Understanding acupuncture anesthesia from a foreign perspective： reviewing Acupuncture Anesthesia in the People's Republic of China. / 异域视角下对针刺麻醉的理解：以《针刺麻醉在中国》为例.

"Acupuncture Anesthesia in the People's Republic of China： A Trip Report of the American Acupuncture Anesthesia Study Group" (Report for short) is the first extraterritorial systematic investigation and evaluation report in the history of acupuncture anesthesia in China. After Report was released to the public, it has not drawn much attention in China. At the moment when acupuncture anesthesia is extended to perioperative treatment, by reviewing the Report, the differences in understanding acupuncture anesthesia were analyzed from a foreign perspective. Report involves the clinical observation of surgery under acupuncture anesthesia, the analysis on the factors of acupuncture anesthesia in therapeutic effects and the relevant mechanisms, and the differences in the research methods and foci on the recognition of acupuncture anesthesia between China and foreign countries. In association with the development of acupuncture anesthesia during the past 65 years and the conclusion in Report, the paper briefly describes the development and perfection of acupuncture anesthesia, the historical verification to the conclusions in Report and the limitations in modern acupuncture anesthesia. It provides some inspiration for the development of acupuncture anesthesia, acupuncture-moxibustion medicine and life science in the future.

Dendrobium officinale Polysaccharides as a Natural Functional Component for Acetic-Acid-Induced Gastric Ulcers in Rats.

Dendrobium officinale is an important edible and medicinal plant, with the Dendrobium officinale polysaccharide (DOP) being its primary active constituent, known for its diverse biological activities. In this study, DOP was extracted and characterized for its structural properties. The potential of DOP to ameliorate gastric ulcers (GUs) was investigated using an acetic-acid-induced GU model in rats. The results demonstrated that DOP exerted a multifaceted protective effect against GU, mitigating the deleterious impact on food intake and body weight in rats. DOP exhibited its protective action by attenuating cellular damage attributed to oxidative stress and inflammatory reactions mediated by enhanced activities of SOD, GSH, and GSH-PX, coupled with a downregulation in the expression of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Furthermore, DOP effectively inhibited apoptosis in gastric mucosa cells of acetic-acid-induced GU rat models and facilitated the self-repair of damaged tissues. Remarkably, the DOP-200 and DOP-400 groups outperformed omeprazole in reducing the expression of IL-6 and malondialdehyde (MDA) in tissues, as well as IL-1ß, IL-6, and TNF-α in serum. These groups also exhibited an improved expression of SOD in tissues and SOD, GSH, and GSH-PX in serum. A Western blot analysis of gastric mucosa demonstrated that the DOP-200 and DOP-400 groups significantly reduced the expression of NF-κBp65, phosphorylated NF-κBp65, FoxO3a, and Bim. The observed antagonism to GU appeared to be associated with the NF-κB cell pathway. Additionally, qRT-PCR results indicate that DOP reduced the mRNA transcription levels of IL-6, and TNF-α, which shows that the healing of GU is related to the reduction in the inflammatory reaction by DOP. However, the expression of EGF and VEGF decreased, suggesting that the mechanism of DOP inhibiting GU may not be directly related to EGF and VEGF, or there is an uncertain competitive relationship between them, so further research is needed.

Preliminary exploration of herbal tea products based on traditional knowledge and hypotheses concerning herbal tea selection: a case study in Southwest Guizhou, China.

BACKGROUND: Herbal tea usually refers to "beverage plants that do not belong to the genus Camellia", and it holds a significant historical legacy as a traditional beverage among specific regions and ethnic groups. In light of this, our research aims to investigate and analyze the traditional knowledge pertaining to herbal tea plants used by local people in the Qianxinan Buyi and Miao Autonomous Prefecture, Guizhou Province. We also initiated preliminary efforts to create tea products from herbal tea leaves using various processing techniques. Additionally, we attempted to test hypotheses to elucidate how local people select herbal tea plants. METHODS: Data related to the use of herbal tea plants in this study were collected through semi-structured interviews and participatory observations in four villages in Qianxinan. Quantitative indicators, including the relative frequency of citation (RFC) and the relative importance (RI) value, were calculated, and the availability of plants was also evaluated. General linear model was performed to examine the relationship between the frequency of citation and resource availability, as well as the correlation between the relative frequency of citation and the relative importance, to test both the resource availability hypothesis and the versatility hypothesis. Centella asiatica tea was processed using techniques from green tea, black tea and white tea, with a preliminary sensory evaluation conducted. RESULTS: A total of 114 plant species were documented as being used for herbal teas by local residents, representing 60 families and 104 genera. Of these, 61% of herbal tea plants were found growing in the wild, and 11 species were exotic plants. The family with the highest number of species was Asteraceae (20 species). The study identified 33 major medicinal functions of herbal tea, with clearing heat-toxin and diuresis being the most common functions. General linear model revealed a strong correlation (correlation coefficient of 0.72, p < 0.001) between the frequency of citation and plant availability, as well as a significant correlation (correlation coefficient of 0.63, p < 0.001) between RFC and RI. Under different processing conditions, the characteristics of Centella asiatica tea exhibited variations and were found to be suitable for consumption. CONCLUSION: The consumption of herbal tea serves as a preventive measure against common ailments for local residents. The resource availability hypothesis, diversification hypothesis and the versatility hypothesis were shown to provide some insight into "how and why local communities select plants for use." Exotic herbal tea plants in the study area also possess valuable therapeutic properties. The processing and production of Centella asiatica herbal tea products hold promising prospects.

Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with altered bowel habits. Several clinical studies have demonstrated the effectiveness of acupuncture and moxibustion for IBS. Many systematic reviews of acupuncture and moxibustion for IBS have been published in recent years, but their results are not entirely consistent. OBJECTIVE: To evaluate the methodological, reporting, and evidence quality of systematic reviews of acupuncture and moxibustion for IBS. SEARCH STRATEGY: Systematic reviews of acupuncture and moxibustion for IBS published before February 20, 2023 were searched in eight databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Periodicals, and China Biology Medicine. The keywords used for literature search were acupuncture, moxibustion, systematic review, meta-analysis, and irritable bowel syndrome. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomized controlled trials of acupuncture and moxibustion for IBS were included. DATA EXTRACTION AND ANALYSIS: Relevant information was independently extracted by two investigators. The A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020), and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to evaluate the methodological quality, reporting quality and evidence quality, respectively. RESULTS: A total of 342 studies were retrieved and 15 systematic reviews were included. The results of AMSTAR 2 showed low methodological quality in 2 studies and very low methodological quality in the remaining 13 studies, with main issues being failure to register a protocol, incomplete search strategy, not providing a list of excluded studies, incomplete consideration of the risk of bias in the included studies, and a failure to assess the publication bias. The results of PRISMA 2020 showed seriously deficient reporting quality of 2 studies, somewhat deficient reporting quality of 12 studies, and relatively complete reporting quality of 1 study, with the main problems being lack of a complete search strategy, non-availability of a list of excluded studies with justification for their exclusion, not conducting heterogeneity and sensitivity analyses, not evaluating the credibility of the evidence, and not registering the protocol. The results of GRADE showed that the quality of the evidence is low or very low. CONCLUSION: Most included systematic reviews interpreted findings to suggest that acupuncture and moxibustion have benefits for IBS. However, there is a need to improve the methodological, reporting and evidence quality of the systematic reviews. Larger, multicenter, rigorously designed randomized controlled trials and high-quality systematic reviews are required to obtain more robust evidence. PLEASE CITE THIS ARTICLE AS: Ma YY, Hao Z, Chen ZY, Shen YX, Liu HR, Wu HG, Bao CH. Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review. J Integr Med. 2024; 22(1): 22-31.

Rapid identification of chemical constituents and dynamic metabolic profile of Shenqi-Tiaoshen formula in rat plasma based on UPLC-Q-TOF/MSE.

Shenqi-Tiaoshen formula (SQTSF) is a traditional Chinese medicine (TCM) prescription that has been employed in the treatment of chronic obstructive pulmonary disease (COPD). Clinical practice has demonstrated that SQTSF is an effective prescription for stable COPD. However, owing to the complexity of TCM prescription, there is a lack of in-depth understanding of the chemical components of SQTSF and its in vivo metabolism studies. In this study, a comprehensive analytical strategy based on ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was established to identify the chemical components, the absorbed components, and the metabolites of SQTSF given by gavage in rats, and analyze their dynamic changes. As a result, 86 chemical components of SQTSF were characterized, which were mainly categorized into flavonoids, saponins, organic acids, terpenoids, etc. Among them, 13 compounds were confirmed unambiguously by reference standards. Furthermore, 20 prototype components and 46 metabolites were detected in rat plasma at different time points. It was found that one prototype component and thirteen metabolites could be detected during the entire 24 h, indicating that these compounds were slowly eliminated and thus accumulated in vivo over a prolonged duration. Interestingly, the phenomenon that three prototype components and fourteen metabolites reappeared after a period of disappearance from the plasma was found. It was also observed that different prototype components may generate the same metabolite. The metabolic processes of SQTSF in rats mainly included oxidation, reduction, hydration, demethylation, deglycosylation, methylation, acetylation, glucuronidation, glutathionylation, and associated combination reactions. Overall, the present study identified the chemical components of SQTSF and their dynamic metabolic profile in rat plasma, which provided a systematic and applicable strategy for screening and characterization of the prototype components and metabolites of TCM compound preparations.

