Intergrative metabolomic and transcriptomic analyses reveal the potential regulatory mechanism of unique dihydroxy fatty acid biosynthesis in the seeds of an industrial oilseed crop Orychophragmus violaceus.

BACKGROUND: Orychophragmus violaceus is a potentially important industrial oilseed crop due to the two 24-carbon dihydroxy fatty acids (diOH-FA) that was newly identified from its seed oil via a 'discontinuous elongation' process. Although many research efforts have focused on the diOH-FA biosynthesis mechanism and identified the potential co-expressed diacylglycerol acyltranferase (DGAT) gene associated with triacylglycerol (TAG)-polyestolides biosynthesis, the dynamics of metabolic changes during seed development of O. violaceus as well as its associated regulatory network changes are poorly understood. RESULTS: In this study, by combining metabolome and transcriptome analysis, we identified that 1,003 metabolites and 22,479 genes were active across four stages of seed development, which were further divided into three main clusters based on the patterns of metabolite accumulation and/or gene expression. Among which, cluster2 was mostly related to diOH-FA biosynthesis pathway. We thus further constructed transcription factor (TF)-structural genes regulatory map for the genes associated with the flavonoids, fatty acids and diOH-FA biosynthesis pathway in this cluster. In particular, several TF families such as bHLH, B3, HD-ZIP, MYB were found to potentially regulate the metabolism associated with the diOH-FA pathway. Among which, multiple candidate TFs with promising potential for increasing the diOH-FA content were identified, and we further traced the evolutionary history of these key genes among species of Brassicaceae. CONCLUSION: Taken together, our study provides new insight into the gene resources and potential relevant regulatory mechanisms of diOH-FA biosynthesis uniquely in seeds of O. violaceus, which will help to promote the downstream breeding efforts of this potential oilseed crop and advance the bio-lubricant industry.

Methylmalonic acid, vitamin B12, and mortality risk in patients with preexisting coronary heart disease: a prospective cohort study.

BACKGROUND: The inconsistent relationship between Vitamin B12 (B12), methylmalonic acid (MMA, marker of B12 deficiency) and mortality was poorly understood, especially in patients with coronary heart disease (CHD). This study aims to investigate the association of serum MMA, and B12-related biomarkers (serum level, dietary intake, supplement use, and sensibility to B12) with all-cause and cardiovascular mortality in adults with CHD. METHODS: The data of this study were from a subcohort within the US National Health and Nutrition Examination Survey (NHANES). We included adults with preexisting CHD with serum MMA and B12, and dietary B12 intake measurements at recruitment. All participants were followed up until 31 December 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CI of mortality risk. RESULTS: Overall, 1755 individuals (weighted mean [SE] age, 65.2 [0.5] years; 1047 men [weighted 58.5%]) with CHD were included, with geometric mean levels of serum MMA 182.4 nmol/L, serum B12 494.5 pg/ml, and dietary B12 intake 4.42 mg/day, and percentage of B12 supplements use 39.1%. During a median follow-up of 7.92 years, 980 patients died. Serum B12 concentration, dietary B12 intake and supplements use were not significantly associated with mortality risk (each p ≥ 0.388). In contrast, individuals in the top tertile of MMA had multivariable-adjusted HRs (95% CIs) of 1.70 (1.31-2.20) for all-cause mortality, and 2.00 (1.39-2.89) for cardiovascular mortality (both p trend < 0.001) compared to those in the bottom tertile of MMA. MMA-related mortality risk was particularly higher among participants with sufficient serum B12 (p < 0.001). CHD patients with increased levels of both MMA and B12 had a doubled mortality risk compared to those with lower MMA and B12 (p < 0.001). CONCLUSION: MMA accumulation but not serum or dietary vitamin B12 was associated with increased cardiovascular mortality risk among patients with CHD. This paradox may be related to decreased response to vitamin B12.

Cardiac-targeted delivery of nuclear receptor RORα via ultrasound targeted microbubble destruction optimizes the benefits of regular dose of melatonin on sepsis-induced cardiomyopathy.

