[Effect of Bushen Huoxue（） recipe on autophagy of ovariectomized rat chondrocytes based on Akt/mTOR signaling pathway].

OBJECTIVE: To investigate whether Bushen Huoxue recipe can protect articular cartilage by regulating Akt/mTOR signaling pathway to promote the autophagy of chondrocytes in ovariectomized rats. METHODS: Among 30 SPF 12-week-old female SD rats weighing （247.0±7.0） g, 6 were randomly selected as the blank control group, and the remaining rats were randomly divided into model group, BSHXR-L group, BSHXR-M group and BSHXR-H group, with 6 rats in each group. The protective effect of Bushen Huoxue recipe on articular cartilage injury in rats was determined by visual observation score, muscovine O-solid green staining and immunohistochemistry. The expression of autophagy related proteins was detected by Western-blot, and the relative expression of Akt, mTOR and downstream autophagy genes was detected by qPCR. RESULTS: After modeling, BSHXR （L, M, H） groups could alleviate the histological damage of cartilage. Immunohistochemistry showed that the expression of Collagen-Ⅱand Aggrecan gradually increased, and the expression of MMP-13 gradually decreased, and the differences between BSHXR-M and BSHXR-H groups and model group were statistically significant （P<0.05）. The results of Western-blot showed that the autophagy pathway proteins p-Akt/Akt and p-mTOR/mTOR were inhibited in the BSHXR（L, M, H） groups, and the expressions of downstream proteins Beclin-1 and LC3Ⅱwere gradually increased, while p62 was gradually decreased, showing a dose effect. QPCR results showed that BSHXR（L, M, H） groups could promote the relative expression of Beclin-1 and LC3ⅡmRNA, and inhibit the relative expression of p62, Akt, mTOR mRNA, and the differences were statistically significant compared with model group （P<0.05）. CONCLUSION: Bushen Huoxue recipe can enhance the cartilage autophagy response by inhibiting the Akt/mTOR signaling pathway, and then protect the cartilage.

Consensus Paper: Ataxic Gait.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.

Effects of Golden Plaster on Knee Osteoarthritis: A Multicenter Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Golden plaster is the preferred and most commonly used in China for pain reduction in patients with knee osteoarthritis (OA). However, there was no evidence-based medical evidence about its effect in relieving pain of knee OA patients. Here, a multicenter randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy and safety of golden plaster for the improvement of pain relief and function's obstacle in patients with knee OA. METHODS: 320 patients with knee OA were enrolled at four hospitals and randomly divided into the treatment group and the control group with 160 subjects in each group. Patients in treatment group were treated with golden plaster, and those in control group with placebo plaster. The study cycle in both groups was 21 days. Patient visits were documented before treatment and 7-, 14-, and 21-day follow-ups after treatment. The outcomes included VAS score, WOMAC score, and adverse events. RESULTS: Compared to the control group, the VAS score in the treatment group was significantly decreased after treatment with golden plaster for 7 days, 14 days, and 21 days. Compared to the control group, the WOMAC score in the treatment group was significantly decreased 14 days and 21 days. The incidence rate of adverse events had no statistical difference between both the groups. CONCLUSIONS: In conclusion, our study, for the first time by carrying on the double-blind and placebo-controlled randomized trial, showed that golden plaster can effectively alleviate the pain of knee and improve the physical function in the patients with knee OA. This trial is registered with ChiCTR-TRC-13003418.

Effect of repetitive transcranial magnetic stimulation on patients with severe depression: a study protocol for systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Depression is characterised by easy recurrence, high disability and high burden, and antidepressant therapy is the standard treatment. However, its treatment effect on patients with severe depressive disorder has been unsatisfactory. Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS), as a neurotherapy, can effectively mitigate the severity of depressive symptoms. Yet, more evidence is still required for TMS to treat severe depression. This study will be the first systematic review of the efficacy and tolerability of TMS for treating severe depression. We expect it to guide future clinical practice of TMS for the treatment of psychiatric disorders. METHODS AND ANALYSIS: We will search for the randomised controlled trial (RCT) involving rTMS for treating depression in eight electronic databases, including PubMed, Web of Science, EMBASE, the Cochrane Library and Wanfang Database, from publication up to September 2021. We will define Improvement in depressive symptoms, the difference between pretreatment (baseline) and post-treatment as the primary outcomes. The difference between pretreatment and post-treatment changes in resting state fMRI will be regarded as the secondary outcomes. Quality assessment of the included articles will be independently performed according to the Cochrane Risk of Bias tool. ETHICS AND DISSEMINATION: Ethical approval is not essential because there is no need to collect individual patient data. And this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42020211460.

