Network pharmacology analysis and animal experiment validation of neuroinflammation inhibition by total ginsenoside in treating CSM.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a degenerative pathology that affects both upper and lower extremity mobility and sensory function, causing significant pressure on patients and society. Prior research has suggested that ginsenosides may have neuroprotective properties in central nervous system diseases. However, the efficacy and mechanism of ginsenosides for CSM have yet to be investigated. PURPOSE: This study aims to analyze the composition of ginsenosides using UPLC-MS, identify the underlying mechanism of ginsenosides in treating CSM using network pharmacology, and subsequently confirm the efficacy and mechanism of ginsenosides in rats with chronic spinal cord compression. METHODS: UPLC-Q-TOF-MS was utilized to obtain mass spectrum data of ginsenoside samples. The chemical constituents of the samples were analyzed by consulting literature reports and relevant databases. Ginsenoside and CSM targets were obtained from the TCMSP, OMIM, and GeneCards databases. GO and KEGG analyses were conducted, and a visualization network of ginsenosides-compounds-key targets-pathways-CSM was constructed, along with molecular docking of key bioactive compounds and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenosides on CSM. Chronic spinal cord compression rats were intraperitoneally injected with ginsenosides (50 mg/kg and 150 mg/kg) and methylprednisolone for 28 days, and motor function was assessed to investigate the therapeutic efficacy of ginsenosides for CSM. The expression of proteins associated with TNF, IL-17, TLR4/MyD88/NF-κB, and NLRP3 signaling pathways was assessed by immunofluorescence staining and western blotting. RESULTS: Using UPLC-Q-TOF-MS, 37 compounds were identified from ginsenoside samples. Furthermore, ginsenosides-compounds-key targets-pathways-CSM visualization network indicated that ginsenosides may modulate the PI3K-Akt signaling pathway, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway and Apoptosis by targeting AKT1, TNF, MAPK1, CASP3, IL6, and IL1B, exerting a therapeutic effect on CSM. By attenuating neuroinflammation through the TNF, IL-17, TLR4/MyD88/NF-κB, and MAPK signaling pathways, ginsenosides restored the motor function of rats with CSM, and ginsenosides 150 mg/kg showed better effect. This was achieved by reducing the phosphorylation of NF-κB and the activation of the NLRP3 inflammasome. CONCLUSIONS: The results of network pharmacology indicate that ginsenosides can inhibit neuroinflammation resulting from spinal cord compression through multiple pathways and targets. This finding was validated through in vivo tests, which demonstrated that ginsenosides can reduce neuroinflammation by inhibiting NLRP3 inflammasomes via multiple signaling pathways, additionally, it should be noted that 150 mg/kg was a relatively superior dose. This study is the first to verify the intrinsic molecular mechanism of ginsenosides in treating CSM by combining pharmacokinetics, network pharmacology, and animal experiments. The findings can provide evidence for subsequent clinical research and drug development.

A comprehensive and systematic review of the potential neuroprotective effect of quercetin in rat models of spinal cord injury.

CONTEXT: Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid. OBJECTIVE: This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research. DATA SOURCES: PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI. STUDY SELECTION: Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality. RESULTS: In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days (p < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females (p = 0.008). Quercetin was also associated with improved inclined plane test score (p = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA (p < 0.0001) and MPO (p = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased (p = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI. CONCLUSIONS: Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI.

Efficacy of five-step shoulder manipulation for rotator cuff-related shoulder pain: protocol for a multicenter randomized controlled trial.

