Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia.

Background and Aims: The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H2S) on platelet autophagy. Methods: Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H2S donor), hydroxocobalamin (an H2S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days. Results: Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H2S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H2S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count. Conclusions: Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H2S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.

Compositional and functional alterations of gut microbiota in patients with stroke.

BACKGROUND AND AIMS: There is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied. METHODS AND RESULTS: We performed a case-control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4-V5 regions), and TMAO was determined via liquid chromatography-tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p < 0.05). The TMAO level in the plasma of patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% CI = 0.08-0.55, p = 0.0093). Notably, the composition and the function of gut microbiota in the LAA stroke group were significantly different from those in the control group (FDR-adjusted p-value < 0.05). There was no significant association between gut microbiota and CE stroke in our study. CONCLUSION: This study provides evidence for significant compositional and functional alterations of the gut microbiome in patients with LAA stroke. Gut microbiota might serve as a potential biomarker for patients with LAA stroke.

Captopril inhibits calpain­mediated apoptosis of myocardial cells in diabetic rats and improves cardiac function.

To explore the effects of captopril on calpain­mediated apoptosis of myocardial cells and cardiac function in diabetic rats, 30 adult male Sprague­Dawley rats were randomly divided into three groups: Negative control (NC group), untreated diabetic rats (DM group) and diabetic rats treated with captopril (Cap group). Diabetes was induced by streptozotocin injection. Captopril was intragastrically administered at a daily dose of 50 mg/kg for 12 weeks; the NC and DM groups received an equivalent volume of saline. After 12 weeks of treatment, left ventricular systolic pressure (LVSP), left ventricular end­diastolic pressure (LVDEP), maximal rate of left ventricular pressure increase (+dp/dtmax), maximal rate of left ventricular pressure decrease (­dp/dtmax) and left ventricular mass index (LVMI) were measured. The levels of calpain­1, calpain­2, B­cell lymphoma (Bcl)­2, Bcl­2 associated protein X (Bax) and total caspase­3 were detected in cardiac tissue by western blot analysis. The apoptotic index (AI) was assessed with a terminal deoxynucleotidyl transferase­mediated dUTP nick­end labeling assay. The ultrastructure of cardiac tissue was determined by transmission electron microscopy. Compared with the NC group, LVDEP and LVMI were increased, whereas LVSP, +dp/dtmax and ­dp/dtmax were decreased in the DM group. In the Cap group, LVDEP and LVMI were decreased, whereas LVSP, +dp/dtmax and ­dp/dtmax were increased compared with the DM group. Bcl­2 protein expression was decreased, whereas the levels of calpain­1, calpain­2, Bax and total caspase­3 protein were increased in the DM group, compared with the NC group. Cap treatment increased Bcl­2 protein expression and decreased calpain­1, calpain­2, Bax and total caspase­3 protein expression compared with the DM group. Additionally, the AI was increased in the DM group compared with the NC group, and decreased in the Cap group compared with the DM group. Furthermore, ultrastructural examination demonstrated that myocardial cell injury was reduced in the Cap group compared with the DM group. Therefore, captopril improved myocardial structure and ventricular function, by inhibiting calpain­1 and calpain­2 activation, increasing Bcl­2 expression, reducing Bax expression and subsequently inhibiting caspase­3­dependent apoptosis.

Adenosine A(2A) receptor activation reverses hypoxia­induced rat pulmonary artery smooth muscle cell proliferation via cyclic AMP­mediated inhibition of the SDF1­CXC4 signaling pathway.

