Two new quinoline alkaloid with neuroprotective activities from Xylaria longipes.

Two new quinoline alkaloids with an α, ß-unsaturated amide side chain, xylarinines A and B (1 and 2), were isolated from the ethyl acetate extracts of Xylaria longipes solid fermentation. The structures of these were primarily determined though NMR and HRESIMS data analysis. The absolute configuration of compound 1 was assigned using experimental and calculated ECD data. The neuroprotective effects of compounds 1 and 2 against glutamate-induced damage in PC12 cells were evaluated in vitro bioassay. The results demonstrated that both compounds significantly improved cell viability, inhibited apoptosis, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH) levels, and reduced intracellular reactive oxygen species (ROS) accumulation. These findings suggested that these mechanisms contribute to the neuroprotective effects of the compounds.

Efficacy of Acupuncture for Chronic Spontaneous Urticaria : A Randomized Controlled Trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.

Lifestyle-based nomogram for identifying the Chaoshan inhabitants of China at high risk of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.

Chinese Herbal Medicine for the Treatment of Adult Viral Myocarditis: An Overview of Systematic Reviews and Meta-analyses of Randomized Controlled Trials.

PURPOSE: Viral myocarditis (VMC) is a life-threatening disease that can affect all ages and genders, with middle-aged adults being particularly susceptible. Numerous systematic reviews have been conducted to investigate the efficacy and safety of Chinese herbal medicine (CHM) in treating adult viral myocarditis (AVM). The objective of this study was to conduct a comprehensive overview of systematic reviews and meta-analyses of randomized controlled trials (RCTs) regarding the efficacy and safety of CHM for AVM. METHODS: A comprehensive systematic search was conducted across 8 electronic databases from their inception to June 23, 2022, augmented by manual searches of the gray literature. Systematic reviews were independently selected and data extracted in accordance with predetermined criteria by 2 reviewers. Included systematic reviews were assessed for methodologic and reporting quality using Assessing the Methodological Quality of Systematic Reviews 2 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of evidence relating to outcome measures was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Recalculation of effect sizes and subsequent determination of 95% CIs were conducted with either a fixed-effects or random-effects model. FINDINGS: The current overview of systematic reviews included a total of 6 systematic reviews, which reported on 67 RCTs with a participant pool of 5611 individuals. The findings of our study indicate that the combination of CHM and Western medications had positive effects on the effective rate, cure rate, ECG recovery, atrial premature contraction/premature ventricular contraction, left ventricular ejection fraction, myocardial enzymes, and improvement of clinical symptoms for AVM. The adverse drug reactions in the combination therapy group were generally less than or lighter than that in the Western medication group (relative risk = 0.79; 95% CI, 0.44-1.40; P > 0.05, I2 = 0). IMPLICATIONS: Our research results provide evidence that combining CHM with Western medicine could offer potential benefits for patients with AVM. However, the number of studies included in our review is limited and the methodologic quality of these studies is modest. Therefore, there are potential uncertainties regarding the conclusion that CHM with Western medication may benefit patients with AVM. We call for more large-scale, high-quality studies with standardized designs to further verify and support our findings. This would promote a better understanding of the efficacy and safety profile of CHM and provide reliable reference evidence for clinical practice and policy making. Moreover, future research should explore optimal drug combinations, examine therapeutic doses and durations of CHM combination therapy, and evaluate its long-term efficacy and safety.

Acupuncture for Patients with Chronic Spontaneous Urticaria: A Randomized, Sham-Controlled Pilot Trial.

