Associations of educational attainment with Sepsis mediated by metabolism traits and smoking: a Mendelian randomization study.

Objective: Sepsis constitutes a significant global healthcare burden. Studies suggest a correlation between educational attainment and the likelihood of developing sepsis. Our goal was to utilize Mendelian randomization (MR) in order to examine the causal connection between educational achievement (EA) and sepsis, while measuring the mediating impacts of adjustable variables. Methods: We collected statistical data summarizing educational achievement (EA), mediators, and sepsis from genome-wide association studies (GWAS). Employing a two-sample Mendelian randomization (MR) approach, we calculated the causal impact of education on sepsis. Following this, we performed multivariable MR analyses to assess the mediation proportions of various mediators, including body mass index (BMI), smoking, omega-3 fatty acids, and apolipoprotein A-I(ApoA-I). Results: Genetic prediction of 1-SD (4.2 years) increase in educational attainment (EA) was negatively correlated with sepsis risk (OR = 0.83, 95% CI 0.71 to 0.96). Among the four identified mediators, ranked proportionally, they including BMI (38.8%), smoking (36.5%), ApoA-I (6.3%) and omega-3 (3.7%). These findings remained robust across a variety of sensitivity analyses. Conclusion: The findings of this study provided evidence for the potential preventive impact of EA on sepsis, which may be influenced by factors including and metabolic traits and smoking. Enhancing interventions targeting these factors may contribute to reducing the burden of sepsis.

[Mechanism of protective effect of resveratrol on poor ovarian response in mice].

This study aims to investigate the therapeutic effects and potential mechanisms of resveratrol(Res) on poor ovarian response(POR) in mice. The common target genes shared by Res and POR were predicted by network pharmacology, used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and then validated by animal experiments. The mice with regular estrous cycle after screening were randomized into normal, POR, and low-and high-dose(20 and 40 mg·kg~(-1), respectively) Res groups. The normal group was administrated with an equal volume of 0.9% sodium chloride solution by gavage, and the mice in other groups with tripterygium glycosides suspension(50 mg·kg~(-1)) by gavage for 2 weeks. After the modeling, the mice in low-and high-dose Res groups were treated with Res by gavage for 2 weeks, and the mice in normal and POR groups with an equal volume of 0.9% sodium chloride solution by gavage. Ovulation induction and sample collection were carried out on the day following the end of treatment. Vaginal smears were collected for observation of the changes in the estrous cycle, the counting of retrieved oocytes, and the measurement of ovarian wet weight and ovarian index. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of anti-mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in the serum. The ovarian tissue morphology and granulosa cell apoptosis were observed by hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL), respectively. Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT), forkhead box O(FOXO) 3a, hypoxia-inducible factor(HIF)-1α, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). A total of 222 common targets shared by Res and POR were collected. GO annotation indicated that these targets were mainly involved in oxidative stress response. KEGG enrichment analysis revealed that Res can intervene in POR via PI3K/AKT, HIF-1, and FOXO signaling pathways. Animal experiments showed that the model group had higher rate of estrous cycle disorders, lower number and poorer morphology of normally developed follicles at all levels, more atretic follicles, higher apoptosis of ovarian granulosa cells, lower number of retrieved oocytes, lower ovarian wet weight and ovarian index, higher serum levels of FSH and LH, lower levels of AMH and E_2, higher expression levels of HIF-1α, FOXO3a and Bax, and lower expression levels of PI3K, AKT, and Bcl-2 in the ovarian tissue than the normal group. Compared with the POR group, low-and high-dose Res decreased the rate of estrous cycle disorders, improved the follicle number and morphology, reduced atretic follicles, promoted the apoptosis of ovarian granulosa cells, increased retrieved oocytes, ovarian wet weight and ovarian index, and lowered serum FSH and LH levels. Moreover, Res down-regulated the expression levels of HIF-1α, FOXO3a and Bax, and up-regulated the expression levels of PI3K, AKT and Bcl-2 in the ovarian tissue. In summary, Res can inhibit apoptosis and mitigate poor ovarian response in mice by regulating the PI3K/AKT/FOXO3a and HIF-1α pathways.

