Study on the molecular mechanism of Guizhi Jia Shaoyao decoction for the treatment of knee osteoarthritis by utilizing network pharmacology and molecular docking technology.

BACKGROUND AND OBJECTIVE: Guizhi Jia Shaoyao decoction (GSD) is widely used in the clinical treatment of knee osteoarthritis (KOA). However, the underlying molecular mechanisms remain unclear. The aim of this study was to explore functional mechanisms of GSD in treating KOA by utilizing network pharmacology-based approaches. METHODS: Candidate components and targets of GSD were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. NCBI, Genecards, Drugbank, and Therapeutic Target Database (TTD) were used to establish a target database for KOA. Then, an interactive network diagram of "drugs-active components-targets" was plotted with Cytoscape open source bioinformatics software. A protein-protein interaction network was constructed and related protein interaction relationships were analyzed based on the STRING database. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway-enrichment analysis were conducted based on intersected targets. Molecular docking provided an assessment tool for verifying binding of components and targets. It was performed by AutoDock molecular modeling simulation software. RESULTS: In all, 103 active components were successfully identified, and corresponding 133 targets were searched for treating KOA. Functional enrichment analysis suggested that GSD exerts its pharmacological effect in treating KOA by regulating multiple pathways, such as PI3K-Akt, tumor necrosis factor, Toll-like receptor (TLR), and nuclear factor kappa B signaling pathways. Molecular docking analysis depicted that representative components bound firmly to key targets. CONCLUSION: This study revealed the synergistic effects of multiple components, targets, and pathways of GSD for treating KOA. This would enhance the understanding of potential molecular mechanisms of GSD for treating KOA and lay a foundation for further experimental research.

Short-term effects of kinesiology taping on static and dynamic balance in healthy subjects.

Background: As a therapeutic tool, kinesiology taping (KT) has become increasingly popular for musculoskeletal injuries utilized by physiotherapists. KT has been found to have effects on facilitating muscle strength by generating a concentric pull on the fascia. However, little is known about KT in the improvement of dynamic and static balance. This study aims to explore whether KT on the quadriceps muscle has any immediate effects on static and dynamic balance. Methodology: Twenty-seven healthy individuals (13 males and 14 females, aged 22 to 29) were recruited in a crossover study with two conditions: KT and no taping. KT was applied to the quadriceps muscle for the taping group, with the control receiving no taping. Pre- and post-test measurements were taken to give an indication of the effect of the tape on balance performance. Center of Pressure Excursion (COPE) and Time to Stabilization (TTS) when landing from a hop test and Y Balance test combined score (YBTCS) were used to assess a stabilizing balance activity and a dynamic balance. The pre- and post-intervention were collected, with differences explored using repeated measures ANOVA with time and condition (tape) factor analysis. Results: We found a significant improvement (p ≤ 0.05) with a moderate to large effect size in YBTCS between KT and no taping, indicating enhanced balance performance in the KT group. However, no significant difference (p ≥ 0.05) with small to moderate effect size was found in COPE or TTS between the two conditions during landing tests, suggesting similar balance capabilities in these specific measures. Conclusion: The use of KT shows no significant immediate effect on static balance in healthy individuals when applied to the quadriceps muscles; however, it demonstrates a positive immediate effect on dynamic balance.

Which method for femoral component sizing when performing kinematic alignment TKA? An in silico study.

