Xinyang tablet alleviated cardiac dysfunction in a cardiac pressure overload model by regulating the receptor-interacting serum/three-protein kinase 3/FUN14 domain containing 1-mediated mitochondrial unfolded protein response and mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. AIMS OF THE STUDY: In the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. MATERIALS AND METHODS: Transverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5'-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro, HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. RESULTS: In the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. CONCLUSIONS: Our findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT.

A complementary method with PFBBr-derivatization based on a GC-EI-MS platform for the simultaneous quantitation of short-, medium- and long-chain fatty acids in murine plasma and feces samples.

Fatty acids (FAs) are essential molecules in all organisms and are involved in various physiological and pathophysiological processes. Pentafluorobenzyl bromide (PFBBr) is commonly used for FA derivatization for gas chromatography-mass spectrometry (GC-MS) quantification by chemical ionization (CI). While CI is the conventional ionization mode for PFBBr derivatization, the electron ionization (EI) source has also demonstrated efficacy in achieving satisfactory analytical performance for the analysis of PFB esters. In this study, we present a novel approach utilizing PFBBr-derivatization on a GC-EI-MS platform to quantitatively analyze a comprehensive range of 44 fatty acids (FAs) spanning from C2 to C24. The method's sensitivity, precision, accuracy, linearity, recovery, and matrix effect were rigorously validated against predetermined acceptance criteria. In comparison to the conventional CI ionization mode, the utilization of PFBBr-derivatization in GC-EI-MS exhibits a wider range of applications and achieves comparable sensitivity levels to the conventional CI platform. By using this method, we successfully quantified 44 FAs in plasma and feces samples from the mice with deoxynivalenol (DON)-induced kidney injury. Among these, the levels of most FA species were increased in the DON-exposure group compared with the control group. The orthogonal partial least squares discriminant analysis (OPLS-DA) of all the tested FAs showed a visual separation of the two groups, indicating DON exposure resulted in a disturbance of the FA profile in mice. These results indicate that the established method by integration of GC-MS with PFBBr derivatization is an efficient approach to quantify the comprehensive FA profile, which includes short-, medium- and long-chain FAs. In addition, our study provides new insights into the mechanism underlying DON exposure-induced kidney injury.

Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial.

BACKGROUND: As one of the most common musculoskeletal ailments, chronic nonspecific low-back pain (CNLBP) causes persistent disability and substantial medical expenses. Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising. Recent guidelines indicate a reduced role for medicines in the management of CNLBP. OBJECTIVE: The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm, compared to nonsteroidal anti-inflammatory drug (NSAID) with a capsaicin plaster, in the treatment of CNLBP. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a prospective multicenter randomized clinical trial enrolling patients from January 1, 2022 to December 31, 2022. A total of 156 patients with CNLBP were randomized into two parallel groups. Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally. Patients in the test group were treated with cupping and scraping using a medical device and medicated balm. MAIN OUTCOME MEASURES: Primary outcome was pain recorded using the visual analogue scale (VAS). Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale (JOA) and the traditional Chinese medicine (TCM) syndrome integral scale (TCMS) as assessment tools. RESULTS: Between baseline and postintervention, all changes in outcome metric scales were statistically significant (P < 0.001). Compared to the control group, patients in the test group had a significantly greater treatment effect in all outcome variables, as indicated by lower VAS and TCMS scores and higher JOA scores, after the one-week intervention period (P < 0.001). Further, according to the findings of multivariate linear regression analysis, the participants' pain (VAS score) was related to their marital status, age, smoking habits and body mass index. No adverse reactions were reported for any participants in this trial. CONCLUSION: The effectiveness of TCM combined with the new physiotherapy tool is superior to that of NSAID combined with topical plasters, regarding to pain intensity, TCM symptoms and quality of life. The TCM plus physiotherapy also showed more stable and long-lasting therapeutic effects. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (ChiCTR2200055655). Please cite this article as: He JY, Tu XY, Yin ZF, Mu H, Luo MJ, Chen XY, Cai WB, Zhao X, Peng C, Fang FF, Lü C, Li B. Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial. J Integr Med. 2024; 22(1): 39-45.