OBJECTIVE: To determine the feasibility of conducting a full-scale randomized controlled trial (RCT) and investigate the basic information and safety of acupuncture for patients with chronic spontaneous urticaria (CSU). METHODS: A total of 80 participants with CSU from July 2018 to July 2019 were randomly assigned to receive active acupuncture (n=41) on a fixed prescription of acupoints or sham acupuncture (n=39) with superficial acupuncture on non-acupuncture points through the completely randomized design. Patients in both groups received 5 sessions per week for 2 weeks, and participants were followed for a further 2 weeks. Feasibility was assessed by recruitment and randomization rates, retention of participants, treatment protocol adherence, and the incidence of adverse events (AEs). The clinical primary outcome was the changes from baseline weekly urticaria activity scores (UAS7) after treatment at 2 weeks. Secondary outcomes included the Visual Analogue Scale (VAS) score of itching intensity, Dermatology Life Quality Index (DLQI), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA). RESULTS: A total of 80 participants were enrolled. The recruitment rate of 24.02%, randomization rate of 100%, a loss rate of 6.25%, and no obvious AEs were observed in either group. The decrease from baseline in the mean UAS7 total score at week 2 in the active acupuncture group was -8.63 (95%CI, -11.78 to -5.49) and -6.21 (95%CI, -9.43 to -2.98) in the sham acupuncture group for a between-group difference of -2.42 (95% CI, -6.93 to 2.07). The change in the DLQI, VAS of itching intensity, HAMA, and HAMD were a slightly better improvement trend in the active acupuncture group than the sham acupuncture group, but the between-group difference was not significant. CONCLUSIONS: Active acupuncture had a better improvement trend in alleviating symptoms, improving quality of life and regulating the mood of anxiety and depression in patients with CSU than sham acupuncture. (Registration Nos. AMCTR-ICR-18000190 and ChiCTR2100054776).

[Integrated strategy for biomarkers of stable coronary heart disease with phlegm and blood stasis syndrome based on RNA-seq and network pharmacology].

This study aimed to analyze the biological foundation and biomarkers of stable coronary heart disease(CHD) with phlegm and blood stasis(PBS) syndrome based on RNA-seq and network pharmacology. Peripheral blood nucleated cells from five CHD patients with PBS syndrome, five CHD patients with non-PBS syndrome, and five healthy adults were collected for RNA-seq. The specific targets of CHD with PBS syndrome were determined by differential gene expression analysis and Venn diagram analysis. The active ingredients of Danlou Tablets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the "component-target" prediction was completed through PubChem and SwissTargetPrediction. The "drug-ingredient-target-signaling pathway" network of Danlou Tablets against CHD with PBS syndrome was optimized by Cytoscape software. After the target biomarkers were identified, 90 participants were enrolled for diagnostic tests, and 30 CHD patients with PBS syndrome were included in before-and-after experiment to determine the therapeutic effect of Danlou Tablets on those targets. As revealed by RNA-seq and Venn diagram analysis, 200 specific genes were identified for CHD with PBS syndrome. A total of 1 118 potential therapeutic targets of Danlou Tablets were predicted through network pharmacology. Through integrated analysis of the two gene sets, 13 key targets of Danlou Tablets in the treatment of CHD with PBS syndrome were screened out, including CSF1, AKR1C2, PDGFRB, ARG1, CNR2, ALOX15B, ALDH1A1, CTSL, PLA2G7, LAP3, AKR1C3, IGFBP3, and CA1. They were presumably the biomarkers of CHD with PBS syndrome. The ELISA test further showed that CSF1 was significantly up-regulated in the peripheral blood of CHD patients with PBS syndrome, and was significantly down-regulated after Danlou Tablets intervention. CSF1 may be a biomarker for CHD with PBS syndrome, and it is positively correlated with the severity of the disease. The diagnostic cut-off of CSF1 for CHD with PBS syndrome was 286 pg·mL~(-1).

Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling.

OBJECTIVE: To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC). METHODS: According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy. RESULTS: EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA. CONCLUSION: EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.