BACKGROUND: Rotator cuff-related shoulder pain (RCRSP) is the most common cause of shoulder disorders. In China, manipulation has been used extensively for the treatment of patients with RCRSP. However, high-quality clinical evidence to support the therapeutic effect of manipulation is still limited. METHODS: A multicenter, participant-, outcome assessor-, and data analyst-blinded, randomized, placebo-controlled trial will be conducted. A total of 280 participants with RCRSP will be recruited from three hospitals and randomly assigned to a five-step shoulder manipulation (FSM) group or a sham manipulation (SM) group. Each group will receive four weekly treatment sessions, with all participants performing exercises at home for 12 weeks. Assessments, namely the Constant-Murley score, visual analog scale, range of motion, and 36-Item Short Form Survey, will be made at baseline, 4, 12, 18, and 24 weeks. Adverse events during the study will also be recorded. DISCUSSION: This is a pragmatic clinical trial to evaluate the efficacy and safety of FSM in patients with RCRSP. The findings of this study will provide worthy clinical evidence for manual therapy for RCRSP. TRIAL REGISTRATION: China Registered Clinical Trial Registration Center ChiCTR2000037577. Registered on 29 August 2020.

[Design and application of a new type of fascia stretching cup].

In order to comprehensively stretch human fascia, adjust the biomechanical balance of fascia system and promote the recovery of physiological function of fascia, a new type of fascia stretching cup is designed. This design is composed of two or more silica gel cups and elastic stretching belts between cups. The bottom surface of the silica gel cup has an annular exhaust groove, which can increase the adsorption capacity of the cup to the skin. In the meanwhile, a removable magnet is placed in the groove at the top of each silica gel cup to assist analgesia. This design is suitable for the prevention and treatment of acute and chronic tendon and bone diseases with imbalance of meridians and tendons.

Identification of a Novel 2,8-Diazaspiro[4.5]decan-1-one Derivative as a Potent and Selective Dual TYK2/JAK1 Inhibitor for the Treatment of Inflammatory Bowel Disease.

In this study, we described a series of 2,8-diazaspiro[4.5]decan-1-one derivatives as selective TYK2/JAK1 inhibitors. Systematic exploration of the structure-activity relationship through the introduction of spirocyclic scaffolds based on the reported selective TYK2 inhibitor 14l led to the discovery of the superior derivative compound 48. Compound 48 showed excellent potency on TYK2/JAK1 kinases with IC50 values of 6 and 37 nM, respectively, and exhibited more than 23-fold selectivity for JAK2. Compound 48 also demonstrated excellent metabolic stability and more potent anti-inflammatory efficacy than tofacitinib in acute ulcerative colitis models. Moreover, the excellent anti-inflammatory effect of compound 48 was mediated by regulating the expression of related TYK2/JAK1-regulated genes, as well as the formation of Th1, Th2, and Th17 cells. Taken together, these findings suggest that compound 48 is a selective dual TYK2/JAK inhibitor, deserving to be developed as a clinical candidate.

Combination of Ephedra sinica stems and Terminalia chebula fruits produces new ephedrine derivatives in vivo that diminish the permeability to BBB while retaining airway dilation and hepatoprotective effects.

ETHNOPHARMACOLOGICAL RELEVANCE: The stems of Ephedra sinica and the fruits of Terminalia chebula are combined using in traditional Mongolian medicine formula "Gurigumu-7" for liver diseases. E. sinica stems contains ephedrine with broncho-dilatory activity. However, ephedrine can pass through the blood-brain barrier (BBB) and excite the central nervous system (CNS) to cause insomnia and restlessness. AIM OF THE STUDY: The present study was to investigate the structures and bioactivities of new compounds formed in vivo after co-administration of E. sinica stems and T. chebula fruits. MATERIALS AND METHODS: Pharmacokinetic investigation was carried out in rats. A parallel artificial membrane permeability measurement system was used to determine BBB permeability. Ex vivo experiments using tracheal rings of guinea pig was performed to examine the tracheal relaxation effect. In vivo hepatoprotective tests were carried out in Tg (fabp10a: dsRed) liver transgenic zebrafish. The fluorescent probe, 2,7-dichlorodihydrofluorescein diacetate, was used to measure reactive oxygen species, and UHPLC-MS was used to determine glutathione concentrations after derivatization with N-ethylmaleimide. RESULTS: New ephedrine derivatives (1 and 2) formed in vivo and reached their maximum serum concentrations at 0.5 h after administration of the two herbal drugs. Compounds 1 and 2 showed lower BBB permeability than ephedrine, suggesting that they have less adverse effects on the CNS. Compounds 1 and 2 relaxed the tracheal rings and had strong hepatoprotective effect on transgenic zebrafish with liver specific expression of RFP. Compounds 1 and 2 significantly reduced the level of reactive oxygen species while increasing that of glutathione in thioacetamide-treated zebrafish, which might be the hepatoprotective mechanism. CONCLUSION: These results provided evidences that the chemical constituents in various herbal drugs in a medicinal formula can interact to generate new compounds with fewer side effects and increased or additive bioactivity.