[Effects of Yizhi Tiaoshen acupuncture on learning and memory function and the expression of phosphorylated tau protein in the hippocampus of Alzheimer's disease model rats].

OBJECTIVE: To observe the effects of Yizhi Tiaoshen (benefiting mental health and regulating the spirit) acupuncture on learning and memory function, and the expression of phosphorylated tubulin-associated unit (tau) protein in the hippocampus of Alzheimer's disease (AD) model rats, and explore the effect mechanism of this therapy on AD. METHODS: A blank group and a sham-operation group were randomly selected from 60 male SD rats, 10 rats in each one. AD models were established in the rest 40 rats by the intraperitoneal injection of D-galactose and okadaic acid in the CA1 region of the bilateral hippocampus. Thirty successfully-replicated model rats were randomly divided into a model group, a western medication group and an acupuncture group, 10 rats in each one. In the acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Sishencong" (EX-HN 1), "Neiguan" (PC 6), "Shenmen" (HT 7), "Xuanzhong" (GB 39) and "Sanyinjiao" (SP 6); and the needles were retained for 10 min. Acupuncture was given once daily. One course of treatment was composed of 6 days, with the interval of 1 day; the completion of treatment included 4 courses. In the western medication group, donepezil hydrochloride solution (0.45 mg/kg) was administrated intragastrically, once daily; it took 7 days to accomplish one course of treatment and a completion of intervention was composed of 4 courses. Morris water maze (MWM) and novel object recognition test (NORT) were used to assess the learning and memory function of the rats. Using HE staining and Nissl staining, the morphological structure of the hippocampus was observed. With Western blot adopted, the protein expression of the tau, phosphorylated tau protein at Ser198 (p-tau Ser198), protein phosphatase 2A (PP2A) and glycogen synthase kinase-3ß (GSK-3ß) in the hippocampus was detected. RESULTS: There were no statistical differences in all of the indexes between the sham-operation group and the blank group. Compared with the sham-operation group, in the model group, the MWM escape latency was prolonged (P<0.05), the crossing frequency and the quadrant stay time in original platform were shortened (P<0.05), and the NORT discrimination index (DI) was reduced (P<0.05); the hippocampal cell numbers were declined and the cells arranged irregularly, the hippocampal neuronal structure was abnormal and the numbers of Nissl bodies decreased; the protein expression of p-tau Ser198 and GSK-3ßwas increased (P<0.05) and that of PP2A decreased (P<0.05). When compared with the model group, in the western medication group and the acupuncture group, the MWM escape latency was shortened (P<0.05), the crossing frequency and the quadrant stay time in original platform were increased (P<0.05), and DI got higher (P<0.05); the hippocampal cell numbers were elevated and the cells arranged regularly, the damage of hippocampal neuronal structure was attenuated and the numbers of Nissl bodies were increased; the protein expression of p-tau Ser198 and GSK-3ß was reduced (P<0.05) and that of PP2A was increased (P<0.05). There were no statistically significant differences in the above indexes between the acupuncture group and the western medication group (P>0.05). CONCLUSION: Acupuncture therapy of "benefiting mental health and regulating the spirit" could improve the learning and memory function and alleviate neuronal injure of AD model rats. The effect mechanism of this therapy may be related to the down-regulation of GSK-3ß and the up-regulation of PP2A in the hippocampus, and then to inducing the inhibition of tau protein phosphorylation.

Baicalin induces ferroptosis in osteosarcomas through a novel Nrf2/xCT/GPX4 regulatory axis.

