoptosis rate of VECs rose up (p = 0.018*). There was no significant difference on cell numbers at S phase (p = 0.25), but cell numbers at G1 phase decreased (p = 0.039*) and at G2 phase increased (p = 0.047*). With the increase of allicin concentrations, the ability of tube formation for VECs significantly decreased (p < 0.001*). Comparing with control group, the expression of PCNA and BCL-2 decreased (p < 0.001*), while the expression of BAX increased significantly (p < 0.001*). Regarding to JAK2/STAT3 pathway, the expression levels of JAK3 and STAT3 decreased significantly with the increase of allicin concentrations (p < 0.001*). Allicin can suppress the activity of VECs probably by regulating JAK2/STAT3 pathway.

Background: To date, there has been no effective treatment for intervertebral disc degeneration (IDD). Nucleus pulposus-derived mesenchymal stem cells (NPMSCs) showed encouraging results in IDD treatment, but the overexpression of reactive oxygen species (ROS) impaired the endogenous repair abilities of NPMSCs. 6-gingerol (6-GIN) is an antioxidant and anti-inflammatory reagent that might protect NPMSCs from injury., Aim: To investigate the effect of 6-GIN on NPMSCs under oxidative conditions and the potential mechanism., Methods: The cholecystokinin-8 assay was used to evaluate the cytotoxicity of hydrogen peroxide and the protective effects of 6-GIN. ROS levels were measured by 2´7´-dichlorofluorescin diacetate analysis. Matrix metalloproteinase (MMP) was detected by the tetraethylbenzimidazolylcarbocyanine iodide assay. TUNEL assay and Annexin V/PI double-staining were used to determine the apoptosis rate. Additionally, autophagy-related proteins (Beclin-1, LC-3, and p62), apoptosis-associated proteins (Bcl-2, Bax, and caspase-3), and PI3K/Akt signaling pathway-related proteins (PI3K and Akt) were evaluated by Western blot analysis. Autophagosomes were detected by transmission electron microscopy in NPMSCs. LC-3 was also detected by immunofluorescence. The mRNA expression of collagen II and aggrecan was evaluated by real-time polymerase chain reaction (RT-PCR), and the changes in collagen II and MMP-13 expression were verified through an immunofluorescence assay., Results: 6-GIN exhibited protective effects against hydrogen peroxide-induced injury in NPMSCs, decreased hydrogen peroxide-induced intracellular ROS levels, and inhibited cell apoptosis. 6-GIN could increase Bcl-2 expression and decrease Bax and caspase-3 expression. The MMP, Annexin V-FITC/PI flow cytometry and TUNEL assay results further confirmed that 6-GIN treatment significantly inhibited NPMSC apoptosis induced by hydrogen peroxide. 6-GIN treatment promoted extracellular matrix (ECM) expression by reducing the oxidative stress injury-induced increase in MMP-13 expression. 6-GIN activated autophagy by increasing the expression of autophagy-related markers (Beclin-1 and LC-3) and decreasing the expression of p62. Autophagosomes were visualized by transmission electron microscopy. Pretreatment with 3-MA and BAF further confirmed that 6-GIN-mediated stimulation of autophagy did not reduce autophagosome turnover but increased autophagic flux. The PI3K/Akt pathway was also found to be activated by 6-GIN. 6-GIN inhibited NPMSC apoptosis and ECM degeneration, in which autophagy and the PI3K/Akt pathway were involved., Conclusion: 6-GIN efficiently decreases ROS levels, attenuates hydrogen peroxide-induced NPMSCs apoptosis, and protects the ECM from degeneration. 6-GIN is a promising candidate for treating IDD., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest in regard to the present manuscript. The authors alone are responsible for the content and writing of the article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose : To investigate the protective effect of naringin (Nar) on H 2 O 2 -induced apoptosis of nucleus pulposus-derived mesenchymal stem cells (NPMSC) and the potential mechanism in this process. Methods : Rat NPMSC were cultured in MSC culture medium or culture medium with different concentrations of H 2 O 2 . Nar or the combination of Nar and LY294002 was added into the culture medium to investigate the effects of Nar. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The apoptosis rate was determined using Annexin V/PI dual staining and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assays. Additionally, the levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. ATP level in NPMSC was analyzed via ATP detection kit. Mitochondrial ultrastructure change was observed through transmission electron microscope (TEM). Levels of apoptosis-associated molecules (cleaved caspase-3, Bax and Bcl-2) were evaluated via RT-PCR and western blot, respectively. Results : The cells isolated from NP met the criteria for MSC. H 2 O 2 significantly promoted NPMSC apoptosis in a dose and time-dependent manner. Nar showed no cytotoxicity effect on NPMSC up to a concentration of 100 μM for 24 h. Nar exhibited protective effects against H 2 O 2 -induced NPMSC apoptosis including apoptosis rate, expressions of proapoptosis and antiapoptosis related genes and protein. Nar could also alleviate H 2 O 2 -induced mitochondrial dysfunction of increased mitochondrial ROS production, reduced MMP, decreased intracellular ATP and mitochondrial ultrastructure change. However, these protected effects were inhibited after LY294002 treatment. Conclusions : Our results demonstrated that Nar efficiently attenuated H 2 O 2 -induced NPMSC apoptosis and mitochondrial dysfunction. The activation of ROS-mediated PI3K/Akt pathway may be the potential mechanism in this process.