[Study on the mechanism of electroacupuncture repairing intestinal barrier via regulating mast cell in rats with diarrhea-predominant irritable bowel syndrome].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on mast cell activation-related substances and intestinal barrier function in diarrhea-predominant irritable bowel syndrome (IBS-D) model rats, so as to explore its underlying mechanisms. METHODS: Thirty female SD rats were randomly divided into control group, model group and EA group, with 10 rats in each group. IBS-D model was established by chronic unpredictable mild stress combined with senna solution gavage. Rats in the EA group received EA treatment (2 Hz/15 Hz，0.1-1.0 mA) at "Zusanli" (ST36), "Taichong"(LR3) and "Tianshu"(ST25), 20 min per day, for a total of 14 days, with sides alternated daily. Visceral pain threshold was used to evaluate visceral hypersensitivity, diarrhea index was used to evaluate diarrhea degree. After all treatments, the pathological scores of colon were recorded after HE staining, the contents of cholecystokinin (CCK), substance P (SP), tryptase (TPS) and adenosine triphosphate (ATP) in colon were detected by ELISA, and the expressions of colonic tight junction protein ZO-1 and occludin were detected by Western blot. RESULTS: Compared with the control group, the visceral pain threshold, the expression levels of colonic ZO-1 and occludin proteins decreased (P<0.01), while the diarrhea index, the contents of colonic CCK, SP, TPS and ATP were significantly increased (P<0.01) in the model group. After intervention, in comparison with the model group, the visceral pain thre-shold, the protein expression levels of colonic ZO-1 and occludin protein increased (P<0.01), while the diarrhea index, the contents of colonic CCK, SP, TPS and ATP were significantly decreased (P<0.01) in the EA group. CONCLUSION: EA can significantly alleviate the symptoms of visceral hypersensitivity and diarrhea in IBS-D rats. Its mechanism may be related to down-regulating colonic CCK, SP, TPS and ATP, inhibiting mast cell activation and degranulation, and up-regulating colonic barrier tight junction proteins.

Acupuncture for Patients With Chronic Tension-Type Headache: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Whether acupuncture is effective for chronic tension-type headache (CTTH) is inconclusive. We aimed to examine the effectiveness of acupuncture with a follow-up period of 32 weeks. METHODS: We conducted a randomized controlled trial, and 218 participants who were diagnosed with CTTH were recruited from June 2017 to September 2020. The participants in the intervention group received 20 sessions of true acupuncture (TA group) over 8 weeks. The acupuncture treatments were standardized across participants, and each acupuncture site was needled to achieve deqi sensation. Each treatment session lasted 30 minutes. The participants in the control group received the same sessions and treatment frequency of superficial acupuncture (SA group)-defined as a type of sham control by avoiding deqi sensation at each acupuncture site. The main outcome was the responder rate at 16 weeks after randomization (week 16) and was followed up at week 32. A responder was defined as a participant who reported at least a 50% reduction in the monthly number of headache days (MHDs). RESULTS: Our study included 218 participants (mean age: 43.1 years, mean disease duration: 130 months, MHDs: 21.5 days). The responder rate was 68.2% in the TA group (n=110) versus 48.1% in the SA group (n=108) at week 16 (odds ratio, 2.65; 95%CI, 1.5 to 4.77; p<0.001); and it was 68.2% in the TA group versus 50% in the SA group at week 32 (odds ratio, 2.4; 95%CI, 1.36 to 4.3; p<0.001). The reduction in MHDs was 13.1±9.8 days in the TA group versus 8.8±9.6 days in the SA group at week 16 (mean difference, 4.3 days; 95%CI, 2.0 to 6.5; p<0.001), and the reduction was 14±10.5 days in the TA group versus 9.5±9.3 days in the SA group at week 32 (mean difference, 4.5 days; 95%CI, 2.1 to 6.8; p<0.001). Four mild adverse events were reported; three in the TA group versus one in the SA group. CONCLUSION: The 8-week TA treatment was effective for the prophylaxis of CTTH. Further studies might focus on the cost-effectiveness of the treatment. TRIAL: Registration Information: ClinicalTrials.gov: NCT03133884 (https://clinicaltrials.gov/ct2/show/NCT03133884) CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that acupuncture (achieving deqi sensation) reduces mean headache days (per month) in patients with chronic tension-type headache.

Effect of acupuncture on postoperative ileus after laparoscopic elective colorectal surgery: A prospective, randomised, controlled trial.

