Efficacy and safety of Dengyinnaotong Capsule in patients with Cognitive impairment caused by cerebral Small Vessel Disease: study protocol of a multicenter, randomized, open-label, controlled trial (De-CSVD trial).

BACKGROUND: Cerebral small vessel disease (CSVD) is a common syndrome in the older population, with a prevalence ranging from 5% in subjects aged 50 years to almost 100% in those aged 90 years and older. It is regarded to be a major cause of vascular cognitive impairment. Existing prevention and treatment approaches have not yet shown ideal clinical outcomes. Dengyinnaotong Capsule has shown great potential for improving cognitive function. This trial (De-CSVD trial) is designed to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive function in patients with CSVD . METHODS: This multicenter, randomized, open-label, controlled trial is planned to recruit at least 270 patients with mild cognitive impairment related to CSVD in 25 centers in China. Recruitment started on 10 May 2021 and is foreseen to end on 31 December 2022. The final follow-up of participants will be completed by the end of March 2023. Participants will be randomized in a ratio of 1:1 to the experimental group (routine basic treatment plus Dengyinnaotong Capsule) or the control group (routine basic treatment). The primary outcome is the change in the Montreal Cognitive Assessment score from baseline to week 12. Secondary outcomes are changes in Shape Trail Test, Activities of Daily Living, Geriatric Depression Scale, and Dizziness Handicap Inventory score from baseline to week 12, new vascular events, and the changes in serum level of homocysteine, high-sensitivity C-reactive protein, and D-dimer from baseline to week 4 and 12, respectively. The exploratory outcome is the changes in the Tinetti performance-oriented mobility assessment score from baseline to week 12. Safety assessment is performed by monitoring vital signs, general biochemical examinations, 12-lead electrocardiogram examinations, and incidence of cardiovascular and cerebrovascular ischemia or bleeding events. Visits will be performed at week 0 (baseline, pre-randomization), week 4, and week 12 in the treatment period (post-randomization). DISCUSSION: This trial is the first to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive impairment in patients with CSVD. The findings of this study might provide convincing evidence regarding the efficacy of Dengyinnaotong Capsule in patients with mild cognitive impairment related to CSVD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045831. Registered on 25 April 2021.

[Effects of wenhua juanbi recipe on TNF-alpha and IL-1beta in peripheral blood of rheumatoid arthritis patients].

OBJECTIVE: To observe the clinical effect of Wenhua Juanbi Recipe (WJR) in treating rheumatoid arthritis (RA), its effects in reducing the dosage of Western medicine used and stabilizing condition of disease, as well as its influences on peripheral blood levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and anti-cyclic citrullinated peptide antibody (anti-CCP), for the sake of exploring its preliminary acting mechanism. METHODS: One hundred patients with RA were randomly assigned to 2 groups, the control group and the treated group, 50 in each group. All were treated with oral administration of methotrexate (MTX,7.5 mg per week), sulfasalazine (0.5 g, tid) and meloxicam (Mobic, 7.5 mg, bid), but to the treated group WJR was given additionally. The therapeutic course for both groups was 3 months. Clinical effect, changes of symptoms and physical signs, dosages of western medicines used, and laboratory indices in 2 groups after treatment were observed, and cases of relapse 3 months after treatment were figured out. RESULTS: The total effective rate in the treated group was higher than that in the control group (88.0% vs 76.0%, P<0.05). The improvements in scores of symptoms and signs [joint pain (0.61 +/- 0.59), swelling (1.49 +/- 1.20), tenderness (0.90 +/- 0.69), movement (0.68 +/- 0.62), griping strength (68.56 +/- 6.50) mm Hg, morning stiff time (23.26 +/- 9.26) min], and in levels of laboratory indices (TNF-alpha, IL-1beta, anti-CCP, RF, ESR, CRP, PLT and Ig) in the treated group after treatment were significantly superior to those in the control group (P<0.05 or P<0.01). The dosages of MTX [(82.11 +/- 11.35) mg vs (94.75 +/- 10.23) mg] and meloxicam [(108.85 +/- 16.13) mg vs (189.63 +/- 18.44) mg] used, and the relapse rate in the treated group were lower significantly (P<0.05, P<0.01) than those in the control group respectively. CONCLUSIONS: Effect of combined therapy of WJR and Western medicines is superior to that of using Western medicines alone in treating RA; WJR can reduce the dosages of Western medicines used and the relapse rate, as well as stabilize the condition of illness. It has the effects of immune regulating and anti-inflammatory reaction. Its mechanism for treating RA is possibly the inhibition on cytokines of TNF-alpha and IL-1beta.

[Clinical randomized study of bee-sting therapy for rheumatoid arthritis].