INTRODUCTION: The kinematically alignment (KA) technique for TKA aims to reproduce the pre-arthritic knee anatomy, including both the femoro-tibial and femoro-patellar joints. An in silico study was conducted to compare 3 different femoral component sizing techniques to identify the anatomical landmark which allows closest restoration of the native trochlear anatomy. Our study's question was: what was the best method for sizing the femoral component when performing KA-TKA? It was hypothesized that sizing the femoral component by aiming to restore the groove height would be the best method to restore the native trochlear anatomy. METHODS: GMK sphere® (Medacta) femoral component 3D models were virtually kinematically aligned on 30 tri-dimensional (3D) bony osteoarthritis knee models. The femoral component was mediolaterally positioned to match distal native and prosthetic grooves. Three methods were used to size the femoral component: a conventional method with the anterior femoral cut flush to the femoral cortex (C-KATKA) and two alternative personalized methods aiming to recreate either the medial facet's height (ATM-KATKA) or the groove's height (ATG-KATKA). In-house analysis software was used to compare native and prosthetic trochlear articular surfaces and mediolateral implant overhangs. RESULTS: Compared with the C-KATKA, ATG-KATKA and ATM-KATKA techniques increased the component size by a mean of 0.90 (SD 0.31, min 0.5 to max 1.5) (p<0.001) and 1.02 (SD 0.31, min 0.5 to max 1.5) (p<0.001), respectively. C-KATKA technique substantially proximally understuffed the trochleae with maximum values of 7.11mm (SD 1.39, min 3.93mm to max 10.57mm) in the medial facet, 4.72mm (SD 1.27, min 1.46mm to max 6.86mm) in the lateral facet and 4.51mm (SD 1.40, min 1.92mm to max 7.30mm) in the groove, respectively. Alternative techniques understuffed medial facet with maximum values of 5.07mm (SD 1.29, min 2.83mm to max 8.34mm) and 4.70mm (SD 1.52, min 0.83mm to max 8.04mm) for ATG-KATKA and ATM-KATKA techniques, respectively. There was no significant understuffing of the groove or lateral facet for alternative techniques (ATM and ATG). The ATM-KATKA and ATG-KATKA techniques generated mediolateral implant overhang, mainly postero-lateral, with a rate of 90.0% and 86.7%, respectively. In this study, no mediolateral implant overhang was found for C-KATKA. DISCUSSION/CONCLUSION: The C-KATKA technique substantially understuffs the native trochlear articular surfaces in medial, lateral and groove parts. Alternative techniques (ATM-KATKA and ATG-KATKA) for sizing the femoral component better restore the native trochlear anatomy but also generate a high rate of postero-lateral implant overhangs. Would this postero-lateral implant overhang be clinically deleterious remains unknown? The aspect ratio of contemporary femoral TKA implants can probably be optimized to allow a better anatomical restoration of the anterior femoral compartment. LEVEL OF EVIDENCE: II, in silico study.

Worldwide Research Trends on Diabetic Foot Ulcers (2004-2020): Suggestions for Researchers.

OBJECTIVES: Diabetic foot ulcer (DFU) is one of the devastating complications of diabetes. It has high mortality and disability rates. The number of research articles on DFUs has increased. This study was designed to explore the global trends and research hotspots of DFUs to benefit researchers in shaping future research directions. METHODS: Literatures relating to DFU from 2004 to 2020 were retrieved from the Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). The current status of DFU research (including publications, journals, the performances of relevant countries, institutions, and authors and the research trends and hotspots of DFU) was analyzed with the WoSCC. VOSviewer v1.6.10.0 was utilised for cocitation, coauthorship, cooccurrence analyses, and bibliographic coupling. RESULTS: A total of 5869 publications on DFUs were retrieved. We performed a longitudinal review of publications over 17 years: 4500 articles and 865 review articles on DFUs published from 2004 to 2020 were analyzed. The total citation was 107,296. The USA (n = 1866), England (n = 606), and China (n = 599) were the three largest contributors. The University of Washington had the greatest number of publications within this time period (n = 103), and it had the most cooperative units and was in the core position in all research institutions, followed by the University of Manchester (n = 94) and the University of Miami (n = 92). Armstrong DG (91/1.69%) and Lavery LA (55/1.19%) should be regarded as scholars who have made outstanding contributions. The top journal with the greatest total link strength was Diabetes Care. Analysis showed that the global research hotspots of DFU focused on lower limb amputation, diabetic foot infection, and treatment and management of DFU. Studies on osteomyelitis, wound therapy and management, multidisciplinary integration and mechanism of DFUs, and its related diseases are the research fronts that should be closely watched in the future. CONCLUSIONS: This study revealed the current research status and hotspots in the domain of DFU over the past 17 years, which can help researchers to further pinpoint potential perspectives on hot topics and research frontiers.

