[Treatment of Knee Osteoarthritis with Acupuncture plus Intra-articular Injection of Sodium Hyaluronate].

OBJECTIVE: To examine the clinical benefits of acupuncture combined with intra-articular injection of sodium hyaluronate for knee osteoarthritis (KOA) patients. METHODS: A total of 150 KOA patients were randomized into simple medication and acupuncture plus medication (combined treatment) groups (n＝75 in each). For all the patients, intra-articular injection of sodium hyaluronate (2 mL) was performed once a week for 5 weeks, and for patients of the combined treatment group, filiform needles were separately inserted into unilateral or bilateral Zusanli (ST 36), Liangqiu (ST 34), Yanglingquan (GB 34), Yinlingquan (SP 9), Xiyangguan (GB 33), Dubi (ST 35), Neixiyan (EX-LE 4) and Xuehai (SP 10) according to the focus, and manipulated with the uniform reinforcing and reducing technique, followed by retaining the needles for 30 min. The acupuncture treatment was given once every day or every other day, 5 weeks in total. The visual analog scale (VAS) was used to assess the pain severity of knee-joint, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) employed to assess the 1) pain severity during various positions or movements (20 points), 2) severity of joint stiffness (8 points), and 3) difficulty in performing daily functional activities (68 points). The therapeutic effect was evaluated according to the decreased level of WOMAC subscale scores and improvement of daily activities. RESULTS: After the treatment, the VAS scores of both medication and combined treatment groups were decreased significantly in comparison with their own pre-treatment in each group (P<0.05), and that of the combined treatment group was significantly lower than that of the medication group (P<0.05). WOMAC and daily activity fin-dings showed that of the two 75 KOA patients in the medication and combined treatment groups, 16 (21.33%) and 32 (42.67%) experienced marked improvement, 46 (61.33%) and 38 (50.67%) were improved, and 13 (17.33%) and 5 (6.67%) ineffective, with the total effective rates being 82.67% and 93.33%, respectively. The therapeutic effect of the combined treatment group was apparently superior to that of the simple medication group (P<0.05). CONCLUSION: Acupuncture combined with intra-articular injection of sodium hyaluronate is effective in improving KOA patients' pain severity and other symptoms as well as functional activities.

Safety and feasibility of chronic transvenous phrenic nerve stimulation for treatment of central sleep apnea in heart failure patients.

INTRODUCTION: Central sleep apnea (CSA) is common in patients with heart failure (HF) and is associated with poor quality of life and prognosis. Early acute studies using transvenous phrenic nerve stimulation (PNS) to treat CSA in HF have shown a significantly reduction of CSA and improvement of key polysomnographic parameters. In this study, we evaluated the safety of and efficiency chronic transvenous PNS with an implanted neurostimulator in HF patients with CSA. METHODS: This study was a prospective, nonrandomized evaluation of unilateral transvenous PNS in eight HF patients with CSA. The stimulation lead, which connected to a proprietary neurostimulator, was positioned in either the left pericardiophrenic or right brachiocephalic vein. Monitoring during implantation and 6-monthly follow-ups were performed. RESULTS: Six of the implanted eight patients completed the study (one was lost to follow-up; one died from pneumonia). Neither side effects nor adverse events related to stimulation occurred. During the 6-monthly follow-ups, one patient had a lead dislodgement in the first month and the lead was subsequently repositioned. No additional lead dislodgements occurred. There were no significant changes in sleep habits, appetite, bleeding or infections. Compared with the parameters before stimulator implantation, there were significant improvement in apnea-hypopnea index, central apnea index, left ventricular ejection fraction and 6-min walk distance (all P < 0.01). CONCLUSIONS: Use of chronic transvenous PNS appears to be safe and feasible in HF patients with CSA. Large multicenter studies are needed to confirm safety and efficacy in this population.

[Chemical constituents from Barringtonia racemosa].

To investigate the chemical constituents from Barringtonia racemosa, twelve compounds were isolated by chromatography methods and identified as 3ß-p-E-coumaroymaslinic acid (1), cis-careaborin (2), careaborin (3), maslinic acid (4), 2α, 3ß, 19α-trihydroxyolean-12-ene-24, 28-dioic acid (5), 3ß-p-Z-coumaroylcorosolic acid (6), corosolic acid (7), 1α, 2α, 3ß, 19α-tetrahydroxyurs-12-en-28-oic acid (8), 19α-hydroxyl ursolic acid (9), 3α, 19α-dihydroxyurs-12-en-24, 28-dioic acid (10), tormentic acid (11), 3-hydroxy-7, 22-dien-ergosterol（12） by the NMR and MS data analysis. Among them, compounds 1-4,7-12 were obtained from the genus Barringtonia for the first time. All the compounds didn't show nocytotoxic activity against MCF-7 and A549 cell lines (IC50>50 mg•L⁻¹).

Adiponectin protects rat myocardium against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.

Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders such as heart failure, hypertension, atherosclerosis, and arrhythmia and so on. Of the many associated factors, chronic intermittent hypoxia (CIH) in particular is the primary player in OSAS. To assess the effects of CIH on cardiac function secondary to OSAS, we established a model to study the effects of CIH on Wistar rats. Specifically, we examined the possible underlying cellular mechanisms of hypoxic tissue damage and the possible protective role of adiponectin against hypoxic insults. In the first treatment group, rats were exposed to CIH conditions (nadir O2, 5-6%) for 8 hours/day, for 5 weeks. Subsequent CIH-induced cardiac dysfunction was measured by echocardiograph. Compared with the normal control (NC) group, rats in the CIH-exposed group experienced elevated levels of left ventricular end-systolic dimension and left ventricular end-systolic volume and depressed levels of left ventricular ejection fraction and left ventricular fractional shortening (p<0.05). However, when adiponectin (Ad) was added in CIH + Ad group, we saw a rescue in the elevations of the aforementioned left ventricular function (p<0.05). To assess critical cardiac injury, we detected myocardial apoptosis by Terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) analysis. It was showed that the apoptosis percentage in CIH group (2.948%) was significantly higher than that in NC group (0.4167%) and CIH + Ad group (1.219%) (p<0.05). Protein expressions of cleaved caspase-3, cleaved caspase-9, and cleaved-caspase-12 validated our TUNEL results (p<0.05). Mechanistically, our results demonstrated that the proteins expressed with endoplasmic reticulum stress and the expression of reactive oxygen species (ROS) were significantly elevated under CIH conditions, whereas Ad supplementation partially decreased them. Overall, our results suggested that Ad augmentation could improve CIH-induced left ventricular dysfunction and associated myocardial apoptosis by inhibition of ROS-dependent ER stress.

Adiponectin protects the genioglossus of rats against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome, characterized by chronic intermittent hypoxia (CIH), is closely correlated with genioglossus dysfunction. CIH has been identified to mediate mitochondrial damage in genioglossus. It has been reported that endoplasmic reticulum stress (ERS) could be induced by mitochondrial dysfunction. This study aimed to investigate the role of ERS in CIH-induced genioglossus injury, as well as the possible intervention effect of adiponectin (Ad) supplement in rats. METHODS: Forty-five male Wistar rats were randomly divided into three groups and submitted to room air (group A, n=15) as a control or CIH (groups B and C, n=15, respectively). Throughout the exposure period, intravenous Ad was given in group C; while intravenous normal saline was simultaneously given in groups A and B. After 35-day exposure, genioglossus samples were obtained from the pentobarbital-anaesthetized rats via surgical dissection, following blood sampling. Western blotting was applied to detect expressions of ERS signals and associated apoptotic pathways in genioglossus. Serum adiponectin levels were assessed via enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant hypoadiponectinemia was revealed in group B only (P < 0.05). Compared to those in groups A and C, expressions of markers involved in ERS, such as glucose regulated protein 78 (GRP78), p-PERK, phosphorylated eukaryotic initiation factor 2a (p-eIF2a), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1a (p-IRE1a), spliced X-Box binding protein 1 (XBP1s) and activating transcription factor 6 (ATF6), were significantly enhanced in group B (all P < 0.01); while no significant difference was shown between groups A and C (all P > 0.05). ERSassociated apoptotic pathways were remarkably activated in group B. The involved markers detected as the expression of CCAAT/enhancer binding protein homologous protein (CHOP), B-cell lymphoma/leukemia associatied X protein (BAX) and caspase-12 were significantly elevated (all P < 0.01). Transvenous adiponectin supplement improved the above CIHinduced pathological changes in group C. CONCLUSION: Beyond hypoadiponectinemia, CIH could enhance ERS and induce activation of ERS-associated apoptotic pathways in genioglossus, which could be significantly improved by adiponectin supplement.

Transvenous phrenic nerve stimulation in patients with Cheyne-Stokes respiration and congestive heart failure: a safety and proof-of-concept study.

BACKGROUND: Cheyne-Stokes respiration (CSR), which often occurs in patients with congestive heart failure (CHF), may be a predictor for poor outcome. Phrenic nerve stimulation (PNS) may interrupt CSR in patients with CHF. We report the clinical use of transvenous PNS in patients with CHF and CSR. METHODS: Nineteen patients with CHF and CSR were enrolled. A single stimulation lead was placed at the junction between the superior vena cava and brachiocephalic vein or in the left-side pericardiophrenic vein. PNS stimulation was performed using Eupnea System device (RespiCardia Inc). Respiratory properties were assessed before and during PNS. PNS was assessed at a maximum of 10 mA. RESULTS: Successful stimulation capture was achieved in 16 patients. Failure to capture occurred in three patients because of dislocation of leads. No adverse events were seen under maximum normal stimulation parameters for an overnight study. When PNS was applied following a series of central sleep apneic events, a trend toward stabilization of breathing and heart rate as well as improvement in oxygen saturation was seen. Compared with pre-PNS, during PNS there was a significant decrease in apnea-hypopnea index (33.8 ± 9.3 vs 8.1 ± 2.3, P = .00), an increase in mean and minimal oxygen saturation as measured by pulse oximetry (89.7% ± 1.6% vs 94.3% ± 0.9% and 80.3% ± 3.7% vs 88.5% ± 3.3%, respectively, all P = .00) and end-tidal CO2 (38.0 ± 4.3 mm Hg vs 40.3 ± 3.1 mm Hg, P = .02), but no significant difference in sleep efficiency (74.6% ± 4.1% vs 73.7% ± 5.4%, P = .36). CONCLUSIONS: The preliminary results showed that in a small group of patients with CHF and CSR, 1 night of unilateral transvenous PNS improved indices of CSR and was not associated with adverse events.