Background: Postoperative ileus after colorectal surgery is a frequent problem that significantly delays recovery, increases perioperative costs, and negatively impacts on daily life, physical and psychosocial functioning, and wellbeing. We investigated the effect of acupuncture at different single acupoint combined with standard care on postoperative ileus. Methods: In this single-centre, three-arm, prospective, randomised trial, we enrolled patients with primary colorectal cancer undergoing elective colorectal resection at Cancer Hospital Chinese Academy of Medical Science in Beijing, China. Patients were randomly assigned (1:1:1) to receive either electroacupuncture (EA) at ST36 or ST25 combined with standard care (two EA groups) once daily from post-operative days 1-4, or standard care alone (standard care group). The co-primary outcomes were time to first flatus and time to defecation assessed in the intention-to-treat population. This study is registered with Chictr.org.cn, ChiCTR1900027466. Finding: Between Nov 15, 2019, and Sep 30, 2020, 129 patients were assessed for eligibility, 105 patients (35 patients per group) were enrolled and included in the intention-to-treat analysis. After receiving EA at ST36, the time to first flatus and defecation were shorter (between-group difference -10.98 [97.5% CI -21.41 to -0.56], p = 0·02 for flatus; -25.41 [-47.89 to -2.93], p = 0·02 for defecation). However, we did not observe a significant difference in time to first flatus and defecation between the EA at ST25 group and standard care group (between-group difference -5.54 [97.5% CI -15.78 to 4.70], p = 0·26 for flatus; -17.69 [-40.33 to 4.95], p = 0·08 for defecation). There were no serious adverse events. Interpretation: Compared with standard care alone, standard care combined with EA at ST36, but not ST25, significantly enhances bowel function recovery in a postoperative setting to patients with colorectal cancer with laparoscopic elective colorectal resection. Funding: The National Key R&D Program of China (No: 2019YFC1712100) and the National Science Fund for Distinguished Young Scholars (No:81825024).

Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy.

BACKGROUND: LncRNA AK044604 (regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3ß play important roles in diabetic nephropathy (DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3ß-induced podocyte injury. METHODS: Diabetic db/db mice received Risa-inhibition adeno-associated virus (AAV) via tail vein injection, and intraperitoneal injection of lithium chloride (LiCl). Blood, urine, and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells (MPCs) were cultured and treated with Risa-inhibition lentivirus (LV), EX-527, and LiCl. MPCs were collected under different stimulations as noted. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blotting analysis, transmission electron microscopy, Periodic Acid-Schiff staining, and immunofluorescence staining. RESULTS: Risa and activated GSK3ß were overexpressed, but Sirt1 was downregulated in DN mice and high glucose-treated MPCs (P < 0.001, db/m vs. db/db, NG or HM vs. HG), which was correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1 (P < 0.001, db/m vs. db/db, NG or HM vs. HG). In contrast, Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury, which could be abrogated by EX-527 (P < 0.001, db/db + Risa-AAV vs. db/db, HG + Risa-LV vs. HG). Furthermore, LiCl treatment could restore GSK3ß-mediated autophagy of podocytes (P < 0.001, db/db + LiCl vs. db/db, HG + LiCl vs. HG), suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy. CONCLUSION: Risa could inhibit autophagy by regulating the Sirt1/GSK3ß axis, thereby aggravating podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.

Mapping thalamic-anterior cingulate monosynaptic inputs in adult mice.

The anterior cingulate cortex (ACC) is located in the frontal part of the cingulate cortex, and plays important roles in pain perception and emotion. The thalamocortical pathway is the major sensory input to the ACC. Previous studies have show that several different thalamic nuclei receive projection fibers from spinothalamic tract, that in turn send efferents to the ACC by using neural tracers and optical imaging methods. Most of these studies were performed in monkeys, cats, and rats, few studies were reported systematically in adult mice. Adult mice, especially genetically modified mice, have provided molecular and synaptic mechanisms for cortical plasticity and modulation in the ACC. In the present study, we utilized rabies virus-based retrograde tracing system to map thalamic-anterior cingulate monosynaptic inputs in adult mice. We also combined with a new high-throughput VISoR imaging technique to generate a three-dimensional whole-brain reconstruction, especially the thalamus. We found that cortical neurons in the ACC received direct projections from different sub-nuclei in the thalamus, including the anterior, ventral, medial, lateral, midline, and intralaminar thalamic nuclei. These findings provide key anatomic evidences for the connection between the thalamus and ACC.

