Mendelian randomization analyses reveal causal relationship between liver volume and stroke.

BACKGROUND: Observational studies have suggested a potential association between abdominal viscera volume and increased risk of stroke. However, the causal relationship remains unclear. This study aims to utilize Mendelian randomization (MR) to explore the genetic causal relationship between them. METHODS: We conducted MR analysis to study the causal effects of five abdominal viscera volumes on stroke. The genetic variations of abdominal viscera volume were obtained from the UK Biobank, and the summary data for stroke and ischemic stroke were acquired from the MEGASTROKE consortium. This study employed inverse variance weighting (IVW), MR Egger, and weighted median methods. IVW served as the primary MR analysis method, supplemented by other sensitivity analyses to validate the robustness of the results. RESULTS: We found that liver volume can causally increase the risk of stroke [odds ratio (OR): 1.13, 95 % confidence interval (CI): 1.03-1.25, P = 0.013] and ischemic stroke (OR: 1.14, 95 % CI: 1.03-1.26, P = 0.012). No causal relationships between other abdominal viscera volumes and stroke and ischemic stroke appeared to be present (P > 0.05). Sensitivity analyses confirmed the robustness of the results. CONCLUSION: Our research findings indicate a causal relationship between liver volume and stroke, highlighting the potential role of liver volume in the onset of stroke. However, further basic and clinical research is needed to delve into the specific mechanisms underlying the relationship between liver volume and stroke, and to implement interventions aimed at reducing the impact of liver volume on stroke risk.

Nicotinamide mononucleotide attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma.

Nicotinamide adenine dinucleotide (NAD+) is an essential element in cellular metabolism that regulates fundamental biological processes. Growing evidence suggests that a decline in NAD+ is a common pathological factor in various diseases and aging. However, its role in airway epithelial barrier function in response to asthma remains underexplored. The current study aims to explore the efficacy of restoring cellular NAD+ concentration through supplementation with the NAD+ precursor, nicotinamide mononucleotide (NMN), in the treatment of allergic asthma and to investigate the role of SIRT3 in mediating the effects of NAD+ precursors. In this research, NMN alleviated airway inflammation and reduced mucus secretion in house dust mite (HDM)-induced asthmatic mice. It also mitigated airway epithelial barrier disruption in HDM-induced asthma in vitro and in vivo. But inhibition of SIRT3 expression abolished the effects of NMN. Mechanistically, HDM induced SIRT3 SUMOylation and proteasomal degradation. Mutation of these two SIRT3 SUMO modification sites enhanced the stability of SIRT3. Additionally, SIRT3 was targeted by SENP1 which acted to de-conjugate SUMO. And down-regulation of SENP1 expression in HDM-induced models was reversed by NMN. Collectively, these findings suggest that NMN attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma. Blockage of SIRT3 SUMOylation emerges as for the treatment of allergic asthma.

Remediation of petroleum-contaminated site soil by bioaugmentation with immobilized bacterial pellets stimulated by a controlled-release oxygen composite.

Bioaugmentation techniques still show drawbacks in the cleanup of total petroleum hydrocarbons (TPHs) from petroleum-contaminated site soil. Herein, this study explored high-performance immobilized bacterial pellets (IBPs) embed Microbacterium oxydans with a high degrading capacity, and developed a controlled-release oxygen composite (CROC) that allows the efficient, long-term release of oxygen. Tests with four different microcosm incubations were performed to assess the effects of IBPs and CROC on the removal of TPHs from petroleum-contaminated site soil. The results showed that the addition of IBPs and/or CROC could significantly promote the remediation of TPHs in soil. A CROC only played a significant role in the degradation of TPHs in deep soil. The combined application of IBPs and CROC had the best effect on the remediation of deep soil, and the removal rate of TPHs reached 70%, which was much higher than that of nature attenuation (13.2%) and IBPs (43.0%) or CROC (31.9%) alone. In particular, the CROC could better promote the degradation of heavy distillate hydrocarbons (HFAs) in deep soil, and the degradation rates of HFAs increased from 6.6% to 33.2%-21.0% and 67.9%, respectively. In addition, the IBPs and CROC significantly enhanced the activity of dehydrogenase, catalase, and lipase in soil. Results of the enzyme activity were the same as that of TPH degradation. The combined application of IBPs and CROC not only increased the microbial abundance and diversity of soil, but also significantly enhanced the enrichment of potential TPH-biodegrading bacteria. M. oxydans was dominant in AP (bioaugmentation with addition of IBPs) and APO (bioaugmentation with the addition of IBPs and CROC) microcosms that added IBPs. Overall, the IBPs and CROC developed in this study provide a novel option for the combination of bioaugmentation and biostimulation for remediating organic pollutants in soil.

