Berberine improves intralipid-induced insulin resistance in murine.

Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 µM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature; BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.

FSHR ablation induces depression-like behaviors.

Alteration in reproductive hormones profile is associated with the increasing risk of menopausal depression in women. Serum follicle-stimulating hormone (FSH) level is changed during the menopause transition, while the effect of FSH on menopausal depression has remained undefined. In this study we investigated whether or how FSH affected menopausal depression in postmenopausal (ovariectomized) FSHR knockout mice (Fshr-/-). We found that Fshr-/- mice displayed aggravated depression-like behaviors, accompanied by severe oxidative stress in the whole brain, resulted from significantly reduced glutamate cysteine ligase modifier subunit (GCLm) in glutathione synthesis and glucose-6-phosphate dehydrogenase (G6PD) in NADP/NADPH transition. Importantly, administration of ROS scavenger N-acetyl cysteine (NAC, 150 mg · kg-1 · d-1, i.p. for 12 weeks) attenuated the depression-like behaviors of Fshr-/- mice. Consistent with these in vivo experiment results, we found that pretreatment with FSH (50, 100 ng/mL) dose-dependently increased protein levels of GCLm and G6PD, and decreased the ROS production in N2a mouse neuroblastoma cells. These findings demonstrate that FSH signaling is involved in pathogenesis of menopausal depression, and likely to maintain the redox-optimized ROS balance in neurons.

HuoXue QianYang QuTan Recipe attenuates left ventricular hypertrophy in obese hypertensive rats by improving mitochondrial function through SIRT1/PGC-1α deacetylation pathway.

Mitochondrial dysfunction plays a vital role in the progression of left ventricular hypertrophy (LVH). Previous studies have confirmed that the disorder of SIRT1/PGC-1α deacetylation pathway aggravated mitochondrial dysfunction. HuoXue QianYang QuTan Recipe (HQQR) is a commonly used prescription that has shown therapeutic effects on obesity hypertension and its complications. However, the potential mechanisms are still unclear. In the present study, obesity hypertension (OBH) was established in rats and we investigated the efficacy and mechanisms of HQQR on LVH. Rats were divided into the five groups: (1) WKY-ND group, (2) SHR-ND group, (3) OBH-HF group, (4) OBH-HF/V group and (5) OBH-HF/H group. We evaluated body weight, Lee index and blood pressure (BP) before and every 2 weeks after treatment. After 10 weeks of treatment, we mainly detected glycolipid metabolic index, the severity of LVH, mitochondrial function along with SIRT1/PGC-1α deacetylation pathway. Our results showed that HQQR significantly lowered body weight, Lee index, BP and improved the disorder of glycolipid metabolism in OBH rats. Importantly, we uncovered HQQR could alleviate mitochondrial dysfunction in OBH rats by regulating SIRT1/PGC-1α deacetylation pathway. These changes could be associated with the inhibition of LVH.

Clinical Profile and Significance of Mucocutaneous Lesions of Primary Sjögren's Syndrome: A Large Cross-sectional Study with 874 Patients.

BACKGROUND: Mucocutaneous lesions are common features of primary Sjögren's syndrome (pSS), but only a few studies have focused on them. To demonstrate the profile of mucocutaneous lesions of pSS and further explore their potential clinical significance, we performed a cross-sectional study on 874 patients. METHODS: Demographic data, clinical manifestations, and laboratory results of 874 pSS patients were collected. Patients were divided into two groups according to the presence of mucocutaneous lesions. Differences in primary symptoms and systemic impairments between the two groups were analyzed. Results of laboratory tests were also compared after excluding those who had taken corticosteroid from both groups. One-year follow-up was done, and occurrences of various new complications were compared. RESULTS: Among the 874 pSS patients, 181 patients had mucocutaneous lesions, accounting for 20.7%. Multiple mucocutaneous manifestations were displayed, and the top four most common types of lesions were purpuric eruptions (39.8%), urticaria (23.8%), Raynaud's phenomenon (14.9%), and angular stomatitis (9.9%). Incidences of pulmonary interstitial fibrosis, pulmonary bullae, leukopenia, and anemia were significantly higher among patients with mucocutaneous lesions (P < 0.05). Increase in IgG and decrease in C4 among patients with mucocutaneous lesions displayed statistical significance after excluding patients from both groups who had taken corticosteroid (P < 0.05). After one-year follow-up, patients with mucocutaneous lesions presented a slightly higher incidence of new complications compared to those without. CONCLUSIONS: Mucocutaneous manifestations of pSS patients were common and diverse. Patients with mucocutaneous manifestations had more systemic damages, higher level of IgG, and lower level of serum C4, suggesting a higher activity of the primary disease.