Delayed callose degradation restores the fertility of multiple P/TGMS lines in Arabidopsis.

Photoperiod/temperature-sensitive genic male sterility (P/TGMS) is widely applied for improving crop production. Previous investigations using the reversible male sterile (rvms) mutant showed that slow development is a general mechanism for restoring fertility to P/TGMS lines in Arabidopsis. In this work, we isolated a restorer of rvms-2 (res3), as the male sterility of rvms-2 was rescued by res3. Phenotype analysis and molecular cloning show that a point mutation in UPEX1 l in res3 leads to delayed secretion of callase A6 from the tapetum to the locule and tetrad callose wall degradation. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis demonstrated that the tapetal transcription factor ABORTED MICROSPORES directly regulates UPEX1 expression, revealing a pathway for tapetum secretory function. Early degradation of the callose wall in the transgenic line eliminated the fertility restoration effect of res3. The fertility of multiple known P/TGMS lines with pollen wall defects was also restored by res3. We propose that the remnant callose wall may broadly compensate for the pollen wall defects of P/TGMS lines by providing protection for pollen formation. A cellular mechanism is proposed to explain how slow development restores the fertility of P/TGMS lines in Arabidopsis.

Effectiveness and safety of acupuncture for treating functional constipation: An overview of systematic reviews.

BACKGROUND: Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders. Dissatisfaction with medications prescribed to treat FC may lead patients to seek alternative treatments. Numerous systematic reviews (SRs) examining the use of acupuncture to treat FC have reported inconsistent results, and the quality of these studies has not been fully evaluated. OBJECTIVE: In this overview, we evaluated and summarized clinical evidence on the effectiveness and safety of acupuncture for treating FC and evaluated the quality and bias of the SRs we reviewed. SEARCH STRATEGY: The search strategy was structured by medical subject headings and search terms such as "acupuncture therapy" and "functional constipation." Electronic searches were conducted in eight databases from their inception to September 2020. INCLUSION CRITERIA: SRs that investigated the effectiveness and safety of acupuncture for managing FC were included. DATA EXTRACTION AND ANALYSIS: Two authors independently extracted information and appraised the methodology, reporting accuracy, quality of evidence, and risk of bias using the following critical appraisal tools: (1) A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); (2) Risk of Bias in Systematic Reviews (ROBIS); (3) Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A); and (4) the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A κ index was used to score the level of agreement between the 2 reviewers. RESULTS: Thirteen SRs that examined the clinical utility of acupuncture for treating FC were identified. Using the AMSTAR 2 tool, we rated 92.3% (12/13) of the SRs as "critically low" confidence and one study as "low" confidence. Using the ROBIS criteria, 38.5% (5/13) of the SRs were considered to have "low risk" of bias. Based on PRISMA-A, 76.9% (10/13) of the SRs had over 70% compliance with reporting standards. The inter-rater agreement was good for AMSTAR 2, ROBIS, and PRISMA-A. Using the GRADE tool, we classified 22.5% (9/40) of the measured outcomes as "moderate" quality, 57.5% (23/40) as "low" quality, and 20.0% (8/40) as "very low" quality. The inter-rater agreement was moderate when using GRADE. Descriptive analyses indicated that acupuncture was more efficacious than sham acupuncture for improving weekly complete spontaneous bowel movements (CSBMs) and for raising the Bristol Stool Form Scale (BSFS) score. Acupuncture appeared to be superior to anti-constipation drugs for improving weekly spontaneous bowel movements, the total effective rate, and the Patient Assessment of Constipation Quality of Life score. Although ten SRs mentioned the occurrence of adverse events, serious adverse events were not associated with acupuncture treatment. CONCLUSION: Acupuncture may be more efficacious than sham acupuncture for improving CSBMs and BSFS scores and may be superior to anti-constipation drugs for improving bowel movement frequency, as well as quality of life. Limitations to current studies and inconsistent evidence suggest a need for more rigorous and methodologically sound SRs to draw definitive conclusions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020189173.