Comparison of Thyroglobulin and Thyroid Function in Pregnant Women between Counties with a Median Urinary Iodine Concentration of 100-149 µg/L and 150-249 µg/L.

Objective: This study explored whether thyroglobulin and thyroid disease prevalence rates were higher in pregnant Chinese women with a median urinary iodine concentration of 100-149 µg/L, compared with those with a median urinary iodine concentration of 150-249 µg/L maintained through sustainable universal salt iodization. Methods: This was a cross-sectional study in which 812 healthy pregnant women were enrolled to collect samples of their household edible salt, urine, and blood during their routine antenatal care in the 18 counties in Fujian Province, China. The levels of salt iodine concentration, urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody and thyroglobulin antibody were assessed during the routine antenatal care visits. Results: The median UIC (mUIC) in pregnant women was 130.8 µg/L (interquartile range = 91.5-198.1 µg/L) in the counties with an mUIC of 100-149 µg/L (Group I), and 172.0 µg/L (interquartile range = 123.5-244.4 µg/L) in the counties with an mUIC of 150-249 µg/L (Group II). Goiter prevalence and thyroid nodule detection rates showed no difference between Group I and Group II ( P > 0.05). Except for FT4 values, the TSH, FT4, FT3, Tg and Tg values > 40 (µg/L) and the thyroid diseases prevalence rate (TDR) showed no significant differences between Group I and Group II ( P > 0.05), whether or not iodine supplementation measures were taken. Conclusion: Compared with an mUIC of 150-249 µg/L, not only there was no difference in thyroid morphology, but also the Tg value, rate of Tg values > 40 µg/L, and TDR were not higher in pregnant women in the counties with an mUIC of 100-149 µg/L achieved through sustainable universal salt iodization in Fujian Province, China.

Three novel dalbergiphenol hybrids from the heartwood of Dalbergia cochinchinensis.

A novel discovery of two hybrid benzodioxepin-dalbergiphenol epimers, named cochindalbergiphenols A-B (1-2), and a benzofuran-dalbergiphenol hybrid, named cochindalbergiphenol C (3), were isolated and identified from the heartwood of Dalbergia cochinchinensis. The structures of all the isolated compounds were identified through NMR and HRESIMS techniques, while the absolute configurations were determined by comparing the experimental and calculated ECD spectra. Compounds 1-3 exhibited potential protective effects against hypoxia/reoxygenation (H/R) induced injury in H9c2 cells.

Scutellarein regulates the PTEN/AKT/NFκB signaling pathway to reduce pirarubicin related liver inflammation.

The side effects of chemotherapy drugs have been hindering the progress of tumor treatment. The liver is the metabolic site of most drugs, which leads to the frequent occurrence of liver injury. Classical chemotherapy drugs such as pirarubicin (THP) can also cause dose­dependent hepatotoxicity, and the related mechanism is closely related to liver inflammation. Scutellarein (Sc) is a potential Chinese herbal monomer exhibiting liver protection activity, which can effectively alleviate the liver inflammation caused by obesity. In the present study, THP was used to establish a rat model of hepatotoxicity, and Sc was used for treatment. The experimental methods used included measuring body weight, detecting serum biomarkers, observing liver morphology with H&E staining, observing cell apoptosis with TUNEL staining, and detecting the expression of PTEN/AKT/NFκB signaling pathways and inflammatory genes with PCR and western blotting. However, whether Sc can inhibit the liver inflammation induced by THP has not been reported. The experimental results showed that THP led to the upregulation of PTEN and the increase of inflammatory factors in rat liver, while Sc effectively alleviated the aforementioned changes. It was further identified in primary hepatocytes that Sc can effectively inhabited PTEN, regulate AKT/NFκB signaling pathway, inhibit liver inflammation and ultimately protect the liver.

Current role and future perspectives of electroacupuncture in circadian rhythm regulation.