The occurrence and the subsequent development of pulmonary arterial hypertension (PAH) involve complicated mechanisms. Of these, the proliferation of pulmonary artery smooth muscle cells (PASMCs) has been indicated to be closely associated with its progression. Therefore, therapeutic methods targeting PASMCs to inhibit proliferation is an effective method for alleviating PAH. The present study was designed to determine the role of the adenosine A(2A) receptor (A2A receptor) in hypoxia­induced rat PASMC (RPASMC) proliferation. Primary RPASMCs were isolated from the pulmonary artery of adult male SD rats, cultured and used for the following experiments. The mRNA level and protein expression of CXCR4 were measured by reverse transcription­quantitative polymerase chain reaction and western blot analysis, respectively. The cell proliferation of RPASMCs was measured using a cell proliferation assay kit. In the present study, it was demonstrated that the proliferation of RPASMCs was partially mediated by activation of the stromal cell­derived factor 1 (SDF1)­CXC chemokine receptor 4 (CXCR4) axis under hypoxic conditions. In addition, SDF1­α alone upregulated the mRNA and protein expression levels of CXCR4, and stimulated the proliferation of RPASMCs. The protein expression of CXCR4 and the cell proliferation were markedly inhibited by application of A2A receptor agonist CGS21680 or cyclic adenosine monophosphate (cAMP) under hypoxic conditions or treatment with SDF1­α and was reversed by the A2A receptor antagonist SCH58261 or 8­bromoadenosine­3',5'­cyclic monophosphorothioate. These results demonstrated that the inhibition of SDF1­CXC4 signaling by the activation of A2A receptor and subsequent increase in the level of cAMP may be a potential method to ameliorate PAH.

[Progress on surgical treatment for femoral head-preservering in the precollapse stage of femoral head necrosis].

Osteonecrosis of the femoral head(ONFH), a refractory disease characterized by death of the osteocytes and the bone marrow due to inadequate blood supply caused by various mechanisms, usually leads to the collapse of the femoral head and malfunction of the hip joint. The crux is to diagnose ONFH early in the precollapse stage and prevent subsequent progression of collapsing through early interventions, thus delaying or avoiding the replacement of the hip joint. A number of joint salvaging operation treatments for early stage ONFH are available. However, there has been no consensus with regard to the ideal treatment. The main trend now is to unite core decompression with bone-grafting, tantalum rod, bone marrow mesenchymal stem cell (BMSC) and other treatments. Also there are ways of osteotomy altering the angle of the femoral neck to relocate necrotic tissue from the weight-bearing segment. The implanting of tantalum rod remains controversial and the advent of bone marrow mesenchymal stem cell (BMSC) holds huge potential.

Induction of heme oxygenase-1 ameliorates vascular dysfunction in streptozotocin-induced type 2 diabetic rats.

AIMS: To explore the effects of heme oxygenase-1 (HO-1) on vascular dysfunction in high fat diet streptozotocin-induced type 2 diabetic (T2D) rats. METHODS: Rats received a high-fat diet followed by a low dose of streptozotocin (30 mg/kg) to induce T2D. T2D rats were treated with hemin (1, 5, or 25mg/kg) or carbon monoxide-releasing molecule-2 (CORM-2, 5 mg/kg) for 4 weeks. Isometric contractions of aortic rings were measured. The expression of cyclooxygenase-2 (COX-2) and activities of HO, SOD, and MDA were evaluated. RESULTS: The fasting blood glucose, blood insulin levels, and IR index in T2D rats were higher than those in the control group, which were ameliorated by HO-1 inducer hemin. The antidiabetic effect was accompanied by enhanced HO activity. The vascular relaxation response to ACh was decreased in T2D rats, while treatment with hemin could prevent such decrease in vasorelaxation. An increase in COX-2 expression was found in the aortas of T2D rats. Treatment of T2D rats with COX-2 inhibitor NS398 restored ACh-induced vasodilation. COX-2 overexpression in T2D rats was inhibited by hemin. Hemin treatment also inhibited the decline of SOD activity and the increase of MDA content in the aorta of T2D rats. CORM-2, an agent which releases the HO-1 product CO, could mimic the beneficial effect of hemin. CONCLUSION: Induction of HO-1 with hemin ameliorates the abnormality of endothelium-dependent vascular relaxation in T2D rats. A possible mechanism involves suppression of reactive oxygen species production and inhibition of COX-2 up-regulation induced by diabetes mellitus.

[The effects of ACEI on calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats].

