Integrated Transcriptomics and Metabolomics Analysis Reveals the Effects of Cutting on the Synthesis of Flavonoids and Saponins in Chinese Herbal Medicine Astragalus mongholious.

Astragali Radix, derived from the roots of Astragalus mongholicus, is a traditional Chinese medicine containing flavonoids and saponins as its key ingredients. With a shortage in the wild sources of the herbal plant, it is especially important to explore a cultivation mode for A. mongholicus for medicinal purposes. Cutting, a physical environmental stress method, was used in this study with the objective of improving the quality of this herbal legume. We found that cutting of the top 1/3 of the aboveground part of A. mongholicus during the fruiting period resulted in a significant increase in the content of flavonoids and saponins, as well as in root growth, including length, diameter, and dry weight. Furthermore, the leaves were sampled and analyzed using a combined transcriptome and metabolome analysis approach at five different time points after the treatment. Sixteen differentially expressed unigenes (DEGs) involved in the biosynthesis of flavonoids were identified; these were found to stimulate the synthesis of flavonoids such as formononetin and calycosin-7-O-ß-D-glucoside. Moreover, we identified 10 DEGs that were associated with the biosynthesis of saponins, including astragaloside IV and soyasaponin I, and found that they only regulated the mevalonic acid (MVA) pathway. These findings provide new insights into cultivating high-quality A. mongholicus, which could potentially alleviate the scarcity of this valuable medicinal plant.

Research progress on mechanism of acupuncture in treating functional constipation. / é’ˆåˆºæ²»ç–—åŠŸèƒ½æ€§ä¾¿ç§˜çš„æœºåˆ¶ç ”ç©¶è¿›å±•.

Acupuncture treatment for functional constipation (FC) is characterized by precise efficacy, rapid onset of action in the early stages, long-term stable effects, and overall regulation. This paper reviews recent literatures on acupuncture treatment for FC, indicating that acupuncture acts from multiple perspectives and pathways, including promoting intestinal motility, regulating intestinal microbiota, modulating the brain-gut axis, alleviating intestinal inflammation, and improving rectal hyposensitivity. Future research could delve into the mechanical sensation conduction mechanisms of acupuncture in improving rectal hyposensitivity, identify key intestinal microbiota genera and metabolic characteristics regulated by acupuncture, explore the network relationships among different mechanisms, and clarify the differential mechanisms of various acupuncture treatment protocols to optimize clinical therapy and enhance the clinical efficacy of acupuncture for FC.

Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway.

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

Effect of electroacupuncture on enteric neuronal autophagy in functional constipation mice. / ç”µé’ˆå¯¹åŠŸèƒ½æ€§ä¾¿ç§˜å°é¼ è‚ é“ç¥žç»å ƒè‡ªå™¬æ°´å¹³çš„å½±å“.

OBJECTIVES: To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower he-sea and front-mu points of large intestine based on enteric neuronal autophagy. METHODS: A total of 40 SPF Kunming mice were randomly divided into 5 groups (n = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry. RESULTS: Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (P<0.01, P<0.05), and numbers (P<0.01), wet weight (P<0.01, P<0.05) and water content (P<0.05, P<0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (P<0.05), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (P<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (P<0.01,P<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (P<0.05,P<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group. CONCLUSIONS: Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.

Acupuncture as an adjunctive therapy for gastric ulcer: A modified Delphi consensus study.

BACKGROUND: Acupuncture is often used as an adjunctive therapy for gastric ulcer (GU). However, there is still a lack of evidence on the appropriate and optimal interventions for acupuncture. This study aimed to optimize the acupuncture treatment of gastric ulcers based on expert consensus for guiding acupuncturists in clinical practice. METHODS: To conduct this study, research evidence was gathered from databases in both Chinese and English. After discussion, preliminary clinical questions were developed. Following three rounds of multidisciplinary clinical expert consultation, the initial consensus questionnaire was formed after testing and modification by team members. A Delphi consensus was ultimately reached to answer the questionnaire and develop guidance for acupuncture treatment. A 9-point Likert-type scale was used to measure the agreement of expert consensus, where a score of 80% between 7 and 9 was defined as "agreement." RESULTS: After two rounds of Delphi voting, a total of 35 items reached an agreement. These items can be roughly divided into 6 domains. According to expert consensus, the application of acupuncture for gastric ulcer should follow a semistandardized approach. Based on the syndrome differentiation, the main acupoints recommended are Zusanli (ST36), Zhongwan (CV12), Neiguan (PC6), and Sanyinjiao (SP6), while the adjunct acupoints include Taichong (LR3), Guanyuan (CV4), Xuehai (SP10), and Taixi (KI3). In the experience of experts, adverse events associated with acupuncture are typically mild and often manifest as subcutaneous hematomas. CONCLUSION: There is a lack of definitive acupuncture guidelines that can effectively determine the optimal therapeutic approach for the treatment of gastric ulcer. This expert consensus provides recommendations for clinical research and practice of acupuncture, with a particular focus on the selection of acupoints. However, further exploration through rigorous studies is necessary due to the limited availability of clinical evidence.

Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

Gastroprotective effects of Machilus zuihoensis Hayata bark against acidic ethanol-induced gastric ulcer in mice.

Background and aim: In traditional medicine, Machilus zuihoensis Hayata bark (MZ) is used in combination with other medicines to treat gastric cancer, gastric ulcer (GU), and liver and cardiovascular diseases. This study aims to evaluate the gastroprotective effects and possible mechanism(s) of MZ powder against acidic ethanol (AE)-induced GU and its toxicity in mice. Experimental procedure: The gastroprotective effect of MZ powder was analyzed by orally administering MZ for 14 consecutive days before AE-inducing GU. Ulcer index (UI) and protection percentage were calculated, hematoxylin and eosin staining and periodic acid-Schiff staining were performed, and gastric mucus weights were measured. The antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and possible signaling pathway(s) were studied. Results and conclusion: Pretreatment with MZ (100 and 200 mg/kg) significantly decreased 10 µL/g AE-induced mucosal hemorrhage, edema, inflammation, and UI, resulted in protection percentages of 88.9% and 93.4%, respectively. MZ pretreatment reduced AE-induced oxidative stress by decreasing malondialdehyde level and restoring superoxide dismutase activity. MZ pretreatment demonstrated anti-inflammatory effects by reducing both serum and gastric tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß levels. Furthermore, MZ pretreatment exhibited anti-apoptotic effect by decreasing Bcl-2 associated X protein/B-cell lymphoma 2 ratio. The gastroprotective mechanisms of MZ involved inactivations of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways. Otherwise, 200 mg/kg MZ didn't induce liver or kidney toxicity. In conclusion, MZ protects AE-induced GU through mucus secreting, antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and inhibitions of NF-κB and MAPK signaling pathways.

Effects of acupuncture on gut microbiota and short-chain fatty acids in patients with functional constipation: a randomized placebo-controlled trial.

Objective: To comprehensively evaluate the effect of acupuncture on gut microbiota, identify specific microbes closely related to the clinical efficacy of acupuncture, and explored the role of short-chain fatty acids (SCFAs). Methods: A randomized placebo-controlled trial was conducted with 80 FC patients and 28 healthy controls (HCs). FC patients randomly received 16 acupuncture (n = 40) or sham acupuncture (n = 40) sessions over 4 weeks; HCs received no treatment. The change in the proportion of patients with mean weekly complete spontaneous bowel movements (CSBMs) was considered as the primary outcome measure. Moreover, the composition and the predictive metabolic function of the gut microbiota from feceal samples were analyzed by 16S rRNA gene sequencing, while feceal SCFAs were identified via gas chromatography-mass spectrometry (GC-MS). Results: Compared to sham acupuncture, acupuncture significantly increased the proportion of CSBM responders, and improved spontaneous bowel movements (SBMs), straining, stool consistency, and quality of life. Moreover, Sequencing of 16S rRNA genes revealed that acupuncture improved ß-diversity and restored the composition of gut microbiota. Specifically, the abundance of beneficial bacteria such as g_Lactobacillus increased while that of pathogenic bacteria such as g_Pseudomonas decreased after acupuncture, which were significantly correlated with alleviated symptoms. Moreover, ten microbes including g_Coprobacter, g_Lactobacillus, and g_Eubacterium_coprostanoligenes_group might be considered acupuncture-specific microbes, and formed a stable interaction network. Additionally, GC-MS analysis indicated that acupuncture increased the content of butyrate acid in the gut, which was positively correlated with an increase in defecation frequency and a decrease in acupuncture-related pathogens. Finally, acupuncture specific-microbes including g_Coprobacter, g_Lactobacillus, g_Pseudomonas, g_Eubacterium_coprostanoligenes_group, g_Erysipelotrichaceae_UCG.003, g_Prevotellaceae_UCG.001, and g_Rolstonia could accurately predict the clinical efficacy of acupuncture (AUC = 0.918). Conclusion: Acupuncture could effectively improve clinical symptoms in FC patients, and was associated with gut microbiota reshaping and increased butyrate acid levels. Moreover, key microbial genera such as g_Coprobacter and g_Lactobacillus was predictive of acupuncture efficacy in treating FC. Future studies are required to validate the causal relationship between key microbial genera and acupuncture clinical efficacy, and should explore further metabolic pathways for designing personalized treatment strategies. Clinical Trial Registration: http://www.chictr.org.cn, Identifier: ChiCTR2100048831.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