Efficacy and safety of acupuncture as a complementary therapy for sepsis: a systematic review and meta-analysis.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by dysregulation of the host response to infection. Acupuncture is used for treatment of inflammatory diseases; however, its effectiveness and safety as a complementary therapy for sepsis has not been fully explored. METHODS: Data were retrieved from eight databases. Randomized controlled trials (RCTs) that compared acupuncture plus conventional therapies versus conventional therapies alone were included. Pre-specified primary outcomes were mortality at 28 days and Acute Physiologic and Chronic Health Evaluation (APACHE) II scores. RESULTS: A total of 17 studies with 1099 participants were included in this study. In terms of the primary outcomes, acupuncture plus routine therapy reduced mortality at 28 days (risk ratio (RR)): 0.69, 95% confidence interval (CI): 0.52 to 0.91, p < 0.001) and APACHE II scores (mean difference (MD): -2.84, 95% CI: -4.09 to -1.58, p < 0.001) at day 7 after treatment compared with routine therapy alone. In terms of secondary outcomes, acupuncture plus routine therapy reduced white blood cell counts and levels of procalcitonin (PCT), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and lactic acid and intra-abdominal pressure (IAP), and improved CD3+, CD4+ and monocytes of human leukocyte antigen (HLA)-DR at day 7 after treatment compared with routine therapy alone. However, acupuncture plus routine therapy had no significant effects on levels of IL-10, C-reactive protein (CRP), CD8+ and CD4+/CD8+ ratios compared with routine therapy alone. Quality of evidence was low to very low for all parameters (GRADE). CONCLUSION: The available evidence showed that combination of acupuncture and routine therapy may have benefit for sepsis compared with use of routine therapy only. Due to the low degree of certainty regarding its effects, further research is required. TRIAL REGISTRATION NUMBER: ICRD42019141491 (PROSPERO).

Blockade of CBX4-mediated ß-catenin SUMOylation attenuates airway epithelial barrier dysfunction in asthma.

Epithelial barrier dysfunction is involved in the pathogenesis of asthma. Previous studies show that SUMOylation can regulate epithelial junction molecule localization. However, the role of SUMOylation in epithelial barrier dysfunction in asthma remains unclear. This study found that inhibition of SUMOylation attenuates house dust mite (HDM)-induced epithelial barrier dysfunction. The SUMOylation levels of junction molecules were determined by co-immunoprecipitation (CO-IP) and proximity ligation assay (PLA). HDM treatment significantly enhanced SUMOylation levels of ß-catenin, while no effect was seen on ZO-1, Occludin, and E-cadherin SUMOylation levels. Inhibition of ß-catenin SUMOylation through 2-D08 treatment or SUMOylation modification site mutant (K233A) promoted its membrane localization and repressed Wnt/ß-catenin signaling. Further, we identified that CBX4, an E3 ligase, mediated SUMOylation of ß-catenin. Knockdown of CBX4 promoted ß-catenin membrane localization and improved epithelial barrier function. In vivo analysis showed that AAV6-shCBX4-mediated knockdown of CBX4 attenuated HDM-induced allergic airway inflammation and epithelial barrier dysfunction. The findings showed that inhibiting ß-catenin SUMOylation by targeting CBX4 mitigated HDM-induced epithelial barrier dysfunction in asthma.

[Development of China Musculoskeletal Questionnaire and item selection].