Exploring the mechanism of Shenqisherong pill against cervical spondylotic myelopathy by network pharmacology and molecular docking.

BACKGROUND: Shenqisherong pill (SQSRP) has been used clinically to treat cervical spondylotic myelopathy (CSM) with satisfactory results; however, its active ingredients and mechanisms are unclear. The present study aimed to explore the active ingredients and molecular mechanisms of SQSRP against CSM using network pharmacology and molecular docking. METHODS: The compounds in SQSRP were obtained from public databases and related literature, and oral bioavailability (≥30%) and drug-likeness (≥0.18) were screened using absorption, distribution, metabolism, and excretion (ADME) criteria. Compounds-related and CSM-related target genes were identified using public databases, and the overlapping genes between compounds and CSM target genes were identified using a Venn diagram. Cytoscape and STRING were used to construct, visualize, and analyze the interaction network between these overlapping targets. Gene Ontology (GO) and KEGG pathway enrichment analysis of overlapping targets used Omicshare tools and constructed a compound-overlapping targets network, target-pathway network, and compound-target-pathway network using Cytoscape. Finally, molecular docking software was used to verify the targets. RESULTS: A total of 447 compounds in SQSRP were identified, and ADME screening identified 96 compounds as potentially active ingredients. A total of 249 compound-related genes and 280 CSM-related genes were identified using public databases, and 53 overlapping genes were identified. The results of compound targets and protein-protein interaction network analysis showed that the pharmacological effects of SQSRP against CSM involved 56 compounds and 53 genes. The results of GO and KEGG pathway enrichment analysis suggested that the therapeutic effects of SQSRP against CSM were exerted by reducing inflammation, inhibiting apoptosis, and protecting neurons. The molecular mechanisms may be strongly associated with PI3K-Akt, MAPK, IL-17, and TNF, which might be pivotal signaling pathways. CONCLUSIONS: The active ingredients and mechanisms of SQSRP against CSM were investigated using network pharmacology. The findings proved that the pill could treat CSM through multi-component, multi-target, and multi-pathway synergy and provide a theoretical basis for the subsequent extraction of active ingredients from SQSRP.

Evaluation on two types of paramyosin vaccines for the control of Haemaphysalis longicornis infestations in rabbits.

BACKGROUND: Haemaphysalis longicornis is an obligate hematophagous ectoparasite that transmits a variety of pathogens causing life-threatening diseases in humans and animals. Paramyosin (Pmy) is not only an invertebrate-specific myofibrillar protein but also an important immunomodulatory protein. Therefore, it is one of the ideal candidate antigens for vaccines. METHODS: We conducted two vaccine trials to evaluate the protective efficacy of Pmy recombinant protein (rPmy) and peptide vaccine (KLH-LEE). Each rabbit was immunized with three doses of rPmy or KLH-LEE adjuvanted with Freund's complete/incomplete at 500 µg/dose at 2-week intervals before challenge with 40 female H. longicornis/rabbit. PBS plus adjuvant, Trx or KLH was used as control group. The antibodies of rabbits were detected by ELISA. Then, female ticks were fed on the rabbits until detachment. RESULTS: ELISA results showed that both vaccines induced rabbits to produce antibodies. Compared with the Trx group, the engorgement weight, oviposition and hatchability of the rPmy group decreased by 8.87%, 26.83% and 38.86%, respectively. On the other hand, engorgement weight, oviposition and hatchability of female ticks in the KLH-LEE group correspondingly resulted in 27.03%, 53.15% and 38.40% reduction compared with that of the KLH group. Considering the cumulative effect of vaccination on the evaluated parameters, results showed 60.37% efficacy of the rPmy vaccine formulation and 70.86% efficacy in the KLH-LEE group. CONCLUSIONS: Pmy and particularly epitope LEE have potential for further development of an effective candidate vaccine to protect the host against tick infection. GRAPHIC ABSTARCT.