Construction and Validation of Prediction Model of Severe Abdominal Pain Post-Transarterial Chemoembolization in Patients with HBV-Associated Primary Liver Cancer.

Objective: This study is aimed at constructing and evaluating a prediction model of severe abdominal pain post-transcatheter arterial chemoembolization in patients with HBV-related primary liver cancer. Methods: Patients with HBV-associated primary liver cancer who received transarterial chemoembolization (TACE) from March 2019 to March 2022 in the Interventional Therapy Department of our hospital were selected as the subjects, and the included 160 patients were randomly divided into modeling group (n = 120) and validation group (n = 40) in a ratio of 3 : 1. Visual analog scale (VAS) was used to assess pain severity. 120 patients in the modeling group were divided into no/mild abdominal pain group and severe abdominal pain group. The clinical data of the patients, including gender, age, TACE treatment history, vascular invasion, maximum diameter of tumor, infarction degree, preoperative Eastern Oncology Collaboration Group (ECOG) score, and Lipiodol dosage, were analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the prediction model for severe abdominal pain post-TACE. Results: A total of 116 patients (72.50%) had severe abdominal pain after TACE. Univariate analysis showed that severe abdominal pain after TACE in the modeling group was associated with TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score (all P < 0.05), but not related to gender, age, vascular invasion, and Lipiodol dosage (all P > 0.05). Logistic regression analysis showed that TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score were all independent influencing factors for acute abdominal pain post-TACE in HBV-HCC patients (all P < 0.05). The prediction model equation was Y = -3.673 + 1.722 × TACE treatment history + 1.175 × tumor maximum diameter + 2.064 × infarction degree + 1.555 × preoperative ECOG score. Goodness-of-fit test results showed no significant difference between the established prediction model and the observed value (χ 2 = 1.645, P = 0.560) and R 2 = 0.821, suggesting that the prediction ability of the model was relatively accurate. ROC analysis results showed that the area under the curve (AUC) of severe abdominal pain after TACE was 0.916 (0.862~0.970) and 0.902 (95% CI: 0.841~0.963) in the modeling group and the verification group, respectively. Conclusion: TACE treatment history, tumor maximum diameter, infarction degree, and preoperative ECOG score are independent influencing factors for severe abdominal pain post-TACE in patients with HBV-HCC, and the prediction model established on this basis has good application value.

Manual Therapy and Related Interventions for Carpal Tunnel Syndrome: A Systematic Review and Meta-Analysis.

Objective: Systematic review and meta-analysis to assess the efficacy of Manual therapy and related interventions in the treatment of carpal tunnel syndrome (CTS) based on Boston carpal tunnel questionnaire. Design: Systematic review and meta-analysis. Subjects: Carpal tunnel syndrome. Interventions: Manual therapy and related interventions versus other therapies or manual therapy and related interventions plus other therapies versus other therapies. Outcomes measures: Boston carpal tunnel questionnaire. Results: A total of 6 studies were included, including 211 cases in the manual therapy group and 211 cases in the control group. The quality of the included articles was high, and the results of meta-analysis showed that manual therapy and related interventions were superior in terms of improving the Boston carpal tunnel questionnaire Symptom Severity score in patients with CTS (standardised mean difference [SMD] -1.13, 95% CI -1.40 to -0.87), were superior to control groups in terms of improving the Boston carpal tunnel questionnaire functional capacity scale in patients with CTS (SMD -1.01,95% CI -1.24 to -0.77). Conclusion: The results of this meta-analysis suggested that manual therapy and related interventions were better than control groups in treating CTS. Manual therapy and related interventions could relieve the symptoms of patients with CTS and promote the recovery of hand function. Manual therapy and related interventions should be considered clinically effective methods for treating CTS. Registration: The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; No. CRD 42020201389). Contribution of the Article: Manual therapy and related interventions could relieve the symptoms of patients with CTS and promote the recovery of hand function. Manual therapy and related interventions should be considered clinically effective methods for treating CTS.