[Limited external fixation of plastic cardboard for the treatment of senile comminuted humeral fracture].

OBJECTIVE: To explore clinical efficacy of limited external fixation with plastic paperboard in treating senile proximal comminuted humeral fracture. METHODS: From June 2015 to December 2017, 32 senile patients with proximal comminuted fracture of humerus were treated with plasticized cardboard after manual external fixation. Among them, including 13 males and 19 females aged from 55 to 85 years old with an average of(68.22±8.36) years old; 18 patients on the left side and 14 patients on the right side; all patients were regularly review shoulder X-rays and performed appropriate functional exercises. Constant-Murley shoulder joint scoring was used to evaluate clinical effects. RESULTS: Thirty-two patients were followed up for 3 to 12 months with an average of (4.97±2.39) months. All patients were underwent functional exercise under guidance of physicians. Nine patients were treated with topical Chinese herbal moist heat compresses to promote shoulder function recovery. Thirty-one patients were obtained fracture healing, the time ranged from 5 to 12 weeks with an average of(7.44±1.72)weeks. One patient was not healed due to comminuted fracture of fracture end and the separation was large, the blood supply to humeral head was insufficient for necrosis absorption. Postoperative Constant-Murley shoulder score at 3 months was 87.56±6.93; 15 patients got excellent results, 14 good, 2 fair and 1 poor. CONCLUSIONS: Limited external fixation with plastic paperboard for the treatment of senile proximal comminuted humeral fracture could ensure biomechanical stability of fracture, promote early recovery of shoulder joint function and shorten recovery time.

Golden plaster for pain therapy in patients with knee osteoarthritis: study protocol for a multicenter randomized, double-blind, placebo-controlled trial.

BACKGROUND: Osteoarthritis is a relatively common musculoskeletal disorder that increases in prevalence with age. Worldwide, knee osteoarthritis is one of the leading causes of disability, particularly in the elderly. In numerous trials of agents for long-term pain therapy, no well-established and replicable results have been achieved. Complementary and alternative medical approaches have been employed for thousands of years to relieve knee osteoarthritis pain. Among herbal medicines, the golden plaster is the preferred and most commonlyused method in China to reduce pain in patients with knee osteoarthritis, as it causes few adverse effects. The purpose of this study will be to evaluate the efficacy and safety of golden plaster on pain in patients with knee osteoarthritis. METHODS/DESIGN: This study will be a multicenter randomized, double-blind, placebo-controlled trial. A total of 320 participants aged 45 to 79 years with knee osteoarthritis, whose scores on a visual analog scale (VAS) are more than 20 mm,will be randomly allocated into a treatment group and a control group. A golden plaster will be administered externally to participants in the treatment group for 2 weeks, while the control group will receive a placebo plaster externally for 2 weeks. Follow-up will be at regular intervals during a 4-week period with a VAS score for pain, quality of life, and complications. DISCUSSION: This study will be a methodologically sound randomized controlled trial to assess pain relief after the intervention of golden plaster, compared to a placebo intervention in patients with knee osteoarthritis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR-TRC-13003418.

[Study on the projection method based on principal component of tobacco near-infrared spectrum and application in redrying model].

The present paper briefly describes the application of near-infrared spectroscopy technology in tobacco. Two methods for solving projection vector based on the principal component of near-infrared spectrum are reported. They are named as projection of basing on principal component and Fisher criterion by principal component analysis method (PPF_PCA for short) and projection of basing on principal component and Fisher criterion by solving eigenvalue (PPF_Eig for short), and they are studied and compared in the application and evaluation of the redrying model. The result of the first-dimensional projection on 9 kinds of tobacco leaf grading samples shows that, the diversity of the first-dimensional projection values of inter-class and intra-class by the PPF_PCA method is both larger than that by the PPF_Eig method, and the mean absolute deviation of the mean projection values of inter-class by the PPF_PCA method is about 1.26 times that of the PPF_Eig method. At the same time, this result is interpreted by using the contribution rate of the first-dimensional projection values. That is, the contribution rate of first-dimensional projection values by the PPF_PCA method is 93%, while the contribution rate of first-dimensional projection values by the PPF_Eig method is 77%. The former is about 1.21 times the later. Therefore, the first-dimensional projection values by PPF PCA method include more information of diversity of both inter-class and intra-class. The similarity of samples inter-class and the diversity of samples intra-class can be evaluated more objectively from first-dimensional projection figure(on 9 kinds of tobacco leaf grading samples, 33 kinds of tobacco leaf grading samples and 6 redrying blending models), so it is more convenient to be used as a reference for the redrying model of tobacco, and it has a good application prospect in other formulation design of agricultural products (traditional Chinese medicine etc.).