[Temporal and spatial variations of extreme climatic events in Songnen Grassland, Northeast China during 1960-2014]. / 1960­2014年松嫩草地极端气候事件的时空变化.

Fourteen extreme climatic indices related with main regional meteorological disasters and vegetation growth were calculated based on daily data from 13 meteorological stations during 1960-2014 in Songnen Grassland, Northeast China. Then, the variation trend and the spatial and temporal patterns of climatic extreme events were analyzed by using regression analysis, break trend analy-sis, Mann-Kendall test, Sen's slope estimator and moving t-test method. The results indicated that summer days (SU25), warm days (TX90P), warm nights (TN90P) and warm spell duration (WSDI) representing extremely high temperatures showed significant increasing trends (P<0.05). Meanwhile, frost days (FD0), cold days (TX10P), cold nights (TN10P) and cold spell duration indicator (CSDI) representing extremely low temperatures showed obviously decreasing trends. The magnitudes of changes in cold indices (FD0, TX10P, TN10P and CSDI) were clearly greater than those of warm indices (SU25, TX90P, TN90P and WSDI), and that changes in night indices were larger than those of day indices. Regional climate warming trend was obvious from 1970 to 2009, and the most occurrences of the abrupt changes in these indices were identified in this period. The extreme precipitation indices did not show obvious trend, in general, SDII and CDD experienced a slightly decreasing trend while RX5D, R95P, PRCPTOT and CWD witnessed a mildly increasing trend. It may be concluded that regional climate changed towards warming and slightly wetting in Songnen Grassland. The most sensitive region for extreme temperature was distributed in the south and north region. Additionally, the extreme temperature indices showed clearly spatial difference between the south and the north. As for the spatial variations of extreme precipitation indices, the climate could be characterized by becoming wetter in northern region, and getting drier in southern region, especially in southwestern region with a high drought risk.

[Clinical Observation of Chaihu Guizhi Decoction in Treating SAPHO Syndrome].

Objective To evaluate the clinical efficacy and safety of Modified Chaihu Guizhi De- coction on SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Methods Totally 40 patients with SAPHO syndrome were randomized to the treatment group(20 cases) and control group(20 cases). The treatment group was treated with Modified Chaihu Guizhi Decoction, and the control group with alendronate sodium 70 mg each week. The therapeutic course for all was 12 weeks. The Visual Analogue Scale (VAS) pain scores, bath ankylosing spondylitis activity index (BASDAI) , bath ankylosing spondylitis functional index(BASFI) , erythrocyte sedimentation rate(ESR) and hypersensitivity C reactive protein (hs-CRP) were measured before and after treatment. Adverse events were observed. Results The VAS, BASDAI, and BASFI score significantly improved compared with baseline in the treatment group (P <0. 01 , P <0. 05). The VAS and BASDAI score of the treatment group improved compared with the control group after treatment (P <0. 05). Three patients in the control group reported adverse events with digestive tract symptoms, while there was no obvious adverse drug reactions in the treatment group. Conclusions Modified Chaihu Guizhi Decoction was superior to alendronate sodium in the treat- ment of SAPHO syndrome without obvious adverse drug reactions.

[Gastric dynamics analysis of TEAS combined SNP induced general anesthesia when controlled hypotension dropped to 60% of the MAP baseline].