OBJECTIVE: To investigate the effects of angiotensin converting enzyme inhibitor (ACEI) captopril on Calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats. METHODS: Thirty adult male SD rats were randomly divided into 3 groups (n = 10), normal control group (NC group), diabetes mellitus group (DM group)and captopril treated group (Cap group). Streptozocin (STZ) were used to make the model of diabetes mellitus, captopril was administrated by gavage at the dose of 50 mg/kg every day, while in NC group and DM group the same volume of normal saline was administrated. Twelve weeks later, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVDEP), maximal rise rate of left ventricular pressure (+ dp/dtmax) and maximal fall rate of left ventricular pressure (- dp/dtmax) were detected; Western blot was used to detect the expression of Calpain-1 Calpain-2, Bcl-2, Bax and total Caspase3 protein; apoptosis index (AI) were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: Compared with NC group, LVDEP was significantly higher; LVSP, + dp/dtmax and - dp/dtmax were significantly decreased (P < 0.05); Bcl-2 protein expression was decreased; the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were increased; the value of AI was significantly increased. Compared with DM group, LVDEP was significantly lower; LVSP, + dp/dtmax and - dp/dtmax were significantly increased (P < 0.05); Bcl-2 protein expression was increased, the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were decreased; the value of AI was significantly decreased (P < 0.05). CONCLUSION: Captopril can protect diabetic myocardial structure through inhibiting activation of Calpain-1 and Calpain-2, up-regulating the expression of Bcl-2, down-regulating the expression of Bax to inhibit Caspase3 dependent apoptosis, thereby improving the ventricular function and myocardial structure.

[Expression of steroidogenic enzymes in the rat model of polycystic ovary syndrome].

The aim of the present study was to investigate the expression changes of three steroidogenic enzymes in the polycystic ovary syndrome (PCOS). Thirty Sprague-Dawley (SD) rats were randomly divided into normal control (NC) group and PCOS group. PCOS rat model was established by DHEA injection. The serum levels of progesterone, estrogen and testosterone were measured by immunoradioassay or enzyme immunoassay. The cellular distributions of 3ß-hydroxy steroid dehydrogenase (3ß-HSD), 17ß-hydroxy steroid dehydrogenase (17ß-HSD) and cytochrome P450 aromatase (P450arom) in ovaries were detected by immunohistochemistry. The expression levels of 3ß-HSD, 17ß-HSD and P450arom were detected by RT-PCR and Western blot. The results showed that the serum levels of estrogen and testosterone of PCOS group were significantly higher than those of the NC group. There was no significant difference of serum progesterone level between the PCOS and NC groups. Compared with the NC group, the PCOS group showed increased mRNA and protein expressions of both 3ß-HSD and 17ß-HSD, as well as reduced P450arom mRNA and protein expressions. These results suggest that 3ß-HSD and 17ß-HSD, but not P450arom, may participate in the ovarian hormonal regulation in the present rat model of PCOS.

[Effects of extract of ginkgo biloba on learning and memory ability and NGF and NT-3 expression in diabetic rats].

OBJECTIVE: To investigate the effect of extract of Ginkgo Biloba(EGB) on nerve growth factor(NGF) and Neurotrophin-3(NT-3) expression of hippocampus neurons in streptozotocin-induced type I diabetic rats. METHODS: Thirty male SD rats were divided into three groups (n = 10): the control group, diabetic group and EGB-treated group. Strepozotocin were injected intraperitoneally in the later two groups to induce diabetes. EGB-treated group was injected intraperitoneally with EGB, and the same volume of normal saline was injected to the other groups. Concentration of blood glucose and body weight and behaviour were dynamicly monitored. At the end of the 12th week, morphological changes of the hippocampus neurons were observed under microscopy by HE stain. The expression of NGF and NT-3 were assayed by Western blot and RT-PCR respectively. RESULTS: Compared with diabetic group, the behaviour and body weight (P < 0.05) and the concentration of blood glucose (P < 0.05) were significantly improved and the escape latency of Morris water maze test (P < 0.05) was significantly shortened, while the platform searching score was significantly increased (P < 0.01) in EGB treated group; The pathological changes of hippocampus neurons were significantly attenuate by EGB treated; The expression of NGF and NT-3 in hippocampus neurons were significantly increased which assayed by Western blotting and RT-PCR respectively (P < 0.05) in EGB treated group. CONCLUSION: EGB may improve the learning and memory ability of diabetic rats the mechanism may be attributed to its improvement of the expression of NGF and NT-3 and reducing apoptosis in hippocampus neurons.

[The role of JNK in apoptosis of renal tubular epithelial cells in diabetic rats with fluctuant high blood glucose].