BACKGROUND: Osteosarcomas (OS) is a kind of malignant bone tumor which occurs primarily in children and adolescents, and the clinical therapeutics remain disappointing. As a new programmed cell death, ferroptosis is characterized by iron dependent and intracellular oxidative accumulation, which provides a potential alternative intervene for the OS treatment. Baicalin, a major bioactive flavone derived from traditional Chinese medicine Scutellaria baicalensis, has been proved to have anti-tumor properties in OS. Whether ferroptosis participated in the baicalin mediated anti-OS activity is an interesting project. PURPOSE: To explore the pro-ferroptosis effect and mechanisms of baicalin in OS. METHODS/STUDY DESIGN: Pro-ferroptosis effect of baicalin on cell death, cell proliferation, iron accumulation, lipid peroxidation production was determined in MG63 and 143B cells. The levels of glutathione (GSH), oxidized (GSSG) glutathione and malondialdehyde (MDA) were determined by enzyme linked immunosorbent assay (ELISA). The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Glutathione peroxidase 4 (GPX4) and xCT were detected by western blot in baicalin-mediated ferroptosis regulation. In vivo, a xenograft mice model was adopted to explore the anticancer effect of baicalin. RESULTS: In the present study, it was found that baicalin significantly suppress tumor cell growth in vitro and in vivo. By promoting the Fe accumulation, ROS formation, MDA production and suppressing the ratio of GSH/GSSG, baicalin was found to trigger ferroptosis in OS and ferroptosis inhibitor ferrostatin-1 (Fer-1) successfully reversed these suppressive effects, indicating that ferroptosis participated in the baicalin mediated anti-OS activity. Mechanistically, baicalin physically interacted with Nrf2, a critical regulator of ferroptosis, and influenced its stability via inducing ubiquitin degradation, which suppressed the Nrf2 downstream targets GPX4 and xCT expression, and led to stimulating ferroptosis. CONCLUSIONS: Our findings for the first time indicated that baicalin exerted anti-OS activity through a novel Nrf2/xCT/GPX4-dependent ferroptosis regulatory axis, which hopefully provides a promising candidate for OS treatment.

Plantamajoside attenuates cardiac fibrosis via inhibiting AGEs activated-RAGE/autophagy/EndMT pathway.

Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.

Role of Mitophagy in Myocardial Ischemia/Reperfusion Injury and Chinese Medicine Treatment.

Mitophagy is one of the important targets for the prevention and treatment of myocardial ischemia/reperfusion injury (MIRI). Moderate mitophagy can remove damaged mitochondria, inhibit excessive reactive oxygen species accumulation, and protect mitochondria from damage. However, excessive enhancement of mitophagy greatly reduces adenosine triphosphate production and energy supply for cell survival, and aggravates cell death. How dysfunctional mitochondria are selectively recognized and engulfed is related to the interaction of adaptors on the mitochondrial membrane, which mainly include phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced kinase 1/Parkin, hypoxia-inducible factor-1 α/Bcl-2 and adenovirus e1b19k Da interacting protein 3, FUN-14 domain containing protein 1 receptor-mediated mitophagy pathway and so on. In this review, the authors briefly summarize the main pathways currently studied on mitophagy and the relationship between mitophagy and MIRI, and incorporate and analyze research data on prevention and treatment of MIRI with Chinese medicine, thereby provide relevant theoretical basis and treatment ideas for clinical prevention of MIRI.

Effects of Yizhi Tiaoshen acupuncture on learning and memory function and the expression of phosphorylated tau protein in the hippocampus of Alzheimer's disease model rats / 中国针灸