Cinobufacini injection delays hepatocellular carcinoma progression by regulating lipid metabolism via SREBP1 signaling pathway and affecting macrophage polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinobufacini injection, an aqueous extract of the toad, is a commonly used anti-tumor animal herbal medicine in clinical practice. It has the effects of detoxifying, reducing swelling, and relieving pain. AIMS OF THE STUDY: To investigate the effects of Cinobufacini injection on hepatocellular carcinoma progression by regulating lipid metabolism and macrophage polarization in the tumor microenvironment and to identify the potential molecular mechanisms. MATERIALS AND METHODS: To establish the axillary transplantation tumor model of hepatocellular carcinoma Hepa1-6 in C57BL/6 mice, and to evaluate the inhibitory effect of Cinobufacini injection on hepatocellular carcinoma in vivo as well as drug delivery security. Combined metabolomics and transcriptomics analysis of the effect of Cinobufagin Injection on tumor microenvironment. An in vitro mouse co-culture model of peritoneal macrophages and Hepa1-6 cells was established to research the effects of Cinobufacini injection on macrophage polarization, hepatocellular carcinoma cell growth, migration, and changes in lipid metabolism. Cinobufacini injection inhibition of the AMPK/SREBP1/FASN signaling pathway regulating cholesterol metabolism and affecting macrophage polarization was examined using qRT-PCR, lentiviral transfection, immunofluorescence, and Western blot. RESULT: In vivo experiments demonstrated that Cinobufacini injection treatment significantly inhibited the growth of Hepa1-6 hepatomas, along with a reduction in cholesterol content and a decrease in the percentage of M2 macrophages in tumor tissue. In vitro, we found that Cinobufacini injection inhibits IL-4-induced M2 macrophage polarization, reduces the cholesterol content of Hepa1-6 cells in a co-culture system, and inhibits the promotion of hepatocellular carcinoma cells by M2 macrophages. In addition, successful overexpression of SREBP1 in Hepa1-6 cells showed more pronounced cellular activity whereas Cinobufacini injection inhibited this change and reduced intracellular lipid levels. CONCLUSION: Cinobufacini injection inhibits cholesterol synthesis within the tumor microenvironment via the AMPK/SERBP1/FASN signaling pathway, which in turn blocks the M2 polarization of macrophages, leading to the weakening of hepatocellular carcinoma growth and migration, and the promotion of its apoptosis. Our findings provide an important Introduction to understanding the molecular mechanism of Cinobufacini injection's anticancer activity and provide reliable theoretical and experimental support for its clinical application.

Paris polyphylla saponins II inhibits invasive, migration and epithelial-mesenchymal transition of melanoma cells through activation of autophagy.

Malignant melanoma is a kind of malignant tumor derived from normal epidermal melanocytes or original nevus cells. It has a high degree of malignancy, rapid progress, dangerous condition, and poor prognosis. In recent years, the innovation of traditional Chinese medicine has broadened the scope and effect of tumor treatment. It is a hotspot and breakthrough to find new anti-tumor invasion and migration drugs from natural plants or traditional Chinese medicine. This study explored the role of PPII in promoting autophagy to inhibit EMT of melanoma cells, the role of the PI3K/Akt signaling pathway in the invasion and migration of melanoma cells induced by PPII. We found that PPII effectively inhibited the proliferation, invasion and migration of melanoma B16 and B16F10 in vitro, and induced autophagy. We also established the xenograft tumor and metastatic tumor model of C57BL/6 mice with B16F10 cells. Results showed that PPII effectively inhibited the growth of transplanted tumors, induced autophagy and inhibited the expression level of EMT related protein; Metastasis experiment showed that PPII inhibited the invasion and migration of B16F10, the effect of inhibiting lung metastasis is the most significant. Further mechanism studies showed that the inhibition of PPII on melanoma invasion and migration is related to its induction of autophagy and then inhibition of EMT.

Molecular mechanism of angiogenesis for cerebral infarction rats by acupuncture intervention based on sonic hedgehog signaling pathway.

