Zuogui Wan alleviates ovariectomy-induced osteoporosis by maintaining FoxO3 and increasing NK1R.

Sixty Sprague-Dawley female rats were randomly divided into sham-operated groups and five ovariectomy (OVX) subgroups. Rats subjected to sham and OVX were treated with the vehicle, alendronate, and Zuogui Wan (ZGW) at the doses of low, medium and high lyophilized powder daily for 3 months, respectively. The gene or protein expression of NK1R, PPAR γ, and OSX were assayed by either quantitative polymerase chain reaction or Western blot analysis. The results showed that compared with the OVX group, ZGW could reduce the level of PPARγ and increase the levels of OSX and. Meanwhile, ZGW could prevent bone loss. In addition, we found ZGW upregulated for the NK1R mRNA or protein expression by promoting the expression level of transcription factor FoxO3 and increasing its binding to the NK1R promoter region -700/-200 sequence. These results suggest that the regulation of FoxO3 and NK1R played a role and contributed to the mechanism of ZGW underlying the increase in bone mass in the OVX rat model.

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The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight.

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C18H16O8) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.

Zuogui Wan improves trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats by regulating orexin-A and orexin receptor.

OBJECTIVE: To investigate the protective effects of Zuogui Wan (ZGW) on bone loss induced by ovariectomy (OVX) and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model. METHODS: Fifty Sprague-Dawley female rats were randomly divided into sham-operated (sham) group and four OVX subgroups. Rats subjected to sham and OVX were treated with the vehicle (OVX, 1 mL/100 g weight, n = 10), 17ß-estradiol (E2, 50 µg*kg-1*d-1), and ZGW at the doses of 2.3 (ZGW-L) and 4.6 (ZGW-H) g/kg/day lyophilized powder daily for 3 months, respectively. The serum biochemical parameters of 17ß-estrogen (17ß-E2), tartrate-resistant acid phosphatase (TRACP-5b) and bone alkaline phosphatase (BALP) were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones. Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur. The gene or protein expression of orexin-A, orexin receptor 1 (OX1R), orexin receptor 2 (OX2R), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were assayed by either quantitative polymerase chain reaction or Western blot analysis. RESULTS: Compared with the OVX group, ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and17ß-E2 (P < 0.01). Meanwhile, ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number, and arranging the trabeculae structure properly. Compared with the OVX group, it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae, and OPG in the tibiae of ZGW groups (P < 0.01, < 0.05), while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae (P < 0.01). CONCLUSION: ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.

[Effect of thunder-fire moxibustion combined with vibration training on low back pain of primary osteoporosis].

OBJECTIVE: To compare the therapeutic effect of thunder-fire moxibustion combined with vibration training and simple vibration training on low back pain of primary osteoporosis by Young's modulus of ultrasonic wave, and seek an objective evaluating method. METHODS: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. The patients in the two groups were treated with vibration training using whole body vibration treatment bed. In the observation group, thunder-fire moxibustion was applied at Yaoyangguan (GV 3), Mingmen (GV 4), Ganshu (BL 18), Shenshu (BL 23) and Dachangshu (BL 25). The treatment was given once every other day, 3 times a week for 4 weeks. The visual analogue score (VAS), real-time shear wave elastography (RTSWE) and medical outcomes study 36-item short-form hearth survey (SF-36) were used to evaluate pain intensity, multifidus muscle tone (Young's modulus) and quality of life before treatment, after 4-week treatment and 1 month after treatment. RESULTS: Compared before treatment, the VAS scores, Young's modulus of multifidus muscle and 5 dimensions of SF-36 (physical condition, body pain, general health, social function and mental health) after 4-week treatment and 1 month after treatment were significantly improved in the two groups (all P<0.05), the physiological role in the observation group after 4-week treatment and 1 month after treatment were improved (both P<0.05). In the observation group, the VAS scores, Young's modulus of multifidus muscle and 3 dimensions of SF-36 (physiological role, body pain and general health) after 4-week treatment and 1 month after treatment were superior to the control group (all P<0.05). CONCLUSION: The therapeutic effect of thunder-fire moxibustion combined with vibration training is superior to simple vibration training in relieving low back pain intensity and multifidus muscle tone, and improving quality of life for primary osteoporosis. RTSWE technique can be an objective examination method to evaluate pain.

