Biportal Endoscopic Spinal Cord Stimulation Paddle Lead Implantation: Technical Note and Preliminary Clinical Results.

OBJECTIVE: This study aims to elucidate a novel, minimally invasive surgical technique using a biportal endoscope for the implantation of spinal cord stimulation (SCS) paddle leads and to report the preliminary results of its clinical application. MATERIALS AND METHODS: The perioperative data of patients who underwent the biportal endoscopic SCS paddle lead implantation in our department were collected; the surgical procedure was delineated, and the clinical outcomes were assessed. RESULTS: From February 2022 to December 2023, six patients underwent biportal endoscopic SCS paddle lead implantation. The median follow-up time was nine months (range one to three months). The median intraoperative blood loss was 30 mL (range 25-50 mL), and the median operative time was 87.5 minutes (range 75-110 minutes). One patient experienced severe neck pain during the operation, whereas the other five patients experienced no surgical complications. One patient was found to have a slight lead migration three months after surgery, which did not affect the therapeutic effect. The median visual analogue scale (VAS) of the surgical area was 0.5 (range 0-2), 2.5 (range 1-4), and 0.5 (range 0-1) during the operation and one day and one week after the operation, respectively. The median VAS of the six patients' primary disease was 8 (range 7-9) before surgery and 2.5 (range 1-4) at the last postoperative follow-up (pain reduction ≥50%). CONCLUSION: Paddle lead systems for SCS can be implanted successfully using a biportal endoscopic technique.

Nanoliter-Scale Droplet-Droplet Microfluidic Microextraction Coupled with MALDI-TOF Mass Spectrometry for Metabolite Analysis of Cell Droplets.

The further miniaturization of liquid-phase microextraction (LPME) systems has important significance and major challenges for microscale sample analysis. Herein, we developed a rapid and flexible droplet-droplet microfluidic microextraction approach to perform nanoliter-scale miniaturized sample pretreatment, by combining droplet-based microfluidics, robotic liquid handling, and LPME techniques. Differing from the previous microextraction methods, both the extractant and sample volumes were decreased from the microliter scale or even milliliter scale to the nanoliter scale. We utilized the ability of a liquid-handling robot to manipulate nanoliter-scale droplets and micrometer-scale positioning to overcome the scaling effect difficulties in performing liquid-liquid extraction of nanoliter-volume samples in microsystems. Two microextraction modes, droplet-in-droplet microfluidic microextraction and droplet-on-droplet microfluidic microextraction, were developed according to the different solubility properties of the extractants. Various factors affecting the microextraction process were investigated, including the extraction time, recovery method of the extractant droplet, static and dynamic extraction mode, and cross-contamination. To demonstrate the validity and adaptability of the pretreatment and analysis of droplet samples with complex matrices, the present microextraction system coupled with MALDI-TOF mass spectrometry (MS) detection was applied to the quantitative determination of 7-ethyl-10-hydroxylcamptothecin (SN-38), an active metabolite of the anticancer drug irinotecan, in 800-nL droplets containing HepG2 cells. A linear relationship (y = 0.0305x + 0.376, R2 = 0.984) was obtained in the range of 4-100 ng/mL, with the limits of detection and quantitation being 2.2 and 4.5 ng/mL for SN-38, respectively.

Manipulating Femtoliter to Picoliter Droplets by Pins for Single Cell Analysis and Quantitative Biological Assay.

Herein, we developed an automated and flexible system for performing miniaturized liquid-liquid reactions and assays in the femtoliter to picoliter range, by combining the contact printing and the droplet-based microfluidics techniques. The system mainly consisted of solid pins and an oil-covered hydrophilic micropillar array chip fixed on an automated x- y- z translation stage. A novel droplet manipulation mode called "dipping-depositing-moving" (DDM) was proposed, which was based on the programmable combination of three basic operations, dipping liquids and depositing liquids with the solid pins and moving the two-dimensional oil-covered hydrophilic pillar microchip. With the DDM mode, flexible generation and manipulation of small droplets with volumes down to 179 fL could be achieved. For overcoming the scale phenomenon specially appeared in picoliter-scale droplets, we used a design of water moat to protect the femtoliter to picoliter droplets from volume loss through the cover oil during the droplet generation, manipulation, reaction and assay processes. Moreover, we also developed a precise quantitative method, quantitative droplet dilution method, to accurately measure the volumes of femtoliter to picoliter droplets. To demonstrate its feasibility and adaptability, we applied the present system in the determination of kinetics parameter for matrix metalloproteinases (MMP-9) in 1.81 pL reactors and the measurement the activity of ß-galactosidase in single cells (HepG2 cells) in picoliter droplet array. The ultrasmall volumes of the droplet reactors avoided the excessive dilution to the reaction solutions and enabled the highly sensitive measurement of enzyme activity in the single cell level.

