Effect of nonalcoholic fatty liver disease on glucose and lipid metabolism during pregnancy / 中华内分泌代谢杂志

Objective:To investigate the effect of nonalcoholic fatty liver disease (NAFLD) on glucose and lipid metabolism during pregnancy.Methods:A retrospective analysis was performed in women who gave birth in Minhang Hospital Affiliated to Fudan University from January 2013 to June 2020. The data on demographic, clinical examination, and delivery were obtained via electronic medical record abstraction. According to the ultrasound imaging, all pregnant women were divided into NAFLD group and control group. The difference of glucose and lipid metabolism indexes, incidence of gestational diabetes mellitus, and gestational hypertension between two groups were compared. Logistic regression model was used to examine potential associations between NAFLD and metabolic related adverse pregnancy outcomes.Results:A total of 14 708 pregnant women with a mean age of (29.1±4.7) years and a mean body mass index of (21.0±2.8) kg/m 2 were included in our study. Of those eligible women, 554 (3.8%) were confirmed by ultrasound as NAFLD. Pregnant women with NAFLD presented higher circulating levels of fasting glucose [(4.2±0.5)mmol/L vs (4.1±0.5)mmol/L, P<0.01], 1 h plasma glucose [(7.4±1.7)mmol/L vs (6.6±1.6)mmol/L, P<0.01] and 2 h plasma glucose [(6.2±1.4)mmol/L vs (5.7±1.3)mmol/L, P<0.01] after glucose loading, HbA 1C [(5.2±0.4)% vs (5.1±0.5)%, P<0.01], triglyceride [(2.1±1.1)mmol/L vs (1.6±0.7)mmol/L, P<0.01], total cholesterol [(4.8±0.8)mmol/L vs (4.7±0.9)mmol/L, P<0.01], low density lipoprotein-cholesterol [(2.6±0.7)mmol/L vs (2.5±0.7)mmol/L, P<0.01], uric acid [(224.1±51.8)μmol/L vs (203.0±45.9)μmol/L, P<0.01] level. After adjusting for potential confounders, NAFLD significantly increased the risk of gestational diabetes mellitus ( OR=1.722, 95% CI 1.079-2.747, P=0.023) and gestational hypertension ( OR=3.845, 95% CI 2.247-6.582, P<0.001). Conclusions:Compared to non NAFLD, women with a diagnosis of NAFLD had more significant glucose and lipid metablic aberrations during pregnancy and increased incidence of gestational diabetes and gestational hypertension. Pregnant women with NAFLD should be closely monitored on glucose and lipid metabolism and blood pressure to prevent gestational diabetes mellitus and hypertension.

YAP is oppositely regulated in iPSC-induced cardiovascular progenitor cell and vascular smooth muscle cell differentiation / 中国病理生理杂志

AIM:To explore whether YAP protein is important in induced pluripotent stem cell ( iPSC)-induced cardiovascular progenitor cell and/or vascular smooth muscle differentiation .METHODS:Using episomal vector based reprogramming , we generated human iPSCs from donor fibroblasts .We used both this iPSCs and human H 1 embryonic stem cells to differentiate into vascular smooth muscle cells (VSMCs) through cardiovascular progenitor cells (CVPC).Western blotting, qPCR and immunofluorescence microscopy were used to check the expression of YAP and related genes during this differentiation process .RESULTS:The results showed that iPSCs expressed pluripotent stem cell markers, such as Oct4, Nanog, Sox2, TRA-1-60 and SSEA3, and could form teratoma in SCID mice.YAP was highly expressed in pluripotent stem cells , but dramatically decreased when CVPC differentiation started .YAP gradually increased dur-ing CVPC three-day differentiation.The TAZ and YAP binding partner TEAD1, but not TEAD2 and TEAD4, have similar expression pattern in CVPC differentiation .Immunofluorescence result confirmed that YAP was activated and accumulated in nucleus .Interesting-ly, both YAP and phosphorylated YAP expression decreased to very low level after CVPC differentiated into VSMCs in 7 days.TEAD4 and TAZ also decreased, while TEAD1, TEAD2 and TEAD3 expression did not change during VSMC differentiation .CONCLU-SION:YAP and TEAD1 expression increased during CVPC differentiation , while YAP and TEAD4 expression decreased from CVPC to VSMCs differentiation , which suggested YAP might have different function during diverse cell differentiation .