Hydroxysafflor yellows alleviate thrombosis and acetaminophen-induced toxicity in vivo by enhancing blood circulation and poison excretion.

BACKGROUND: Hydroxysafflor yellow A (HSYA) from the flower of Carthamus tinctorius (Safflower) has been reported to have various pharmacological effects. However, little is known about the bioactivities of other chemical constituents in Safflower and the relationship between enhancement of blood circulation and hepatoprotection by HSYA. PURPOSE: The present research was to evaluate the antithrombotic and hepatoprotective activities of HSYA and C, examine their mechanisms of actions, including influence on the excretion velocity of acetaminophen, and the relationship between the antithrombotic, hepatoprotective, and other bioactivities. METHODS: The hepatoprotective activities were examined by acetaminophen (APAP)-induced zebrafish toxicity and carbon tetrachloride (CCl4)-induced mouse liver injury. The concentrations of APAP in zebrafish and APAP that was excreted to the culture media were quantified by UHPLC-MS. The anti-thrombosis effect of HSYA and C were examined by the phenylhydrazine (PHZ)-induced zebrafish thrombosis. RESULTS: HSYA and HSYC showed robust protection on APAP-induced toxicity and PHZ-induced thrombosis. The hepatoprotective effects of HSYA and C were more potent than that of the positive control, acetylcysteine (61.7% and 58.0%, respectively, vs. 56.9% at 100 µM) and their antithrombosis effects were more robust than aspirin (95.1% and 86.2% vs. 52.7% at 100 µM). HSYA and C enhanced blood circulation, rescued APAP-treated zebrafish from morphological abnormalities, and mitigated APAP-induced toxicity in liver development in liver-specific RFP-expressing transgenic zebrafish. HSYC attenuated CCl4-induced mouse liver injury and regulated the levels of HIF-1α, iNOS, TNF-α, α-SMA, and NFκB in liver tissues. HSYA was also protective in a dual thrombotic and liver toxicity zebrafish model. By UHPLC-MS, HSYA accelerated the excretion of APAP. CONCLUSION: HSYA and C are the bioactive constituents of Safflower that are responsible for the herbal drug's traditional use in promoting blood circulation to remove blood stasis. Safflower and its chalcone constituents may protect from damage due to exogenous or disease-induced endogenous toxins by enhancing the excretion velocity of toxins.

Post-Marketing Surveillance of Qishe Pill () Use for Management of Neck Pain in a Chinese Patient Cohort to Determine its Safety, Tolerability and Effectiveness.

OBJECTIVE: To evaluate the safety and effectiveness of Qishe Pill () on neck pain in real-world clinical practice. METHODS: A multi-center, prospective, observational surveillance in 8 hospitals across Shanghai was conducted. During patients receiving 4-week Qishe Pill medication, Visual Analogue Scale (VAS) and Neck Disability Index (NDI) assessments have been used to assess their pain and function, while safety monitoring have been observed after 2 and 4 weeks. RESULTS: Results from 2,023 patients (mean age 54.5 years) suggest that the drug exposure per unit of body mass was estimated at 3.41 ± 0.62 g/kg. About 8.5% (172/2,023) of all participants experienced adverse events (AEs), while 3.8% (78/2,023) of all participants experienced adverse reaction. The most common AEs were gastrointestinal events and respiratory events. The VAS score (pain) and NDI score (function) significantly decreased after 4-week treatment. An effect-quantitative analysis was also conducted to show that the normal clinical dosage may be consider as 3-4 g/kg, at which dosage the satisfactory pain-relief effect may achieve by 40-mm reduction in VAS. CONCLUSION: These findings showed that patients with cervical radiculopathy who received Qishe Pill experienced significant improvement on pain and function. (Registration No. NCT01875562).