Efficacy and Safety of Acupuncture Combined with Herbal Medicine in Treating Gouty Arthritis: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Gouty arthritis is a common metabolic disease caused by long-term purine metabolism and elevated serum uric acid. In recent years, the incidence of gouty arthritis has been increasing year by year. As an effective method for treating gouty arthritis, acupuncture combined with herbal medicine has been widely used in clinical practice. However, the evidence for the treatment needs to be evaluated through systematic review and meta-analysis. Methods. The Cochrane Library, PubMed, Web of Science, EMBASE, China CBM database, Clinical Trials, CNKI, China Wanfang database, and VIP information database were searched from the establishment of each database to March 2021. Randomized controlled trials (RCTs) were included in the study, and the therapeutic effects of acupuncture combined with herbal medicine versus conventional therapy, or acupuncture combined with herbal medicine versus anti-inflammatory drugs, or acupuncture combined with herbal medicine versus acupuncture/herbal medicine alone were compared in the subjects with gouty arthritis. Two authors screened all references, assessed the risk of bias, and independently extracted the data. The binary outcome was summarized using 95% confidence intervals (CIs) and risk ratios (RRs). The overall quality of the evidence was assessed with hierarchy, and meta-analysis was performed with a random-effects model. RESULTS: A total of 14 randomized controlled trials (1,065 participants, 540 treatment groups, and 525 control groups) with treatment courses of 5 to 21 days were included. Acupuncture combined with herbal medicine and acupuncture was compared in three trials, acupuncture combined with herbal medicine and conventional therapy was compared in 14 of them, and acupuncture combined with herbal medicine and anti-inflammatory drugs was compared in 8 of them. The clinical efficacy (clinical symptoms, serological tests, and visual analogue scale (VAS) results) was significantly improved in the acupuncture combined with herbal medicine treatment group (P=0.0005, 95% CI 0.03 to 0.13; 687 participants; 8 trials), and the efficacy in reducing uric acid was also better (P < 0.00001; 95% CI -102.89, -68.37; 100 participants; 2 trials; evidence with moderate quality). The effect of acupuncture combined with herbal medicine was better than that of acupuncture alone (RR 1.22, 95%CI 1.06 to 1.41; 139 participants; 3 trials), the effect of acupuncture combined with herbal medicine was better than that of herbal medicine alone (RR 1.31 95%CI 1.08 to 1.57, 100 participants, 2 trials, evidence with moderate quality), and the effect of acupuncture combined with herbal medicine was better than that of colchicine (P = 0.02, RR 1.14 95%CI 1.02 to 1.27, 2 trials, evidence with moderate quality). The incidence of adverse events was considerably different between the two groups, and the acupuncture combined with herbal medicine group was significantly superior to the control group in terms of adverse events (P < 0.00001; 95% CI (0.08 to 0.32)). CONCLUSIONS: The efficacy of acupuncture combined with herbal medicine was better than conventional drug therapy in treating gouty arthritis. The study results must be interpreted with caution due to the high or unclear risk of bias of the trials included in the study. PROSPERO registration number: CRD42020202544. INPLASY registration number: 202090006.

Advances in Experimental and Clinical Research of the Gouty Arthritis Treatment with Traditional Chinese Medicine.

Gouty arthritis (GA) is a multifactorial disease whose pathogenesis is utterly complex, and the current clinical treatment methods cannot wholly prevent GA development. Western medicine is the primary treatment strategy for gouty arthritis, but it owns an unfavorable prognosis. Therefore, the prevention and treatment of GA are essential. In China, traditional Chinese medicine (TCM) has been adopted for GA prevention and treatment for thousands of years. Gout patients are usually treated with TCM according to their different conditions, and long-term results can be achieved by improving their physical condition. And TCM has been proved to be an effective method to treat gout in modern China. Nevertheless, the pharmacological mechanism of TCM for gout is still unclear, which limits its spread. The theory of prevention and treatment of gout with TCM is more well acknowledged in China than in abroad. In this article, Chinese herbs and ancient formula for gout were summarized first. A total of more than 570 studies published from 2004 to June 2021 in PubMed, Medline, CNKI, VIP, Web of Science databases and Chinese Pharmacopoeia and traditional Chinese books were searched; the current status of TCM in the treatment of GA was summarized from the following aspects: articular chondrocyte apoptosis inhibition, antioxidative stress response, inflammatory cytokine levels regulation, uric acid excretion promotion, immune function regulation, uric acid reduction, and intestinal flora improvement in subjects with gout. The literature review concluded that TCM has a specific curative effect on the prevention and treatment of GA, particularly when combined with modern medical approaches. However, lacking a uniform definition of GA syndrome differentiation and the support of evidence-based medicine in clinical practice have provoked considerable concern in previous studies, which needs to be addressed in future research.

A systematic review and meta-analysis for Chinese herbal medicine Duhuo Jisheng decoction in treatment of lumbar disc herniation: A protocol for a systematic review.