[Involvement of Pirt /TRPV1 signaling in acupuncture-induced reduction of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of Pirt (a regulator of TRPV1) in the dorsal root ganglia (DRG) and transient receptor potential vanilloid 1 (TRPV1, a molecular sensor of noxious heat and capsaicin) in the colonic mucosa in rats suffering from diarrhea-predominant irritable bowel syndrome (IBS-D), so as to explore its mechanisms underlying alleviation of visceral hypersensitivity of IBS-D. METHODS: Forty SD rats (half male and half female) were randomly assigned to control, model, EA, and medication groups by lottery, with 10 rats in each group. The IBS-D model was established by chronic unpredictable mild stress (CUMS) and gavage of senna soaking fluid. Rats in the EA group received EA (2 Hz/15 Hz,0.1-1 mA) stimulation of unilateral "Tianshu"(ST25), "Zusanli" (ST36), "Sanyinjiao"(SP6) and "Taichong"(LR3) for 15 min once a day for 14 days, and rats of the medication group received intragastric administration of pinave-rium bromide (10 mL/kg, 2.7 mg/mL) once daily for 14 days. The visceral pain threshold (VPT) was measured by using abdominal wall withdrawal reflex (AWR) test. The diarrhea index （loose stool rate ［total number of loose stool/total number of defecation］ X mean loose degree ［0-4 grades according to the filter paper stain diameter］ in 6 h/d） was used to assess the severity of diarrhea. The expression of Pirt in the DRG and TRPV1 in the colonic mucosa tissue was detected using immunohistochemistry. RESULTS: After modeling, the VPT was obviously reduced (P<0.01), while the diarrhea index, mean optical density of Pirt and TRPV1 were remarkably increased in the model group relevant to the control group (P<0.01). After the interventions, the VPT was obviously increased while the diarrhea index, and the mean optical density of Pirt and TRPV1 was noticeably decreased in both EA and the medicine groups in contrast to the model group (P<0.01). No significant differences were found between the EA and medicine groups in up-regulating VPT and down-regulating the diarrhea index, and Pirt and TRPV1 expression (P>0.05). CONCLUSION: EA can effectively alleviate visceral hypersensitivity in IBS-D rats, which may be related to its effect in down-regulating the expression level of DRG Pirt and colonic TRPV1.

[Formulation of technical guidelines in line with characteristics and principles of traditional Chinese medicine changes to improve quality of such preparations--interpretation of Technical guidelines for the study of pharmaceutical changes in traditional Chinese medicines].

In leading the high-quality development of Chinese medicine preparations, it is an important link to formulate the scientific, reasonable, and feasible guidelines for the change of Chinese medicines in accordance with the change characteristics and principles of the Chinese medicines is an important work to promote the Technical guidelines for the study of pharmaceutical changes in traditional Chinese medicines was formed by a broad consensus based on the characteristics and research results of the pharmaceutical changes in Traditional Chinese Medicines(TCM)with the principles of science and risk management. This guideline has clarified the basic principles and requirements for the evaluation of changes in TCM, specified the research and verification work of common change scenarios, defined the boundaries of changes in TCM, and proposed to encourage the use of new technologies, new methods, and new excipients that meet product characteristics. It will definitely promote the quality improvement and the secondary development of TCM. In this article, the revision background and main content of the guideline were introduced, and the main features of the Guideline were analyzed, in order to provide references for the industry.