The effects of acarbose therapy on reductions of myocardial infarction and all-cause death in T2DM during 10-year multifactorial interventions (The Beijing Community Diabetes Study 24).

To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The study population of Beijing Community Diabetes Study (BCDS) were type 2 diabetes (T2DM) living in 21 communities in Beijing. All patients received comprehensive intervention in accordance with the Chinese guidelines for the prevention and treatment of diabetes. Professors in endocrinology from top tier hospitals regularly visited the communities for consultations, which was a feature of this study. A total of 1797 T2DM in BCDS study had complete screening data, including blood glucose, blood pressure, lipid profiles and acarbose continuous therapy. After 10-year follow-up, the risks of CVD outcomes were assessed according to whether patients had received acarbose therapy or not. All patients were followed-up to assess the long-term effects of the multifactorial interventions. At baseline, compared with the acarbose therapy free in T2DM, there was no significant difference in achieving the joint target control in patients with acarbose therapy. From the beginning of 8th year follow-up, the joint target control rate in patients with acarbose therapy was significantly higher than that of acarbose therapy free. During the 10-year follow-up, a total of 446 endpoint events occurred, including all-cause death, cardiovascular events, cerebrovascular events. The incidences of myocardial infarction (from the 4th year of follow-up) and all-cause death (from the 2nd year of follow-up) in patients who received acarbose therapy were significantly lower than that of acarbose therapy free respectively. In Cox multivariate analyses, there were significant differences in incidences of myocardial infarction and all-cause death between afore two groups during the 10-year follow-up, and the adjusted HRs were 0.50 and 0.52, respectively. After multifactorial interventions, T2DM with acarbose therapy revealed significant reductions of myocardial infarction and all-cause death. The long-term effects of with acarbose therapy on improving joint target control might be one of the main reasons of myocardial infarction and all-cause death reduction.Trial Registration: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

Characterization of the complete chloroplast genome of Chlorophytum comosum (Liliaceae).

Chlorophytum comosum is a perennial ornamental plant in the family Liliaceae, it is also a valuable medicinal plant. To enrich the genetic resources of C. comosum, its chloroplast genome was determined by Illumina sequencing data. The chloroplast genome is a typical quadripartite structure with a size of 153,983 bp, of which the LSC region is 83,471 bp, the SSC region is 18,010 bp, and the pair of IR regions is 26,251 bp. The overall GC content is 37%. It contains 131 genes, including 85 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Phylogenetic analyses showed that C. comosum is closely related to Chlorophytum rhizopendulum. However, it can be distinguished from other plants. This study enriches the sequence resources of C. comosum and provides important data for the development of molecular identification markers.

Identification, functional characterization, and estrogen regulation on gonadotropin-releasing hormone in the spotted scat, Scatophagus argus.

Gonadotropin-releasing hormone (GnRH) is a key neuropeptide of the reproductive system. However, little is known about the role of GnRH in the spotted scat (Scatophagus argus). Here, three GnRH subtypes (cGnRH-II, sGnRH, and sbGnRH) were identified in the spotted scat. cGnRH-II and sGnRH were only expressed in the brains and gonads of both male and female fish, exhibiting a tissue-specific expression pattern, while sbGnRH was expressed at different transcription levels in all examined tissues. During ovarian maturation, hypothalamus-associated sbGnRH was upregulated, while the expression of sGnRH was variable and cGnRH-II first increased and then decreased. In vivo experiments showed that sbGnRH significantly promoted the expression of fsh and lh genes in a dose-dependent manner and exhibited a desensitization effect on lh expression at high concentrations. For sGnRH and cGnRH-II, only high concentrations could induce fsh and lh expression. Furthermore, treatment with highly concentrated sbGnRH peptide also induced fsh and lh expression, whereas the sGnRH and cGnRH-II peptides only induced fsh expression in vitro. 17ß-Estradiol (E2) significantly inhibited the expression of sbGnRH mRNA in a dose-dependent manner and did not impact sGnRH and cGnRH-II mRNA levels in vivo or in vitro. The inhibitory effect of E2 on sbGnRH expression was attenuated by the estrogen receptor (ER) broad-spectrum antagonist (fulvestrant) and the ERα-specific antagonist (methyl-piperidinopyrazole), respectively, implying that the feedback regulation on sbGnRH is mediated via ERα. This study provides a theoretical basis for the reproductive endocrinology of the spotted scat by studying GnRH.