OBJECTIVE: To develop a draft questionnaire (China Musculoskeletal Questionnaire, CMQ) for evaluating of musculoskeletal workload and associated potential hazardous working conditions as well as musculoskeletal symptoms of workers in Sitting Posture. METHODS: Multi-methods, which include the reviewing references, the summarizing results of preliminary studies, the reviewing ergonomic tools, the consulting experts and occupational health workers and the interviewing or discussing with individual workers in sitting posture, were used in developing item pool. The experts and epidemiologists of occupational health scored the importance of every single item in the item pool, and then the survey and sampling were carried out in 325 workers of sitting posture who completed the questionnaire. On the basis of these data, the methods including experts scoring, item analysis, Cronbach's α analysis and factor analysis were synthetically used to select the reliable items which consisted of the formal questionnaire. RESULTS: The standard of the CMQ, which consists of 34 items on musculoskeletal workload and associated potentially hazardous working conditions, can be divided into nine indices (dynamic loads, static loads, repetitive loads, forces-exertion, prolong time, climatic factors, vibration, position and ergonomic environmental factors). CONCLUSION: The CMQ possesses good content validity, and the items of CMQ are divergent, reliable and typical. However, the reliability and validity of CMQ should be validated.

Efficacy of acupuncture for melasma: A protocol of systematic review and meta-analysis.

BACKGROUND: Melasma is a common acquired hyperpigmentation of the skin. The clinical manifestations are light brown or dark brown patches symmetrically distributed on the cheeks, forehead, and mandibular with different shades and unclear borders. The treatment of melasma is extremely challenging due to its easy relapse and hard to cure. As a classical method of traditional Chinese medicine, acupuncture has been used to treat melasma in clinical practice. However, there is no systematic review and meta-analysis of acupuncture on melasma. This study aims to assess the efficacy of acupuncture for melasma. METHODS: We will perform a comprehensive retrieval in the following electronic databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Wan Fang Database, VIP database, Chinese Biomedical Literature Service System (SinoMed), Chinese Biomedicine (CBM) database, and TCM Literature Analysis from inception to July 1, 2021, to identify any eligible study. We include all randomized controlled trials (RCTs) without any limitation of blinding or publication language, and exclude cohort studies and case reports. The meta-analyses will be conducted by using the Stata16. We will use the Cochrane risk of bias tool for randomized trials to assess the risk of bias of included studies. The X2 and I2 tests will be utilized to assess the statistical heterogeneity of evidence. We will conduct a meta-analysis if the studies can be combined. Otherwise, a narrative synthesis will be performed. Article screening and data extraction will be independently evaluated by 2 reviewers trained in methodology according to the established selection criteria. Any disagreements between the 2 reviewers will be resolved by reaching a consensus with the other authors (the third reviewer). RESULTS: This study will systematically evaluate the clinical efficacy of acupuncture for melasma. CONCLUSION: The conclusion of this study will provide evidence to ensure the efficacy of acupuncture for melasma, so as to provide an objective and scientific basis for clinical practice. ETHICS AND DISSEMINATION: No ethical approval will be required because the data used are not linked to individual patient. The results of this review will be published in a peer-reviewed journal. REGISTRATION NUMBER: INPLASY2021110097.

[Effect of umbilical moxibustion on phlegm damp constitution and intestinal flora].

OBJECTIVE: To observe the effect of umbilical moxibustion on phlegm damp constitution and intestinal flora, and explore the mechanism of umbilical moxibustion in improving phlegm damp constitution. METHODS: A total of 60 subjects with phlegm damp constitution were randomly divided into an observation group and a control group, 30 cases in each group. The control group was given TCM health guidance, such as diet and exercise; on the basis of the control group, umbilical moxibustion was applied in the observation group, 7 moxa cones each time, 2 times a week for 8 weeks. Before and after intervention, the indexes (transformation score of phlegm damp constitution, body mass, body mass index [BMI], waist circumference, hip circumference, heart rate and blood pressure) related to phlegm damp constitution were recorded in the two groups. The intestinal flora was detected with 16S rDNA sequencing technology in the two groups. RESULTS: After intervention, the transformation score of phlegm damp constitution, body mass, BMI, waist circumference and hip circumference were decreased compared before intervention in the observation group (P<0.001, P<0.01, P<0.05), the transformation score of phlegm damp constitution and waist circumference were decreased compared before intervention in the control group (P<0.001, P<0.05); the transformation score of phlegm damp constitution and waist circumference in the observation group were lower than the control group (P<0.001, P<0.05). After intervention, the relative abundance of Eubacterium hallii in the observation group was increased (P<0.01), the relative abundance of Blautia in the control group was decreased (P<0.05). CONCLUSION: Umbilical moxibustion may reshape the intestinal flora by up-regulating the relative abundance of Eubacterium hallii, thus improving phlegm damp constitution.