BACKGROUND: To study the factors of the Sonic Hedgehog (Shh) signaling pathway after permanent cerebral ischemic and the effects by acupuncture. METHODS: Male Wistar rats were divided into Electro-acupuncture (EA) group, Model Control (MC) group, and blank control (Control) group. EA and MC were divided into 9 phases, namely 1 h, 3 h, 6 h, 9 h, 12 h, 24 h, 3 d, 7 d, and 12 d after the operation. The neurological deficits and permanent cerebral ischemic volume were observed. The immunofluorescence method was used to examine the angiogenesis. (Polymerase Chain Reaction) PCR and (Immunohistochemistry) IHC were used to test the changes in Shh, Ptch, Smo, and Gli2 mRNA and proteins. RESULTS: The neurological severity scores (NSS) of the Control was 0, the score of the EA group was less than that of the MC. The cerebral permanent ischemic volume of the Control was 0 %, and the EA group's was smaller than that of the MC. The expression of copositive cells in the EA group was higher than the MC's from 12 h to 12 d, and the EA group had more peripheral blood vessels. The rat brain expressions of Shh, Ptch, Smo and Gli2 mRNA and proteins in the MC was higher than that of the Control, the rat brain expression of the EA group was higher than that of the MC. CONCLUSIONS: EA can upregulate the expression of the Shh signaling pathway factors, thereby promoting angiogenesis.

A UPLC-QTOF/MS-based hepatic tissue metabolomics approach deciphers the mechanism of Huachansu tablets-based intervention against hepatocellular carcinoma.

Huachansu (HCS) tablets, classified as well-known traditional Chinese medicine (TCM) preparation, have been proved to be effective in the treatment of hepatocellular carcinoma (HCC) in clinical studies. However, the underlying mechanism of HCS tablets against HCC has not been comprehensively elucidated. In this study, a rat model of HCC was established with diethylnitrosamine (DEN) inducer. The efficacy of HCS tablets against HCC was assessed through liver histopathological examination and evaluation of biochemical indicators. A metabolomics method based on UPLC-Q-TOF/MS combined with multivariate data analysis was established to identify differential metabolites related to the inhibition effect of HCS tablets on HCC, and then the relevant metabolic pathway analysis was performed to investigate the anti-HCC mechanisms of HCS tablets. The results showed that compared to the control group, the HCC model group showed a significant increase in the values of HCC-related biochemical indicators and the number of tumor nodules, indicating the successful establishment of the HCC rat model. Upon treatment with HCS tablets, the values of HCC-related biochemical indicators decreased, liver fibrosis and nuclear deformation were also significantly alleviated. A total of 15 differential metabolites associated with the anti-tumor effect of HCS tablets on HCC were screened and annotated through hepatic tissue metabolomics studies. Analysis of metabolic pathways revealed that the therapeutic effects of HCS tablets on HCC mainly involved the pentose and glucuronate interconversions and arachidonic acid metabolism. Further western blotting corroborated that the alteration in arachidonic acid (AA) level after the intervention of HCS tablets was related to the inhibition of cPLA2α expression in rat liver tissues. In conclusion, HCS tablets exhibit a certain anti-tumor effect on HCC, and the metabolomics method based on UPLC-Q-TOF/MS combined with further verification at the biochemical level is a promising way to reveal its underlying mechanism.

[ZHANG Jian-bin's clinical experience in treatment of depressive disorder based on the theory of governor vessel].

Depressive disorder is manifested as emotional and physical abnormality. Theoretically, the governor vessel is distributed along the spine, related to the brain and communicated with five zang and six fu organs. It is the key meridian for understanding the various symptoms of depressive disorder. Depressive disorder is caused by dysfunction, stagnation or emptiness of the governor vessel, resulting in malnutrition of the brain. In clinical diagnosis and treatment, based on the theory of the governor vessel, the etiology and pathogenesis are analyzed in the patients with depressive disorder. In order to achieve harmonizing mutually the mental and physical conditions, acupuncture is delivered to adjust the spirit and physical state, moving cupping is to regulate the governor vessel, tuina manipulation is to promote meridians and collaterals and physical exercise is to coordinate the body and the spirit.

[Effect of mild moxibustion at 45 ℃ with different durations at "Zusanli" （ST36） on the inflammatory factors in the abdominal aorta of hyperlipidemia rats].