OBJECTIVE: To observe the effect of gastric dynamics by transcutaneous electrical acupoint stimulation (TEAS) combined general anesthesia when controlled hypotension dropped to 60% of the mean arterial prenssure (MAP) baseline, and to provide experimental evidence for organ protection in clinical controlled hypotension. METHODS: Eighteen male beagles were randomly divided into three groups, the general anesthesia group (blank), the general anesthesia induced controlled hypotension group (control), and the general anesthesia combined TEAS induced controlled hypotension group (experiment), 6 in each group. Controlled hypotension was performed in the latter two groups with isoflurane inhalation and intravenous injection of sodium nitroprusside (SNP). The mean arterial pressure (MAP) was lowered to 60% of the MAP baseline and kept for 60 min. Controlled hypotension was not performed in Beagles of the control group. For Beagles in the experiment group, TEAS [2/100 Hz, (4 ± 1) mA] was applied to bilateral Hegu (LI4), Quchi (LI11), Zusanli (ST36), and Sanyinjiao (SP6) from stable physiological conditions to the end of maintaining stages. Changes of EGG frequencies and EGG amplitudes were monitored. Serum levels of gastrin (GAS) and motilin (MTL) were also detected at corresponding time points during and after experiment. RESULTS: As for the pressure control effect of TEAS combined general anesthesia in the controlled hypotension, during the process of controlled hypotension (T1-T4), MAP levels of two controlled pressure groups remained relatively stable, and were kept at 60% of the MAP baseline. When the blood pressure dropped to the target low MAP and maintained at 60 min (T1-T4), EGG amplitudes of Beagles in all the three groups showed decreasing tendency. But it was more obviously lower than its basic level in the control group (P <0.05), while it was not obviously decreased in the experiment group (P < 0.05). EGG frequencies of Beagles in all the three groups showed no obvious change during this stage. By the end of the MAP rising stage (T8), the EGG amplitude of the experimental group was significantly higher than that of the control group and the blank group (P < 0.05), while it didn' t show any obvious increase in the control group. During this period, EGG frequencies of the two controlled hypotension groups decreased more than those of the blank group. Two h after rising blood pressure (at T9), EGG amplitudes and frequencies in the two controlled hypotension groups basically restored to their respective baselines and levels of the blank group at T9. At 2 h (T9) after controlled hypotension, serum levels of GAS and MTL were lower than those of basic levels in the two controlled hypotension groups (P <0.05). However, serum levels of GAS and MTL had an increasing trend in the two controlled hypotension groups at 24-72 h (T10-T12). Besides, the increasing speed and amplitude was better in experiment group than in the control group at T10-T12. However, there was no statistical difference between the two groups (P > 0.05). At 72 h (T12) serum levels of GAS and MTL had basically restored to their basic levels in the two controlled hypotension groups and that of the blank control group. CONCLUSION: EGG amplitudes could be effectively improved in TEAS combined general anesthesia for controlled hypotension at 60% of the MAP baseline, the recovery of the serum GAS level accelerated, gastric power improved and stomach protected.

[Ginkgo leaves tablet improved the memory quotient of patients with mild cognitive impairment: a clinical observation].

OBJECTIVE: To observe the effect of Ginkgo Leaves Tablet (GLT) on memory quotient (MQ) of mild cognitive impairment (MCI) patients. METHODS: One hundred and thirteen patients were randomly assigned to the control group (55 cases) and the treatment group (58 cases). Patients in the control group received dietetic therapy and physical exercises, while those in the treatment group additionally took GLT, 19.2 mg each time, three times daily. The treatment course was 12 months for all. The MQ of all the patients was assessed by WMS-RC before treatment,at 6-month of treatment, and 12-month of treatment. RESULTS: Compared with the control group, the improvement of MQ increased in the treatment group 0.5 and 1 year after treatment (P < 0.05). The clinical efficiency of MQ obviously increased in the treatment group (48.28% and 50.00%), showing statistical difference when compared with the control group (30.91% and 27.27%, P < 0.05, P < 0.01). There was statistical difference in added scores of recognition, regeneration, understanding, and recitation test at 6-month of treatment and 12-month of treatment between the treatment group and the control group (P < 0.05, P < 0.01). CONCLUSION: GLT was effective in improving MQ of MCI patients, especially in improving recognition, regeneration, understanding, and recitation test.

[Effects of transcutaneous electrical acupoint stimulation combined with general anesthesia for controlled hypotension on heart function and oxidation resistance of myocardium].