In recent years, in-depth research on chronobiology has been conducted, and the circadian rhythm has become a new target for the treatment of diseases. Circadian rhythms are closely related to the normal physiological functions of organisms. Increasing evidence indicates that circadian rhythm disorders are the pathological basis of diseases such as sleep disorders, depression, cardiovascular diseases, and cancer. As an economical, safe, and effective treatment method, electroacupuncture has been widely used in clinical practice. In this paper, we summarize the current literature on electroacupuncture's regulation of circadian rhythm disorders and circadian clock genes. In addition, we briefly explore the optimization of electroacupuncture intervention programmes and the feasibility of implementing electroacupuncture intervention programmes at selected times in clinical practice. We conclude that electroacupuncture may have good application prospects in circadian rhythm regulation, but this conclusion needs to be confirmed by clinical trials.

A carrier-free nano-drug assembled via π-π stacking interaction for the treatment of osteoarthritis.

Osteoarthritis (OA) is considered to be the most common joint disorder. Exogenous drug intervention is one of the effective means for OA treatment. Clinical applications of numerous drugs are restricted owing to the short retention as well as rapid clearance in the joint cavity. A wide variety of carrier-based nanodrugs have been developed, but additional carriers may bring unexpected side effects or even toxicity. Herein, by exploiting the spontaneous fluorescence of Curcumin, we designed a new carrier-free self-assembly nanomedicine Curcumin (Cur)/icariin (ICA) nanoparticles with adjustable particle size, which is composed of two small-molecule natural drugs assembled via π-π stacking interaction. Experimental results revealed that Cur/ICA NPs endowed with little cytotoxicity, high cellular uptake and sustained drug release, could inhibit secretion of inflammatory cytokines and reduce cartilage degeneration. Moreover, both the in vitro and in vivo experiments showed the NPs exerted superior synergism effects in anti-inflammatory and cartilage protection than either Cur or ICA alone, and self-monitored its retention by autofluorescence. Thus, the new self-assembly nano-drug combining Cur and ICA represents a new strategy for the treatment of osteoarthritis.

[The specificity of body surface temperature of relevant back-shu points in patients with chronic persistent asthma based on infrared thermal imaging technology].

OBJECTIVE: To detect the body surface temperature of the relevant back-shu points in patients with chronic persistent asthma by infrared thermal imaging technology, and observe the specific changes of the body surface temperature of the relevant back-shu points under the condition of lung disease. METHODS: Forty-five patients with chronic persistent asthma (observation group) and 45 healthy subjects (control group) were selected. The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) were measured by BK-MT02A medical infrared thermography. RESULTS: The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in the observation group was higher than that in the control group (P<0.01, P<0.05). The body surface temperature of bilateral Feishu (BL 13) and Geshu (BL 17) was higher than that of ipsilateral Pishu (BL 20) and Shenshu (BL 23) in the two groups (P<0.01, P<0.05). There was no statistically significant difference in body surface temperature between ipsilateral Feishu (BL 13) and Geshu (BL 17), between ipsilateral Pishu (BL 20) and Shenshu (BL 23) (P>0.05). CONCLUSION: The pathological increase of body surface temperature of Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in patients with chronic persistent asthma indicates that above acupoints have specificity in reflecting lung diseases. The Feishu (BL 13) and Geshu (BL 17), which have significantly increased body surface temperature, not only provide objective basis for the pathological pathogenesis of "deficiency in origin and excess in symptom" in patients with chronic persistent asthma, but also reflect the different expressions of different acupoints on the same meridian for the lung diseases.

[UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood].

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Progress on traditional Chinese medicine in treatment of ischemic stroke via the gut-brain axis.

Ischemic stroke is a common issue that severely affects the human health. Between the central nervous system and the enteric system, the " Gut-Brain " axis, the bidirectional connection involved in the neuro-immuno-endocrine network, is crucial for the occurrence and development of ischemic stroke. Ischemic stroke can lead to change in the gut microbiota and gastrointestinal hormones, which will then reversely affect the disease development. Traditional Chinese Medicine (TCM) has unique advantages with reference to the treatment for ischemic stroke. The latest research revealed that a significant portion of medicines and prescriptions of TCM exert their therapeutic effects by improving the gut microbiota and regulating the secretion of gastrointestinal hormones. The present review summarized the Chinese medicines that play a therapeutic role in cerebral ischemia through regulating the "Gut-Brain" axis and described the corresponding mechanisms. This study attempts to provide reference for clinical selection of Chinese medicines and helps better understand the relevant mechanisms of action.