Mongolian Medicine echinops prevented postmenopausal osteoporosis and induced ER/AKT/ERK pathway in BMSCs.

Hormone replacement medicine such as traditional Chinese medicine has proven to be effective in decreasing the risk of osteoporosis. Mongolian medicine echinops prevents osteoporosis, but its mechanism remains unclear. In this study, we explored the mechanism underlying echinops prevents and treats postmenopausal osteoporosis. Osteoporosis model was established by ovariectomy in rats. Rats were treated to Echinops (16.26, 32.5, or 65 mg/kg/day) by oral gavage for 3 months. Bone mineral density (BMD) was detected by micro-CT detection of left proximal medial metaphyseal tibia. Hematoxylin and eosin (H&E) and toluidine blue O staining were also performed. Serum levels of E2, ALP and testosterone were examined. Bone marrow-derived bone marrow stem cells (BMSCs) were isolated and treated with echinops-containing serum. Estrogen receptors (ER) including ERα and ERß in bone specimens and BMSCs were detected by qRT-PCR. Cell viability and colon formation of BMSCs were detected. Expressions of ERα, ERß, AKT, p-AKT, ERK, and p-ERK in BMSCs were detected by western blot. Results showed that echinops significantly increased trabecular interconnectivity, thickness of trabeculae, and connection of trabecula. Echinops significantly increased BMD and E2, but significantly reduced ALP and testosterone in dose-dependent manners. Echinops induced ERα and ERß in both bone specimens and BMSCs. Echinops enhanced cell viability and ability of colony formation of BMSCs, and increased ERα, ERß, p-AKT, and p-ERK. Thus, Mongolian echinops reduced bone loss and delayed the occurrence and development of osteoporosis, and increased ERα, ERß, p-AKT, and P-ERK in BMSCs. These results provide experimental basis for clinical prevention and treatment of postmenopausal osteoporosis by echniops.

Effect of Zuoguiwan on osteoporosis in ovariectomized rats through RANKL/OPG pathway mediated by ß2AR.

ETHNOPHARMACOLOGICAL RELEVANCE: The deficiency of kidney Yin is the main pathogenesis of postmenopausal osteoporosis (PMOP) according to traditional Chinese medicine (TCM). Zuoguiwan (ZGW) is among the classical prescriptions in TCM and has been applied to various diseases that are due to deficiency of kidney Yin, including osteoporosis, fractures, menopausal syndromes. However, the underlying mechanism of ZGW in treating PMOP remains poorly understood. AIM OF THE STUDY: ZGW, a traditional Chinese prescription, has been used to nourish Yin and reinforce the kidney since ancient times. The investigation aimed to explore the mechanism of ZGW via the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway as mediated by the ß2-adrenergic receptor (ß2AR) in an osteoporosis rat model. MATERIALS AND METHODS: An osteoporosis model induced by ovariectomy was established in rats. A total of 40 female Sprague-Dawley rats were randomly assigned into bilateral ovariectomy group (OVX), sham operated group (Sham), 17ß-estradiol-treated positive group (E2, 25 µg/kg/d), ZGW low-dose group (ZGW-L, 2.3 g/kg/d lyophilized powder) and ZGW high-dose group (ZGW-H, 4.6 g/kg/d lyophilized powder). The serum markers of bone turnover were measured using enzyme-linked immunosorbent assay (ELISA). The morphological structure changes in bones were detected through H&E staining. Local bone mineral density (BMD) and trabecular bone microarchitecture of the right distal femur were measured and evaluated by using micro-CT. Furthermore, the mRNA and protein expressions levels of ß2AR, OPG and RANKL were measured by qPCR and Western blot analysis. RESULTS: Compared with the OVX group, ZGW groups showed significantly reduced levels of serum tartrate-resistant acid phosphatase 5b (TRACP-5b) and ß-cross-linked c-telopeptide of type I collagen (ß-CTX) (P ＜ 0.01), increased levels of serum bone-specific alkaline phosphatase (BALP) (P ＜ 0.01) and OPG (P ＜ 0.05), prevention of OVX-induced bone loss, and improved microarchitecture of the trabecular bone of distal femur. Moreover, ZGW mediated the osteoporosis syndrome by reducing the empty bone lacunae, promoting the ordered arrangement of trabeculae structure, and increasing the trabeculae structure thickness. Furthermore, in ZGW groups, the protein expression of OPG in the tibia was notably up-regulated (P ＜ 0.01), whereas the mRNA and protein expression of ß2AR in the hippocampus (P ＜ 0.01), and the protein expressions levels of ß2AR (P ＜ 0.01) and RANKL (P ＜ 0.05) in the tibia were down-regulated compared with OVX group. CONCLUSIONS: ZGW through its protective effects, stimulates bone formation and suppresses bone resorption. The underlying mechanism of ZGW in improving perimenopausal syndrome and increasing bone mass might be attributed to the regulation of RANKL/OPG, as mediated by ß2AR. Therefore, ZGW may be used as an alternative treatment for PMOP.