Effects of acupuncture for nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease, which may develop gradually into nonalcoholic steatohepatitis, liver fibrosis, and cirrhosis. As a classical method of traditional Chinese medicine, acupuncture has been used to treat NAFLD in clinical practice. However, there is no systematic review and meta-analysis of acupuncture on NAFLD. There is an urgent need to evaluate the clinical efficacy of acupuncture for NAFLD. METHODS: We will perform a comprehensive retrieval in the following electronic databases: MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, PubMed, Science Citation Index Expanded (Web of Science), Epistemonikos, China National Knowledge Infrastructure (CNKI) database, Wanfang Data Knowledge Service Platform, Chinese Scientific Journals Database (VIP), Chinese Biomedical Literature Service System (SinoMed), and other databases from their inception to October 2020. We will select the qualified studies for data extraction and assess the quality and risk of bias, independently. The meta-analyses will be conducted by using the RevMan 5.3. RESULTS: This study will provide a reliable basis for the treatment of NAFLD with acupuncture. CONCLUSION: The findings will be an available reference to evaluate whether acupuncture is an effective intervention for patient with NAFLD. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/VFYXH.

Jiaji (EX-B2)-Based Electroacupuncture Preconditioning Attenuates Early Ischaemia Reperfusion Injury in the Rat Myocardium.

BACKGROUND: Acupuncture preconditioning was able to reduce the extent of ischaemia reperfusion (I/R) injury. Previous studies have shown that electroacupuncture (EA) pretreatment at T4-T5 Jiaji (EX-B2) acupoints had cardioprotective effects against myocardial I/R injury. However, the molecular mechanism remains inconclusive. METHODS: Wistar rats were pretreated with electroacupuncture for 7 days at the Neiguan (PC6), T4-T5 Jiaji (EX-B2), Yanglingquan (GB34), and Quchi (LI11) acupoints, which belong to different meridians. Then, we investigated the genome-wide gene expression profiles of rats prestimulated at these acupoints after I/R injury. RESULTS: Our study revealed previously unknown cardioprotective roles of T4-T5 Jiaji (EX-B2) acupoints in the I/R progression. The extent of myocardial injury was significantly decreased in the Jiaji group compared with the I/R group. In addition, our data are among the first to link the EA preconditioning at Neiguan (PC6) acupoints and circadian rhythm in the I/R model. Also, for the first time, we explored the meridian and acupoint specificity involved in EA pretreatment at the heart meridian, in which Yanglingquan and Quchi acupoints were selected as the control group for heart-divergent-meridian and nonheart-meridian acupoints. CONCLUSIONS: The present study suggested that EA pretreatment at Jiaji alters genome-wide gene expression and protects the rat myocardium against I/R injury, which are most likely through neurohumoral regulation.

[Effect of "Jiaji" (EX-B2)-electroacupuncture preconditioning on expression of myocardial cytochrome P450 enzyme in rats with acute myocardial ischemia-reperfusion injury].