OBJECTIVE: To investigate the effects of mild moxibustion at 45°C on the chronic inflammatory response of the abdominal aorta in rats with hyperlipidemia and the effects of different moxibustion durations. METHODS: Thirty-six SD rats were randomly divided into the following groups： blank control group (2 weeks), model group (2 weeks), moxibustion group (2 weeks), blank group (4 weeks), model group (4 weeks), and moxibustion group (4 weeks). A model of hyperlipidemia with chronic inflammation was established through high-fat diet feeding for 8 weeks. Rats in the moxibustion groups received mild moxibustion treatment at bilateral "Zusanli"(ST36) at 45 °C, 10 min every time, once a day, for consecutive 2 or 4 weeks. The morphology of the abdominal aorta in each group was observed by using HE staining. Contents of serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), endothelin-1 (ET-1) and the contents of nitric oxide (NO), ox-LDL, and ET-1 in the abdominal aorta were measured by using ELISA. Protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta of rats in each group were detected by using Western blot and real-time fluorescence quantitative PCR respectively. The positive expression of IL-6 in the abdominal aorta of rats was detected by Immunofluorescence. RESULTS: Compared to the blank control group, rats in the model group had increased contents of LDL, TC, TG, ox-LDL, VCAM-1, ICAM-1, IL-6, TNF-α, and ET-1 in the serum, increased contents of ox-LDL and ET-1 in the abdominal aorta, increased protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta(P<0.01, P<0.05, P<0.001), with decreased HDL content in the serum, decreased NO content in the abdominal aorta (P<0.01, P<0.05), as well as dark pink abdominal aorta, rough textures in the adventitia, media, and intima, and rough endothelial layer. Compared to the model group(2 weeks), LDL, ICAM-1, ET-1 contents in the serum, ox-LDL content in the abdominal aorta were decreased(P<0.05), while serum IL-6 and TNF-α contents, and NO content in the abdominal aorta were significantly increased(P<0.01, P<0.05), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(2 weeks). Compared to the model group(4 weeks), contents of LDL, TC, TG, VCAM-1, ICAM-1, IL-6, TNF-α, ox-LDL, and ET-1 in the serum, ox-LDL and ET-1 contents in abdominal aorta, protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta were significantly decreased(P<0.05, P<0.01), while HDL content in the serum and NO content in the abdominal aorta were significantly increased(P<0.05, P<0.01), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks). In addition, content of HDL in the serum were significantly increased(P<0.05), while TNF-α content in the serum, protein expression of IL-6 in the abdominal aorta were significantly decreased (P<0.001, P<0.05), with smoother vascular walls, and clearer nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks), in comparison with the moxibustion group(2 weeks). CONCLUSION: Mild moxibustion of 45 °C at ST36 can improve vascular endothelial damage and inflammatory response induced by high-fat diet by regulating serum lipids, vascular tone, adhesion molecules, and inflammatory factors, of which the effect of moxibustion intervention for 4 weeks is more significant.

Metabolic profiling of Qi-Yu-San-Long decoction in rat feces by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry combined with a post-targeted screening strategy.

Research into traditional Chinese medicine metabolism in feces is one of the key avenues to understanding the fate of traditional Chinese medicines in vivo. In this study, we used ultraperformance liquid chromatography-quadrupole time-of-flight MS in combination with a post-targeted screening strategy to identify the prototype components and metabolites in rat feces after oral administration. Based on our group's previous research, the component database of Qi-Yu-San-Long decoction (QYSLD) was established. Prototype components were screened from the fecal samples based on summarized chromatographic and MS behaviors. According to the chemical structure characteristics of related compounds, the possible metabolic pathways were inferred, and the metabolites related to QYSLD were predicted. We extracted ion chromatograms by predicting the m/z values of metabolite excimer ions and identified related metabolites based on their retention time and fragmentation behavior. A total of 93 QYSLD-related xenobiotics were confirmed or tentatively identified in rat fecal samples, and the results indicated that the main metabolic pathways of QYSLD were hydrolysis, deglycosylation, oxidation, reduction, decarboxylation, methylation and acetylation. This study presents a rapid method for identifying the prototype components and metabolites, and offers valuable insights into the biotransformation profiling of QYSLD in rat feces.

The quality evaluation system of a famous traditional Chinese medicine Huaganjian decoction was established.

Huaganjian decoction (HGJD) has been widely used clinically to treat liver injuries and gastritis. However, the quality evaluation system for HGJD is not perfect. In this study, paeoniflorin, hesperidin, geniposide, naringin, and quercetin were employed as quality markers. The quantitative analysis of these five components in HGJD was conducted using a high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry method. This method underwent validation for linearity, precision, accuracy, repeatability, and recovery. In summary, a reliable quantitative method was successfully employed to establish a comprehensive quality evaluation of HGJD.

Efficacy and safety of Huashi Baidu granule plus Nirmatrelvir-Ritonavir combination therapy in patients with high-risk factors infected with Omicron (B.1.1.529): A multi-arm single-center, open-label, randomized controlled trial.