OBJECTIVE@#To observe the effects of Yizhi Tiaoshen (benefiting mental health and regulating the spirit) acupuncture on learning and memory function, and the expression of phosphorylated tubulin-associated unit (tau) protein in the hippocampus of Alzheimer's disease (AD) model rats, and explore the effect mechanism of this therapy on AD.@*METHODS@#A blank group and a sham-operation group were randomly selected from 60 male SD rats, 10 rats in each one. AD models were established in the rest 40 rats by the intraperitoneal injection of D-galactose and okadaic acid in the CA1 region of the bilateral hippocampus. Thirty successfully-replicated model rats were randomly divided into a model group, a western medication group and an acupuncture group, 10 rats in each one. In the acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Sishencong" (EX-HN 1), "Neiguan" (PC 6), "Shenmen" (HT 7), "Xuanzhong" (GB 39) and "Sanyinjiao" (SP 6); and the needles were retained for 10 min. Acupuncture was given once daily. One course of treatment was composed of 6 days, with the interval of 1 day; the completion of treatment included 4 courses. In the western medication group, donepezil hydrochloride solution (0.45 mg/kg) was administrated intragastrically, once daily; it took 7 days to accomplish one course of treatment and a completion of intervention was composed of 4 courses. Morris water maze (MWM) and novel object recognition test (NORT) were used to assess the learning and memory function of the rats. Using HE staining and Nissl staining, the morphological structure of the hippocampus was observed. With Western blot adopted, the protein expression of the tau, phosphorylated tau protein at Ser198 (p-tau Ser198), protein phosphatase 2A (PP2A) and glycogen synthase kinase-3β (GSK-3β) in the hippocampus was detected.@*RESULTS@#There were no statistical differences in all of the indexes between the sham-operation group and the blank group. Compared with the sham-operation group, in the model group, the MWM escape latency was prolonged (P<0.05), the crossing frequency and the quadrant stay time in original platform were shortened (P<0.05), and the NORT discrimination index (DI) was reduced (P<0.05); the hippocampal cell numbers were declined and the cells arranged irregularly, the hippocampal neuronal structure was abnormal and the numbers of Nissl bodies decreased; the protein expression of p-tau Ser198 and GSK-3βwas increased (P<0.05) and that of PP2A decreased (P<0.05). When compared with the model group, in the western medication group and the acupuncture group, the MWM escape latency was shortened (P<0.05), the crossing frequency and the quadrant stay time in original platform were increased (P<0.05), and DI got higher (P<0.05); the hippocampal cell numbers were elevated and the cells arranged regularly, the damage of hippocampal neuronal structure was attenuated and the numbers of Nissl bodies were increased; the protein expression of p-tau Ser198 and GSK-3β was reduced (P<0.05) and that of PP2A was increased (P<0.05). There were no statistically significant differences in the above indexes between the acupuncture group and the western medication group (P>0.05).@*CONCLUSION@#Acupuncture therapy of "benefiting mental health and regulating the spirit" could improve the learning and memory function and alleviate neuronal injure of AD model rats. The effect mechanism of this therapy may be related to the down-regulation of GSK-3β and the up-regulation of PP2A in the hippocampus, and then to inducing the inhibition of tau protein phosphorylation.

Comparative study of the inflammatory factor in patients with COPD in different traditional Chinese medicine syndrome / 中国医师杂志

Objective:The changes of serum inflammatory factors in patients with chronic obstructive pulmonary disease (COPD) with different traditional Chinese medicine (TCM) syndrome types were compared, and the characteristics and significance of inflammatory factors in COPD were discussed from the perspective of traditional Chinese and western medicine.Methods:A total of 100 patients with COPD who met the inclusion criteria and were admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2021 to September 2022 were selected and divided into phlegm turbation obstructing lung group ( n=50) and lung and kidney qi deficiency group ( n=50) according to TCM syndrome types. Twenty healthy subjects in the same period were selected as control group. Serum levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and other inflammatory factors were compared in each group. Results:The MCP-1, IL-6, ESR, CRP, white blood cell count (WBC) and procalcitonin (PCT) of COPD patients in phlegm turbation obstructing lung group were significantly higher than those in lung and kidney qi deficiency group (all P<0.05). The WBC, MCP-1, MIP-1α, IL-6, ESR and CRP of COPD patients in the lung and kidney qi deficiency group were significantly higher than those in the control group (all P<0.05). In the phlegm turbation obstructing lung group, the MIP-1α, MCP-1, IL-6, ESR, CRP, WBC, and PCT were significantly higher than those in the control group (all P<0.05). Conclusions:Patients with COPD have inflammatory reactions, and the inflammatory reactions of patients with phlegm turbation obstructing lung syndrome are more obvious than those with lung and kidney qi deficiency syndrome. The inflammatory factors MCP-1, MIP-1α, IL-6, ESR, CRP, WBC, PCT and other indicators could be used to judge the degree of COPD inflammation, which had certain clinical guiding significance for different syndrome types of COPD patients.

Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

Litchi chinensis seed prevents obesity and modulates the gut microbiota and mycobiota compositions in high-fat diet-induced obese zebrafish.