A psychrotolerant actinobacterium, designated strain J5903 T , was isolated from an alkaline soil sample from the rhizosphere of Suaeda salsa collected in desertification land surrounding Jiuliancheng Nur in Hebei Province, PR China. Cells of the isolate were Gram-stain-positive, aerobic, non-motile and non-spore-forming cocci. Strain J5903 T grew optimally at 20‒25 °C, at pH 7.0‒7.5 and with <1 % (w/v) NaCl. The cell-wall peptidoglycan type was B2γ with d-2,4-diaminobutyric acid and l-2,4-diaminobutyric acid as diagnostic amino acids. The muramyl residue was acetyl type. The menaquinones were MK-11, MK-12, MK-10 and MK-13. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and one unidentified glycolipid. The major whole-cell fatty acids were anteiso-C 15 : 0 , iso-C 16 : 0 and anteiso-C 17 : 0 . The genomic DNA G+C content was 69.1 mol%. It shared the highest average nucleotide identity and digital DNA-DNA hybridization values with Planctomonas deserti 13S1-3 T . Phylogenies based on genome sequence showed that strain J5903 T and P. deserti 13S1-3 T formed a robust cluster with high bootstrap support. Strain J5903 T shared typical chemotaxonomic characteristics with P. deserti 13S1-3 T . Combining the polyphasic taxonomic evidence, strain J5903 T represents a novel species of the genus Planctomonas , for which the name Planctomonas psychrotolerans sp. nov. is proposed. The type strain is J5903 T (=DSM 101894 T =CGMCC 1.15523 T ).

A novel moderately halophilic, filamentous actinobacterium, designated as XMNu-373 T , was isolated from a saline-alkaline soil sample collected from the Mongolia Plateau, Dongwu County, Inner Mongolia Autonomous Region, PR China. The isolate grew optimally at 28‒37 °C, pH 7.0‒8.0 and with 2-5 % (w/v) NaCl. The substrate mycelia fragmented into rod-like elements, and the white aerial mycelia formed spore chains at maturity. The predominant menaquinone was MK-9(H 4 ). The polar lipids were diphosphatidylglycerol, three unidentified phosphoglycolipids, an unidentified aminophospholipid, two phosphatidylinositol mannosides, four unidentified phospholipids, phosphatidylglycerol and two unidentified lipids. The major cellular fatty acids were iso-C 16 : 0 , anteiso-C 17 : 0 and anteiso-C 15 : 0 . The genomic DNA G+C content was 66.2 mol%. It shared high 16S rRNA gene sequence similarities to Phytoactinopolyspora halotolerans YIM 96448 T (96.1 %) and Phytoactinopolyspora endophytica EGI 60009 T (96.0 %). Phylogenetic trees based on 16S rRNA gene sequences revealed that strain XMNu-373 T resided in the clade of family Jiangellaceae , and it formed a monophyletic branch distinct from four other recognized type species in the subclade of the genus Phytoactinopolyspora . On the basis of polyphasic taxonomic evidence, strain XMNu-373 T represents a novel species of the genus Phytoactinopolyspora , for which the name Phytoactinopolyspora mesophila sp. nov. is proposed. The type strain is XMNu-373 T (=JCM 33740 T =CGMCC 4.7654 T ).