Effects of puerarin on expression of apelin and its receptor of 2K1C renal hypertension rats / 中国中药杂志

<p><b>OBJECTIVE</b>To examine the change of puerarin on the expression of apelin and its receptor of the two-kidney, one-clip (2K1C) rats.</p><p><b>METHOD</b>Tirty male Sprague-Dawley rats were randomly divided into normal control group (C), model group (M) and puerarin group (P). The mean of carotid arterial pressure (mCAP), mean of left ventricular end diastolic pressure (LVEDP), and the weight ratio of left ventricular mass (left ventricle plus septum) to bodyweight (LVM/BW) were measured to evaluate the model of 2K1C renal hypertension. The concentrations of apelin in the plasma and left ventricle (LV) were measured with radioimmunoassay. Apelin mRNA and APJ mRNA expressed in the LV were examined by reverse transcription-polymerase chain reaction (RT-PCR). The peptides of apelin and APJ expressed in the LV were detected with immunohistochemistry (IHC).</p><p><b>RESULT</b>Compared with C group, the mCAP, LVEDP and LVM/BW of M group were higher 36.58%, 333.8% and 20.24%, respectively (P<0.05, P<0.01, P<0.01). Compared with M group, LVEDP and LVM/BW of P group were lower 65.24% and 13.12%, respectively (both P<0.05). However mCAP was of no significant difference between these two groups. The levels of apelin-36 in the plasma and LV of M group were respectively higher 18.56% and 207.38% than those of C group (both P<0.05), while ones of P group were lower 24.21% and 49.40% than those of M group (both P<0.05). The expressions of apelin mRNA and APJ mRNA at left ventricle tissues of 2K1C rats were higher 77.66% and 119.00% (both P<0.05) than those of C group. The ones of P group were lower 27.40% and 45.66% than those of M group (both P<0.01). The IHC results indicate that the expressions of apelin and APJ peptides at left ventricle tissues of 2K1C rats were higher 129.51% and 154.1% (both P<0.01) than those of C group, respectively. Whereas the ones of P group were lower 65.36% and 62.87% than those of M group (both P<0.01).</p><p><b>CONCLUSION</b>Through regulating apelin/APJ system puerarin has protective effect on the development of left ventricular hypertrophy by renal hypertension.</p>

A randomized study comparing topotecan plus cisplatin versus etoposide plus carboplatin for previously untreated small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>Topotecan is one of active agents for relapsed small cell lung can-cer (SCLC), some studies have shown that it is effective against SCLC as the first-line drug. This study is to assess the efficacy, toxicity and survival rate of topotecan plus cisplatin (TP) versus etoposide plus carboplatin (CE) in patients with previously untreated SCLC.</p><p><b>METHODS</b>Sixty-four patients with previously untreated SCLC were randomly assigned to receive either TP or CE. Topotecan 0.75 mg/(m²×d) via a 30-min intravenous infusion on days 1 to 5 and cisplatin 25 mg/(m²×d) on days 1 to 3 with hydration were given to patients in TP group. Carboplatin 300 mg/m² on day 1 and etoposide 100 mg/d on days 1 to 5 were given to patients in CE group. Treatment was repeated every 21 days. Responses and toxicities were evaluated in patients who received two cycles of chemotherapy. Patients with limited disease SCLC received thoracic irradiation or operation after the completion of chemotherapy.</p><p><b>RESULTS</b>Overall response rate was 75.0% in TP group and 68.8% in CE group. The median survival time was 10.5 months in TP group and 9.6 months in CE group. 1-, 2- and 3-year survival rate were 40.6%, 18.8% and 9.4% in TP group and 34.4%, 15.6% and 9.4% in CE group respectively. There were no significant differences in response rate, median survival time and survival rate between two groups (P > 0.05). Myelosuppression, nausea and vomiting, and alopecia were the most common toxicities, there was no significant difference in grade III and IV toxicities between two groups (P > 0.05).</p><p><b>CONCLUSIONS</b>TP has similar response rate and survivals with CE, and its toxicities are acceptable. TP regimen is an effective first-line treatment for SCLC.</p>