BACKGROUND: Huashi Baidu granule (HSBD) and Paxlovid (Nirmatrelvir-Ritonavir) are antiviral Chinese patent medicine and western medicine specially developed for treating coronavirus disease 2019 (COVID-19). Their efficacy and safety in treating COVID-19 are still under investigated. PURPOSE: To assess and compare the efficacy and safety of HSBD, Paxlovid, and the combination in treating high-risk patients infected with SARS-CoV-2 Omicron. STUDY DESIGN: The study was a prospective single-center, open-label, randomized, controlled clinical trial conducted from April 18 to June 5, 2022. (ClinicalTrial.gov registration number: ChiCTR2200059390) METHODS: 312 severe patients aged 18 years and older infected with SARS-CoV-2 Omicron from Shuguang Hospital in Shanghai were randomly allocated to HSBD monotherapy (orally 137 g twice daily for 7 days, n = 105), Paxlovid monotherapy (orally 300 mg of Nirmatrelvir plus 100 mg of Ritonavir every 12 h for 5 days, n = 103), or combination therapy (n = 104). The primary outcome was SARS-CoV-2 nucleic acid negative conversion within 7-day treatment. The secondary outcome included hospital discharging conditions, severe conversion of symptom, and adverse events. RESULTS: Of 312 participants, 85 (82%) of 104 in combination therapy, 71 (68%) of 105 in HSBD monotherapy, and 73 (71%) of 103 in Paxlovid monotherapy had a primary outcome event. The hazard ratios of primary outcome were 1.37 (95% CI 1.03 - 1.84, p = 0.012) for combination versus HSBD, 1.28 (0.98-1.69, p = 0.043) for combination versus Paxlovid, and 0.88 (0.66-1.18, p = 0.33) for HSBD versus Paxlovid. There was no statistical difference of efficacy between HSBD and Paxlovid, while combination therapy exhibited more effective than either alone. For secondary outcomes, the hospital discharging rates within 7 days exhibited the significant increase in combination therapy than in HSBD or Paxlovid monotherapy (71% (74/104) vs 55% (58/105) vs 52% (54/103), p < 0.05). The risk of severe conversion of symptom showed no statistical significance among three interventions (1% (1/104) vs 3% (3/105) vs 3% (3/103), p > 0.05). No severe adverse events occurred among combination therapy and monotherapies in the trial. CONCLUSION: For patients with severe COVID-19, HSBD exhibits similar efficacy to Paxlovid, while combination therapy is more likely to increase the curative efficacy of Omicron variant than monotherapies, with few serious adverse events.

Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

An integrated analytical strategy to decipher the metabolic profile of alkaloids in Compound Kushen injection based on UHPLC-ESI-QTOF/MSE.

Compound Kushen injection (CKI) is a kind of sterilised water-soluble traditional Chinese medicine preparation that has been used for the clinical treatment of a variety of cancers (hepatocellular carcinoma, lung cancer, etc.) for 19 years. However, to date, the metabolism-related study on CKI in vivo has not been conducted.An integrated analytical strategy was established to investigate the metabolic profile of alkaloids of CKI in rat plasma, urine, and faeces based on ultra-high performance liquid chromatography-electrospray quadrupole time-of-flight mass spectrometry in MSE mode (UHPLC-ESI-QTOF/MSE).Nineteen prototype alkaloids (including 12 matrine-type alkaloids, 2 cytisine-type alkaloids, 3 lupinine-type alkaloids, and 2 aloperine-type alkaloids) of CKI were identified in vivo. Furthermore, 71 metabolites of alkaloids (including 11 of lupanine-related metabolites, 14 of sophoridine-related metabolites, 14 of lamprolobine-related metabolites, and 32 of baptifoline-related metabolites) were tentatively characterised. Metabolic pathways involved in the metabolism of phase I (include oxidation, reduction, hydrolysis, and desaturation), phase II (mainly include glucuronidation, acetylcysteine or cysteine conjugation, methylation, acetylation, and sulphation), and associated combination reactions.The integrated analytical strategy was successfully used to characterise the prototype alkaloids and their metabolites of CKI in vivo, and the results laying a foundation for further study its pharmacodynamic substances.