OBJECTIVE: To explore the signal transduction mechanisms of apoptosis in renal tubular epithelial cells in diabetic rats with fluctuant high blood glucose. METHODS: Healthy SD rats were randomly divided into 3 groups: normal control group (A), stable high blood glucose group (B) and fluctuant high blood glucose group (C). Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg), and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time point every day. The superoxide dismutase (SOD) activity and the content of malonaldehyde (MDA) in renal tissue homogenate were detected with colorimetry. The protein expression of Nox4 and JNK were examined by immunohistochemistry and Western blot. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). RESULTS: After 12 experimental weeks, significantly increased cell apoptosis, up-regulation of Nox4 and P-JNK expression in renal tubular epithelial cells were observed in B and C groups compared with those in A group. The MDA content increased and SOD activity decreased in renal tissue in B and C groups. Above effects were more obviously shown in C group. CONCLUSION: Fluctuant high blood glucose induced more apoptosis of renal tubular epithelial cell than stable high blood glucose in diabetic kidney, which might be related to the activation of JNK signal transduction pathway.

[Association between polymorphisms of inflammatory factor genes and coronary heart disease].

OBJECTIVE: To investigate the association between genetic polymorphisms of inflammatory factors and susceptibility to coronary heart disease(CHD) in southern Chinese Han population. METHODS: Using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) method, the genotypes of five inflammatory factors (BRCA1-associated protein, a disintegrin and metalloproteinase 8, inter-alpha-trypsin inhibitor H3, interleukin-15, cyclooxygenase-2) were anaylzed in 283 CHD patients diagnosed by angiography and 176 controls. RESULTS: In these inflammatory factors, the 270T/C and 90A/G polymorphisms of the BRAP gene showed a significant association with CHD. The allele and genotype frequencies of BRAP gene were consistent with those predicted by Hardy-Weinberg equilibrium (chi-square=0.878, P> 0.05; chi-square=0.776, P> 0.05, respectively). The frequencecies of 270C and 90G alleles in CHD patients was significantly higher than those of the control group (29.51% vs. 21.31%, P=0.006; 30.04% vs. 21.31%, P=0.004, respectively). Compared with 270TT and 90AA, 270CC and 90GG genotypes had a significantly increased CHD risk by Logistic regression analysis (OR=4.51, 95%CI: 1.41-14.45, P=0.011; OR=5.09, 95%CI: 1.60-16.26, P=0.006, respectively). This association was still signifcant after adjustment for the sex, age, smoke, hypertension, diabetes, plasma total cholesterol and low density lipoprotein levels. No evidence of association was found for other single nucleotide polymorphisms. CONCLUSION: The 270T/C and 90A/G polymorphisms in the BRAP gene may contribute to an increased risk of CHD among southern Chinese Han population.

[Role of P38-MAPK signal transduction pathway and effect of panax notoginoside in rats with hypoxic hypercapnia pulmonary hypertension].

OBJECTIVE: To investigate the role and significance of P38-MAPK in the pathological process of hypoxic hypercapnia pulmonary hypertension in rats, and the protection of panax notoginoside (PNS). METHODS: (1) To set up rat pathological model of hypoxic hypercapnia pulmonary hypertension: seventy two male SD rats (200 280 g) were randomly divided into six groups (n = 12), which were normal group (N group), hypoxic hypercapnia for 3-day group (H3d), hypoxic hypercapnia for 1-week group(H1w), hypoxic hypercapnia for 2-week group (H2w), hypoxic hypercapnia for 4-week group (H4w) and PNS-injected group (Hp). The rats of PNS -injected group were injected PNS before being placed in the chamber (50 mg/(kg x d), ip), and other groups were injected normal sodium (2 ml/kg, ip). (2) The shapes of pulmonary artery were detected by HE staining. (3) Western blot was used to study the protein expression of p38-MAPK. The expression of p38-MAPK in lung tissue and pulmonary blood vessel was investigated by immunohistochemistry. RESULTS: (1) The ratio of vessel wall area/total area (WA/ TA) in H1w, H2w, H4w and Hp group was higher than that of N group (P < 0.05), but that of H3d group did not change obviously (P > 0. 05 vs N group). The ratio of WA/TA in Hp group was obviously lower than that of H4w, group (P < 0.05). (2) The levels of P-p38 protein was markedly ascended in H3d group (0.225 +/- 0.071) compared with N group (0.012 +/- 0.006), and expression of P-p38 protein was significantly positive in H1w, H2w, H4w groups. (P < 0.05). (3) As P-p38 protein in pulmonary arterial tunica intima and tunica media, sterile expression in N group (0.099 +/- 0.015) and H3d group (0.107 +/- 0.013) contrasted to H4w group (0.124 +/- 0.025, P < 0.05), then tended to rise in H2w, H4w group (P < 0.05). (4) In pulmonary tissue, the levels of P-p38 protein in PNS-injected group were lower 53.02% (P < 0.05) than those in H4w group. In pulmonary arterial tunica intima and tunica media the levels of P-p38 protein in PNS-injected group were lower 87.33% (P < 0.05) than those in H4w group. CONCLUSION: p38-MAPK as a signal transduction may play an important role in the development of hypoxia induced pulmonary hypertension. The effect of PNS on reducing pulmonary hypertension and improving pulmonary vascular wall remodeling may be related to its inhibiting expression of p38 MAPK.