Obesity continues to be a global public health challenge. Litchi chinensis seed is rich in bioactive ingredients with pharmacological effects, such as hypoglycemic activity and anti-oxidation. This study aimed to assess the potential anti-obesity effects of L. chinensis seed and the changes of gut microbiota and mycobiota compositions in obese zebrafish induced by a high-fat diet. The anti-obesity effects were supplemented and validated in high-fat diet-induced obese mice. In this study, various chemical components of L. chinensis seed water and ethanol extracts were detected using UHPLC-QE-MS, and both extracts showed strong in vitro antioxidant activities. Network pharmacology analysis showed the potential of the extracts to improve obesity. Litchi chinensis seed powder, water and ethanol extracts decreased the weight of obese zebrafish, improved lipid accumulation and lipid metabolism, regulated appetite, and inhibited cell apoptosis and inflammation of the liver and intestine. They showed similar effects in obese mice, and also reduced the weight of fat tissues, regulated insulin resistance and glucose metabolism, and improved the intestinal barrier. Additionally, L. chinensis seed modulated the compositions of gut microbiota and mycobiota in zebrafish, with the regulation of the proportion of bacteria that produce short-chain fatty acids or affect intestine health, including Cetobacterium, Trichococcus, Aeromonas, Staphylococcus, and Micrococcaceae, and the proportion of fungi that produce mycotoxins or have special metabolic capacities, including Penicillium, Candida, Rhodotorula, and Trichoderma. Spearman's correlation analysis revealed the potential link between zebrafish obesity parameters, gut bacteria and fungi. Overall, these findings indicated that L. chinensis seed effectively improved obesity.

Expert Consensus on Sepsis Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

To give full play to the therapeutic advantages of traditional Chinese medicine （TCM） in sepsis， clarify the entry point of integrated TCM and western medicine， further standardize the clinical treatment of TCM， develop a recognized and integrated treatment protocol of TCM and western medicine， and improve the clinical efficacy on sepsis，the Chinese Association of Chinese Medicine organized TCM and western medicine experts specialized in sepsis treatment to conduct in-depth discussions on the advantages of TCM and integrated TCM and western medicine in the treatment of sepsis based on the TCM etiology and pathogenesis of sepsis， a representative acute and critical disease. They emphasized the pathogenesis characteristics of asthenia of healthy Qi and sthenia of pathogenic factors and summarized the roles of Chinese medicine in correcting the imbalance of inflammatory response， improving blood coagulation dysfunction， and relieving organ damage. Furthermore， they proposed the treatment protocol with integrated TCM and western medicine， which is expected to provide references for actual clinical treatment and scientific research.

Efficacy evaluation of acupuncture combined with acupoint application in the treatment of intestinal dysfunction secondary to mechanical ventilation in elderly patients with emergency sepsis / 中国医师杂志

Objective:To compare the efficacy of conventional Western medicine alone and acupuncture combined with acupoint application in treating intestinal dysfunction secondary to mechanical ventilation in elderly patients with emergency sepsis.Methods:A retrospective analysis was performed on 111 elderly patients with mechanical ventilation for sepsis admitted to the emergency department of Dongzhimen Hospital of Beijing University of Chinese Medicine from January 2019 to June 2021. They were divided into two groups according to the time of admission: Western medicine treatment group alone (patients from January 2019 to December 2019, n=47) and acupuncture combined with acupoint application group (patients from January 2020 to June 2021, n=64). Acupuncture combined with acupoint application group was treated with acupuncture combined with acupoint application on the basis of conventional Western medicine. The intestinal dysfunction score, abdominal circumference and mortality after 4 weeks were compared between the two groups. Results:The abdominal circumference and intestinal dysfunction score in acupuncture combined with acupoint application group were significantly lower than those before treatment [(100.56±9.34)cm vs (106.25±9.74)cm; (0.92±0.72)point vs (2.31±0.69)point, all P< 0.05], while there was no significant difference in the above indexes before and after treatment in the Western medicine treatment group (all P>0.05). The abdominal circumference, intestinal dysfunction score and mortality after 4 weeks in the acupuncture combined with acupoint application group were significantly lower than those in the Western medicine treatment group [(100.56±9.34)cm vs (108.09±10.52)cm; (0.92±0.72)point vs (2.43±0.62)point; (29.7%, 19/64) vs (48.9%, 23/47), all P<0.05]. Conclusions:The curative effect of acupuncture combined with acupoint application in the treatment of intestinal dysfunction secondary to mechanical ventilation in elderly patients with sepsis in emergency is better than that of routine treatment of Western medicine alone. The gastrointestinal function and prognosis of patients have been significantly improved, which is worthy of clinical promotion.