BACKGROUND: Large-dose melatonin treatment in animal experiments was hardly translated into humans, which may explain the dilemma that the protective effects against myocardial injury in animal have been challenged by clinical trials. Ultrasound-targeted microbubble destruction (UTMD) has been considered a promising drug and gene delivery system to the target tissue. We aim to investigate whether cardiac gene delivery of melatonin receptor mediated by UTMD technology optimizes the efficacy of clinically equivalent dose of melatonin in sepsis-induced cardiomyopathy. METHODS: Melatonin and cardiac melatonin receptors in patients and rat models with lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-induced sepsis were assessed. Rats received UTMD-mediated cardiac delivery of RORα/cationic microbubbles (CMBs) at 1, 3 and 5 days before CLP surgery. Echocardiography, histopathology and oxylipin metabolomics were assessed at 16-20 h after inducing fatal sepsis. RESULTS: We observed that patients with sepsis have lower serum melatonin than healthy controls, which was observed in the blood and hearts of Sprague-Dawley rat models with LPS- or CLP-induced sepsis. Notably, a mild dose (2.5 mg/kg) of intravenous melatonin did not substantially improve septic cardiomyopathy. We found decreased nuclear receptors RORα, not melatonin receptors MT1/2, under lethal sepsis that may weaken the potential benefits of a mild dose of melatonin treatment. In vivo, repeated UTMD-mediated cardiac delivery of RORα/CMBs exhibited favorable biosafety, efficiency and specificity, significantly strengthening the effects of a safe dose of melatonin on heart dysfunction and myocardial injury in septic rats. The cardiac delivery of RORα by UTMD technology and melatonin treatment improved mitochondrial dysfunction and oxylipin profiles, although there was no significant influence on systemic inflammation. CONCLUSIONS: These findings provide new insights to explain the suboptimal effect of melatonin use in clinic and potential solutions to overcome the challenges. UTMD technology may be a promisingly interdisciplinary pattern against sepsis-induced cardiomyopathy.

Qingyihuaji Formula promotes apoptosis and autophagy through inhibition of MAPK/ERK and PI3K/Akt/mTOR signaling pathway on pancreatic cancer in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyihuaji Formula (QYHJ), a widely used traditional Chinese medicine (TCM), has been used to treat patients with cancer in China. However, the effect and mechanism of QYHJ on pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIM OF THE STUDY: This study aimed to explore the roles and evaluate the possible underlying molecular mechanisms of QYHJ and its core component in PDAC using label-free quantitative proteomics in conjunction with network pharmacology-based analysis. MATERIALS AND METHODS: By screening differentially expressed proteins (DEPs) in proteomics and QYHJ-predicted gene sets, we identified QYHJ-related PDAC targets annotated with bioinformatic analysis. A subcutaneous tumor model was established to assess the role of QYHJ in vivo. The effects of quercetin (Que), a core component of QYHJ, on cell proliferation, migration, invasion, apoptosis, and autophagy in SW1990 and PANC-1 cells were investigated in vitro. Immunohistochemistry, western blotting, mRFP-GFP-LC3 adenovirus, and kinase analysis were used to determine the underlying mechanisms. RESULTS: Bioinformatics analysis revealed that 41 QYHJ-related PDAC targets were closely related to the cellular response to nitrogen compounds, positive regulation of cell death, regulation of epithelial cell apoptotic processes, and chemokine signaling pathways. CASP3, SRC, STAT1, PTPN11, PKM, and PAK1 with high expression were identified as hub DEPs in the PPI network, and these DEPs were associated with poor overall survival and STAT 1, MAPK/ERK, and PI3K/Akt/mTOR signaling pathways in PDAC patients. QYHJ significantly promoted tumor death in nude mice. Moreover, quercetin inhibited the proliferation, migration, and invasion of PDAC cells. Additionally, Que induced apoptosis and autophagy in PDAC cells. Mechanistically, QYHJ and Que significantly activated STAT 1 and remarkably inhibited the MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vivo and in vitro, respectively. Importantly, ERK1/2 inactivation contributes to que-induced apoptosis in SW1990 and PANC-1 cells. CONCLUSIONS: These results suggest that QYHJ and Que are promising anti-PDAC avenues that benefit from their multiform mechanisms.

A drug screening to identify novel combinatorial strategies for boosting cancer immunotherapy efficacy.