An Analysis of the Anti-Neuropathic Effects of Qi She Pill Based on Network Pharmacology.

BACKGROUND: Qi She Pill (QSP) is a traditional prescription for the treatment of neuropathic pain (NP) that is widely used in China. However, no network pharmacology studies of QSP in the treatment of NP have been conducted to date. OBJECTIVE: To verify the potential pharmacological effects of QSP on NP, its components were analyzed via target docking and network analysis, and network pharmacology methods were used to study the interactions of its components. MATERIALS AND METHODS: Information on pharmaceutically active compounds in QSP and gene information related to NP were obtained from public databases, and a compound-target network and protein-protein interaction network were constructed to study the mechanism of action of QSP in the treatment of NP. The mechanism of action of QSP in the treatment of NP was analyzed via Gene Ontology (GO) biological process annotation and Kyoto Gene and Genomics Encyclopedia (KEGG) pathway enrichment, and the drug-like component-target-pathway network was constructed. RESULTS: The compound-target network contained 60 compounds and 444 corresponding targets. The key active compounds included quercetin and beta-sitosterol. Key targets included PTGS2 and PTGS1. The protein-protein interaction network of the active ingredients of QSP in the treatment of NP featured 48 proteins, including DRD2, CHRM, ß2-adrenergic receptor, HTR2A, and calcitonin gene-related peptide. In total, 53 GO entries, including 35 biological process items, 7 molecular function items, and 11 cell related items, were identified. In addition, eight relevant (KEGG) pathways were identified, including calcium, neuroactive ligand-receptor interaction, and cAMP signaling pathways. CONCLUSION: Network pharmacology can help clarify the role and mechanism of QSP in the treatment of NP and provide a foundation for further research.

Shi-Style Cervical Mobilizations Versus Massage for Cervical Vertigo: A Multicenter, Randomized, Controlled Clinical Trial.

Objectives: Large sample and high-quality evidence to evaluate the preliminary safety of the mobilizations and massage for cervical vertigo are not yet available. Thus, the present study aimed to investigate the comparative effectiveness and preliminary safety of Shi-style cervical mobilizations (SCM) compared with traditional massage (TM) in cervical vertigo patients. Design: A prospective, multicenter, open-label, randomized, controlled clinical trial with a 1:1 allocation ratio. Settings: Five academic medical centers. Subjects: A total of 360 adult patients with a diagnosis of cervical vertigo. Interventions: The patients were randomly allocated to either an SCM (n = 180) or TM (n = 180) group. The patients were treated during six sessions over 2 weeks. The primary outcome was the Dizziness Handicap Inventory (DHI) total scale score, and secondary outcomes included the DHI subscales, Chinese version of the Short-Form 36 Health Survey (CSF-36), and adverse events (AEs). Outcomes were assessed in the short term at 2 weeks, 1 month, and 3 months, and in the intermediate term at 6 months after randomization. Results: Significant changes were observed from the baseline in the DHI total scale and subscales at 2 weeks and 1, 3, and 6 months in both groups (all p < 0.05). However, the differences between the two groups were not significant (all p > 0.05). Furthermore, we noted significant changes from the baseline in SF-36 scores at 2 weeks in both groups (all p < 0.05), whereas CSF-36 scores were not significantly higher in the SCM group (all p > 0.05) compared with the TM group. No serious AEs were reported in either of the two groups. Conclusions: No differences in outcomes were detected between the SCM and TM groups in terms of treatment of cervicogenic dizziness. Efficacy trials are required to determine whether the improvement observed for each treatment was causally related to the interventions.

