Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

Pingchan Granule for Motor Symptoms and Non-Motor Symptoms of Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: Pingchan granule (PCG) is a traditional Chinese medicine for treating Parkinson's disease (PD). Objective: This study aimed at evaluating the efficacy and safety of PCG for motor and non-motor symptoms of PD. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 292 participants with mild-to-moderate PD were included and followed for 36 weeks (24 week treatment, 12-week follow-up after intervention), randomly assigned at a 1:1 ratio to receive PCG or placebo. The primary outcomes included the severity of motor symptoms assessed by the Unified Parkinson's disease Rating Scale (UPDRS) part 3 (UPDRS-III) score and the rate of disease progression assessed by the total UPDRS score. Secondary outcomes included non-motor symptoms assessed using the Scale for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), Parkinson's disease Sleep Scale (PDSS), 24-item Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), UPDRS part 2 (UPDRS-II), and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores. Assessments were done at baseline (T0), 12 weeks (T1), 24 weeks (T2), and 36 weeks (T3). Results: Generalized estimating equation analyses revealed that the PCG group had significantly better improvement in UPDRS-III score at T1, T2, and T3 [time-by-group interaction, T1: ß, -0.92 (95% CI, -1.59--0.25; p = 0.01); T2: ß, -2.08 (95% CI, -2.90--1.27; p < 0.001); T3: ß, -4.54 (95% CI, -5.37--3.71; p < 0.001))]. The PCG group showed a greater decrease (rate of disease change) in the total UPDRS score between T0 and T2 [-2.23 (95% CI, -2.72--1.73; p < 0.001) points per week vs. -0.21 (95% CI, -0.80-0.39; p = 0.50) points per week in the placebo group, p < 0.001]. Ameliorations of SCOPA-AUT, PDSS, HAM-D, HAM-A, UPDRS-II, and PDQ-39 scores were also observed. Conclusion: PCG had a long-lasting and extensive symptomatic efficacy for both motor and non-motor symptoms of PD with good tolerance. Trial registration: Chinese Clinical Trial Register, ChiCTR-INR-17011949.

Hyperbaric Oxygen Preconditioning Protects Against Cerebral Ischemia/Reperfusion Injury by Inhibiting Mitochondrial Apoptosis and Energy Metabolism Disturbance.

Hyperbaric oxygen (HBO) therapy is considered a safe and feasible method that to provide neuroprotection against ischemic stroke. However, the therapy mechanisms of HBO have not been fully elucidated. We hypothesized that the mechanism underlying the protective effect of HBO preconditioning (HBO-PC) against cerebral ischemia/reperfusion injury was related to inhibition of mitochondrial apoptosis and energy metabolism disorder. To test this hypothesis, an ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in rats. HBO-PC involved five consecutive days of pretreatment before MCAO. In additional experiments, X chromosome-linked inhibitor of apoptosis protein (XIAP) and second mitochondria-derived activator of caspases (SMAC) shRNA and NC plasmids were intraventricularly injected into rat brains after MCAO (2 h). After 24 h, all rats underwent motor function evaluation, which was assessed by modified Garcia scores. TTC staining for the cerebral infarct and cerebral edema, and TUNEL staining for cell apoptosis, were also analyzed. Reactive oxygen species and antioxidative enzymes in rat brains were detected, as well as mitochondrial complex enzyme activities, ATP levels, and Na+/K+ ATPase activity. Western blot was used to detect apoptotic proteins including Bcl-2, Bax, caspase-3, caspase-9, cyc-c, XIAP, and SMAC. HBO-PC remarkably reduced the infarct volume and improved neurological deficits. Furthermore, HBO-PC alleviated oxidative stress and regulated the expression of apoptosis-related proteins. Moreover, HBO-PC inhibited the decrease in ATP levels, mitochondrial complex enzyme activities, and Na+/K+ ATPase activity to maintain stable energy metabolism. XIAP knockdown weakened the protective effect of HBO, whereas SMAC knockdown strengthened its protective effect. The effects of HBO-PC can be attributed to inhibition of ischemia/hypoxia-induced mitochondrial apoptosis and energy metabolism disturbance. The action of HBO-PC is related to the XIAP and SMAC signaling pathways.

[Effects of Chinese herbal medicine Tianqi Pingchan Granule on G protein-coupled receptor kinase 6 involved in the prevention of levodopa-induced dyskinesia in rats with Parkinson disease].