[Effects of astragalus and angelica on bone marrow stem cells proliferation and VEGF protein expression in vitro].

OBJECTIVE: To observe the effects of Astragalus and Angelica on bone marrow stem cells (BMSU) proliteratlon mn vitro and investigate its possible mechanism. METHODS: Five 200 to 220 g SD rats were fed with a high fat diet for 4 weeks and given 30 mg/kg streptozotocin (STZ) twice develop type II diabetes from July 2009 to February 2010. The rats with blood glucose concentrations of 16.7 mmol/L or more were considered diabetic. Bone Marrow Stem Cells (BMSC) were collected and isolated by density gradient centrifugation. The BMSC were divided into 4 groups,including empty control group, Astragalus group, Angelica group and Astragalus plus Angelica group. DMEM of 100 microl was added in empty control group. DMEM of 100 microl containing Astragalus (1100 mg/L), Angelica (1100 mg/L) and Astragalus (1100 mg/L) combine with Angelica(220 mg/L) were added in Astragalus group, Angelica group and Astragalus plus Angelica group respectively. The cell proliferation was detected by MTT method, and the concentration of VEGF in the supernatant was determined by ELISA. The VEGF expression was analyzed by Western Blot after 14 days incubation. RESULTS: The BMSC proliferation and the VEGF concentration in the supernatant and the BMSC VEGF protein expression significantly increased in Astragalus group and Astragalus plus Angelica group compared to those of empty control group (P < 0.05 or P < 0.01). The above effects were more strong in Astragalus plus Angelica group (P < 0.05). CONCLUSION: Astragalus with Angelica or used separately could promote BMSC proliferation. The mechanism might induce the VEGF protein expression in BMSC. And the independent use of Angelica has no above effect.

[Effects of ambroxol combined with low-dose heparin on TNF-alpha and IL-1beta in rabbits with acute lung injury].

OBJECTIVE: To investigate the intervention and mechanism of ambroxol combined with low-dose heparin on oxidative stress, TNF-alpha and IL-1beta in rabbits with acute lung injury (ALI). METHODS: Twenty-four healthy Japanese rabbits were randomly divided into three groups: (1) Normal saline control group (NC), (2) Oleic acid injury group (OA), (3) Ambroxol + low-dose heparin therapy group (AH). After the success of ALI model, AH group was injected ambroxol + low-dose heparin, while the NC group and OA group were injected the same dose of normal saline by the same method. Arterial oxygen tension (PaO2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) at different time points were determined. The pathological manifestation of both side lungs was observed at the end of expeiment. The activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), xanthine oxidase (XO) and the content of malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenate were tested. The apoptosis index was detected. The lung wet/dry (W/D) ratio was calculated. The pathological changes in lung tissue were observed by light microscopy, and the ultrastructural changes of lung tissue were observed by electron microscopy. RESULTS: (1) The instructive injury induced by ALI observed under electron microscope and light microscope and W/D was decreased significantly in AH group. (2) PaO2 was improved significantly in AH group, compared with that in OA group (P < 0.01). (3) The activity of GSH-Px and SOD in AH group increased significantly (P < 0.01 or P < 0.05) but the activity of XO and the content of MDA decreased significantly (P < 0.01), compared with those in OA group. (4) Except the content of IL-1beta in serum before treatment, the content of IL-1beta and TNF-alpha in serum, BALF, lung tissue homogenate of OA group increased significantly (P < 0.01), and those were obviously improved in AH group. (5) Apoptosis index (AI) in AH group decreased significantly (P < 0.01) compared with that in OA group. CONCLUSION: In ALI induced by OA, IL-1beta and TNF-alpha increases significantly and involved in the occurrence and development of ALI. Ambroxol combined with low-dose heparin can reduce lung cells oxidative stress to inhibit the release of IL-1beta and TNF-alpha, which play a role in the treatment of ALI.