Effects of chronic intermittent hypoxia on genioglossus in rats.

OBJECTIVE: The objective of this study was to investigate the effects of chronic intermittent hypoxia (CIH) on genioglossal ultrastructure and mitochondrial function as well as the intervention role of adiponectin (Ad). METHODS: Forty-two Wistar rats were randomly divided into three groups with 14 rats in each. Rats in group A were kept breathing normal air, while rats in both groups B and C received the same CIH environment (a 2-min cycle, 1 min on, 1 min off with a nadir O(2) at 4-5%, 8 h/day for successive 5 weeks). However, rats in group C was given regular intravenous Ad injection (10 µg per time, twice a week for successive 5 weeks). A simultaneous intravenous injection of saline (0.5 ml per time) was carried in groups A and B. At the end of experiment, the genioglossal ultrastructure, the serum adiponectin levels, the mitochondrial membrane potential (ΔΨ(m)), and activities of respiratory chain complexes I and IV in mitochondrion of genioglossal cells were compared among groups. RESULTS: Serum Ad level was significantly lower in group B than that in group A (P < 0.01). In group B, there were genioglussal myofibril discontinuities, lysis of myofilament, edema of mitochondria, and disruption of cristae, vacuolus, and lysis of some mitochondria. These pathological changes were less significant in group C. The relative value of ΔΨ(m) was the lowest in group B but the highest in group A (P < 0.01), with group B in between. The concentrations of mitochondrial complexes I and IV in group B were the lowest but became higher and higher from group C to A, with a significant difference among groups (all P < 0.05). CONCLUSION: CIH could lead to hypoadiponectinemia, impaired genioglossal ultrastructure, and mitochondrial dysfunction. These changes could be improved by supplement of Ad.

[Effect of chronic intermittent hypoxia on mitochondrial function of rat genioglossus cells and intervention role of adiponectin].

OBJECTIVE: To investigate the effect of chronic intermittent hypoxia (CIH) on mitochondrial function in genioglossus cells of rats and intervention role of adiponectin (Ad). METHODS: Thirty-nine healthy male Wistar rats were randomly divided into 3 groups, normal control (NC) group, CIH group and CIH + Ad group with 13 rats in each. Rats in NC group were kept breathing normal air, while rats in both CIH and CIH + Ad groups experienced the same CIH environment (CIH 8 h/day for successive 5 weeks). However, rats in CIH + Ad group was given intravenous Ad supplement at the dosage of 10 µg, twice a week for successive 5 weeks. At the end of experiment (day 35), the levels of plasma adiponectin, mitochondrial membrane potential activities of respiratory chain complexes I and IV in mitochondrion of genioglossus cells were compared among different groups. RESULTS: Serum Ad level was significantly lower in CIH group than that in NC group [(1108 ± 112) ng/ml vs (2241 ± 121) ng/ml, P < 0.01]. Serum Ad level in CIH + Ad group [(1889 ± 119) ng/ml] was significantly higher than that in NC group but lower than that in CIH group (all P < 0.01). Mitochondrial membrane potential was significantly lower in CIH group than that in NC group [(1.82 ± 0.11) vs (2.09 ± 0.14), P < 0.01]. Mitochondrial membrane potential in CIH + Ad group (1.98 ± 0.09) was higher than that in CIH group but lower than that in NC group (all P < 0.05). The concentrations of mitochondrial respiratory chain complexes I and IV in CIH group (35.68 ± 1.73) µmol×min(-1)×mg(-1) and (2.37 ± 0.11) nmol×min(-1)×mg(-1), respectively) were the lowest but became higher from CIH + Ad group [(37.18 ± 1.95) µmol×min(-1)×mg(-1) and (2.49 ± 0.09) nmol×min(-1)×mg(-1), respectively] to NC group (39.02 ± 1.38) µmol×min(-1)×mg(-1) and (2.81 ± 0.12) nmol×min(-1)×mg(-1), respectively), with a significant difference between NC and CIH groups (P < 0.01), between CIH + Ad and CIH groups (P < 0.05), as well as between CIH + Ad and NC groups (P < 0.05). CONCLUSION: CIH could lead to hypoadiponectinemia and impaired mitochondrial function in genioglossus cells of rats. Since such changes could be partially improved by supplement of adiponectin, it was suggested that hypoadiponectinemia might be involved in CIH-induced impairment of genioglossus energy metabolism.