Clinical Value of Hospital-Community-Family Integrated Nursing Model in the Treatment of Patients with Hyperlipidemia Pancreatitis.

Objective: This study aimed to observe the impact of the hospital-community-family integrated nursing paradigm on the compliance, psychological state, and blood lipid levels in patients with hyperlipidemia pancreatitis (HLP). Methods: Totally 66 HLP patients treated in our institution between June 2018 and June 2021 were randomized to Exp group and Con group. The Exp group received the hospital-community-family integrated nursing mode, whereas Con group adopted conventional nursing. Outcome measures included patient compliance, mental state, and blood cholesterol levels. Results: Patients with integrated nursing exhibited markedly higher compliance than those with conventional nursing, as evinced by higher scores of compliance behavior, compliance awareness, medication attitude, and treatment attitude (P < 0.05). Integrated nursing offered more potent mitigation of negative emotions of patients than conventional nursing (P < 0.05). Integrated nursing resulted in better enhanced quality of life of patients versus conventional nursing (P < 0.05). Superior blood lipid amelioration was observed in patients after integration nursing versus those after conventional nursing, demonstrated by a higher serum high-density lipoprotein (HDL) level, and lower levels of triglycerides (TG), cholesterol (TC), and low-density lipoprotein (LDL) (P < 0.05). Patients were more satisfied with integrated nursing (96.97%) than conventional nursing (72.73%), suggesting a high patient acceptance of the nursing mode (P < 0.05). Conclusion: The hospital-community-family integrated nursing model provides a viable alternative to enhance HLP patients' compliance and optimize their psychological state and blood lipid levels, demonstrating good potential for clinical promotion.

Acupuncture benefits to women with recurrent implantation failure: A propensity score-matched cohort study.

Objectives: The current study aims to assess the effectiveness of acupuncture in improving the live birth rate (LBR), ongoing pregnancy rate (OPR), clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), and pregnancy loss (early abortion rate, late abortion rate, ectopic pregnancy rate) in patients with recurrent implantation failure (RIF). Design: This retrospective study compares the outcomes of patients with RIF who underwent frozen embryo transfer (FET) with or without acupuncture. Setting: The medical records of patients diagnosed with RIF and visiting Chengdu Xi'nan Gynecological Hospital between January 2018 and June 2021 were reviewed. The Chengdu Xi'nan Gynecological Hospital Ethics Committee approved this retrospective study (No. 2021-029). Participants: A total of 923 patients with RIF who underwent FET were included in this study. The patients were divided into two groups: the Acupuncture (n = 303) and the Non-acupuncture groups (n = 620). Exposure: The Acupuncture group consisted of 303 RIF patients who received acupuncture therapy in addition to standard hormone replacement therapy (HRT)/delayed hormone replacement therapy (d-HRT) for FET. The Non-acupuncture group consisted of 620 RIF patients who received only standard HRT/d-HRT for FET. Primary and secondary outcome measures: The primary outcome was the LBR. The secondary outcome referred to OPR, CPR, BPR, and pregnancy loss. Results: The Acupuncture group had significantly higher BPR (P = 0.08) and CPR (P = 0.049) than the Non-acupuncture group. A potentially higher LBR (P = 0.16) and OPR (P = 0.248) were observed in the Acupuncture group than in the Non-acupuncture group. However, the survival analysis did not show that acupuncture significantly promoted live birth. Conclusions: Acupuncture is an appropriate adjunctive technique in the in vitro fertilization process as it improves biochemical and clinical pregnancies. Therefore, it is necessary to be cautious about the role of acupuncture throughout the whole pregnancy cycle.

Systematic review of acupuncture to improve ovarian function in women with poor ovarian response.