Quality value transmitting of substance benchmarks in Danggui Buxue Decoction / 中国中药杂志

To clarify the key quality attributes of substance benchmarks in Danggui Buxue Decoction(DBD), this study prepared 21 batches of DBD substance benchmarks, and established two methods for detecting their fingerprints, followed by the identification of peak attribution and similarity range as well as the determination of extract and transfer rate ranges and contents of index components ferulic acid, calycosin-7-O-β-D-glucoside, and astragaloside Ⅳ. The mass fractions and transfer rates of DBD substance benchmarks from different batches were calculated as follows: ferulic acid(index component in Angelicae Sinensis Radix): 0.037%-0.084% and 31.41%-98.88%; astragaloside Ⅳ(index component in Astragali Radix): 0.021%-0.059% and 32.18%-118.57%; calycosin-7-O-β-D-glucoside: 0.002%-0.023% and 11.51%-45.65%, with the extract rate being 18.4%-36.1%. The similarity of fingerprints among 21 batches of DBD substance benchmarks was all higher than 0.9. The quality control method for DBD substance benchmarks was preliminarily established based on the HPLC fingerprint analysis and index component determination, which has provided a basis for the subsequent development of DBD and the quality control of novel related preparations.

Research model integrating "both medicinal and adjuvant properties" for essential oils from Chinese medicinal: based on characterization of medicinal properties / 中国中药杂志

Essential oils(EOs) from Chinese medicinals, which can be used as adjuvants and exert certain therapeutic effect, are directly used in Chinese medicine formulas. Conventional research strategy for EOs from Chinese medicinals is to compare the efficacy of the prescriptions before and after the addition of EOs, and the penetration-enhancing mechanisms of EOs remain unclear. In modern research on EOs from Chinese medicinals, the method for studying chemical penetration enhancers is often used, which fails to reflect the overall efficacy of EOs. This study clarified the property regularity of EOs from Chinese medicinals as transdermal penetration enhancers, and thereby proposed a research model which integrated the medicinal and adjuvant properties of EOs from Chinese medicinals via "component-delivery-effect" characterization route. The core concept is that constituents of EOs from Chinese medicinals and their delivery process play a key role in their external application. This research model is expected to serve as a reference for further research on EOs from Chinese medicinals for transdermal application.

Predictive Biomarkers for Postmyocardial Infarction Heart Failure Using Machine Learning: A Secondary Analysis of a Cohort Study.

BACKGROUND: There are few biomarkers with an excellent predictive value for postacute myocardial infarction (MI) patients who developed heart failure (HF). This study aimed to screen candidate biomarkers to predict post-MI HF. METHODS: This is a secondary analysis of a single-center cohort study including nine post-MI HF patients and eight post-MI patients who remained HF-free over a 6-month follow-up. Transcriptional profiling was analyzed using the whole blood samples collected at admission, discharge, and 1-month follow-up. We screened differentially expressed genes and identified key modules using weighted gene coexpression network analysis. We confirmed the candidate biomarkers using the developed external datasets on post-MI HF. The receiver operating characteristic curves were created to evaluate the predictive value of these candidate biomarkers. RESULTS: A total of 6,778, 1,136, and 1,974 genes (dataset 1) were differently expressed at admission, discharge, and 1-month follow-up, respectively. The white and royal blue modules were most significantly correlated with post-MI HF (dataset 2). After overlapping dataset 1, dataset 2, and external datasets (dataset 3), we identified five candidate biomarkers, including FCGR2A, GSDMB, MIR330, MED1, and SQSTM1. When GSDMB and SQSTM1 were combined, the area under the curve achieved 1.00, 0.85, and 0.89 in admission, discharge, and 1-month follow-up, respectively. CONCLUSIONS: This study demonstrates that FCGR2A, GSDMB, MIR330, MED1, and SQSTM1 are the candidate predictive biomarker genes for post-MI HF, and the combination of GSDMB and SQSTM1 has a high predictive value.