OBJECTIVE: To investigate the effects of Tianqi Pingchan (TQPC) Granule, a compound traditional Chinese herbal medicine with antitremor activity, on levodopa-induced dyskinesia and the expression of G protein-coupled receptor kinase 6 (GRK6) in rats with Parkinson disease (PD). METHODS: The hemi-Parkinsonian rat model was established by sterotaxically injecting 6-hydroxydopa (6-OHDA) to the right medial forebrain bundle. Rats with PD were randomly divided into 5 groups with 5 in each. PD group was intraperitoneally injected with vitamin C; levodopa group was intraperitoneally injected with levodopa and benserazide; low-, medium- and high-dose TQPC Granule groups were intraperitoneally injected with levodopa and benserazide and treated with different dosages of TQPC Granule by gavage for 29 d. Another 5 rats were served as control with sham-operation. The behaviors of rats were observed and classified with abnormal involuntary movement (AIM) score. The expression of GRK6 in the striate of rats was detected by immunohistochemical method and Western blotting. RESULTS: AIM score was increased and the expression of GRK6 protein in lesion side was decreased after the long-tern treatment with levodopa and benserazide in rats. The AIM scores of rats with PD were decreased after TGPC Granule treatment. Immunohistochemical results showed that the number of GRK6-positive cells in medium- and high-dose TQPC Granule groups was increased as compared to that in the levodopa group (P<0.05). The expression level of GRK6 protein was increased in medium-dose TQPC Granule group when compared with the levodopa group (P<0.01), which was observed by Western blotting. CONCLUSION: TGPC Granule can increase the expression of GRK6, inhibit the increase of AIM, and reduce the incidence of levodopa-induced dyskinesia in rats with PD.

[Analysis of antibiotics treatment in 86 cases of liver transplant recipients].

OBJECTIVE: To analyze the characteristic of bacterial infections, and the relationship between antibiotics treatment and bacterial infections after liver transplantation, and to prevent antibiotic-resistant bacterial infections. METHODS: 86 liver transplant recipients were retrospected. Different indexes including limited daily dose, the frequency of medication, drug use index were used to evaluate the rationality of the use of antibiotics, three-dimensional test was used to explore extended-spectrum beta-lactamase and AmpC enzyme of Gram-negative bacteria. RESULTS: The major pathogens of infection after liver transplantation were Enterococcus faecalis, Enterobacter cloacae, fungi and E. coli. Pre-operative antibiotic utilization rate was 83.7%, it was mainly a single use of antibiotics; After- operative antibiotic usage was 100.0%, it was mainly joint use of two or three antibiotics; The top 3 antibiotics used were cephalosporins, the combined enzyme inhibitors and penicillin. Antibiotics with drug utilization index (DUI) more than 1.1 included ampicillin and Lalin proxy. 43.3% and 31.8% of Gram -Negative bacteria produced ESBLs and AmpC, respectively, while 21.3% Gram -Negative bacteria produced two enzymes. CONCLUSION: There is high incidence of bacterial infections after liver transplantation. The use of antibiotics is high dose, high-frequency and reasonable; High resistance of bacterial infections was prone to develop and the prevention of the high resistance of bacterial infections is very important.

The osteoprotective effect of Radix Dipsaci extract in ovariectomized rats.

AIM: The objective of the present study was to systematically evaluate the effects of Radix Dipsaci extract (RDE) on postmenopausal osteoporosis. MATERIALS AND METHODS: OVX or sham operations were performed on sixty 3-month-old virgin Sprague-Dawley rats that were divided into six groups: sham control group (sham, n=10); OVX control group (OVX, n=10); 17beta-estradiol treatment group (E2, n=10); three Radix Dipsaci extract treatment groups RDE100 (n=10), RDE300 (n=10) and RDE500 (n=10). The treatment began 4 weeks after the surgery and lasted for 16 weeks. Bone mass, bone turnover and strength were analyzed by DEXA, biochemical markers and three-point bending test. The trabecular bone microarchitecture was evaluated by MicroCT. RESULTS: 16 weeks treatment of RDE slowed down the body weight gain and prevented the loss of bone mass induced by the OVX. The prevention effect on bone loss was due to altering the rate of bone remodeling, which could be inferred from the decreased level of bone turnover markers, such as serum ALP, OC and urinary DPD. The changes of urinary calcium and phosphorus excretion provided the same evidence. The treatment could also enhance the bone strength and prevent the deterioration of trabecular microarchitecture. CONCLUSIONS: Our study provides evidence that Radix Dipsaci extract will have potential to be used for treatment of postmenopausal osteoporosis.

Protective effects of Rheum tanguticum polysaccharide against hydrogen peroxide-induced intestinal epithelial cell injury.

AIM: To describe the effect of Rheum tanguticum polysaccharide (RTP) on hydrogen peroxide-induced human intestinal epithelial cell injury. METHODS: Hydrogen peroxide (100 micromol/L) was introduced to induce human intestinal epithelial cell injury. Cells were pretreated with RTP (30,100,300 microg/mL) for 24 h before exposure to hydrogen peroxide. Cell viability was detected by MTT assay and morphological observation. Acridine orange staining and flow cytometry were performed to assess cell apoptosis. Lactate dehydrogenase (LDH) activity, production of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by spectrophotometry with corresponding assay kits. RESULTS: Following exposure to H(2)O(2), a marked decrease in cell survival and SOD activity, increased production of MDA, LDH leakage and cell apoptosis were found. Pretreatment of the cells with RTP could significantly elevate cell survival, SOD activity and decrease the level of MDA, LDH activity and cell apoptosis. CONCLUSION: RTP may have cytoprotective and anti-oxidant effects against H(2)O(2)-induced intestinal epithelial cell injury by inhibiting cell apoptosis and necrosis. This might be one of the possible mechanisms of RTP for the treatment of ulcerative colitis in rats.