BACKGROUND: Chimeric antigen receptor (CAR) T cells and immune checkpoint blockades (ICBs) have made remarkable breakthroughs in cancer treatment, but the efficacy is still limited for solid tumors due to tumor antigen heterogeneity and the tumor immune microenvironment. The restrained treatment efficacy prompted us to seek new potential therapeutic methods. METHODS: In this study, we conducted a small molecule compound library screen in a human BC cell line to identify whether certain drugs contribute to CAR T cell killing. Signaling pathways of tumor cells and T cells affected by the screened drugs were predicted via RNA sequencing. Among them, the antitumor activities of JK184 in combination with CAR T cells or ICBs were evaluated in vitro and in vivo. RESULTS: We selected three small molecule drugs from a compound library, among which JK184 directly induces tumor cell apoptosis by inhibiting the Hedgehog signaling pathway, modulates B7-H3 CAR T cells to an effector memory phenotype, and promotes B7-H3 CAR T cells cytokine secretion in vitro. In addition, our data suggested that JK184 exerts antitumor activities and strongly synergizes with B7-H3 CAR T cells or ICBs in vivo. Mechanistically, JK184 enhances B7-H3 CAR T cells infiltrating in xenograft mouse models. Moreover, JK184 combined with ICB markedly reshaped the tumor immune microenvironment by increasing effector T cells infiltration and inflammation cytokine secretion, inhibiting the recruitment of MDSCs and the transition of M2-type macrophages in an immunocompetent mouse model. CONCLUSION: These data show that JK184 may be a potential adjutant in combination with CAR T cells or ICB therapy.

The sociodemographic characteristics and clinical features of the late-life depression patients: results from the Beijing Anding Hospital mental health big data platform.

BACKGROUND: The sociodemographic characteristics and clinical features of the Late-life depression (LLD) patients in psychiatric hospitals have not been thoroughly studied in China. This study aimed to explore the psychiatric outpatient attendance of LLD patients at a psychiatric hospital in China, with a subgroup analysis, such as with or without anxiety, gender differences. METHODS: This retrospective study examined outpatients with LLD from January 2013 to August 2019 using data in the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) in Beijing Anding Hospital. Age, sex, number of visits, use of drugs and comorbid conditions were extracted from medical records. RESULTS: In a sample of 47,334 unipolar depression patients, 31,854 (67.30%) were women, and 15,480 (32.70%) were men. The main comorbidities of LDD are generalized anxiety disorder (GAD) (83.62%) and insomnia (74.52%).Among patients with unipolar depression, of which benzodiazepines accounted for the largest proportion (77.77%), Selective serotonin reuptake inhibitors (SSRIs) accounted for 59.00%, a noradrenergic and specific serotonergic antidepressant (NaSSAs) accounted for 36.20%. The average cost of each visit was approximately 646.27 yuan, and the cost of each visit was primarily attributed to Western medicine (22.97%) and Chinese herbal medicine (19.38%). For the cost of outpatient visits, depression comorbid anxiety group had a higher average cost than the non-anxiety group (p < 0.05). There are gender differences in outpatient costs, men spend more than women, for western medicine, men spend more than women, for Chinese herbal medicine, women spend more than men (all p < 0.05). The utilization rate of SSRIs and benzodiazepines in female patients is significantly higher than that in male patients (p < 0.05). CONCLUSION: LLD patients are more commonly women than men and more commonly used SSRIs and NaSSAs. Elderly patients with depression often have comorbid generalized anxiety. LLD patients spend most of their visits on medicines, and while the examination costs are lower.

Effects of autotoxicity and allelopathy on seed germination and seedling growth in Medicago truncatula.

Autotoxicity is a form of intraspecific allelopathy, in which a plant species inhibits the establishment or growth of the same species through the release of toxic chemical compounds into the environment. The phenomenon of autotoxicity in crops is best traced in alfalfa (Medicago sativa). A close relative of alfalfa, M. truncatula, has been developed into an excellent model species for leguminous plants. However, it is not known whether M. truncatula has autotoxicity. In this study, M. truncatula root exudates showed a negative impact on the growth of M. truncatula seedlings, indicating autotoxicity. Detailed analyses with plant extracts from M. truncatula and alfalfa revealed varying degrees of suppression effects in the two species. The extracts negatively affected seed germination potential, germination rate, radicle length, hypocotyl length, synthetic allelopathic effect index, plant height, root growth, fresh weight, dry weight, net photosynthetic rate, transpiration rate, and stomatal conductance in both M. truncatula and alfalfa. The results demonstrated that autotoxicity and allelopathic effects exist in M. truncatula. This opens up a new way to use M. truncatula as a model species to carry out in-depth studies of autotoxicity and allelopathy to elucidate biochemical pathways of allelochemicals and molecular networks controlling biosynthesis of the chemicals.

[Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation]. / äº§ç§‘å‡ºé™¢åŽå› ä¸¥é‡é«˜èƒ†çº¢ç´ è¡€ç—‡ä½é™¢æ–°ç”Ÿå„¿å ¥é™¢å‰éšè®¿æƒ å†µåŠéšè®¿ä¾ä»Žæ€§å½±å“å› ç´ çš„å¤šä¸­å¿ƒè°ƒæŸ¥.

OBJECTIVES: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. METHODS: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. RESULTS: A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). CONCLUSIONS: Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.

[Intervention mechanism of moxa-cone moxibustion at Shu- and Mu-acupoints on the expression of RORγt/Foxp3 in asthma mice: an analysis based on PI3K signaling pathway].

OBJECTIVE: To explore the effect of moxa-cone moxibustion at "Feishu" (BL13) and "Zhongfu" (LU1) on the contents of related inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), and the expression of phosphatidy-linositol-3-kinase (PI3K), retinoic acid related orphan receptor γt (RORγt) and fork/wing helix transcription factor 3 (Foxp3) in lung tissue in asthma mice. METHODS: Sixty male Balb/c mice were divided into normal, model, LY294002 (an inhibitor of PI3K, LY), electroacupuncture (EA) and moxa-cone moxibustion (moxibustion) groups (n=12 in each group). The asthma model was established by intraperitoneal injection of ovalbumin sensitization. The mice in the LY group were injected with LY 294002 (7.5 mg/kg) via the tail vein. EA or moxa-cone moxibustion was applied at BL13 and LU1 in the EA or moxibustion group once daily for 2 weeks. The levels of immunoglobulin E (IgE), interleukin-4 (IL-4) and interferon-γ (IFN-γ) in serum and BALF were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, RORγt and Foxp3 in lung tissue were detected by real-time fluorescent quantitative polymerase chain reaction (QRT PCR) and immunohistochemistry. RESULTS: Compared with the normal group, the levels of IgE and IL-4 in serum and BALF, the expressions of PI3K and RORγt mRNA and protein in lung tissue were significantly increased (P<0.01), while the levels of IFN-γ, and the expressions of Foxp3 mRNA and protein were significantly reduced (P<0.01) in the model group. Compared with the model group, the levels of IgE and IL-4 in serum and BALF, the expressions of PI3K and RORγt mRNA and protein in lung tissue were significantly decreased (P<0.01, P<0.05), and the levels of IFN-γ in serum and BALF, the expressions of Foxp3 mRNA and protein in lung tissue were significantly increased (P<0.01) in the LY, EA and moxibustion groups. CONCLUSION: Moxa cone moxibustion at Shu- and Mu-acupoints of the lung meridian can reduce airway inflammatory reaction and control asthma attacks in asthma mice, which is closely related to its effects in regulating the expressions of RORγt and Foxp3 through PI3K signaling pathway.

Impact of Music Therapy on Preoperative Anxiety and Degree of Cooperation With Anesthesia Induction in Children With Simple Congenital Heart Disease.

PURPOSE: To evaluate the impact of music therapy (MT) on preoperative anxiety and degree of cooperation with anesthesia induction in children with simple congenital heart disease (CHD). DESIGN: A randomized controlled clinical study. METHODS: Ninety children were randomly assigned to the MT and control groups. The MT groups underwent a preoperative 30-minute session of MT, whereas the control group did not listen to any music and had the same amount of quiet time. The modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) was used to evaluate the patients' preoperative anxiety on entering the anesthesia waiting area (T1), 10 minutes after entering the waiting area (T2), and during the initiation of anesthesia induction (T3); the degree of cooperation with anesthesia induction was assessed using the Induction Compliance Checklist. The mean arterial blood pressure (MAP) and heart rate (HR) at T1, T2, T3, and T4 (the time of successful anesthesia) were also recorded. FINDINGS: One child was excluded from the MT group, and one was excluded from the control group. No difference was found in the mYPAS-SF score, MAP, or HR between the two groups at T1. The mYPAS-SF scores of the MT group were significantly lower than those of the control group at T2 and T3. At T2, T3, and T4, the MAP and HR of the MT group were lower than those of the control group. A statistically significant difference was found in the Induction Compliance Checklist score between the two groups. CONCLUSIONS: MT can reduce preoperative anxiety and improve the degree of cooperation with anesthesia induction.

Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation.