Objective: To determine the effect of acupuncture in treating poor ovarian response (POR). Methods: We searched MEDLINE (via PubMed), EMBASE, Allied and Complementary Medicine Database, CNKI, CBM, VIP database, Wanfang Database, and relevant registration databases from inception to January 30, 2023. In this review, both Chinese and English peer-reviewed literature were included. Only randomized controlled trials (RCTs) using acupuncture as an intervention for POR patients undergoing in vitro fertilization were considered. Results: Seven clinical randomized controlled trials (RCTs) were eventually included for comparison (516 women). The quality of included studies was generally low or very low. For the meta-analysis, seven studies showed that compared with controlled ovarian hyperstimulation (COH) therapy, acupuncture combined with COH therapy could significantly increase the implantation rate (RR=2.13, 95%CI [1.08, 4.21], p=0.03), the number of oocytes retrieved (MD=1.02, 95%CI [0.72, 1.32], p<0.00001), the thickness of endometrium (MD=0.54, 95%CI [0.13, 0.96], p=0.01), and the antral follicle count (MD=1.52, 95%CI [1.08, 1.95], p<0.00001), reduce follicle-stimulating hormone (FSH) levels (MD=-1.52, 95%CI [-2.41, -0.62], p=0.0009) and improve estradiol (E2) levels (MD=1667.80, 95%CI [1578.29, 1757.31], p<0.00001). Besides, there were significant differences in the duration of Gn (MD=0.47, 95%CI [-0.00, 0.94], p=0.05) between the two groups. However, no statistical variation was observed in improving clinical pregnancy rate (CPR), fertilization rate, high-quality embryo rate, luteinizing hormone (LH) value, anti-mullerian hormone (AMH) value, or reducing the dose of gonadotropin (Gn) values between the acupuncture plus COH therapy group and the COH therapy group. Conclusion: Acupuncture combined with COH therapy is doubtful in improving the pregnancy outcome of POR patients. Secondly, acupuncture can also improve the sex hormone level of POR women, and improve ovarian function. Furthermore, more RCTs of acupuncture in POR are needed to be incorporated into future meta-analyses. Systematic review registration: PROSPERO, identifier CRD42020169560.

Amelioration effects of α-viniferin on hyperuricemia and hyperuricemia-induced kidney injury in mice.

BACKGROUND: α-Viniferin, the major constituent of the roots of Caragana sinica (Buc'hoz) Rehder with a trimeric resveratrol oligostilbenoid skeleton, was demonstrated to possess a strong inhibitory effect on xanthine oxidase in vitro, suggesting it to be a potential anti-hyperuricemia agent. However, the in vivo anti-hyperuricemia effect and its underlying mechanism were still unknown. PURPOSE: The current study aimed to evaluate the anti-hyperuricemia effect of α-viniferin in a mouse model and to assess its safety profile with emphasis on its protective effect on hyperuricemia-induced renal injury. METHODS: The effects were assessed in a potassium oxonate (PO)- and hypoxanthine (HX)-induced hyperuricemia mice model by analyzing the levels of serum uric acid (SUA), urine uric acid (UUA), serum creatinine (SCRE), serum urea nitrogen (SBUN), and histological changes. Western blotting and transcriptomic analysis were used to identify the genes, proteins, and signaling pathways involved. RESULTS: α-Viniferin treatment significantly reduced SUA levels and markedly mitigated hyperuricemia-induced kidney injury in the hyperuricemia mice. Besides, α-viniferin did not show any obvious toxicity in mice. Research into the mechanism of action of α-viniferin revealed that it not only inhibited uric acid formation by acting as an XOD inhibitor, but also reduced uric acid absorption by acting as a GLUT9 and URAT1 dual inhibitor as well as promoted uric acid excretion by acting as a ABCG2 and OAT1 dual activator. Then, 54 differentially expressed (log2 FPKM ≥ 1.5, p ≤ 0.01) genes (DEGs) repressed by the treatment of α-viniferin in the hyperuricemia mice were identified in the kidney. Finally, gene annotation results revealed that downregulation of S100A9 in the IL-17 pathway, of CCR5 and PIK3R5 in the chemokine signaling pathway, and of TLR2, ITGA4, and PIK3R5 in the PI3K-AKT signaling pathway were involved in the protective effect of α-viniferin on the hyperuricemia-induced renal injury. CONCLUSIONS: α-Viniferin inhibited the production of uric acid through down-regulation of XOD in hyperuricemia mice. Besides, it also down-regulated the expressions of URAT1 and GLUT9 and up-regulated the expressions of ABCG2 and OAT1 to promote the excretion of uric acid. α-Viniferin could prevent hyperuricemia mice from renal damage by regulating the IL-17, chemokine, and PI3K-AKT signaling pathways. Collectively, α-viniferin was a promising antihyperuricemia agent with desirable safety profile. This is the first report of α-viniferin as an antihyperuricemia agent.