The specificity of body surface temperature of relevant back-shu points in patients with chronic persistent asthma based on infrared thermal imaging technology / 中国针灸

OBJECTIVE@#To detect the body surface temperature of the relevant back-shu points in patients with chronic persistent asthma by infrared thermal imaging technology, and observe the specific changes of the body surface temperature of the relevant back-shu points under the condition of lung disease.@*METHODS@#Forty-five patients with chronic persistent asthma (observation group) and 45 healthy subjects (control group) were selected. The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) were measured by BK-MT02A medical infrared thermography.@*RESULTS@#The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in the observation group was higher than that in the control group (P<0.01, P<0.05). The body surface temperature of bilateral Feishu (BL 13) and Geshu (BL 17) was higher than that of ipsilateral Pishu (BL 20) and Shenshu (BL 23) in the two groups (P<0.01, P<0.05). There was no statistically significant difference in body surface temperature between ipsilateral Feishu (BL 13) and Geshu (BL 17), between ipsilateral Pishu (BL 20) and Shenshu (BL 23) (P>0.05).@*CONCLUSION@#The pathological increase of body surface temperature of Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in patients with chronic persistent asthma indicates that above acupoints have specificity in reflecting lung diseases. The Feishu (BL 13) and Geshu (BL 17), which have significantly increased body surface temperature, not only provide objective basis for the pathological pathogenesis of "deficiency in origin and excess in symptom" in patients with chronic persistent asthma, but also reflect the different expressions of different acupoints on the same meridian for the lung diseases.

Kefir peptides promote osteogenic differentiation to enhance bone fracture healing in rats.

AIMS: Fractures are the result of fragile bone structures after trauma caused by direct or indirect external impact or strong muscular contraction. Most fracture patients undergo surgical fixation to accelerate the healing process and restore the function of mutilated bone. Promoting the healing process remains an important issue for the treatment of bone fractures. Our previous studies demonstrated the remarkable bone-protective effects of kefir peptides (KPs) in ovariectomized rats and mice. In this study, we further evaluate the efficacy of KPs on fracture healing using a rat model of femoral fracture. MAIN METHODS: Fifteen 8-week-old male Sprague Dawley (SD) rats were divided into the sham, mock, and KPs groups, in which the mock and the KPs groups underwent femur-fracture surgery with nail fixation, while the sham group underwent a sham operation. The next day, rats were orally administered with daily 400 mg/kg of KPs (KPs group) or distilled water (sham and mock groups) for four weeks. X-ray imaging, histochemical staining and serum osteogenic markers were applied for fracture healing evaluation. In vitro, mouse bone marrow mesenchymal stem cells (BMMSCs) and MC3T3-E1 line were subjected to osteoblast differentiation in the presence of KPs and compared with no KPs treatment. KEY FINDINGS: The results demonstrated that KPs treatment improved the progression of the fracture healing process (p < 0.05) and significantly increased the expressions of Col1a1, Alp, Spp1, Vegfa and Cox2 mRNA in the femurs of the KPs-treated fractured rats compared to those of the mock-treated fracture rats. In vitro, KPs treatment promoted bone regeneration factor (Col1a1, Alp, M-csf and Phospho1) expression in MC3T3-E1-derived osteoblast cultures (on Day 3) and enhanced osteogenic differentiation and mineralization in BMMSC-derived osteoblast cultures (on Day 17 and Day 21). SIGNIFICANCE: This is the first study to show that KPs can help with fracture healing by promoting osteogenic differentiation, and it also suggests that KPs can be used as a nutritional supplement to accelerate fracture healing.

[Effects of thunder-fire moxibustion on the motor function in the patients of osteoporosis with low skeletal muscle mass： a randomized controlled trial].