Objective: Kidney stone formers have a high rate of stone recurrence after kidney stone removal surgery and there is no effective medication for treatment. Hydroxycitric acid (HCA), which is the major component of Garcinia cambogia extract, can dissolve calcium oxalate crystals in vitro, suggesting that Garcinia cambogia could be used to treat calcium oxalate kidney stone. In this study, we used the Drosophila kidney disease model to evaluate the effect of Garcinia cambogia on the prevention and removal of calcium oxalate stones in vivo., Materials and Methods: Flies were reared in fly food containing different concentrations of GCE for one week. The effect of GCE on preventing the formation of calcium oxalate stone was examined. WT and v-ATPase gene RNAi knockdown flies were reared in fly food with 0.3% NaOx for one week, then fed different concentrations of GCE for one week. The effect of GCE on the removal of calcium oxalate stone was examined., Results: Garcinia cambogia extract dissolves calcium oxalate crystals from Malpighian tubules in both genetic and non-genetic Drosophila kidney stone models compared to citric acid. Hydroxycitric acid also directly dissolves calcium oxalate crystals in Drosophila Malpighian tubules ex vivo., Conclusions: Garcinia cambogia extract removes calcium oxalate kidney stones from Drosophila Malpighian tubules via directly dissolving calcium oxalate stones by HCA. Our study strongly suggests that clinical-grade Garcinia cambogia extract could be used to treat patients with nephrolithiasis in the future.

Objective: To observe the effect of electroacupuncture (EA) on intestinal epithelial mucosal barrier function in diarrhea-predominant irritable bowel syndrome(IBS-D) rats, so as to explore its mechanisms underlying improvement of IBS-D., Methods: Forty SD rats (half male and half female) were randomly divided into control, model, EA and medication (Pinaverium Bromide, PB) groups, with 10 rats in each group. The IBS-D model was established by chronic unpredictable mild stress combined with gavage of Senna-leaf solution. EA (2 Hz/15 Hz，0.1-1 mA) was applied to unilateral "Zusanli"(ST36),"Tianshu" (ST25), "Sanyinjiao"(SP6) and "Taichong"(LR3) alternatively for 15 min, once daily for 14 days. Rats of the medication group was treated by gavage of PB (10 mL·kg -1 ·d -1 ) for 14 days. The visceral sensitivity (pain) was assessed by using the pressure threshold which the inserted rectal balloon catheter air-inflation (connected to a blood pressure gauge) induced stronger abdominal muscular contraction to force the rat's abdomen to lift the experimental stand surface. The diarrhea index was used to evaluate loose stool grade. The expression of Claudin-1 and Occludin (intestinal epithelial tight junction proteins) of colon tissue was detected by immunohistochemistry. The activity of plasma diamine oxidase (DAO) was assayed by using spectrophotometry., Results: Compared with the control group, the diarrhea index and plasma DAO activity in the model group were significantly increased ( P <0.01), while the visceral pain threshold, expression of Claudin-1 and Occludin in the model group were significantly decreased ( P <0.01). After the treatment, the diarrhea index and plasma DAO activity were significantly lower in both EA and medication groups than that in the model group ( P <0.01), and the visceral pain threshold and expression levels of Claudin-1 and Occludin were obviously increased ( P <0.05, P <0.01). No significant differences were found between the EA and medication groups in all the above-mentioned indexes ( P >0.05)., Conclusion: Electroacupuncture can significantly improve abdominal pain and diarrhea in IBS-D model rats, which may be closely associated with its effects in up-regulating the expression of intestinal epithelial tight junction proteins Claudin-1 and Occludin to restore the function of intestinal epithelial mucosal barrier.

Based on the reported data from February 16, 2020 to March 9, 2020 in South Korea including confirmed cases, death cases and recovery cases, the control reproduction number was estimated respectively at different control measure phases using Markov chain Monte Carlo method and presented using the resulting posterior mean and 95% credible interval (C r I). At the early phase from February 16 to February 24, we estimate the basic reproduction number R 0 of COVID-19 to be 4.79(95% C r I 4.38 - 5.2). The estimated control reproduction number dropped rapidly to R c ≈ 0.32(95% C r I 0.19 - 0.47) at the second phase from February 25 to March 2 because of the voluntary lockdown measures. At the third phase from March 3 to March 9, we estimate R c to be 0.27 (95% C r I 0.14 - 0.42). We predict that the final size of the COVID-19 outbreak in South Korea is 9661 (95% C r I 8660 - 11100) and the whole epidemic will be over by late April. It is found that reducing contact rate and enhancing the testing speed will have the impact on the peak value and the peak time.