Major stress hormones suppress the response of macrophages through down-regulation of TLR2 and TLR4.

BACKGROUND: Severe trauma often leads to diminished cytokines especially from macrophages to Toll-like receptor (TLR) agonists. However, the molecular mechanisms remain to be elucidated. As surgical trauma could also induce neuroendocrine hormones to modulate the immune system, we investigated the effects of major hormones, including endogenous glucocorticoid (corticosterone (CORT)), epinephrine (E), and norepinephrine (NE) on the expression and response of TLR2 and TLR4 in macrophages. MATERIALS AND METHODS: Rat macrophages were pretreated by each hormone (1000 ng/mL of CORT, E, and NE) for 24 h, then restimulated with Pam3CSK4 or lipopolysaccharide (LPS) for further 24 h, and supernatant tumor necrosis factor-alpha (TNF-α) was measured. Additionally, macrophages were incubated with different concentrations of hormones (0-10,000 ng/mL) for 48 h or with 1000 ng/mL of hormones for 0-48 h, the expressions of TLR2 and TLR4 and intracellular molecules (MyD88, IRAK1, and TRAF6) in macrophages were analyzed by real-time quantitative polymerase chain reaction (PCR) and RT-PCR, respectively. RESULTS: Pam3CSK4-stimulated TNF-α production was significantly reduced from macrophages pretreated with CORT, and both Pam3CSK4- and LPS-stimulated TNF-α were suppressed with E. Moreover, CORT down-regulated only TLR2 expression in both time- and dose-dependent manner, but both TLR2 and TLR4 mRNA expressions were down-regulated in time- and dose-dependent manner after exposure to E. However, the transcript expression of MyD88, IRAK1, and TRAF6 remained unchanged after exposure to each hormone. CONCLUSIONS: These results suggested that the down-regulation of TLR2 and TLR4 expressions by CORT and E is involved in the hyporesponsiveness of macrophages.

A coordinate-based meta-analysis of acupuncture for chronic pain: Evidence from fMRI studies.

Background: Chronic pain (CP) patients tend to represent aberrant functional brain activity. Acupuncture is an effective clinical treatment for CP, and some fMRI studies were conducted to discover the alternation of brain regions after acupuncture therapy for CP. However, the heterogeneity of neuroimaging studies has prevented researchers from systematically generalizing the central mechanisms of acupuncture in the treatment of CP. Methods: We searched bibliographic databases, including PubMed, EMBASE, PsycINFO, Web of Science Core Collection, ScienceDirect, China Academic Journal Network Publishing Database, etc., and trials registration platforms (From inception to September 1st, 2022). Two independent researchers assessed the study's bias and quality. Furthermore, activation likelihood estimation (ALE) analysis was applied to explore aberrant brain functional activity and acupuncture's central mechanism for CP. Results: Totally 14 studies with 524 CP patients were included in the study. ALE analysis showed that CP patients presented with decreased ALFF/ReHo in the precuneus, posterior cingulate cortex, right inferior parietal lobule, right superior temporal gyrus, cingulate gyrus, superior frontal gyrus, left medial frontal gyrus including medial prefrontal gurus, left middle frontal gyrus. Conclusion: This ALE meta-analysis pointed out that acupuncture could modulate the default mode network, the frontoparietal network to treat CP. This provided a systematic summary of the neuroimage biomarker of acupuncture for the treatment of CP. Systematic review registration: PROSPERO, identifier: CRD42021239633.

[Effect of acupuncture on brain functional connectivity strength in patients with primary dysmenorrhea].