OBJECTIVE: To investigate the intervention effect of transcutaneous electrical acupoint sitmulation (TEAS) on heart under limiting level of controlled hypotension. METHODS: Eighteen male Beagles were randomly divided into a general anesthesia group, a control group and an experimental group, 6 dogs in each group. All animals were applied with general anesthesia, and the animals of the control group and the experimental group were administered with combination of isoflurane and sodium nitroprusside (SNP) for controlled hypotension to 30% mean arterial pressure (30% MAP) of base line for 60 min. In the experimental group, TEAS (2 Hz/100 Hz, 6-8 mA) was applied to "Hegu" (LI4), "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Quchi" (LI 11) from the beginning of physiological conditions stability to the end of maintained low MAP for 60 min. Creatine kinase isoenzymes MB (CK-MB) and lactate dehydrogenase (LDH) activity were detected at the base line and 2 h, 24 h, 48 h, 72 h after operation. Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) in myocardium were observed at 72 h after operation. RESULTS: The peak of LDH arrived at 24 h after operation and then restored in 3 groups. Compared with basal level, the activity of LDH in controlled group at 72 h after operation was significantly increased (P < 0.05), and in the other two groups no obvious change (P > 0.05). The activity of CK-MB arrived to peak from 2 h to 24 h after operation, and then came back gradually in 3 groups. Compared with postoperative 72 h of the same group, the control group at 48 h significantly increased (P < 0.05), while the other two groups had no statistically significant difference (P > 0.05). The content of MDA at 72 h after operation in controlled group was higher significantly than that in the general anesthesia group and the experimental group (both P < 0.05). CONCLUSION: TEAS combined with anesthesia for controlled hypotension can elevate myocardial effect of anti-oxide free radical, reduce the postoperative release of LDH and CK-MB, so as to produce myocardial protection.

[Effects of ginkgo biloba tablet in treating mild cognitive impairment].

OBJECTIVE: To observe the effects of Ginkgo Biloba Tablet (GBT) in treating mild cognitive impairment (MCI). METHODS: Totally 113 MCI patients including 58 outpatients at the cognitive impairment clinics of Huadong Hospital, 34 outpatients at Chinese Medicine Clinics of Dongfang Hospital, and 21 outpatients at Feng-lin Community Health Service Center, were assigned to the control group (55 cases) and the treatment group (58 cases). Basic treatment was given to them all. Those in the treatment group took GBT additionally, 1 tablet each time, 3 times a day for 12 successive months. The mini-mental state examination (MMSE) integral, clock drawing task (CDT) integral, MMSE efficacy, CDT efficacy, and dementia conversion rate were detected before treatment, half a year after treatment, and one year after treatment. RESULTS: There was no significant difference in scores of MMSE and CDT integrals between the two groups before treatment (P>0.05). Compared with before treatment, each score in the treatment group remarkably increased in the treatment group at the 6 months and 12 months after treatment (P<0.01). They were higher than those of the control group at the same time points, showing statistical difference (P<0.01, P<0.05). There was no significant difference in the integrals of MMSE and CDT between the 6 months of treatment and the 12 months of treatment (P>0.05). The total effective rate of MMSE and CDT of the treatment group at the 6 months and 12 months after treatment (MMSE 67.24% and 65.52%; CDT 62.07% and 60.34%) all exceeded those of the control group at the same time points (MMSE 36.36% and 30.91%; CDT 34.55% and 30.91%), showing significant difference (P<0.01). There was no difference in the total effective rate of MMSE and CDT of the treatment group between the two time points (P>0.05). The dementia conversion rates at the 6 months and 12 months after treatment (1.72% and 5.17%) were lower in the treatment group than in the control group (9.09% and 14.55%), showing statistical difference (P<0.05). CONCLUSIONS: One-year GBT could significantly improve the cognitive function of MCI patients. It could also lower the dementia conversion rate.

[Effects of Ginkgo biloba extract in improving episodic memory of patients with mild cognitive impairment: a randomized controlled trial].