BACKGROUND: Although some recent neuroimaging studies have indicated the abnormal brain structure or function in patients with lifelong premature ejaculation (LPE), whether and how the abnormal thalamic function participates in processing sexual behavioral information are still unclear in patients with LPE. AIM: The aim of this study was to assess the changes in the thalamus metabolism and structural integrity in patients with LPE. METHODS: We performed a multimodal magnetic resonance approach in a 3.0 T system, including proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging, and volumetric analysis to detect the differences in thalamic metabolism and structure between 20 patients with LPE and 15 healthy controls. OUTCOMES: We analyzed and correlated the clinical symptoms of the subjects with significant 1H-MRS-based features. Peak areas of N-acetylaspartate, choline, creatine (Cr), and glutamate/glutamine (Glu) were calculated with the LCModel software. RESULTS: Diffusion tensor imaging and volumetric analysis of thalami showed no differences between the 2 groups. On the contrary, 1H-MRS study disclosed that both Glu concentrations and Glu/Cr ratio values in the thalami of patients with LPE were remarkably increased when compared with healthy controls (P < .01 for both variables). In addition, both the intravaginal ejaculatory latency time score and Chinese Index of Sexual Function for Premature Ejaculation-5 score were negatively related to increased Glu concentrations and Glu/Cr ratio values. CLINICAL IMPLICATIONS: Glutamatergic activity changes of thalamus may be an underlying indicator for evaluating sensory conduction efficiency in patients with LPE. STRENGTHS & LIMITATIONS: The present study first found the abnormal thalamic metabolism in patients with LPE and contributed to a better understanding of the LPE etiology. Limitations include a cross-sectional study design with small samples and no examination of other brain areas. CONCLUSION: Our findings show that the increase in glutamatergic activity of thalamus is related to LPE, suggesting that the increased Glu neurotransmission in the thalamus may contribute to the development of premature ejaculation. Xia J-D, Chen F, Zhang Q-J, et al. Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation. J Sex Med 2021;18:275-283.

Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy.

Rationale: Current traditional treatment options are frequently ineffective to fight against ovarian cancer due to late diagnosis and high recurrence. Therefore, there is a vital need for the development of novel therapeutic agents. B7H3, an immune checkpoint protein, is highly expressed in various cancers, representing it a promising target for cancer immunotherapy. Although targeting B7H3 by bispecific T cell-engaging antibodies (BiTE) has achieved successes in hematological malignancies during recent years, attempts to use them for the treatment of solid cancers are less favorable, in part due to the heterogeneity of tumors. Sorafenib is an unselective inhibitor of multiple kinases currently being tested in clinical trials for several tumors, including ovarian cancer which showed limited activity and inevitable side effect for ovarian cancer treatment. However, it is able to enhance antitumor immune response, which indicates sorafenib may improve the efficiency of immunotherapy. Methods: We evaluated the expression of B7H3 in ovarian cancer using online database and validated its expression of tumor tissues by immunohistochemistry staining. Then, B7H3 expression and the effects of sorafenib on ovarian cancer cell lines were determined by flow cytometry. In addition, 2D and 3D ovarian cancer models were established to test the combined therapeutic effect in vitro. Finally, the efficiency of B7H3×CD3 BiTE alone and its combination with sorafenib were evaluated both in vitro and in vivo. Results: Our data showed that B7H3 was highly expressed in ovarian cancer compared with normal samples. Treatment with sorafenib inhibited ovarian cancer cell proliferation and induced a noticeable upregulation of B7H3 expression level. Further study suggested that B7H3×CD3 BiTE was effective in mediating T cell killing to cancer cells. Combined treatment of sorafenib and B7H3×CD3 BiTE had synergistic anti-tumor effects in ovarian cancer models. Conclusions: Overall, our study indicates that combination therapy with sorafenib and B7H3×CD3 BiTE may be a new therapeutic option for the further study of preclinical treatment of OC.

Effectiveness of electroacupuncture (EA) for the treatment of urinary incontinence (UI) in patients with spinal cord injury (SCI): A protocol of systematic review of randomized controlled trials.