OBJECTIVE: To investigate the effect of acupuncture on the brain functional activities of the patients with primary dysmenorrhea based on the resting-state functional magnetic resonance imaging (rs-fMRI), and to provide visual evidence for the central mechanism of acupuncture in treatment of primary dysmenorrhea. METHODS: Forty-two patients of primary dysmenorrhea were enrolled and randomly divided into an observation group (21 cases, 1 case dropped off) and a control group (21 cases, 2 cases dropped off, 3 cases withdrawal). In the observation group, acupuncture was exerted at Sanyinjiao (SP 6) and Guanyuan (CV 4), started 5-7 days before menstrual flow, once a day till menstrual onset, for a total of 3 menstrual cycles. No intervention was applied in the control group. The scores of visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS) were observed in both groups before and after treatment. Based on rs-fMRI, the data of resting-state functional magnetic resonance were collected from two groups before and after treatment. Combined with functional connectivity strength (FCS) and functional connectivity (FC) analysis, the differences of brain regions before and after treatment were compared between the two groups and the correlation was analyzed between their functional connectivity changes and the improvements in VAS and CMSS scores of the patients in the observation group. RESULTS: In the observation group, the scores of VAS and CMSS were all decreased after treatment (P<0.05), while the scores related to the symptom time in CMSS was reduced in comparison with that before treatment in the control group (P<0.05). The score reducing ranges of VAS and CMSS in the observation group were larger than the control group (P<0.05). Compared before treatment, FCS of the right middle cingulate cortex and the left cuneus was increased, while FCS of the left inferior parietal lobule was decreased after treatment in the observation group. In the control group, FCS of the left orbital frontal cortex was increased after treatment. Compared with the control group, FCS of the left anterior insula was increased in the observation group after treatment. FC analysis was performed using the left anterior insula as the seed point. In comparison with the control group, FC of the left anterior insula was increased either with the inferior temporal gyrus or with the right hippocampus; and was decreased either with the middle occipital lobe or with the right dorsolateral prefrontal cortex in the observation group after treatment. In the observation group, FC between the left anterior insula and the right hippocampus was positively correlated with the improvements in symptom severity (r =0.385, P<0.05) and symptom time (r =0.510, P<0.05) of CMSS, and FC between the right dorsolateral prefrontal cortex and the left anterior insula was negatively correlated with the improvement in symptom severity of CMSS after treatment (r =-0.373, P<0.05). CONCLUSION: The anterior insula may be the key brain region in treatment of primary dysmenorrhea with acupuncture. Acupuncture may relieve dysmenorrhea and the related symptoms through strengthening the functional connectivity of anterior insula-limbic system and anterior insula-control network.

Acupuncture modulates the frequency-specific functional connectivity density in primary dysmenorrhea.

Background: The study aimed to investigate how acupuncture modulates brain activities across multiple frequency bands to achieve therapeutic effects in PDM. Methods: A total of 47 patients with PDM were randomly assigned to the verum acupuncture group and sham acupuncture group with three menstrual cycles of the acupuncture course. The fMRI scans, visual analog scale (VAS) scores, and other clinical evaluations were assessed at baseline and after three menstrual-cycles treatments. The global functional connectivity density (gFCD) analyses were performed between the pre-and post-acupuncture course of two groups at full-low frequency band, Slow-3 band, Slow-4 band, and Slow-5 band. Results: After the acupuncture treatments, the patients with PDM in the verum acupuncture group showed significantly decreased VAS scores (p < 0.05). The frequency-dependent gFCD alternations were found in the verum acupuncture group, altered regions including DLPFC, somatosensory cortex, anterior cingulate cortex (ACC), middle cingulate cortex (MCC), precuneus, hippocampus, and insula. The sham acupuncture modulated regions including angular gyrus, inferior frontal gyrus, and hippocampus. The gFCD alternation in DLPFC at the Slow-5 band was negatively in the patients with PDM following verum acupuncture, and S2 at the Slow-4 band was positively correlated with VAS scores. Conclusion: These findings supported that verum acupuncture could effectively modulate frequency-dependent gFCD in PDM by influencing abnormal DLPFC at Slow-5 band and hippocampus at the Slow-3 band. The outcome of this study may shed light on enhancing the potency of acupuncture in clinical practice.

Moxibustion for primary dysmenorrhea: A resting-state functional magnetic resonance imaging study exploring the alteration of functional connectivity strength and functional connectivity.

Introduction: Primary dysmenorrhea (PDM) is a common gynecological disease and chronic pain disorder. Moxibustion, a form of traditional Chinese medicine therapy, has proven to be effective for PDM. However, the central mechanisms of PDM and moxibustion for PDM are still unclear. This study aims to explore the potential central mechanism of PDM and clarify the possible mechanism of moxibustion for relieving pain. Materials and methods: A total of 23 PDM patients and 23 matched healthy controls (HCs) were enrolled. For PDM patients, resting-state functional magnetic resonance imaging (rs-fMRI) data were collected pre- and post-moxibustion treatment of 3 consecutive menstrual cycles, respectively. For HCs, rs-fMRI data were collected in the baseline. The resting-state functional connectivity strength (rs-FCS) analysis and the resting-state functional connectivity (rs-FC) analysis based on the region of interest (ROI) were combined to be conducted. Results: Compared to HCs, PDM patients showed weaker rs-FCS in the left inferior frontal gyrus (IFG). After the moxibustion treatment, rs-FCS in the left IFG was increased with clinical improvement. Then, the left IFG was chosen as ROI, and the rs-FC analysis was conducted. It showed that the left IFG rs-FC in the bilateral anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), the left posterior cingulate cortex (PCC)/precuneus (PCU), and the left parahippocampal gyrus (PHG) decreased after moxibustion treatment, most of which belong to the default mode network (DMN). Conclusion: Our results highlight the role of the left IFG and the DMN in PDM. Specifically, the central mechanism of moxibustion for analgesia may be related to modulating the disorders of the reappraisal and processing of pain stimuli through influencing the cognition of pain.