BACKGROUND: Mild cognitive impairment is a transitional stage between normal aging and dementia. It is important in terms of recognizing memory loss in older people as well as identifying a group of individuals at high risk of developing dementia and who may benefit from preventive strategies. Ginkgo biloba extract has been shown to possess polyvalent properties, such as anti-oxidation, anti-apoptosis and anti-inflammation. Ginkgo biloba extract appears to have a neuroprotective effect against neurodegenerative diseases. OBJECTIVE: To observe the efficacy of Ginkgo biloba leaf tablet in improving episodic memory of mild cognitive impairment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a multicenter, randomized, controlled trial. The authors enrolled generally healthy, ambulatory or ambulatory-aided amnestic subjects with MCI, 60 to 85 years old, who expressed a memory complaint from Huadong Hospital, seven Community Health Centers in Shanghai, and Shanghai First Welfare Institution. A total of 120 MCI patients were randomly assigned to the Ginkgo biloba leaf tablet group (treatment group, 60 cases) and control group (60 cases). The patients in the treatment group took Ginkgo biloba leaf tablets 3 times a day, 19.2 mg each dose. The control group did not receive any intelligence-promoting or vasodilator reflex treatment except some health care. MAIN OUTCOME MEASURES: The patients were tested with nonsense picture recognition of the clinical memory scale and the logical memory test based on the Wechsler memory scale before and after treatment. RESULTS: After 6 months of treatment, the scores of the logical memory test and nonsense picture recognition were increased significantly in the treatment group (P<0.01, P<0.05), while the scores of the two tests from the control group had no statistically significant difference (P>0.05). After treatment, the positive rate of nonsense picture recognition was 55.17% in the treatment group, which was significantly higher than that of the control group at 32.73% (P<0.05). The efficacy rate of logical memory was 58.62% in the treatment group, also higher than 38.18% in the control group (P<0.05). CONCLUSION: Ginkgo biloba leaf tablet showed good efficacy in promoting episodic memory function in MCI patients.

[Effects of transcutaneous electrical acupoint stimulation combined with general anesthesia on changes of gastric dynamics in controlled hypotension dogs].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with general anesthesia on gastric dynamics in controlled hypotension dogs, so as to provide experimental evidence for compound acupuncture anesthesia. METHODS: Eighteen male beagle dogs were randomly divided into general anesthesia group (GA group, n = 6), general anesthesia + controlled hypotension group (GA + OHT group, n = 6) and general anesthesia combined with TEAS + controlled hypotension group (TEAS group, n = 6). The latter two groups were administered with the same anesthetics [isofluane inhalation and intravenous sodium nitroprusside (SNP)] for inducing controlled hypotension (being the 40% of the baseline level). Beagles of the GA group were not treated with controlled hypotension (the initial concentration of SNP = 1 microg/kg x min(-1), and with an increase rate of 1 microg/kg x min(-1) until the controlled hypotension phase). In the TEAS group, TEAS [2 Hz/100 Hz, (4 +/- 1) mA]was applied to "Quchi" (LI 11) , "Zusanli" (ST 36), "Hegu" (LI 4), and "Sanyinjiao" (SP 6) from the beginning of the stable physiological condition phase to the end of the controlled-low mean arterial pressure (MAP) phase. Electrogastrogram (EGG) was recorded, and serum gastrin (GAS) and motilin (MTL) contents were detected by enzyme-linked immunosorbent assay. RESULTS: Compared with the basic level, the amplitude value of EGG at 60 mm after controlled hypotension in the GA + CHT group was significantly lower (P < 0.05), while the amplitude level of EGG of the TEAS group at the time-point of MAP recovery was significantly higher than those of the GA and GA + CHT groups (P < 0.05). No significant changes were found among the 3 groups in the frequency levels of EGG. At the time-points of MAP recovery and 2 h after MAP recovery, serum MTL and GAS levels in the TEAS group were close to their basic level (P > 0.05), and serum GAS level at the time-point of 2 h after MAP recovery in the TEAS group was considerably higher than those in the GA and GA + CHT groups (P < 0.05). Twenty-four, 48 and 72 h after MAP recovery, serum GAS levels in the TEAS group were moderately (24 h and 48 h ) and significantly (72 h) higher than that of the basic level. No significant differences were found between the GA and GA + CHT groups in serum MTL and GAS levels at the time-points of 2, 24, 48 and 72 h after MAP recovery (P > 0.05). CONCLUSION: TEAS combining with general anesthesia for controlled hypotension can improve the amplitude of EGG, and serum MTL and GAS contents, favoring the recovery of gastric dynamics and the functional protection of stomach.