Polymorphisms of genes related to vitamin D metabolism and transportation and its relationship with the risk of osteoporosis: protocol for a multicentre prospective cohort study in China.

INTRODUCTION: Osteoporotic fracture is one of the most common causes of disability and a major contributor to medical care costs in many regions of the world. The polymorphisms of genes related to vitamin D metabolism and transportation are associated with variation in bone mineral density and the risk of osteoporosis. METHODS AND ANALYSIS: The China Community-based Cohort of Osteoporosis study is an observational, longitudinal, multicentre, prospective cohort study for middle-aged and older permanent residents of China, which has been ongoing in six cities since 2016. Female residents aged 45-80 years old and male residents aged 50-80 years old are identified through permanent resident lists. All the enrolled participants will complete questionnaires on their personal characteristics and histories. The bone mineral density of their lumbar vertebrae and left hip will be measured and serum bone metabolism parameters assessed. Polymorphisms of genes related to vitamin D metabolism and transportation will be detected, and their relationship with the risk of osteoporosis, and osteoporotic fracture, will be analysed. About 18 000 residents will be involved in the study. ETHICS AND DISSEMINATION: The study was approved by Institutional Ethics Board of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine (2016LCSY065). Results will be published in peer-reviewed journals. The results of this study are expected to improve the understanding of the association between polymorphisms of genes related to vitamin D metabolism and transportation and the risk of osteoporosis and osteoporotic fracture among middle-aged and older residents of China. TRIAL REGISTRATION NUMBER: NCT02958020.

Study on efficacy and safety of Tong-luo Qu-tong plaster treatment for knee osteoarthritis: study protocol for a randomized, double-blind, parallel positive controlled, multi-center clinical trial.

BACKGROUND: Knee osteoarthritis (KOA) is a common chronic musculoskeletal disorder that seriously affects quality of life. Patients with KOA frequently develop one or more of the following typical symptoms: joint pain, stiffness, joint friction noise and impaired functionality. Traditional Chinese medicine (TCM) has been shown to have a superior effect and a particular advantage in the treatment of KOA; among TCM, the Tong-luo Qu-tong plaster is the convenient and most commonly used method in China to improve symptoms including pain, stiffness and limited mobility in patients with KOA, as it causes few adverse effects. But there is a lack of high-quality clinical evidences to support the therapeutic effect that Chinese adhesive plaster can have in relieving pain and stiffness. The purpose of this study will be to evaluate the efficacy and safety of Tong-luo Qu-tong plaster in patients with KOA. METHODS/DESIGN: This study will be a randomized, double-blind, parallel positive controlled, multi-center clinical trial, a non-inferiority trial design was adopted. A total of 2000 participants older than 40 years, with KOA, will be randomly allocated into an experimental group (n = 1500) and a control group (n = 500). All participants will receive a conventional conservative treatment lasting for 14 days as two courses, once daily. Tong-luo Qu-tong plaster will be administered externally to participants in the experimental group, while the control group will receive a Qi-zheng Xiao-tong plaster. The outcome of the total Western Ontario and McMaster Universities Arthritis Index scores, TCM syndrome quantitative score and visual analog scale scores will be measured during the assessment visits (baseline and 1-week and 2-week follow up). In addition, adverse events related to clinical symptoms and signs and results of laboratory tests will be documented during the clinical trials. DISCUSSION: This study will provide reliable evidence of the effectiveness and safety of Tong-luo Qutong plaster in patients with KOA. If the results are favorable, it is expected that the patients with KOA will benefit from this study, many patients may have a good alternative treatment for KOA. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03309501 . Registered on 8 November 2017.