Experimental study of non-invasive percutaneous electrical stimulator for treatment of obstructive sleep apnea syndrome and its clinical effect / 生物医学工程学杂志

To study the stimulation of the genioglossus with percutaneous biphasic current pulses as a new therapeutical method to treat the obstructive sleep apnea syndrome (OSAS), polysomnography (PSG) was used to synchronously monitor the patient. When OSAS was occurring, the stimulation with the optimal parameter was given in time to make the tongue move forward, the glossopharyngeal airway dilated, the resistance of the upper respiratory tract reduced, the hypoxia at night to be improved and the sleeping structure to be ameliorated because of the function of the dilated muscle of the upper airway. The results of the clinical therapeutic effect indicated that 17 of 22 patients with OSAS had cured effects, 2 of whom improved and 3 of whom were without effect. The effective rate was 77.27%. It is preliminarily proved that this is a new method in the treatment of patients suffered from OSAS.

Clinical study of combined chemotherapy of domestic paclitaxel and vinorelbine plus platinum for advanced non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To evaluate the efficacy and toxicity of combined chemotherapy of domestic paclitaxel and vinorelbine plus cisplatin and carboplatin in the treatment of advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A total of 181 initially treated patients with advanced NSCLC were enrolled in this study and treated by NP (vinorelbine plus cisplatin), TC (domestic paclitaxel plus carboplatin) and TP (domestic paclitaxel plus cisplatin). The efficacy and side effects were analysed after at least two cycles of chemotherapy.</p><p><b>RESULTS</b>The overall response rates (CR+PR) were 42.4% in the NP arm, 40.3% in the TC arm and 43.3% in the TP arm respectively. No significant statistical difference was found among the three groups ( Chi-square= 0.108 6 , P > 0.05). The median survival times were 8.4 months, 9.4 months and 8.9 months respectively in the NP, TC and TP groups ( P > 0.05). The 1-, 2-, 3-year survival rates were 39.0%, 16.9%, 5.1% in the NP group and 41.9%, 21.0%, 6.5% in the TC group and 40.0%, 18.3%, 5.0% in the TP group respectively. No significant statistical difference was found among the three groups ( Chi-square=0.140 4, P > 0.05). The major side effects were myelosuppression, alopecia and nausea/vomiting in the three groups. There were no chemotherapy-related death among the three groups.</p><p><b>CONCLUSIONS</b>The combined regimens of NP, TC and TP are effective and well-tolerated regimens for advanced NSCLC.</p>

Effect of Puerarin on the Apelin and its receptor of lung tissue in chronic hypoxia-hypercapnia rats / 中国药理学通报

Aim To explore the effects of Puerarin on the Apelin and its receptor APJ of lung tissue in rats with hypoxia pulmonary hypertension.Methods Thirty SD rats were randomly divided into normal control group(N),and hypoxia hypercapnia group(F),and hypoxia hypercapnia+Puerarin group(P).The levels of Apelin-36 in serum and in lung tissue were measured by radioimmunity,the expressions of Apelin and APJ in pulmonary tissuse were observed by RT-PCR.Results ①Mean pulmonary arterial pressure(mPAP),weight ratio of RV to LV+S,the levels of Apelin in serum and in lung tissue of group F were significantly higher than those of group N(P

Effect of puerarin on reperfusion injury after thrombolytic therapy in acute pulmonary thromboembolism / 中国药理学通报