Identification and quantitative analysis of the chemical constituents of Gandouling tablets using ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Gandouling tablets are used in a clinical agent for the treatment of hepatocellular degeneration; however, their chemical constituents have not been elucidated. Here, we screened and identified the chemical constituents of Gandouling tablets using ultra-high-performance liquid chromatography (UHPLC)-quadrupole time of flight/mass spectrometry. A method for the quality evaluation of Gandouling tablets was developed by combining the UHPLC fingerprints and the simultaneous quantitative analysis of multiple active ingredients. For fingerprint analysis, 20 shared peaks were identified to assess the similarities among the 10 batches of Gandouling tablets and the similarity was >0.9. The levels of nine representative active ingredients were simultaneously determined to ensure consistency in quality. A total of 99 chemical components were identified, including 18 alkaloids, 20 anthraquinones, 13 flavonoids, 11 phenolic acids, 9 polyphenols, 7 phenanthrenes, 5 sesquiterpenes, 3 curcuminoids, 2 lignans, 2 isoflavones, 2 dianthranones, and 7 other components. The retention times, molecular formulae, and secondary fragmentation information of these compounds were analyzed, and the cleavage pathways and characteristic fragments of some of the representative compounds were elucidated. This systematic analysis used to identify the chemical components of Gandouling tablets lays the foundation for its further quality control and research on their pharmacodynamic substances.

[Electroacupuncture mitigates hyperlipidemia via improving cholesterol metabolism mediated by SCAP/SREBP-2 signaling in liver tissue in rats].

OBJECTIVE: To explore the effect of electroacupuncture (EA) on sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP)/ SREBP-2 signaling and the expressions of its downstream cholesterol metabolism related molecules 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and low-density lipoprotein receptor (LDLR) in the liver tissue in rats with hyperlipidemia (HLP), so as to reveal its mechanisms underlying improvement of HLP. METHODS: Male SD rats were randomly divided into normal control, HLP model and EA groups (n=10/group). The HLP model was established by feeding the rats with high-fat diet for 28 d. Rats in the EA group received EA stimulation (2 Hz/100 Hz, 2 mA) at "Fenglong" (ST40) and "Yinlingquan"(SP9) for 30 min, once daily for 28 d. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) in the serum, the activity of glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) were detected by automatic biochemical analysis. The content of TC in the liver tissue was detected using high performance liquid chromatography. The mRNA and protein expression levels of SCAP, SREBP-2, HMGCR, PCSK9 and LDLR in the liver tissue were measured by using quantitative real-time PCR and Western blot, respectively. The immunofluorescence density of liver SCAP was determined by using immunofluorescence histochemistry. RESULTS: Compared with the normal control group, the contents of liver TC, serum TC, LDL-C, the activities of AST and ALT, and the mRNA and protein expression levels of SCAP, SREBP-2, HMGCR, PCSK9 as well as SCAP immunoactivity were significantly increased (P<0.01), while the LDLR mRNA and protein levels were markedly decreased (P<0.01) in the model group. In comparison with the model group, the contents of liver TC， serum TC, LDL-C, the activities of AST and ALT and the expression of SCAP, SREBP-2, HMGCR, PCSK9 mRNAs and proteins and SCAP immunoactivity were considerably decreased in the EA group (P<0.01), while the LDLR protein level was evidently increased in the EA group (P<0.05). CONCLUSION: EA intervention can inhibit the synthesis of cholesterol in the liver and thus improve hyperlipidemia in HLP rats, which may be realized by down-regulating the protein and mRNA expressions of hepatic SCAP/SREBP-2, HMGCR and PCSK9, and up-regulating LDLR protein.

[Moxibustion of 45 ℃ at "Zusanli" (ST36) improves vascular endothelial oxidative stress in hyperlipidemia rats].