OBJECTIVE: To observe the clinical effect of bee-sting (venom) therapy in the treatment of rheumatoid arthritis (RA). METHODS: One hundred RA patients were randomly divided into medication (control) group and bee-venom group, with 50 cases in each. Patients of control group were treated with oral administration of Methotrexate (MTX, 7.5 mg/w), Sulfasalazine (0.5 g,t. i.d.), Meloxicam (Mobic,7. 5 mg, b. i. d.); and those of bee-venom group treated with Bee-sting of Ashi-points and the above-mentioned Western medicines. Ashi-points were selected according to the position of RA and used as the main acupoints, supplemented with other acupoints according to syndrome differentiation. The treatment was given once every other day and all the treatments lasted for 3 months. RESULTS: Compared with pre-treatment, scores of joint swelling degree, joint activity, pain, and pressing pain, joint-swelling number, grasp force, 15 m-walking duration, morning stiff duration in bee-venom group and medication group were improved significantly (P<0.05, 0.01). Comparison between two groups showed that after the therapy, scores of joint swelling, pain and pressing pain, joint-swelling number and morning stiff duration, and the doses of the administered MTX and Mobic in bee-venom group were all significantly lower than those in medication group (P<0.05, 0.01); whereas the grasp force in been-venom group was markedly higher than that in medication group (P<0.05). In addition, the relapse rate of bee-venom group was obviously lower than that of medication group (P<0.05; 12% vs 32%). CONCLUSION: Combined application of bee-venom therapy and medication is superior to simple use of medication in relieving RA, and when bee-sting therapy used, the commonly-taken doses of western medicines may be reduced, and the relapse rate gets lower.

[Anatomic study of internal fixation of acetabular anterior column plate technique].

OBJECTIVE: To study the best entry points, direction and length of screw in acetabular anterior column plate technique, and to prevent the serious complications of screw penetrating the joint surface. METHODS: Twenty male cadaveric adult semi-pelvic specimen were taken, and the distance from anterior acetabular margin, posterior acetabular margin to anterior inferior iliac spine, iliopubic eminence and pubic tubercle were measured respectively. Determine and make serial cross-sections of the acetabular anterior column, measure the safe angle of screw entry on all entry points of each cross-section, and put all data into software SPSS 10.0 for statistics process. RESULTS: The distance from anterior acetabular margin to anterior inferior iliac spine, iliopubic eminence and pubic tubercle was (25.4 +/- 1.4) mm, (11.8 +/- 0.7) mm and (37.4 +/- 1.5) mm respectively, the distance from posterior acetabular margin to anterior inferior iliac spine, iliopubic eminence was (15.5 +/- 0.9) mm and (29.1 +/- 1.6) mm respectively. On each cross-section, the maximum of the safe entry angle of inclination in 0.5 cm, 1.0 cm and 1.5 cm entry point lateral to the linea terminalis of pelvis was (8.2 +/- 2.2) degrees , (14.9 +/- 3.4) degrees and (26.1 +/- 4.5) degrees respectively. CONCLUSIONS: When plate for internal fixation on acetabular region of anterior column is used, there are three ways to avoid screw penetrating the joint surface. The first way is using short screw in any direction; the second way is using long screw close to the linea terminalis of pelvis, the direction of the screw is parallel to the quadrilateral plate; the third way is using different entry angle and length according to different entry point.

Striatal GDNF administration increases tyrosine hydroxylase phosphorylation in the rat striatum and substantia nigra.

Glial cell line-derived neurotrophic factor (GDNF) improves motor dysfunction associated with aging in rats and non-human primates, in animal models of Parkinson's disease, and may improve motoric function in patients with advanced Parkinson's disease. These improvements are associated with increased dopamine function in the nigrostriatal system, but the molecular events associated with this increase are unknown. In these studies, 100 micro g of GDNF was injected into the striatum of normal aged (24-month-old) male Fischer 344 rats. The protein levels and phosphorylation of TH, ERK1/2, and related proteins were determined by blot-immunolabeling of striatum and substantia nigra harvested 30 days after injection. In GDNF-treated rats, TH phosphorylation at Ser31 increased approximately 40% in striatum and approximately 250% in the substantia nigra. In the substantia nigra, there was a significant increase in ERK1 phosphorylation. In striatum, there was a significant increase in ERK2 phosphorylation. Microdialysis studies in striatum showed that both amphetamine- and potassium-evoked dopamine release in GDNF recipients were significantly increased. These data show that GDNF-induced increases in dopamine function are associated with a sustained increase in TH phosphorylation at Ser31, which is greatest in the substantia nigra and maintained for at least one month following a single striatal administration of GDNF. These findings, taken from the nigrostriatal system of normal aged rats, may help explain the long lasting effects of GDNF on dopamine function and prior studies supporting that a major effect of GDNF involves its effects on dopamine storage and somatodendritic release of dopamine in the substantia nigra.