OBJECTIVE: To observe the effects of thunder-fire moxibustion on the visual analogue scale (VAS) score, Young's modulus of multifidus and 6 m walking speed in the patients of osteoporosis with low skeletal muscle mass. METHODS: Sixty patients of osteoporosis with low skeletal muscle mass were randomly divided into a medication group (30 cases) and a medication+thunder-fire moxibustion group (30 cases). In the medication group, caltrate was prescribed for oral administration, 2 tablets/day （600 mg/tablet）, for 4 weeks. In the medication+thunder-fire moxibustion group, on the base of oral administration with caltrate, thunder-fire moxibustion was exerted at Mingmen (GV4), Yaoyangguan(GV3), and bilateral Shenshu (BL23), Ganshu (BL18) and Dachangshu (BL25), 30 minutes at GV4, GV3 and BL18, and another 30 minutes at BL23 and BL25, once every other day, 3 times a week for 4 weeks. Before and after the treatment, VAS score, Young's modulus of the 4th lumbar multifidus and the average speed of 6 m walking were assessed. RESULTS: After the treatment, the VAS score was decreased (P<0.05, P<0.01) and the speed of 6 m walking was increased (P<0.05, P<0.01) in both groups in comparison with their own pre-treatment. Compared with the medication group, VAS score was decreased remarkably (P<0.05) and the speed of 6 m walking remarkably increased (P<0.01) in the medication+thunder-fire moxibustion group after the treatment. Self-comparison showed that, compared with the same side before the treatment, the value of Young's modulus after the treatment was decreased on both sides in the medication+thunder-fire moxibustion group (P<0.01). After the treatment, compared with the medication group on the same side, the value of Young's modulus was decreased on both sides (P<0.01) in the medication+thunder-fire moxibustion group. CONCLUSION: Thunder-fire moxibustion can relieve pain intensity, decrease the tension of the multifidus, and increase the walking speed.

Acupuncture combined with metformin versus metformin alone to improve pregnancy rate in polycystic ovary syndrome: A systematic review and meta-analysis.

Objective: The aim of this study was to evaluate the comparison between acupuncture combined with metformin versus metformin alone in improving the pregnancy rate of people with polycystic ovary syndrome (PCOS). Methods: A literature search of eight databases resulted in nine randomized controlled trials (RCTs) that assessed the effect of acupuncture combined with metformin on pregnancy rate in PCOS patients compared with metformin alone. Subsequently, data extraction and analysis were conducted to evaluate the quality and risk of bias of the methodological design of the study, and meta-analysis was conducted on the RCT data. Results: Nine RCTs and 1,159 women were included. Acupuncture can improve pregnancy rate. It was analyzed according to the diagnostic criteria of PCOS [Z = 2.72, p = 0.007, relative risk (RR) 1.31, 95% CI 1.08 to 1.60, p = 0.15, I 2 = 41%]. Analysis was performed according to different diagnostic criteria of pregnancy (Z = 3.22, p = 0.001, RR 1.35, 95% CI 1.13 to 1.63, p = 0.12, I 2 = 42%). Acupuncture can improve ovulation rate. Subgroup analysis was performed according to the number of ovulation patients (Z = 2.67, p = 0.008, RR 1.31, 95% CI 1.07 to 1.59, p = 0.04, I 2 = 63%) and ovulation cycle (Z = 3.57; p = 0.0004, RR 1.18, 95% CI 1.08 to 1.29, p = 0.57, I 2 = 0%). Statistical analysis also showed that acupuncture combined with metformin could improve homeostatic model assessment of insulin resistance (HOMA-IR) [mean difference (MD) -0.68, 95% CI -1.01 to -0.35, p = 0.003, I 2 = 83%]. Conclusions: Based on the results of this study, compared with metformin alone, acupuncture combined with metformin has a positive effect on pregnancy rate, ovulation rate, and insulin resistance in PCOS. However, due to the limitations regarding the number and quality of the included studies, the above conclusions need to be verified by further high-quality studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero.

[Effect of moxibustion of "Ganshu"(BL18) and "Shenshu" (BL23) on musculoskeletal interaction in osteoporosis rats].