Optimization of cerebral organoids: a more qualified model for Alzheimer's disease research.

Alzheimer's disease (AD) is a neurodegenerative disease that currently cannot be cured by any drug or intervention, due to its complicated pathogenesis. Current animal and cellular models of AD are unable to meet research needs for AD. However, recent three-dimensional (3D) cerebral organoid models derived from human stem cells have provided a new tool to study molecular mechanisms and pharmaceutical developments of AD. In this review, we discuss the advantages and key limitations of the AD cerebral organoid system in comparison to the commonly used AD models, and propose possible solutions, in order to improve their application in AD research. Ethical concerns associated with human cerebral organoids are also discussed. We also summarize future directions of studies that will improve the cerebral organoid system to better model the pathological events observed in AD brains.

Genomic distribution of quantitative trait loci for yield and yield-related traits in common wheat.

A major objective of quantitative trait locus (QTL) studies is to find genes/markers that can be used in breeding programs via marker assisted selection (MAS). We surveyed the QTLs for yield and yield-related traits and their genomic distributions in common wheat (Triticum aestivum L.) in the available published reports. We then carried out a meta-QTL (MQTL) analysis to identify the major and consistent QTLs for these traits. In total, 55 MQTLs were identified, of which 12 significant MQTLs were located on wheat chromosomes 1A, 1B, 2A, 2D, 3B, 4A, 4B, 4D and 5A. Our study showed that the genetic control of yield and its components in common wheat involved the important genes such as Rht and Vrn. Furthermore, several significant MQTLs were found in the chromosomal regions corresponding to several rice genomic locations containing important QTLs for yield related traits. Our results demonstrate that meta-QTL analysis is a powerful tool for confirming the major and stable QTLs and refining their chromosomal positions in common wheat, which may be useful for improving the MAS efficiency of yield related traits.

Acupuncture for pain relief of women undergoing transvaginal oocyte retrieval: A meta analysis and systematic review protocol.

BACKGROUND: Pain during oocyte retrieval, which can make the in-vitro fertilization process an unpleasant experience, is becoming a common problem. Although there are many analgesic methods available in the clinical setting, they are not therapeutically equivalent, and some are associated with varying adverse reactions. In recent years, acupuncture analgesia has been used in the perioperative period of oocyte retrieval because of its perceived efficacy and safety. The purpose of this systematic review and meta-analysis is to provide evidence that acupuncture is effective in the treatment of vaginal oocyte retrieval pain. METHODS: Electronic searches of the following six databases will be conducted by two qualified reviewers: MEDLINE, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Medicine database, VIP database and Wanfang database. Three clinical trial registries will also be searched: World Health Organization International Clinical Trial Registry Platform, Chinese Clinical Trial Registry, Cochrane Central Register of Controlled Trials and ClinicalTrials.Gov. All searches will cover the period from inception of the database/registry to March 2020 and will be limited to publications in English and Chinese. Data identification, data selection, data extraction, and bias risk assessment will be conducted independently by3ν two or more qualified reviewers, including those who selected the studies. Visual analogue scale scores will be calculated as the primary outcome. Secondary outcomes will include results of other subjective pain rating scales, including Likert scales or other defined numerical or non-numerical scales, self-assessed by patients before, during, and after oocyte retrieval. We will use STATA software (Version 16) to perform meta-analyses, and the Grading of Recommendations, Assessment, Development and Evaluations framework to grade the quality of evidence. If quantitative analysis is not available, a systematic narrative synthesis will be provided. PROSPERO REGISTRATION NUMBER: CRD42020170095.

Moxibustion for Patients with Primary Dysmenorrhea at Different Intervention Time Points: A Randomized Controlled Trial.