Acupressure therapy inhibits the development of diabetic complications in Chinese patients with type 2 diabetes.

OBJECTIVES: The objectives of this study were to investigate the effects of acupressure therapy (AT) on the development and progression of diabetic complications in Chinese patients with type 2 diabetes (T2D). DESIGN AND METHODS: A total of 80 patients with T2D were recruited for a randomized clinical study of the effect of AT on the progression and development of diabetic complications, and 64 patients were followed up for 3 years. All patients with T2D were treated with regular medicines and participated in diet and exercise programs for the control of hyperglycemia and hypertension. The patients in the AT group received additional treatment of a 90-minute AT 4-6 times per week for 3 consecutive years. Their blood lipids, fasting glucose levels, and heart and kidney functions and nerve conduction velocity (NCV) were longitudinally monitored before and every 12 months after AT. RESULTS: Following AT therapy for 3 years, significantly lower levels of total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and higher levels of high-density lipoprotein-cholesterol (HDL-C) were observed and no significantly increased levels of serum creatinine and urine protein were detected in the AT group, as compared with that in controls. Furthermore, the mean values of NCV in the AT group at 2 years post-treatment were significantly greater than those of controls and were further elevated at the end of this study. Therefore, AT inhibited the progression of hyperlipidemia and improved diabetes-associated kidney function and neuropathy in Chinese patients with T2D. CONCLUSIONS: AT may be an effective nonpharmacological adjunctive strategy for alleviating the development and progression of T2D-related complications.

[Relationship between P-selectin and cardiac function in hemorrhagic shock resuscitation: experiment with rats].

OBJECTIVE: To investigate the relationship between the left ventricular function and the expression of P-selectin in the serum and cardiac muscle in hemorrhagic shock resuscitation, and to evaluate the effects of L-arginine (L-Arg) against the harmful effect of P-selectin. METHODS: Thirty SD rats were randomly divided into 3 equal groups: hemorrhagic shock resuscitation (HS) group (undergoing bloodletting until the mean arterial pressure of 40 mm Hg and then re-infusion of the lost blood), L-Arg treatment group (undergoing bloodletting and then re-infusion with L-Arg simultaneously), and normal control (NC) group (undergoing infusion of normal saline). Cannulation was conducted via left carotid artery into the left ventricular to record left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), and left ventricular +/- dp/dtmax. Serum creatine kinase (CK) was detected by colorimetry. Three hours after the HS the rats were killed with samples of blood and apex of heart collected to detect the P-selectin expression by ELISA and immunohistochemistry. Microscopy was used to observe the expression of P-selectin in the vascular endothelial cells and cardiac muscle cells. RESULTS: The LVSP, maximal rate of LV pressure elevation (+ dp/dtmax), and maximal rate of LV pressure depression (- dp/dtmax) of the HS and L-Arg groups were all significantly lower than those of the NC group (all P < 0.01). The LVEDP of the HS and L-Arg groups were all higher than that of the NC group (both P < 0.01). Three hours after resuscitation, the CK levels of the HS and L-Arg groups were significantly higher than that of the NC group (both P < 0.01), and that of the L-Arg groups was significantly lower than that of the HS group (P < 0.05), the P-selectin levels of the serum and cardiac muscle cells of the HS and L-Arg groups were all significantly higher than those of the NC group (both P < 0.01), and those of the L-Arg group were significantly lower than those of the HS group (both P < 0.05). CONCLUSION: After hemorrhagic shock and resuscitation P-selectin may play an important role in cardiac injury, L-Arg can inhibit the expression of P-selectin, thus protecting the cardiac function against the harmful effect of P-selectin.