Effectiveness and Safety of Acupoint Application of Guan Xin Su He Pill () for Patients with Chronic Stable Angina Pectoris: A Multi-Center, Randomized Controlled Trial.

OBJECTIVE: To assess the clinical effectiveness of acupoint application (AP) of Guan Xin Su He Pill (, GXSHP) for patients with chronic stable angina pectoris (CSAP). METHODS: This study was carried out in 3 local hospitals in Chengdu, China. After baseline evaluation, eligible patients were randomly assigned to the placebo application for acupoints (PAA) group or the herbal application for acupoints (HAA) group. Patients in the HAA group underwent AP with herbal powder, which was mainly GXSHP, and patients in the PAA group underwent AP with sham drugs. For each treatment session, unilateral acupoints including Neiguan (PC 6), Danzhong (RN 17), Xinshu (BL 15) and Jueyinshu (BL 14), were stimulated for both groups. AP was performed 3 times a week with a 2-day interval for 4 weeks. The primary outcome was the frequency of angina pectoris attacks per week, while the secondary outcomes included angina pain intensity measured by the Visual Analogue Scale (VAS), dose of rescue oral drugs (nitroglycerin), scores on the Seattle Angina Questionnaire (SAQ), Self-Rating Anxiety Scale scores (SAS) and Self-Rating Depression Scale scores (SDS). Clinical outcomes were measured at week 0, 4 and 8. The safety of AP of GXSHP treatment for CSAP were assessed. RESULTS: A total of 121 patients were enrolled. Baseline characteristics were comparable across the 2 groups. After treatment, the angina attack numbers in the HAA group were significantly reduced from 11.00 to 4.81 (P<0.05). While, for PAA group, the angina frequency was not significantly improved (baseline 10.55; post-treatment 11.05). The HAA group had significantly fewer angina attacks than the PAA group (P<0.05). Pain intensity measured by VAS in HAA group was significantly reduced from 4.06 to 3.02 (P<0.05). While, for PAA group, the VAS was significantly increased (baseline 3.62; post-treatment 3.96; P<0.05). Clinical outcomes showed better improvement after treatment in the HAA group than in the PAA group in terms of oral administration of rescue drugs, SAS, SDS and SAQ scores (P<0.05). The adverse events were also reported. CONCLUSION: AP of GXSHP is a safe and effective treatment for CSAP patients (Registration No. NCT02029118).

[Effect of acupuncture on hippocampal inflammation in rats with intrauterine distress induced hypoxic-ischemic brain injury].