Carbon Dots in Biomedicine: A Review.

Despite the rapid development of science and technology, the effective treatment of cancer still threatens human life and health. However, the success of cancer treatment is closely related to early diagnosis, identification, and effective treatment. In recent years, with the strengthening of the development and research of nanomaterials for cancer diagnosis and treatment, researchers have found that carbon dots (CDs) have the advantages of wide absorption, excellent biocompatibility, diverse imaging characteristics, and photostability and are widely used in various fields, such as sensing, imaging, and drug/gene transportation. Recently, researchers also discovered that CDs could be used as an effective photosensitizer to generate active oxygen or convert light energy into heat under the stimulation of the external lasers, making them have the effects of photothermal and photodynamic therapy for cancer. In this review, we first outline the single-modal and multimodal imaging analysis of CDs in cancer cells. After introducing diversified imaging functions, we focused on the design and the latest research progress of CDs in phototherapy and introduced in detail the strategies of CDs in phototherapy treatment and the challenges faced by clinical applications. We hope that this overview can provide important insights for researchers and accelerate the pace of research on CDs in imaging-guided phototherapy treatment.

Spinal 5-HT2A receptor is involved in electroacupuncture inhibition of chronic pain.

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, and it is a typical disease which can develop chronic pain. Our previous study has proved that endocannabinoid (2-AG)-CB1R-GABA-5-HT pathway is involved in electroacupuncture (EA) mediated inhibition of chronic pain. However, it is still unclear which among the 5-HT receptor subtype is involved in EA evoked 5-HT mediated inhibition of chronic pain in the dorsal spinal cord. 5-HT2A is a G protein-coupled receptor and it is involved in 5-HT descending pain modulation system. We found that EA treatment at frequency of 2 Hz +1 mA significantly increased the expression of 5-HT2A receptor in the dorsal spinal cord and intrathecal injection of 5-HT2A receptor antagonist or agonist reversed or mimicked the analgesic effect of EA in each case respectively. Intrathecal injection of a selective GABAA receptor antagonist Bicuculline also reversed the EA effect on pain hypersensitivity. Additionally, EA treatment reversed the reduced expression of GABAA receptor and KCC2 in the dorsal spinal cord of KOA mice. Furthermore, we demonstrated that intrathecal 5-HT2A receptor antagonist/agonist reversed or mimicked the effect of EA up-regulate of KCC2 expression, respectively. Similarly, intrathecal injection of PLC and PKC inhibitors prevented both anti-allodynic effect and up-regulation of KCC2 expression by EA treatment. Our data suggest that EA treatment up-regulated KCC2 expression through activating 5-HT2A-Gq-PLC-PKC pathway and enhanced the inhibitory function of GABAA receptor, thereby inhibiting chronic pain in a mouse model of KOA.

Hydroxy-Selenomethionine Improves the Selenium Status and Helps to Maintain Broiler Performances under a High Stocking Density and Heat Stress Conditions through a Better Redox and Immune Response.

This study has determined whether hydroxy-selenomethionine (OH-SeMet) exerts a better protective action on broilers against environmental stress than sodium selenite (SS) or seleno-yeast (SY). Day-old male Cobb 500 broilers (12 cages/diet, 9 broilers/cage) were fed a selenium (Se)-deficient diet (0.047 mg/kg) supplemented with SS, SY or OH-SeMet at 0.3 mg Se/kg under a high stocking density and heat stress condition for six weeks. OH-SeMet improved the FCR and Se concentration in the tissues than SS and SY. SY and OH-SeMet both reduced the serum cortisol, T3, IL-6, IgA, IgM and LPS, more than SS, while only OH-SeMet further increased IL-10 and IgG. SY and OH-SeMet improved the intestinal morphology and increased the T-AOC, TXRND, SELENON and OCCLUDIN activities but decreased CLAUDIN2 in the jejunum than SS, while OH-SeMet further improved these values than SY. SY and OH-SeMet both increased SELENOS and TXNRD2 in the muscles than SS, and OH-SeMet further raised T-AOC, GPX4, SELENOP, SELENOW and TXNRD1, and reduced malondialdehyde and protein carbonyl in the muscles than SS and SY. OH-SeMet showed a better ability to maintain the performance and the redox and immune status of broilers under a high stocking density and heat stress challenge than SS and SY.