Aim To study the effect of puerarin on reperfusion injury after thrombolytic therapy in acute pulmonary thromboembolism and its mechanism. Methods Thirty-two Japanese rabbits were randomly divided into sham operation group (group S),Thrombolysis-only group(group T), and Puerarin group(group Pur). Acute pulmonary thromboembolism models of rabbits were established with injection of autologous blood clots through the right heart catheters,haemodynamic monitoring was performed by introducing heart catheter through right jugular vein.The activity of plasma superoxide dismutase (SOD) and content of plasma malondialdehyde (MDA) were detected before embolization,2 h after embolization,2 h and 4 h after thrombolysis. At the end,the rabbits were sacrificed and their lung,removed for histopathologic and electron microscopic investigations. Results ①Pulmonary arterial mean pressure (PAMP) were decreased at 1 hour after thrombolysis both in group T and group Pur(P

Expression of vascular endothelial growth factor in chronic hypoxia and hypercapnia rats and effects of SHENYI Capsule / 中国临床药理学与治疗学

AIM: To explore the roles of vascular endothelial growth factor (VEGF) in hypoxia pulmonary hypertension and effects of SHENYI Capsule. METHODS: Thirty SD rats were randomly divided into normal control group (N), hypoxia hypercapnia group (F), and hypoxia hypercapnia+SHENYI Capsule group (S). The levels of VEGF in serum and lung tissue are measured by ELISA, the ultrastructure of pulmonary arterioles was observed by electron microscopy, and the expression of VEGFmRNA was observed by in situ hybirdization. RESULTS: Mean pulmonary arterial pressure (mPAP), weight ratio of RV to LV+S, the levels of VEGF in serum, and lung tissue of group F were significantly higher than those of group N and group S (P

Effect of nitric oxide on urotensin-Ⅱ expression in pulmonary arterioles of rats chronically exposed to hypoxia-hypercapnia / 中国病理生理杂志

AIM: To investigate the roles of nitric oxide/L-arginine(NO/L-Arg) pathway and urotensin-Ⅱ(UⅡ) in the development of pulmonary hypertension induced by chronic hypoxia-hypercapnia in rats.METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups(n=10): normal control group(A),hypoxia-hypercapnia+saline group(B),hypoxia-hypercapnia+L-Arg liposome group(C) and hypoxia-hypercapnia+N-nitro-L-arginine methyl ester(L-NAME) group(D).Contents of UⅡ,UⅡ mRNA and receptor of UⅡ(UT) mRNA in pulmonary arterioles were measured with immunohistochemistry analysis and in situ hybridization,respectively.Change of small pulmonary vascular microstructure was also investigated.RESULTS:(1) The mean pulmonary artery pressure(mPAP) and the weight ratio of right ventricle to left ventricle plus septum [RV/(LV+S)] in B and D groups were all higher than those in A group(respectively,P

The regulation of nitric-oxide synthase/nitric-oxide system by endogenous carbon monoxide in rats with pulmonary hypertension / 中国病理生理杂志

AIM: To study the role and the mechani sm of heme oxygenas/endogenous carbon monoxide on nitric oxide synthase/nitric oxide system in rats with pulmo nary hypertension induced by hypoxic hypercapnia. METHODS: Spr ague-Dawley rats w ere randomly divided into three groups: control group (A group),hypoxic hypercap n ic group (B group), hypoxic hypercapnia+hemin group (C group). Blood CO concentr at ion (COHb%),NO concentration,HO-1 activity, iNOS, cNOS in blood serum and lung h omogenate were measured, respectively. RESULTS: ① mPAP and RV /(LV+S) of B g roup were significantly higher than those of A and C group( P

Rat urotensin-II-induced main pulmonary artery contractions are mediated by MAPK * / 中国病理生理杂志