The efficacy of the traditional Chinese medicine Jia Wei Niu Bang Zi granule combined with methotrexate in treating active rheumatoid arthritis: A multicenter, randomized, double-blinded controlled clinical trial.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic and autoimmune inflammatory disease ending with the destruction of joints. Current therapies can relieve RA symptoms, but some also bring severe adverse events. Therefore, an effective and safe therapeutic strategy remains to be created to benefit patients with RA by large. Jia Wei Niu Bang Zi granule (NBZG) consisting of RA-fighting Chinese herbals has been used in Longhua Hospital in the last several decades. NBZG has potential therapeutic effect on RA, which should be evaluated by larger sample clinical trial. METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trials will be conducted to determine the efficiency of NBZG in pain relief and joint protection. A total of 120 patients with active RA will be enrolled, and treated with NBZG or placebo for 12 weeks. The primary outcome measurements include rate of American College of Rheumatology (ACR) 50 at 12 weeks' treatment. The 2nd outcome measurements include rate change of ACR20, ACR70, the disease activity score (DAS) 28, 36-item Short-Form Health Survey Questionnaire, Health Assessment Questionnaire - Disability Index, score changes of Patient Assessment of Arthritis Pain, Patient Global Assessment of Arthritis, and the Athens insomnia scale at the same time points. DISCUSSION: Although NBZG has shown efficacy in treating RA in Longhua Hospital for decades, the universality of this efficacy needs evaluated. The results of this trial will provide a convincing evidence about NBZG's efficacy in treating active RA in a large population. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03173040 (registered on May 30, 2017).

Chinese Herbal Medicine for Osteosarcoma in the Mouse: A Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize and critically assess the inhibitory effects of Chinese herbal medicine (CHM) on tumor volume and tumor weight for the treatment of osteosarcoma (OS) in mouse models. METHODS: PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, VIP Database, and Chinese BioMedical (CBM) were searched since their inception dates to March 10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review. RESULTS: CHM may significantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control: pooled mean difference (MD)=-2.90; 95% confidence interval (Cl): -3.50 to -2.31: P<0.01], tumor volume (16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =-2.57; 95% Cl: -3.33 to -1.80; P<0.01) and tumor growth inhibition rate. CONCLUSION: CHM could significantly inhibit the growth of OS in mouse models, which might be supportive for the design of preclinical and clinical trials in future.

[Effect of anti-androgen and progesterone on development of regrowth antlers in 6 year old sika deer].

To investigate the effects of anti-androgen drugs and melengestrol acetate (MGA) on development of regrowth antlers in 6 year old sika deer, twenty healthysika deerwith similar body weight and antler weightwere randomly divided into five groups by using single factor test design: flutamide (n=4), bicalutamide (n=4), progesterone acetate (CPA, n=4), melengestrol acetate (MGA, n=4), control(n=4). All deer were fed with same diets and were housed outside together in an opened fence of 15 m×30 m with free access to water and feed. Treatment groups were injected subcutaneously sustained-release agents of the four drugs respectively when two-branched antlers were harvested. The control group had no special treatment. In the experiment period of 60 d, blood sampleswere collected for 4 times for each deer. The concentration of testosterone in plasma was tested and analyzed to compare the changes between different groups. Development of regrowth antlers was observed. At the end of the experiment, regrowth antlers were weighted and analyzed. The resultsshowed that the weights of regrowth antlers in treatment groups were significantly greater than those from control group and the weight gain (as compared with the control group) was 100.50%, 64.46%, 87.16% and 117.46% respectively in flutamide group, bicalutamide group, progesterone acetate group and melengestrol acetate group. For plasma testosterone concentration, it was not significantly different in the early stage (in the first 35 d), but at the end of the experimen, it was significantly higher than that of earlier stage (P<0.01) in various groups. Testosterone concentration of flutamide treated group was significantly lower than that of the other groups (P<0.01), while the level inbicalutamide and MGA treated groups was significantly higher than that in other groups (P<0.01). The results showed that both anti-androgen drugs and MGA treatment promoted the development of regrowth antlers and increased the weight of regrowth antlers, where the effect was most significant by MGA treatment. From the morphological observation of the antlers, it was found that anti-androgen and MGA treatments prolonged the growth period of regrowth antlers through delaying the ossification of antlers. However, plasma testosterone concentration was not affected by the treatments.