BACKGROUND: Lumbar disc herniation (LDH) is 1 of the most common diseases in orthopedics, which seriously affects people's daily life and brings a heavy burden on society and families. Chinese herbal medicine has been used in clinical practice for a long time and Duhuo Jisheng Decoction (DHJSD) is believed to help alleviate the symptoms of LDH. This systematic review aims to collect evidences from randomized clinical trials and evaluate the efficacy of DHJSD on LDH in order to provide a reference for clinicians and researchers. METHODS: We will comprehensively search the 8 electronic databases until December 2019 to identify related randomized controlled trials, including 4 foreign databases (PubMed, MEDLINE, EMBASE, Cochrane Library) and 4 Chinese databases (China National Knowledge Infrastructure Database, VIP Database, Wanfang Database and China Biology Medicine disc). The data of the World Health Organization International Clinical Trial Registry Platform and the Chinese Clinical Trial Registry also will be searched. The primary outcomes are Japanese Orthopaedic Association scores and visual analog scale scores. The risk of bias will be assessed using the Cochrane Collaboration tool. RevMan (V.5.3) software will be used for meta-analysis. RESULTS: This study will report the results of DHJSD for the treatment of LDH from the literature screening, the basic information of the included studies, the risk of bias of the included studies, treatment effects, safety, and so on. CONCLUSION: This systematic review will evaluate the effectiveness and safety of DHJSD for the treatment of LDH and provide the latest evidence for its clinical application. ETHICS AND DISSEMINATION: This is a literature-based study, therefore it does not require ethical approval. PROSPERO REGISTRATION NUMBER: CRD42019147302.

Needle knife therapy plus sodium hyaluronate injection for knee osteoarthritis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is a worldwide disease and more and more people are suffered from it. With the increasing number of patients, it brings a huge burden on social economy and security system. There are varieties of methods to cure KOA, such as Traditional Chinese Medicine and surgery. Needle knife therapy plus Sodium hyaluronate Injection is one of the prevalent treatments for KOA. Therefore, we perform a systematic review and meta-analysis to evaluate the evidence for the treatment of needle knife therapy plus sodium hyaluronate Injection. METHODS: Randomized controlled trials will be used to compare the effect of needle knife therapy plus sodium hyaluronate injection with needle knife alone for KOA patients. Six studies will be included in this meta-analysis, and the relative risk and weight mean difference with 95% CI for the Lysholm knee score, visual analogue scale, and effective rate will be evaluated by using RevMan 5.3 software. Besides, the bias assessment of the included studies will be evaluated using the Cochrane risk of bias tool, and the Grading of Recommendations, Assessment Development, and Evaluation system will be applied to assess the overall quality of the evidence. RESULTS: From the study we will assess the effectiveness, safety of needle knife therapy plus sodium hyaluronate injection on joint pain relief and functional improvement in patients with KOA. CONCLUSION: The study will provide a new evidence to confirm the effect of needle knife therapy plus sodium hyaluronate injection on KOA, which can further guide the selection of therapy. PROSPERO REGISTRATION NUMBER: CRD42020169602.

[Finite element analysis of bending and standing manipulation in the treatment of lumbosacral joint disorder].

OBJECTIVE: To analyze the displacement, stress and mechanism of lumbosacral joint disorder patients after bending and standing manipulation in the finite element model. METHODS: A three-dimensional finite element model of a patient with lumbosacral joint disorder was established. The finite element analysis method was used to observe and analyze the three loading conditions of the model:axial, 34 degree inclined upward and vertical upward. RESULTS: In the lumbosacral joint disorder model, the L5 vertebral body was concentrated in the middle of the lower endplate, the intervertebral disc was concentrated in the center of the intervertebral disc, and the stress of S1 and related structures were concentrated in the anterior and posterior edges of the vertebral body. After simulated manipulation, stress mainly concentrated in the anterior, posterior and central circular areas of L5 vertebral upper endplate. The posterior structures of vertebral body concentrated in the ventral part of pedicle, isthmus and dorsal part of lamina. The stress of intervertebral disc dispersed in the posterior edge of vertebral body. Displacement results:In the lumbosacral joint disorder model, the left transverse process, the upper and lower articular process and the left part of spinous process were significantly displaced to the left, and the intervertebral disc was protruded forward. After simulated manipulation, the lower notch of L5 vertebral body moved forward and upward; the area of intervertebral foramen increased; the inferior articular process of L5 vertebral body moved forward; the superior articular process of sacrum moved forward and downward; the distance of articular process joints increased; and the displacement of sacrum concentrated on the posterior edge of vertebral body and the median sacral crest. CONCLUSIONS: Successful lumbosacral joint modeling can be carried out by finite element analysis, and the mechanism of bending and erecting manipulation is clear, which is effective and safe for the treatment of lumbosacral joint disorders.