OBJECTIVE: To observe the effect of moxibustion of "Ganshu" (BL18)and "Shenshu" (BL23) on bone mineral density (BMD), biomechanics, bone metabolism and musculoskeletal morphology of osteoporosis (OP) rats, so as to explore its mechanism underlying treatment of OP via bone-muscle interaction. METHODS: Thirty-two female SD rats were randomly divided into sham operation, OP model, moxibustion and medication (nilestriol) groups, with 8 rats in each group. For rats of the sham operation group, a small amount of fat around the ovaries was removed, and those of the other 3 groups received removal of bila-teral ovaries for establishing OP model. Moxibustion was applied to bilateral BL18 and BL23 for 30 min, once every other day, 3 times a week for 12 weeks. Rats of the medication group received gavage of nilestriol (1 mg/kg) once a week for 12 weeks.After the interventions, a dual-energy absorptiometry was used to determine the BMD and bone mineral content of the rats' right femur and the fourth lumbar vertebrae under anesthesia, and three-point bending test used to detect the biomechanical properties (including load, displacement, stiffness) of the right femur. The levels of serum type I collagen C-terminal peptide (CTX-I), acid-resis-tant tartrate phosphatase (TRACP) and estradiol (E2) were determined using enzyme-linked immunosorbent assay, and histopathological changes of the left femur and the quadriceps observed after hematoxylin-eosin (H.E.) staining. RESULTS: Compared with the sham operation group, the BMD and bone mineral contents of the right femur and the fourth lumbar vertebra, the load and stiffness of the right femur, and concentration of serum E2 were significantly decreased (P<0.01, P<0.05), and the displacement of the right femur, and concentrations of serum CTX-Ⅰ and TRACP notably increased in the model group (P<0.01). After the interventions, the decreased levels of BMD and bone mineral contents, the load and stiffness and concentration of serum E2, and the increased levels of the displacement, and concentrations of serum CTX-Ⅰ and TRACP were all reversed by both moxibustion (except the bone mineral content of the fourth lumbar vertebra) and medication (P<0.01,P<0.05). No signi-ficant differences were found between moxibustion and medication in up-regulating the levels of BMD and bone mineral contents, the load and stiffness (except serum E2) and down-regulating the levels of the displacement, and concentrations of serum CTX-Ⅰ and TRACP (P>0.05). H.E. staining revealed that rats in the sham operation group showed mild thinness of the bone cortex, uneven thickness of trabecular bone, with distortion, fracture and osteoporosis of the left femur, and different size of rhabdomyocytes in the right quadriceps femoris muscle, with obvious proliferation of interstitial fibrous tissue and inflammatory cell infiltration, which were relatively and clearly milder in both moxibustion and medication groups. CONCLUSION: Moxibustion of BL18 and BL23 can increase the BMD and bone mineral content, improve biomechanical performance, adjust bone metabolism, and mitigate bone and the attached muscle histopathological changes in OP rats, suggesting that modulating interaction between bones and muscles is probably one of the ideas in the treatment of OP.

Acupuncture Modulates the Spontaneous Activity and Functional Connectivity of Calcarine in Patients With Chronic Stable Angina Pectoris.

Background: Acupuncture is an effective adjunctive therapy for chronic stable angina pectoris (CSAP), while the underlying mechanism is unclear. This study aimed to investigate the central pathophysiology of CSAP and explore the mechanism of different acupoint prescriptions for CSAP from the perspective of brain-heart interaction. Methods: Thirty-seven CSAP patients and sixty-five healthy subjects (HS) were enrolled, and thirty CSAP patients were divided into two acupoint prescriptions groups (Group A: acupoints on the meridian directly related to the Heart; Group B: acupoints on the meridian indirectly related to the Heart). The Magnetic Resonance Imaging data and clinical data were collected at baseline and after treatment. The comparisons of brain spontaneous activity patterns were performed between CSAP patients and HS, as well as between baseline and after treatment in CSAP patients. Then, the changes in resting-state functional connectivity before and after treatment were compared between the two acupoint prescriptions. Results: Chronic stable angina pectoris patients manifested higher spontaneous activity on the bilateral calcarine, left middle occipital gyrus, right superior temporal gyrus, and right postcentral gyrus. After acupuncture treatment, the spontaneous activity of the left calcarine, left cuneus, and right orbitofrontal gyrus was decreased. The left calcarine was identified as region-of-interest for functional connectivity analysis. Compared with group B, CSAP patients in group A had significantly increased functional connectivity between left calcarine and the left inferior temporal gyrus/cerebellum crus 1, left hippocampus, left thalamus, and left middle cingulate cortex after treatment. Thresholds for all comparisons were p < 0.05, Gaussian Random Field corrected. Conclusion: Regulating the aberrant spontaneous activity of the calcarine might be an underlying mechanism of acupuncture for CSAP. The multi-threaded modulation of functional connectivity between calcarine and multiple pain-related brain regions might be a potential mechanism for better efficacy of acupuncture at points on the meridian directly related to the Heart.