5-HT7 Receptor Is Involved in Electroacupuncture Inhibition of Chronic Pain in the Spinal Cord.

Knee osteoarthritis (KOA) is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT1, 5-HT2, and 5-HT3 receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT7 receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT7 receptor is involved in EA analgesia. The 5-HT7 receptor is a stimulatory G-protein (Gs)-coupled receptor that activates adenylyl cyclase (AC) to stimulate cyclic adenosine monophosphate (cAMP) formation, which in turn activates protein kinase A (PKA). In the present study, we found that EA significantly increased the tactile threshold and the expression of the 5-HT7 receptor in the dorsal spinal cord. Intrathecal injection of 5-HT7 receptor agonist AS-19 mimicked the analgesic effect of EA, while a selective 5-HT7 receptor antagonist reversed this effect. Moreover, intrathecal injection of AC and PKA antagonists prior to EA intervention prevented its anti-allodynic effect. In addition, GABAA receptor antagonist bicuculline administered (intrathecal, i.t.) prior to EA intervention blocked the EA effect on pain hypersensitivity. Our data suggest that the spinal 5-HT7 receptor activates GABAergic neurons through the Gs-cAMP-PKA pathway and participates in EA-mediated inhibition of chronic pain in a mouse model of KOA.

On-chip rapid drug screening of leukemia cells by acoustic streaming.

Rapid and personalized single-cell drug screening testing plays an essential role in acute myeloid leukemia drug combination chemotherapy. Conventional chemotherapeutic drug screening is a time-consuming process because of the natural resistance of cell membranes to drugs, and there are still great challenges related to using technologies that change membrane permeability such as sonoporation in high-throughput and precise single-cell drug screening with minimal damage. In this study, we proposed an acoustic streaming-based non-invasive single-cell drug screening acceleration method, using high-frequency acoustic waves (>10 MHz) in a concentration gradient microfluidic device. High-frequency acoustics leads to increased difficulties in inducing cavitation and generates acoustic streaming around each single cell. Therefore, single-cell membrane permeability is non-invasively increased by the acoustic pressure and acoustic streaming-induced shear force, which significantly improves the drug uptake process. In the experiment, single human myeloid leukemia mononuclear (THP-1) cells were trapped by triangle cell traps in concentration gradient chips with different cytarabine (Ara-C) drug concentrations. Due to this dual acoustic effect, the drugs affect cell viability in less than 30 min, which is faster than traditional methods (usually more than 24 h). This dual acoustic effect-based drug delivery strategy has the potential to save time and reduce the cost of drug screening, when combined with microfluidic technology for multi-concentration drug screening. This strategy offers enormous potential for use in multiple drug screening or efficient drug combination screening in individualized/personalized treatments, which can greatly improve efficiency and reduce costs.

Randomized controlled trials of Chinese herbal medicine published in English from 2010 to 2019: a bibliometrics study.

BACKGROUND: As the use of Chinese herbal medicine (CHM) in the international market increases, the number of clinical studies including randomized controlled trials (RCTs) of CHM which published in international journals has also increased. Using bibliometrics, we systematically and comprehensively analyzed the research status of CHM RCTs published in English during the period of 2010 to 2019. METHODS: Electronic searches in MEDLINE, EMBASE, and Cochrane Library databases were undertaken. CHM RCTs published in English between January 2010 and December 2019 were included. We randomly selected 20% from the eligible articles. Descriptive statistical analysis was carried out by extracting information on general information, characteristics of the study participants, interventions, outcomes, and risk of bias assessment of included RCTs. RESULTS: Two hundred and twenty-seven CHM RCTs published in English were included in our study. Chinese Journal of Integrative Medicine was the journal which published most of the relevant papers (22.0%). A total of 45,774 participants were included, sample size ranged from 12 to 3,143 (median: 115). The most common disease was the circulatory diseases (n=36, 15.9%). Decoction was the most common dosage form (28.2%), and "CHM vs. placebo" was the most common type of control (36.1%). The median of the total number of outcomes was 4 (range, 1-14), 92 (40.5%) did not clearly specify any primary outcome, 56 (24.7%) did not report any adverse event, 41 (18.1%) and 68 (30.0%) reported traditional Chinese medicine (TCM)-specific outcomes and quality of life, respectively. Eighty-five (37.4%) did not report sufficient information about the random sequence generation process, 100 (44.1%) used the adequate allocation concealment, 92 (40.5%) blinded participants and key study personnel, and 24 (10.6%) blinded outcome assessors. CONCLUSIONS: Our results provided insight into the research status regarding CHM RCTs published in English during the past decade, this study may be helpful in understanding research trends in this field.