[Preventive Effect of Fangshuan Capsule on PCI-induced Myocardial Damage and Vascular Endo- thelial Injury in Patients with Unstable Angina Pectoris].

Objective To observe the prevention of Fangshuan Capsule (FC) on percutaneous coronary intervention (PCI) induced myocardial damage and vascular endothelial injury in patients with un- stable angina pectoris (UAP). Methods Totally 100 UAP patients undergoing PCI were assigned to the control group and the treatment group by random digit table, 50 in each group. All patients received routine Western medicine therapy. Those in the treatment group additionally took FC, 6 pills each time, three times per day for at least 2 days before PCI operation. The therapeutic course for each group was 2 weeks. The clinical therapeutic effect was observed in the two groups. Heart rate (HR), systolic blood pressure (SBP) , changes of myocardial oxygen consumption ( HR x SBP, kPa/min) were compared. The levels of serum troponin I (cTn 1), creatinine kinase-MB (CK-MB) , myoglobin (MYO) , endothelin (ET), and nitric oxide (NO) were measured before PCI, and 6, 12, 24 h, 3 and 7 days after PCI. Results The markedly effective rate of Chinese medical syndromes was 54% (17/50) and the total effective rate was 94% (47/50) in the treatment group, obviously higher than those of the control group [26% (13/50) and 88% (44/50) ; P <0. 01]. Compared with before treatment in the same group, HR, SBP, myocardial oxygen consumption, and plasma ET level were reduced, plasma NO level was elevated in two groups after treatment (P <0.05, P <0. 01). cTnl concentration increased at 6, 12, 24 h, and day 3 (P <0. 05, P <0. 01 ) ; CK-MB concentration was elevated at 6, 12, and 24 h (P <0. 05, P <0. 01) ; MYO concentration increased at 6 and 12 h (P < 0. 01) in the control group after treatment. cTnl concentration increased at 12 and 24 h (P <0. 05, P <0. 01); CK-MB concentration was elevated at 6 and 12 h (P <0. 05) ; MYO concentration increased at 6 h (P <0. 01) in the treatment group after treatment. Compared with the control group at the same time point, HR, myocardial oxygen consumption, and plasma ET level decreased (P <0. 05); cTnl decreased at 6, 12, and 24 h (P <0. 05); CK-MB concentration decreased at 12 h (P <0. 05); MYO concentration decreased at 6 and 12 h (P <0. 05) in the treatment group after treatment. Conclusion FC could effectively improve scores of Chinese medical syndromes after PCI surgery, reduce myocardial oxygen consumption, attenuate myocar- dial damage and vascular endothelial injury in UAP patients after PCI.