Comparison of Effects and Brain-Gut Regulatory Mechanisms of Acupuncture and Flunarizine for Migraine: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: As a central nervous system disease, migraine often coexists with gastrointestinal disorders, which suggests a disruption of brain-gut regulation. Clinical studies have confirmed that acupuncture and flunarizine not only alleviate migraine attacks but also substantially inhibit accompanying gastrointestinal symptoms. However, it is still not clear how acupuncture and flunarizine regulate the interactions of brain, gut, and microbiome. Therefore, this study will combine neuroimaging technology and gut microbiota detection technology to explore and compare the effects and brain-gut modulating mechanisms of acupuncture and flunarizine for migraine. METHODS: This randomized clinical trial will recruit 66 patients with migraine without aura. Participants will be randomly assigned in a 1 : 1 ratio to an acupuncture group or a control group. The acupuncture treatment strategy is based on experience from our previous study and consensus meetings with clinical experts. Patients will receive 12 sessions of manual acupuncture treatment (once every other day to a total of three times per week, followed by a 2-day break). Flunarizine will be administered at a dose of 5 mg daily in the control group. Participants in both groups will receive treatment for a period of 4 weeks. The primary outcome is the change in frequency of migraine attacks, and the secondary outcomes include the changes in migraine days (days on which migraine attacks occurred), average migraine severity, gastrointestinal symptoms, psychiatric symptoms, and quality of life. Fresh stool samples will be collected, and 16S ribosomal RNA gene sequencing analysis will be used for gut microbiota. Magnetic resonance imaging will be applied to detect between-group changes in brain function. The abovementioned indicators will be collected at baseline, after a 4-week intervention, and at the 12-week follow-up. Discussions. From the perspective of brain-gut regulatory mechanisms, we will combine brain neuroimaging and gut microbiological data to partially reveal the similarities and differences of acupuncture and flunarizine on the treatment of migraine. The trial is registered with ChiCTR2000034417.

Biopharmaceutics classification evaluation for paris saponin VII.

To study the biopharmaceutics characteristics of paris saponin VII (PSVII). The solubility of PSVII was evaluated by measurement of the equilibrium solubility in different solvents and media. The permeability of PSVII was evaluated by measuring the oil/water partition coefficient (lgPapp) and determining the apparent permeability coefficient (PCapp) on a mono-layer Caco-2 cell model. The effects of p-glycoprotein and multidrug resistance related protein 2 on PSVII transport in mono-layer Caco-2 cell model were further investigated. Finally, the small intestinal absorption of PSVII was investigated in rat. In solvents of different pH, the equilibrium solubility of PSVII was quite low, and the dose number of PSVII was larger than 1. The lgPapp of PSVII was less than 0. The apparent permeability coefficient [PCapp(AP-BL)] of PSVII in mono-layer Caco-2 cell model was less than 14.96 × 10-6 cm·s-1, and the efflux ratio of PSVII in mono-layer Caco-2 cell model was less than 1. The transport rate of PSVII in mono-layer Caco-2 cell model was not affected by the inhibitors of p-glycoprotein and multidrug resistance related protein 2. After oral administration, PSVII could be detected in rat intestinal contents, but could not be detected in the small intestinal mucosa. PSVII showed low solubility and permeability, which would result in low oral bioavailability in clinic. PSVII belonged to Class IV compound in biopharmaceutics classification system.

Cupping therapy for patients with chronic urticaria: A systematic review and meta-analysis.

BACKGROUND: Chronic urticaria (CU) is a common skin disease, which has a negative effect on quality of life. Current treatments do not fully control the symptoms of urticaria for many CU patients, thus effective and safe treatments for CU are still needed. OBJECTIVE: This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU. SEARCH STRATEGY: The search strategy looked for the presence of related keywords, such as "chronic urticaria" and "cupping therapy," in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms. INCLUSION CRITERIA: RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English. DATA EXTRACTION AND ANALYSIS: Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions. RESULTS: Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported. CONCLUSION: Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019137451.

[Effect of electroacupuncture on intestinal epithelial mucosal barrier function in rats with diarrhea-predominant irritable bowel syndrome].

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