BACKGROUND: The objective of this study is to examine the effectiveness and safety of electroacupuncture (EA) in the treatment of urinary incontinence (UI) in patients with spinal cord injury (SCI). METHODS: All potential studies will be retrieved from the electronic databases of MEDLINE, EMBASE, Cochrane Library, PsycINFO, Web of Science, CBM, and China National Knowledge Infrastructure from origin of each database up to January 31, 2020. Additionally, we will check other resources, such as Google scholar, dissertations, conference proceedings, and reference lists of included studies. No language and publication date limitations will be considered in the literature resources search. All randomized controlled trials using EA for the treatment of UI in patients with SCI will be included. Two independent investigators will perform study selection, data extraction and study quality assessment. If any conflicts occur, we will invite a third investigator to solve them. Cochrane risk of bias will be used for study quality assessment, and RevMan 5.3 software will be employed for statistical analysis. RESULTS: This study will summarize the most recent evidence to assess the effectiveness and safety of EA for the treatment of UI in patients with SCI. CONCLUSION: The results of this study will provide helpful evidence to determine whether EA is effective and safety for the treatment of UI in patients with SCI or not. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020165562.

A protocol of systematic review and meta-analysis of acupuncture for drug resistant epilepsy.

BACKGROUND: This study aims to appraise the effectiveness and safety of acupuncture for drug resistant epilepsy (DRE). METHODS: We will search all potential randomized controlled trials (RCTs) of acupuncture for patients with DRE from their origin to March 1, 2020: MEDLINE, EMBASE, Cochrane Library, CINAHL, Scopus, WANGFANG, and Chinese Biomedical Literature Database. We will not apply any restrictions to the language and publication date. All RCTs investigating the effectiveness and safety of acupuncture for patients with DRE will be included. Study quality will be appraised by Cochrane risk of bias, and statistical analysis will be scrutinized by RevMan 5.3 software. Whenever possible, a narrative summary to describe study quality and content of the evidence will be performed. RESULTS: This study will provide summarize high quality evidence and will utilize a variety of outcome measurements to verify effectiveness and safety of acupuncture for DRE. CONCLUSION: The results of this study will seek to explore the effectiveness and safety of acupuncture for DRE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020170517.

[Influence of acupuncture combined with rehabilitation therapy on limb motor function and serum cAMP and cGMP in patients with hemiplegia of cerebral ischemic stroke].

OBJECTIVE: To evaluate the therapeutic effect of the combined treatment with balance acupuncture therapy and exercise re-learning rehabilitation therapy and the impact on serum cAMP and cGMP in the patients with hemiplegia of cerebral ischemic stroke. METHODS: A total of 90 patients of hemiplegia of cerebral ischemic stroke were randomized into an observation group and a control group, 45 cases in each one. All of the patients in the two groups received health education, diet guidance, routine symptomatic treatment as well as exercise re-learning rehabilitation therapy. Additionally, in the observation group, balance acupuncture therapy was applied, in which, the acupoints on the yang aspect of the human body, on the governor vessel and bladder meridian were adopted in the morning and those on the yin aspect of the human body, on the conception vessel and kidney meridian were stimulated in the afternoon. In the control group, the regular acupuncture was given. In the two groups, both acupuncture and rehabilitation therapies were given 5 days a week, 2 week-treatment as one course and totally 2 courses were required. Separately, before and after treatment, the score of Fugl-Meyer assessment (FMA) and the score of Chinese stroke scale (CSS) were recorded, the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) detected in serum and the clinical therapeutic effect were evaluated in the two groups. RESULTS: After treatment, FMA score was increased in the patients of either of the groups as compared with that before treatment (P<0.01) and CSS score decreased as compared with that before treatment (P<0.01). After treatment, FMA score in the observation group was higher than that in the control group (P<0.01) and CSS score was lower than the control group (P<0.01). After treatment, the level of serum cAMP of the patients in either of the groups was increased as compared with that before treatment (P<0.01) and that of cGMP decreased as compared with that before treatment (P<0.01). After treatment, the level of cAMP in the observation group was higher than that in the control group (P<0.01) and that of cGMP was lower than the control group (P<0.01). The total effective rate was 93.3% (42/45) in the observation group, better than 73.3% (33/45) in the control group (P<0.01). CONCLUSION: The balance acupuncture therapy combined with exercise re-learning rehabilitation effectively improves the motor function of the affected limb, relieves injury and regulate the levels of serum cAMP and cGMP in the patients with hemiplegia of ischemic stroke.

Can Botulinum Toxin Type A effectively treat neuropathic pain in spinal cord injury?: A protocol of systematic review and meta-analysis.