PURPOSE: To investigate the effectiveness of moxibustion at different times of the menstrual cycle for patients with primary dysmenorrhea (PD). PATIENTS AND METHODS: Participants were 208 patients allocated to three controlled groups: one pre-menstrual treatment group (Group A), one menstrual-onset treatment group (Group B), and one waiting-list group (Group C). Groups A and B received the same intervention of moxibustion on points SP6 and RN4 but at different times. Group C, the waiting-list group, received no treatment throughout the study. Cox Menstrual Symptom Scale (CMSS) score was the primary outcome. Secondary outcomes were visual analog scale (VAS) score of pain intensity, self-rating anxiety scale (SAS) score, and self-rating depression scale (SDS) score. CMSS and VAS scores were obtained at the baseline stage (three cycles), treatment stage (three cycles), and follow-up stage (three cycles), a total of seven evaluations. SAS and SDS scores were obtained on the day of group allocation and the first day of the follow-up stage, a total of two evaluations. RESULTS: Baseline characteristics were comparable across the three groups. Pain duration (CMSS score) was significantly higher in Group C than in the other two groups at each evaluation (P<0.001). There was also a significant difference in the improvement in pain duration between Group B and Group C (P<0.001) throughout the trial. There were no significant changes in pain severity (CMSS score) after the 3-month treatment in Group A and Group B (P>0.05). Secondary outcomes showed that pre-menstrual moxibustion (Group A) was as effective as menstrual-onset moxibustion (Group B) in relieving pain intensity (VAS score) and negative mood (SDS and SAS scores). CONCLUSION: Moxibustion appears as an effective treatment for PD. Pre-menstrual application is more effective than menstrual-onset application. TRIAL REGISTRATION CHICTRORGCN IDENTIFIER: ChiCTR-TRC-14004627.

Dysbindin deficiency in sandy mice causes reduction of snapin and displays behaviors related to schizophrenia.

Schizophrenia (SCZ) is a complex trait with a high heritability. The DTNBP1 gene (encoding dysbindin) is one of the leading susceptible genes of SCZ. This risk gene has been reported to be associated with clinical symptoms such as negative symptoms and cognitive deficits. Although reduction of dysbindin expression in schizophrenic brain tissue has been reported, how this contributes to its symptomatology remains uncertain. The sandy (sdy) mouse, which harbors a spontaneously occurring deletion in the Dtnbp1 gene and expresses no dysbindin protein, provides a unique tool to study the role of dysbindin in SCZ. Our recent findings reveal that the sdy mice exhibit specific defects of neurosecretion and synaptic morphology in hippocampal neurons. We here further described that sdy manifested schizophrenia-like behaviors such as social withdrawal and cognitive deficits. In sdy hippocampus, the steady-state level of snapin (a SNAP25-binding protein and a synaptic priming regulator) was reduced due to loss of dysbindin. We further characterized that a 30-residue peptide in dysbindin (90-119 amino acids) mediated the interaction with snapin. Our results suggest that the destabilization of snapin in sdy mice may lead to abnormal neurotransmission and therefore abnormal behaviors. This further defines the sdy mutant as a potential model in schizophrenia research.

[Expression of N-methyl-D-aspartate receptor 1 in acute intoxicated encephalopathy induced by 1,2-dichloroethane].

OBJECTIVE: To study the role of N-methyl-D-aspartate receptor 1 in acute intoxicated encephalopathy induced by 1,2- dichloroethane(1,2-DCE). METHODS: Forty-two Sprague-Dawley rats, which had been randomly divided into 1 control, 3 exposure and 3 after-exposure observation groups were exposed to 1,2-DCE for 12 hr by continual static inhalation except control group. Dosage of exposure groups was 5.0, 10.0, 20.0 g/m(3) on sequence. That of after-exposure observation groups was 10.0 g/m(3). Rats of after-exposure observation groups were observed continually for 2,4,6 hr after exposure. The expression of N-methyl-D-aspartate receptor-1 (NMDAR1) was detected by immunohistochemical method. RESULTS: NMDAR1 stained neurons were mainly distributed at cerebral cortex and hippocampus. Compared with that of control group, the percentages of positive cells of NMDAR1 increased evidently at 10.0, 20.0 g/m(3) groups (P < 0.05). They were (18.33 +/- 1.86)%, (64.17 +/- 2.86)% at cerebral cortex, (15.5 +/- 1.87)%, (47.83 +/- 2.16)% at hippocampus. The percentages were also elevated obviously in 2, 4, 6 h after-exposure observation groups. They were (39.07 +/- 3.01)% (70.17 +/- 2.93)% (39.83 +/- 2.32)% at cerebral cortex, (16.30 +/- 1.03)% (19.80 +/- 1.17)% (16.50 +/- 1.05)% at hippocampus; Compared with that of 10.0 g/m(3) group, the percentages increased significantly only in 4 hr group at hippocampus. CONCLUSION: The overactivation of NMDAR1 is the main route by which excitatory amino acids chose to join the development of acute intoxicated encephalopathy induced by 1,2-DCE.