Therapeutic Effects of Kefir Peptides on Hemophilia-Induced Osteoporosis in Mice With Deficient Coagulation Factor VIII.

Osteoporosis is a clinically prevalent comorbidity in patients with hemophilia. A preventive effect of kefir peptides (KPs) on postmenopausal osteoporosis has been proved. The aim of this study was to evaluate the therapeutic effect of KPs for the treatment of osteoporosis in coagulation factor VIII (FVIII) gene knockout mice (F8KO), a model of hemophilia A. In this study, male F8KO mice at 20 weeks of age were orally administered different doses of KPs for 8 weeks. The therapeutic effects of KPs were shown in the femoral trabeculae and the 4th lumbar vertebrae, which increased the trabecular bone mineral density (BMD), bone volume (Tb.BV/TV), and trabecular number (Tb.N) and decreased the trabecular separation (Tb.Sp), and they were also observed in the femoral cortical bones, in which the mechanical properties were enhanced in a dose-dependent manner. Characterization of receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and interleukin 6 (IL-6) demonstrated that the serum RANKL/OPG ratio and IL-6 levels were significantly decreased in the F8KO mice after the KP treatment. Tartrate-resistant acid phosphatase (TRAP) staining of mature osteoclasts indicated that the therapeutic effect of KPs in F8KO mice was associated with the functions of KPs to inhibit RANKL-induced osteoclastogenesis by reducing serum RANKL/OPG ratio and IL-6 secretion. The present study is the first to address the potentials of KPs for the treatment of hemophilia-induced osteoporosis in mice and it also provides useful information for the application of KPs as a complementary therapy for the treatment of osteoporosis in hemophilic patients.

[Quality evaluation of Dalbergiae Odoriferae Lignum by HPLC fingerprint and multi-component quantitative analysis].

The present study detected the component content in Dalbergiae Odoriferae Lignum by HPLC fingerprint and the multi-component determination method. HPLC analysis was performed on the Agilent ZORBAX SB-C_(18) column(4.6 mm×250 mm, 5 µm). Acetonitrile-0.5% phosphoric acid aqueous solution with gradient elution was employed as the mobile phase. The flow rate was 1.0 mL·min~(-1) and the column temperature was maintained at 30 ℃. The detection wavelength was 210 nm and the sample volume was 10 µL. The similarity of 18 batches of Dalbergiae Odoriferae Lignum was 0.343-0.779, indicating that there were great differences between different batches of Dalbergiae Odoriferae Lignum. Eighteen common peaks were identified, including eight flavonoids such as liquiritigenin and latifolin. The mass fractions of liquiritigenin, luteolin, naringenin, isoliquiritigenin, formononetin, dalbergin, latifolin, and pinocembrin were in the ranges of 0.134 1%-0.495 2%, 0.028 2%-0.167 0%, 0.016 3%-0.591 3%, 0.053 5%-0.188 0%, 0.142 4%-0.640 1%, 0.068 0%-0.590 7%, 0.003 2%-1.980 7%, and 0.009 6%-0.740 2%, respectively. Eighteen batches of Dalbergiae Odoriferae Lignum were divided into three categories by cluster analysis and eight differential components in Dalbergiae Odoriferae Lignum were marked by partial least-squares discriminant analysis(PLS-DA). The cumulative variance contribution rate was 90.5%. The HPLC fingerprint combined with the multi-component determination method for Dalbergiae Odoriferae Lignum is easy in operation and accurate in results, with good repeatability and reliability. The quality of Dalbergiae Odoriferae Lignum can be evaluated and analyzed by the PLS-DA model. This study is expected to provide a reference for the quality control and clinical application of Dalbergiae Odoriferae Lignum.