BACKGROUND: This protocol aims to assess the efficacy and safety of Botulinum Toxin Type A (BTTA) for the treatment of neuropathic pain (NPP) in patients with spinal cord injury (SCI). METHODS: We will retrieve databases in Cochrane Library, EMBASE, MEDLINE, Excerpta Medica Database, PsychINFO, the Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the beginning to the March 1, 2020. We will consider any potential studies on assessing the efficacy and safety of BTTA for the treatment of NPP in patients with SCI without limitations of language and publication status. Cochrane risk of bias will be used to assess the risk of bias for all included trials. RevMan 5.3 software will be utilized to synthesize the extracted data and to analyze those data. RESULTS: This study will appraise the efficacy and safety based on the current evidence of BTTA for the treatment of NPP in patients with SCI. CONCLUSION: This study will exert high quality clinical trials for exploring the efficacy and safety of BTTA in treating NPP in patients with SCI. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020170474.

[Effect of moxa-cone moxibustion at lung's back-shu points and front-mu points on Th17/Treg balance in mice with asthma].

OBJECTIVE: To observe the effect of moxa-cone moxibustion at lung's back-shu points and front-mu points on the expression of helper T lymphocyte 17 (Th 17)/regulatory T lymphocyte (Treg) in mice with asthma, and to explore the possible mechanism of moxa-cone moxibustion on asthma. METHODS: Sixty SPF-grade healthy male Balb/c mice were randomly divided into a normal group, a model group, an LY294002 group (LY group), an electroacupuncture (EA) group and a moxibustion group, 12 mice in each group. Asthma model was replicated by using ovalbumin (OVA) sensitization. Except the mice in the normal group, all the mice were intraperitoneally injected with sensitization solution (containing 15 µg of OVA and 30 mg of aluminum hydroxide) on the 1st day, 7th day and 14th day, 0.5 mL per mice; from the 15th day, 1% OVA solution was atomized for 20 min, once a day for 2 weeks; the mice in the normal group was treated with identical operations but with 0.9% sodium chloride solution. The mice in the LY group were treated with injection of LY294002 at tail vein on the 13th day, 14th day and 15th day. At the beginning of the 15th day, The mice in the EA group were treated with EA at "Feishu" (BL 13) and "Zhongfu" (LU 1) with disperse-dense wave, frequency of 2 Hz/20 Hz, intensity of 1 mA, 15 min each time, once a day for 2 weeks. The mice in the moxibustion group was treated with moxa-cone moxibustion at "Feishu" (BL 13) and "Zhongfu" (LU 1) from the 15th day, three moxa-cones per acupoint, once a day for 2 weeks. On the 16th day, 18th day and 22nd day, the incubation period of asthma was recorded. On the 29th day, all the samples were collected. The expressions of IL-17 and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were detected by ELISA method. The pathological changes of lung tissue were observed by HE staining. The percentage of Th17, Treg and Th17/Treg ratio in spleen tissue were detected by flow cytometry method. RESULTS: Compared with the normal group, the incubation period of asthma in the model group was significantly shortened (P<0.01), while that in the LY group, the EA group and the moxibustion group was longer than that in the model group (P<0.01). After the intervention, bleeding and inflammatory exudation in the lung tissue were observed in the model group, and a large number of inflammatory cell infiltration around the bronchus and alveoli was found, and extensive consolidation appeared; the pathological changes of lung tissue in the LY group, the EA group and the moxibustion group were significantly reduced, and the structure of bronchus and alveoli was basically normal, and the inflammatory exudation and inflammatory cell infiltration were significantly reduced compared with the model group; the inflammatory reaction in the moxibustion group was slightly less than that in the LY group and the EA group. Compared with the normal group, the content of IL-17 in serum and BALF, the percentage of Th17 and Th17/Treg ratio in spleen tissue in the model group after intervention were increased (P<0.01), while the content of IL-10 in serum and BALF and the percentage of Treg in spleen tissue were decreased (P<0.01, P<0.05). Compared with the model group, the contents of IL-17 in serum and BALF, Th17 percentage and Th17/Treg ratio in spleen tissue in the LY group, the EA group and the moxibustion group were significantly reduced (P<0.01, P<0.05), while the content of IL-10 in serum and BALF and the percentage of Treg in spleen tissue were increased (P<0.01, P<0.05). The above indice had no significant difference among all the intervention groups (P>0.05). CONCLUSION: The Th17/Treg is imbalanced in asthmatic body. The moxibustion at lung's back-shu points and front-mu points can control asthma by regulating Th17/Treg imbalance and restoring immune homeostasis.

Abstinence Following a Motivation-Skill-Desensitization-Mental Energy Intervention for Heroin Dependence: A Three-year Follow-up Result of a Randomized Controlled Trial.