Ethyl acetate extract from Panax ginseng C.A. Meyer and its main constituents inhibit α-melanocyte-stimulating hormone-induced melanogenesis by suppressing oxidative stress in B16 mouse melanoma cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperpigmentation disease involves darkening of the skin color due to melanin overproduction. Panax ginseng C.A. Meyer is a well-known traditional Chinese medicine and has a long history of use as a skin lightener to inhibit melanin formation in China, Korea and some other Asian countries. However, the constituents and the molecular mechanisms by which they affect melanogenesis are not fully clear. AIM OF THE STUDY: The purpose of this study was to identify the active ingredient in Panax ginseng C.A. Meyer extract that inhibits mushroom tyrosinase activity and to investigate the antioxidative capacity and molecular mechanisms of the effective extract on melanogenesis in B16 mouse melanoma cells. MATERIALS AND METHODS: Aqueous extracts of Panax ginseng C.A. Meyer were successively fractionated with an equal volume of chloroform, ethyl acetate, and n-butyl alcohol to determine the effects by examining the activity of mushroom tyrosinase. The effective fraction was analyzed using HPLC and LC-MS. The antioxidative capacity and the inhibitory effects on melanin content, cell intracellular tyrosinase activity, and melanogenesis protein levels were determined in α-melanocyte-stimulating hormone (α-MSH)-treated B16 mouse melanoma cells. RESULTS: The ethyl acetate extract from Panax ginseng C.A. Meyer (PG-2) had the highest inhibiting effect on mushroom tyrosinase, mainly contained phenolic acids, including protocatechuic acid, vanillic acid, p-coumaric acid, salicylic acid, and caffeic acid, and exhibited apparent antioxidant activity in vitro. PG-2 and its main constituents significantly decreased melanin content, suppressed cellular tyrosinase activity, and reduced expression of tyrosinase protein to inhibit B16 cells melanogenesis induced by α-MSH, and no cytotoxic effects were observed. They also inhibited cellular reactive oxygen species (ROS) generation, increased superoxide dismutase (SOD) activity and glutathione (GSH) level in α-MSH-treated B16 cells effectively. And those activities of its main constituents could reach more than 80% of PG-2. The ROS scavengers N-acetyl-L-cysteine (NAC) had a similar inhibitory effect on melanogenesis. CONCLUSIONS: These results suggest that ethyl acetate extract from Panax ginseng C.A. Meyer has the highest effect on inhibiting melanogenesis, and that its main components are polyphenolic compounds, which may inhibit melanogenesis by suppressing oxidative stress. This work provides new insight into the active constituents and molecular mechanisms underlying skin-lightening effect of Panax ginseng C.A. Meyer.

[Effect of 1, 2-dichloroethane on blood brain barrier].

OBJECTIVE: To investigate the effect of 1, 2-dichloroethane (1, 2-DCE) on blood brain barrier. METHODS: Acute toxic encephalopathy model was copied with the consecutive static inhalation of 1, 2-DCE. The water content of brain tissue was measured, and the blood brain barrier permeability was detected with lanthanum nitrate. The brain microvascular endothelial cells and neuroglial cells were cultured in vitro, which were administrated with 1, 2-DCE. The cell morphologic structures were observed under light microscope and electron microscope. RESULTS: (1) The extracellular edema was most found in the cerebral tissue and the leakage of lanthanum particles through the barrier were found with the lanthanum tracking method. (2) The water content in cerebral cortex in the moderate and high dose groups was significantly higher than that in the control group and became severer with the increases of the intoxicated time. The water content in cerebral medulla was significantly increased only at 6 hours after the intoxication. (3) The normal morphological structure of brain microvascular endothelial cells and neuroglial cells could be injured by 1, 2-DCE, and the injury to neuroglial cells caused by 1, 2-DCE occurred earlier and severer than that to brain microvascular endothelial cells. CONCLUSION: 1, 2-DCE can damage blood brain barrier and induce cerebral edema.