[Components of drugs in acupoint sticking therapy and its mechanism of intervention on bronchial asthma based on UPLC-Q-TOF-MS combined with network pharmacology and experimental verification].

UPLC-Q-TOF-MS combined with network pharmacology and experimental verification was used to explore the mechanism of acupoint sticking therapy(AST) in the intervention of bronchial asthma(BA). The chemical components of Sinapis Semen, Cory-dalis Rhizoma, Kansui Radix, Asari Radix et Rhizoma, and Zingiberis Rhizoma Recens were retrieved from TCMSP as self-built database. The active components in AST drugs were analyzed by UPLC-Q-TOF-MS, and the targets were screened out in TCMSP and Swiss-TargetPrediction. Targets of BA were collected from GeneCards, and the intersection of active components and targets was obtained by Venny 2.1.0. The potential targets were imported into STRING and DAVID for PPI, GO, and KEGG analyses. The asthma model induced by house dust mite(HDM) was established in mice. The mechanism of AST on asthmatic mice was explored by pulmonary function, Western blot, and flow cytometry. The results indicated that 54 active components were obtained by UPLC-Q-TOF-MS and 162 potential targets were obtained from the intersection. The first 53 targets were selected as key targets. PPI, GO, and KEGG analyses showed that AST presumedly acted on SRC, PIK3 CA, and other targets through active components such as sinoacutine, sinapic acid, dihydrocapsaicin, and 6-gingerol and regulated PI3 K-AKT, ErbB, chemokine, sphingolipid, and other signaling pathways to intervene in the pathological mechanism of BA. AST can improve lung function, down-regulate the expression of PI3 K and p-AKT proteins in lung tissues, enhance the expression of PETN protein, and reduce the level of type Ⅱ innate immune cells(ILC2 s) in lung tissues of asthmatic mice. In conclusion, AST may inhibit ILC2 s by down-regulating the PI3 K-AKT pathway to relieve asthmatic airway inflammation and reduce airway hyperresponsiveness.

Seabuckthorn polysaccharide ameliorates high-fat diet-induced obesity by gut microbiota-SCFAs-liver axis.

Obesity has been reported to be associated with gut microbiome dysbiosis. seabuckthorn fruits have traditionally been used in Tibetan foods and medicines for thousands of years. Seabuckthorn polysaccharide (SP) is one of the main functional components in seabuckthorn fruits. However, the effects of SP on a high-fat diet (HFD)-induced obesity have not yet been elucidated. The purpose of this study is to explore the amelioration effect of SP on obesity induced by HFD and to reveal its mechanism of gut microbiota and its metabolites. Results showed that 12-week SP (0.1%, w/w) dietary supplementation could significantly reduce body weight gain, serum lipid level and liver triglycerides level in obese mice. Notably, the SP treatment elevated p-AMPKα and PPARα proteins expression stimulated the phosphorylation of ACC1 and inhibited the protein expression of FAS, PPARγ, and CD36 in the mice liver. Further, SP also reorganized the gut microbiome by up-regulating the proportion of Muribaculaceae_unclassified, Bifidobacterium, Rikenellaceae_RC9_gut_group, Alistipes, and Bacteroides, and down-regulating the abundance of Lactobacillus, Firmicutes_unclassified, Dubosiella Bilophila, and Streptococcus in HFD-induced obese mice. Moreover, the production of microbial metabolites short-chain fatty acids (SCFAs) in feces has also increased. In addition, correlation analysis results showed that obesity-ameliorating effects of SP were highly associated with levels of SCFAs in feces. Therefore, the regulation of SP on liver lipid metabolism may be due to the variation of the gut microbiome and raised production of SCFAs. These results indicate that SP could play the part of a potential nutraceutical for ameliorating obesity through regulation of the gut-liver axis.