The high rate of relapse among heroin users remains a significant public concern in China. In the present study, we utilized a Motivation-Skill-Desensitization-Mental Energy (MSDE) intervention and evaluated its effects on abstinence and mental health. Eighty-nine male heroin users in a drug rehabilitation center were enrolled in the study. The participants in the MSDE intervention group (n=46) received MSDE intervention, which included motivational interviewing, coping skills training, eye movement desensitization and reprocessing, and mindfulness-based psychotherapy. The participants in the control group (n=43) received a series of lectures on skills training. A significant increase in Contemplation Ladder score (P<0.001) and decreases in scores on the Obsessive Compulsive Drug Use Scale (P<0.001), Beck Depression Inventory (P<0.001), and Aggression Questionnaire (P=0.033) were found immediately after intervention. Compared to the control group, the MSDE intervention group reported significantly higher abstinence rates (P=0.027) and retention rates (P<0.001) at follow-up. Overall, the MSDE intervention, which uses a combined strategy for relapse prevention, could be a promising approach for preventing relapse among heroin users in China.

Impact of total parenteral nutrition standardization led by pharmacist on quality in postoperative patients with colorectal cancer.

BACKGROUND/OBJECTIVES: Abdominal surgery significantly affects the structure and function of the gastrointestinal system of patients, total parenteral nutrition (TPN) is an important nutrition support method for postoperative patients. However, in the process of TPN practice, the excessive fat emulsion and compound amino-acid prescriptions ratio are often prescribed by doctors. To address the problem, we developed the computerized TPN prescription management system to promote the personalized provision of TPN. The purpose of this study is to evaluate the intervention effects of the computerized TPN prescription management system, which is designed by pharmacists in the Surgical Department of Abdominal Oncology at Zhejiang Cancer Hospital in July 2015. SUBJECTS/METHODS: The computerized TPN prescription management system applied in Surgical Department of Abdominal Oncology on 1 July 2015. The computerized TPN prescription management system was evaluated by comparing the patients who were treated 3 months after the application of the system with the control subjects who were treated 3 months prior to the application of TPN prescription management system in Surgical Department of Abdominal Oncology. RESULTS: In total, 218 TPN prescription-treated patients with colorectal cancer received surgery treatment were analyzed, including 121 subjects who received the treatment 3 months prior to application of TPN prescription system (IPN period) and 97 subjects who received the treatment after 3 months of the system application (SPN period). The rates of optimized TPN prescriptions are 47.1% and 88.7% prior to and after application of TPN prescription review system, respectively (p < 0.001). In detail, prior to application of TPN prescription review system, abnormal glucose-lipid ratio and nitrogen-calorie ratio are the most common problems, which accounted for 74.3 and 97.9%, respectively (p < 0.01). Whereas the proportion of the insufficient dosage of amino acids is 62 and 96.9%, respectively (p < 0.01). Other problems are insufficient dosage of insulin and excessive fat soluble vitamin supplement. After application of TPN prescription review system, as the glucose-lipid ratio and nitrogen-calorie ratio are set up in fixed range according to the nutrition treatment guidelines, only a small amount of TPN prescriptions have the problem of insufficient dosage of compound amino acid. Furthermore, before and after the application of TPN management software, the gender, age, performance status (PS) score and BMI index of the two groups of colorectal cancer patients were not statistically different (p > 0.05). There were significant differences in albumin and prealbumin between the two groups after operation (p < 0.05), and there was a significant difference in total protein (p < 0.001). There were significant differences in alanine aminotransferase and indirect bilirubin between liver and kidney function (p < 0.01), and there were significant differences in aspartate aminotransferase and total bilirubin (p < 0.05). Other total cholesterol, L-γ-glutamyl transferase, direct bilirubin and creatinine were not statistically different (p > 0.05). Blood routine (WBC, Hb and lymphocyte), length of stay and recurrence rate were not statistically different (p > 0.05). CONCLUSIONS: The application of TPN management software not only standardized the doctor's TPN medical advice, but also improved the qualified rate of TPN doctor's advice, thus ensuring the safety of the patient's medication. It also had a positive effect on postoperative recovery of colorectal cancer patients, and ensured the efficacy of the treatment of patients. In addition, it reduced the workload of the pharmacist's audit prescription and improved the efficiency of the audit prescription, and further emphasized the role and value of pharmacists.