OBJECTIVE: To observe the effects of acupuncture on the behavior, serum inflammatory cytokines, hippocampal Nod-like receptor protein 3(NLRP3) inflammasome-related proteins and microglia activation in rats with intrauterine distress induced ischemia-hypoxic brain injury (HIBD), so as to explore the mechanism of acupuncture underlying treatment of HIBD by regulating hippocampal inflammation. METHODS: The HIBD model was established by clipping bilateral uterine arteries for 10 min and delaying caesarean delivery. HIBD rats were randomly divided into model group and acupuncture group according to body weight and litter factors, with 12 rats in each group. Twelve rats delivered normally were regarded as the normal group. Acupuncture was applied to bilateral "Benshen"(GB13) for 10 min, once a day for 14 consecutive days. H.E. staining was used to observe the pathological changes of hippocampus. The three chamber sociability test was used to determine the rat's social ability. The serum IL-1ß and IL-18 levels, the hippocampal expressions of NLRP3, apoptosis associated speck like protein containing CARD(ASC) and cysteinyl aspartate specific proteinase-1(Caspase-1), andionized calcium bindingadaptor molecule-1(IBA-1) were detected by ELISA，Western blot and Immunofluorescence, separately. RESULTS: Compared with the normal group, The hippocampal neurons in the model group are arranged loosely, and the cells are solidified and shrunk and the whole cells are deeply stained. The time of exploring the stranger rat in the model group was significantly reduced (P<0.01). The contents of IL-1ß and IL-18, the expressions of NLRP3, ASC, Caspase-1 and IBA-1 of the model group were higher than those of the normal group (P<0.01, P<0.05, P<0.001). Following acupuncture intervention, the cell structure of hippocampal neurons was improved, and there were fewer cases of cell solidification, atrophy, and deep staining. In comparison with the model group, the time of exploring stranger rat in the acupuncture group was significantly increased (P<0.01). The contents of IL-1ß and IL-18, the expressions of NLRP3, ASC and Caspase-1, and IBA-1 of the acupuncture group were significantly down-regulated than those of the model group (P<0.01, P<0.05). CONCLUSION: Acupuncture can effectively improve the social behavior deficits of HIBD rats，which may be related to inhibition of the expression of inflammatory response proteins NLRP3, ASC and Caspase-1 in the hippocampus, decrease the activation of microglia in the hippocampus, and reduce serum IL-1ß and IL-18, thereby alleviating inflammation.

The Toxicity and Attenuation Methods of Toxic Chinese Materia Medica for its Reasonable Application: A Review.

Over a millennia, traditional Chinese medicine (TCM) has been used to treat various diseases in China. In recent years, more and more Chinese materia medica (CMM) have been studied in scientific research projects, applied in clinical practice, and their extracts have even appeared in some health products. However, the toxicity of some CMM is often overlooked, including hepatotoxicity, nephrotoxicity, neurotoxicity, cardiotoxicity, etc. In this review, the toxic components and their toxicological mechanisms of some toxic CMM were listed according to the chemical structure classification of toxic components. Afterwards, the traditional methods (processing and compatibility) and modern methods (structural modification, biotransformation, etc.) of attenuation of CMM were discussed. Since ancient times, it has been said that "fight fire with fire, fight poison with poison," and toxic CMM are of great significance in the treatment of difficult and severe diseases. The rational application of toxic CMM and their components in clinical practice was also exemplified in this review. While the pharmacological effects of TCMs have been emphasized, the scientific attenuation and rational application of toxic components should be concerned. We hope this review can provide a reference for future related research.

Identification and characterization of isocitrate dehydrogenase 1 (IDH1) as a functional target of marine natural product grincamycin B.

Grincamycins (GCNs) are a class of angucycline glycosides isolated from actinomycete Streptomyces strains that have potent antitumor activities, but their antitumor mechanisms remain unknown. In this study, we tried to identify the cellular target of grincamycin B (GCN B), one of most dominant and active secondary metabolites, using a combined strategy. We showed that GCN B-selective-induced apoptosis of human acute promyelocytic leukemia (APL) cell line NB4 through increase of ER stress and intracellular reactive oxygen species (ROS) accumulation. Using a strategy of combining phenotype, transcriptomics and protein microarray approaches, we identified that isocitrate dehydrogenase 1(IDH1) was the putative target of GCN B, and confirmed that GCNs were a subset of selective inhibitors targeting both wild-type and mutant IDH1 in vitro. It is well-known that IDH1 converts isocitrate to 2-oxoglutarate (2-OG), maintaining intracellular 2-OG homeostasis. IDH1 and its mutant as the target of GCN B were validated in NB4 cells and zebrafish model. Knockdown of IDH1 in NB4 cells caused the similar phenotype as GCN B treatment, and supplementation of N-acetylcysteine partially rescued the apoptosis caused by IDH1 interference in NB4 cells. In zebrafish model, GCN B effectively restored myeloid abnormality caused by overexpression of mutant IDH1(R132C). Taken together, we demonstrate that IDH1 is one of the antitumor targets of GCNs, suggesting wild-type IDH1 may be a potential target for hematological malignancies intervention in the future.