OBJECTIVE: To investigate the effect of "Jiaji"(EX-B2)-electroacupuncture(EA) preconditioning on structural changes of myocardium and expression of cytochrome P450 (CYP450) enzymes in acute myocardial ischemia-reperfusion injury (MIRI) rats. METHODS: Sixty male Wistar rats were randomly divided into sham operation, model, EX-B2, Neiguan (PC6), Yanglingquan(GB34) and Quchi (LI11) groups (n＝10 in each group). The MIRI model was established by occlusion of the descending anterior branch of the left coronary artery for 30 min, followed by reperfusion for 30 min. EA preconditioning (2 Hz/100 Hz, 1 mA) was respectively applied to EX-B2, PC6, GB34, and LI11 for 30 min, once daily for 7 days. Morphological changes of myocardium were observed by H．E. staining. The ultrastructure of myocardial cells was observed by transmission electron microscope (TEM). The protein expression levels of myocardial CYP450 (CYP1A1, CYP2B2, CYP2C11 and CYP4A2) were detected by Western blot. RESULTS: In MIRI rats, myocardial pathological changes as swollen, disorganized arrangement, and partially ruptured myocardial fibers with unclear limit and necrosis and infiltration of lots of inflammatory cells under microscope, and focal myofilament degeneration, dissolution and necrosis with interstitial edema, vague mitochondria with swelling and vacuolation, ruptured and disorganized arrangement of crests under TEM were found in the ischemic area, which was obviously milder in rats of both EX-B2 and PC6 groups. After modeling, the expression of myocardial CYP1A1 and CYP2B2 protein were significantly up-regulated in the model group relevant to the sham operation group (P<0.05). In EA preconditioning groups, the expression levels of CYP1A1 and CYP4A2 proteins in the EX-B2, PC6 and GB34 groups were obviously down-regulated (P<0.01), and those of CYP2B2 and CYP2C11 proteins in both EX-B2 and PC6 groups were markedly up-regulated relevant to the model group (P<0.01). Compared with the EX-B2 group, the expression levels of CYP1A1, CYP4A2 proteins in the LI11 group were significantly up-regulated (P<0.05), and CYP2B2, CYP2C11 proteins were significantly down-regulated (P<0.05). No significant differences were found between the model and sham operation groups in the expression levels of myocardial CYP2C11 and CYP4A2 proteins, between the LI11 and model groups in the expression of CYP1A1, CYP2B2, CYP2C11 and CYP4A2, between the GB34 and model groups in the expression of CYP2B2, CYP2C11 (all P>0.05)．. CONCLUSION: EA preconditioning at EX-B2 and PC6 can suppress MIRI induced up-regulation of myocardial CYP450 ω-hydroxylase CYP1A1 and CYP4A2 expression and further up-regulate the expression of myocardial epoxygenase CYP2B2 and CYP2C11 proteins in acute MIRI rats, thus playing a role in myocardial protection.

Efficacy and safety of acupuncture as a complementary therapy for sepsis: A protocol of systematic review and meta-analysis.

INTRODUCTION: Sepsis is a physiological, pathological, and biochemical syndrome caused by infection. Acupuncture may be useful for sepsis. This systematic review aims to assess the efficacy and safety of acupuncture as a complementary therapy for sepsis. METHODS AND ANALYSIS: We will search PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Wan Fang Database, Chinese Biomedicine (CBM) database, VIP database, and TCM Literature Analysis and Retrieval Database from inception to October 31, 2019 to identify any eligible study. We include all randomized controlled trials (RCTs) without any limitation of blinding or publication language, exclude cohort studies and case reports. Two reviewers will independently select studies, extract and manage data. The primary outcomes include the mortality at 28 days, acute physiology, and chronic health evaluation II scores. The secondary outcomes include the tumor necrosis factor α (TNF-α) counts, interleukin 6 (IL-6) counts, interleukin 10 (IL-10) counts, procalcitonin (PCT), lactic acid, the level of T cell subsets (CD3+, CD4+, CD8+, CD4+/CD8+), monocytes of human leukocyte antigen DR (HLA-DR), C-reactive protein (CRP), the numeration of leukocyte, intra-abdominal pressure, and adverse events or reactions. Statistical analyses will be performed using the Review Manager V.5.3 and R packages Metafor. We will use the Cochrane risk of bias tool for randomized trials to assess the risk of bias of included studies. ETHICS AND DISSEMINATION: This study will not involve personal information. Ethical approval will not be required. We will publish the results in a peer-reviewed journal. PROSPERO TRIAL REGISTRATION NUMBER: CRD42019141491.

[Discussion on the control of treatment amount of acupuncture and moxibustion for peripheral facial paralysis].

To explore the control principles of treatment amount of acupuncture and moxibustion for peripheral facial paralysis. (1) Early stage: in this period, the selected acupoints should be few, therapy should be easy and simple, and the treatment amount should be small and basically constant, which is called constant acupoints and amount. (2) Middle stage: the treatment of this stage should be given with more acupoints and various therapies, the treatment amount should be gradually increasing and reach the peak within a certain time and keep it for an appropriate time, which is called increasing acuponts and amount. (3) Late stage: the treatment at this stage should be given with more acupoints, lesser therapies, and the treatment amount should be gradually decreasding and get the valley point within a certain time, which is called more acupoints and less amount. (4) Sequelae stage: the selection of acupoints at this stage should be focus on areas which there are the obvious symptoms, and solo type of therapy and little treatment amount is required, which is called changing acupoints and little amount. In a word, the best therapeutic effect could be achieved on condition that the control principles of treatment amount for peripheral facial paralysis are followed during the clinical practice.