[Comparative study between electroacupuncture at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery].

OBJECTIVE: To compare the clinical effect between electroacupuncture (EA) at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery. METHODS: Sixty patients with elective radical esophagectomy were randomly divided into a group A, a group B and a control group, 20 cases in each group. The patients in the group A were treated with injection of 20 mL 0.375% ropivacaine at epidural space 30 min before anesthesia induction, followed by normal anesthesia during operation; the patients in the group B were treated with 30 min EA at bilateral Neima point and Neiguan (PC 6) before anesthesia induction, followed by normal anesthesia during operation; the patients in the control group were treated with general anesthesia alone. Patient-controlled intravenous analgesia was applied for all the patients. The mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time points: before acupuncture/epidural puncture (T0), skin incision (T1), extubation (T2) and 2 h after operation (T3); the dosage of anesthetics and extubation time were recorded; the plasma levels of ß-endorphin (ß-EP), 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) were measured at the following time points: T0, T3, 12 h after operation (T4), 24 h after operation (T5) and 48 h after operation (T6). Visual analogue scale (VAS) was used to evaluate the analgesic effect. RESULTS: The MAP at T1 and T2 in the group A was lower than that in group B and control group (P<0.05), and HR at T1 and T2 was lower than that in control group (P<0.05). The MAP and HR at T1 and T2 in the group B were lower than those in the control group (P<0.05). The dosage of remifentanil in the group A and group B was lower than that in the control group (P<0.05), and extubation time was earlier than that in the control group (P<0.05). The content of ß-EP at T4, T5 and T6 in the group B was higher than that in the group A and control group (P<0.05); the contents of 5-HT and PGE2 at T3, T4 and T5 in the group A and group B were lower than those in the control group (P<0.05). The VAS scores at T3, T4 and T5 in the group A and group were lower than those in the control group (P<0.05). CONCLUSION: The preemptive analgesia of EA at Neima point and Neiguan (PC 6) and epidural nerve block could both provide effective perioperative analgesia for thoracic surgery. The EA could better maintain intraoperative hemodynamics and has less physiological disturbance.

Understanding the dual character of negative and positive results in acupuncture-moxibustion clinical trials in foreign countries / 中国针灸

The differences in the objective, starting point, disease spectrum and interventions of acupuncture-moxibustion clinical trials at home and abroad are collected. By taking two articles of acupuncture-moxibustion clinical trials in foreign countries accepted by

[Effect of ligustilide on oxygen and glucose deprivation/reperfusion-induced mitochondria fission in PC12 cells].

This study aimed to investigate the effect and mechanism of ligustilide, the main active ingredient in Ligusticum wallichii, on mitochondria fission after PC12 cell injury induced by oxygen and glucose deprivation/reperfusion(OGD/R). In the experiment, an OGD/R model was established in vitro, and PC12 cells were pre-treated with ligustilide for 3 h, and then the cell viability was detected by CCK-8 method. The effect of different concentrations of ligustilide on the morphology of PC12 cells after OGD/R injury was observed under an inverted microscope. Transmission electron microscopy was used to observe the mitochondrial fission of PC12 cells after OGD/R injury. DCFH-DA immunofluorescence staining method was used to detect intracellular reactive oxygen species(ROS) changes. Changes in mitochondria membrane potential(MMP) were detected by flow cytometry. Hochest 33258 was used to observe the apoptosis of PC12 cells. Western blot was used to detect changes in cytochrome C(Cyt C) content in mitochondria and cytoplasm, and mitochondrial fission-related proteins Drp 1 and Fis 1. All results showed that compared with the model group, ligustilide significantly increased the survival rate of PC12 cells and the number of cells. Further experiments showed that ligustilide inhibited the release of ROS and decline of mitochondrial membrane potential in PC12 cells after OGD/R injury. Moreover, ligustilide reduced the release of Cyt C and promoted the expressions of Drp1 and Fis1 in mitochondrial fission proteins. Verification experiments showed that mitochondrial fission inhibitor mdivi-1 decreased cell survival rate and inhibited fission. The results indicated that ligustilide exerted neuro-protective effects by promoting mitochondrial fission and reducing cell damage. It preliminary proves that the mechanism of ligustilide on ischemic brain injury may be related to the promotion of mitochondrial fission and the maintenance of cell homeostasis.