OBJECTIVE: To explore the antioxidant effect of moxibustion on vascular endothelial function and the under-lying mechanism. METHODS: Forty male SD rats were randomly divided into blank, model, moxibustion and endothelial nitric oxide synthase (eNOS) inhibitor groups, with 10 rats in each group. Hyperlipidemia rat model was established by high fat diet for 8 weeks. Rats in the moxibustion group received 45 ℃ moxibustion at "Zusanli" (ST36) for 10 min once daily for consecutive 4 weeks. Rats in the eNOS inhibitor group received intraperitoneal injection of eNOS inhibitor L-NAME (1 mg/100 g) at the same time of moxibustion intervention. The morphology of abdominal aorta endothelium was observed by HE staining. Lipid deposition in abdominal aorta was observed by oil red O staining. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) in serum and reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD), oxidized LDL lipoprotein (ox-LDL), endothelin-1 (ET-1), eNOS, malondialdehyde (MDA) in serum and abdominal aorta were determined by ELISA. The expression of eNOS in abdominal aorta was detected by immunofluorescence. RESULTS: HE staining of the abdominal aorta showed no significant pathological abnormality in the blank group; the endovascular cortex was rough, and the inner, media and outer membrane were rough in the model group; the nucleus and surrounding tissue structure were clear and the vascular wall was smooth in the moxibustion group; abdominal aorta texture was rough in the eNOS inhibitor group. Compared with the blank group, the area of oil red O staining in abdominal aorta increased (P<0.05); the contents of serum TC, TG and LDL-C increased (P<0.01, P<0.05) while HDL-C decreased (P<0.05); the contents of ET-1 in serum and abdominal aorta were increased (P<0.01, P<0.05) while the contents of NO and eNOS were decreased (P<0.05, P<0.001); the contents of ROS, ox-LDL and MDA in serum and abdominal aorta were increased (P<0.001, P<0.01, P<0.000 1) while the content of SOD in abdominal aorta was decreased (P<0.000 1); the expression level of eNOS in abdominal aorta was decreased (P<0.05) in the model group. Compared with the model group, the area of oil red O staining in abdominal aorta decreased (P<0.05); the contents of TC, TG and LDL-C in serum decreased (P<0.05) while HDL-C increased (P<0.05); the contents of ET-1 in serum and abdominal aorta were decreased (P<0.01, P<0.05) while the contents of NO and eNOS in abdominal aorta were increased (P<0.001, P<0.01); the contents of ROS and MDA in serum and abdominal aorta were decreased (P<0.001, P<0.01, P<0.05), the content of ox-LDL was decreased (P<0.01) and the content of SOD was increased (P<0.000 1) in abdominal aorta; the expression level of eNOS in abdominal aorta was increased (P<0.05) in the moxibustion group. Compared with the moxibustion group, the contents of serum TC, LDL-C and MDA in the eNOS inhibitor group were increased (P<0.05); the contents of ET-1, ROS, ox-LDL and MDA in abdominal aorta were increased (P<0.05), the contents of NO, eNOS and SOD were decreased (P<0.05); the expression level of eNOS in abdominal aorta was decreased (P<0.05). CONCLUSION: 45 ℃ moxibustion at ST36 can protect and repair vascular endothelial injury in abdominal aorta of hyperlipidemia rats and improve the oxidative stress of vascular endothelium.

[Determination of complexation ability of rhubarb with copper ions by ultra-high performance liquid chromatography].

Gandou decoction (GDD) is a traditional Chinese medicine prescription that has been widely used to treat copper metabolism disorders in China with remarkable clinical effect and lower toxicity. However, evaluation of the complexation ability of copper ions is challenging, which hinders screening and discovery of coordinate active ingredients in GDD. An analytical method is needed to determinate the complexation ability of chemical constituents with copper ions. In this study, a rapid and accurate method based on ultra-high performance liquid chromatography (UHPLC) was developed to determine the complexing ability of rhubarb with copper ions. First, the optimal coordination reaction conditions between active ingredients of rhubarb and copper ions were determined. The samples were separated using an Agilent Eclipse Plus C18 column (50 mm×2.1 mm, 1.8 µm) with 5 µL injection volumes. The mobile phase was gradient eluted with methanol and water containing 0.1% (v/v) phosphoric acid at a flow rate of 0.3 mL/min. The detection wavelength was 254 nm and the column temperature was 30 ℃. Under the optimized chromatographic conditions, the rhubarb constituents were effectively separated. Next, peak areas of rhubarb were calculated before and after the coordination reaction between copper ions. The complexing ability of active ingredients in rhubarb with copper ions was evaluated by calculating the rate of changes of their chromatographic peak areas. Finally, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to identify the coordination active ingredients in rhubarb extract. Focusing on the coordination reaction conditions between active ingredients of rhubarb and copper ions revealed that the active ingredients of rhubarb and copper ions reached equilibrium by coordination reaction at pH 9 for 12 h. Methodological evaluation revealed the good stability and repeatability of the method. Under these conditions, 20 major components of rhubarb were identified by UPLC-Q-TOF-MS. According to the coordination rate of each component and copper ions, eight components with strong coordination were screened out (gallic acid 3-O-ß-D-(6'-O-galloyl)-glucopyranoside, aloe emodin-8-O-ß-D-glucoside, sennoside B, l-O-galloyl-2-O-cinnamoyl-glucoside, chysophanol-8-O-ß-D-(6″-O-acetyl)-glucoside, aloe-emodin, rhein and emodin). The respective complexation rates of the components were 62.50%, 29.94%, 70.58%, 32.77%, 34.61%, 26.07%, 28.73% and 31.78%. Compared with other reported methods, the presently developed method can be used to screen the active ingredients of traditional Chinese medicines that have complexing ability with copper ions, especially in complex mixture systems. This study describes an effective detection technology for evaluating and screening the complexing ability of other traditional Chinese medicines with metal ions.