Acupuncture for the treatment of ankle sprain: A protocol for a systematic review and meta-analysis: study protocol.

BACKGROUND: Ankle sprain is one of the most common musculoskeletal injuries in our daily life, which may lead to chronic ankle instability, reducing the quality of patients' life and imposing a heavy burden on social medical security system. There are many kinds of methods treating ankle sprain, which can be divided into the conservative treatments and surgical intervention. Acupuncture is one of the conservative treatments for ankle sprain, especially in China. Therefore, we perform a systematic review and meta-analysis to evaluate the evidence for acupuncture's effectiveness, safety and cost benefits for the treatment. METHODS: For the acquisition of required data of eligible randomized controlled trials (RCTs), literature search will be undertaken from the following database: PubMed, Embase, Web of Science, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang database. Quality assessment of the included studies will be independently performed according to the Cochrane Risk of Bias Tool by 2 investigators and the level of evidence for results will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Statistical analysis will be conducted with Revman 5.3. RESULTS: From the study we will assess the effectiveness, safety and cost benefit of acupuncture on pain relief and functional improvement in patients with ankle sprain. CONCLUSION: The conclusion of this study will provide evidence to ensure the effectiveness, safety and cost benefits of acupuncture on ankle sprain, which can further guide the selection of appropriate interventions. PROSPERO REGISTRATION NUMBER: CRD42018116829.

[Effects of acupuncture on PI3K/Akt/mTOR signaling pathway in rats with premature ovarian failure].

OBJECTIVE: To explore the effects of acupuncture and medication on PI3K/Akt/mTOR signaling pathway in rats with premature ovarian failure. METHODS: Ten of fifty SPF-grade female SD rats were randomly selected into a normal group, and the remaining 40 rats were treated with intraperitoneal injection of cyclophospha mide (30 mg/kg) for consecutive 5 days to establish rat model of premature ovarian failure. Thirty five successful rat models were randomly divided into a model group (9 cases), a medication group (9 cases), an acupuncture group A (9 cases) and an acupuncture group B (8 cases). The rats in the model group and normal group did not receive any treatment. The rats in the medication group were treated with intragastric administration of diethylstil bestrol, once a day. The rats in the acupuncture group A and acupuncture group B were respectively treated with acupuncture at different acupoints, twice a day. All the treatment was given for 4 weeks. After the treatment, enzyme-linked immunosorbent assay (ELISA) was applied to test the levels of estradiol (E2), progesterone (P), follicle stimulating hormone (FSH) and luteotropic hormone (LH). The ovarian tissue sample was processed with hematoxylin eosin (HE) staining as well as RNA and protein extraction to test the mRNA expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERP), phosphatidylinositol 3-kinase/serine/threonine kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR). RESULTS: High-dose short-term in- tervention of cyclophosphamide could establish rat model of premature ovarian failure with a successful rate of 87.5%. Compared with the normal group, the vaginal smear in the model group was featured with signs of estro gen deficiency, early-follicle reduction, structural damage to the follicle, and reducing number of mature follicles; the level of E2 was significantly reduced (P<0.05), levels of P, FSH and ILH were increased (all P<0.05), and mRNA expression of estrogen-related ERP3, PI3K, Akt and mTOR were all reduced (all P<0.05). Compared with the model group, the number of mature follicle was increased in the medication group and acupuncture groups, the levels of E2 was obviously increased (all P<0.05). level of FSH was reduced (all P<0.05), and mRNA expression of PI3K, Akt and mTOR all showed an increasing trend (all P<0.05). The differences of each index result between acupuncture groups and medication group were not significant (all P>0.05). CONCLUSION: Acupuncture has certain advantage for the treatment of premature ovarian failure, which achieves similar therapeu tic effect as estrogen; the possible mechanism may be related to up-regulation of gene and protein expression in PI3K/Akt/mTOR signaling pathway.