AIM:To investigate rat Urotensin-II(ra t U-II)-induced vasoconstriction of rat main pulmonary arteries and the role of mitogen-activated protein kinase(MAPK). METHODS: The main pulmon ary artery was dissected from the male Sprague -Dawley rats and artery ring width was 3-4 mm. Concentration-response curves wer e gene rated to rat U-II(0 03 nmol/L-30 nmol/L).Inhibitor of MAPK,PD 98059(0 1 ?mol/ L -10 ?mol/L) were added into the medium after rat U-II(30 nmol/L)induced vasoc onstriction had reached plateau to construct the relaxant concentration-respons e curves and their EC 50 and E max . RESULTS: Rat U-II was a potent vasoconstrictor of isolated rat main pulmonary arteries [EC 50 =7 95?0 4 0, E max =(14 28?6 34)% of the response to 60 mmol/L KCl]; PD 98059 caused c oncentration-dependent relaxations of rat U-II precontracted arteries [EC 50 =5 91?0 45, E max =(81 39?13 65)%]. CONCLUSION: Rat U- II was a potent vasoconstrictor of rat main pulmonary arteries and this response was med iated through MAPK.

Effect of puerarin on pulmonary arterioles wall collagen metabolism of chronic hypoxia hypercapnia rats / 中国病理生理杂志

AIM:To investigate the effect of puerarin on pulmonary vessel collagen metabolism in pulmonary hypertension rats induced by chronic hypoxia and hypercapnia. METHODS: Collagen Ⅰ,Ⅲ and their mRNA were observed in pulmonary arterioles by the technique of immunohistochemistry and in situ hybridization. RESULTS: ① Light microscopy showed media thickness of pulmonary arterioles was much higher in HH(hypoxic-hypercapnia) group than that of NC(normal control) group, and, vessel cavity turned more straiter in HH group than that of NC group.However, the damage of pulmonary arterioles in HP(hypoxic-pueratin) group was much slighter than that of HH group. ② The levels of plasma ET-1 and lung homogenates Hyr were much higher in HH group than those of NC group( P 0.05). CONCLUSION: Puerarin inhibited the deposition of collagen and improved pulmonary vessel remodeling.

Expression and distribution of osteopontin in the development of pulmonary hypertension induced by hypoxia-hypercapnia / 中国病理生理杂志

AIM: To study the expression and distribution of osteopontin (OPN) in lungs and pulmonary arteries in pulmonary hypertensive rats induced by hypoxia-hypercapnia, and to explore the role of OPN in pathogenesis of pulmonary hypertension. METHODS: Forty-eight male Sprague-Dawley rats (Weight 180 g-220 g) were randomly divided into four groups: normal control group (NC), hypoxic hypercapnia 1-week,2-week and 4-week group (1HH, 2HH and 4HH). The expressions of OPN mRNA and protein in lungs and pulmonary arteries were detected by RT-PCR and immunohistochemistry. ELISA was used to detect the concentration of OPN in lung homogenates. The content of OPN in pulmonary arteries was detected by Western blotting. RESULTS: ① The mean pulmonary artery pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum [RV/(LV+S)] in all hypoxic hypercapniac groups were higher than those in normal control group (P0.05). ② The expression of OPN mRNA was significantly increased in pulmonary arteries and lung tissues in hypoxic hypercapnic groups compared with normal control group (P

Effect of L-arginine liposome on L-arginine transport of pulmonary artery in rats chronically exposed to hypoxia-hypercapnia / 中国病理生理杂志

AIM: To investigate the effect of chronic hypoxia-hypercapnia and L-arginine (L-Arg) liposome on L-Arg transport in rats pulmonary artery. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups, normal control group (NC), chronic hypoxia-hypercapnia group (HH), chronic hypoxia- hypercapnia group+L-Arg (HL) and chronic hypoxia-hypercapnia group+L-Arg liposome (HP). Changes in pulmonary artery L-Arg transport and pulmonary arterial microscopy were observed. RESULTS: (1) The mean pulmonary artery pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV+S) in HH group were higher than those in NC group, and in HP group was lower than that in HH group and HL group, but there was no significant difference between HL group and HH group; (2) At 0.005 mmol/L, 0.01mmol/L, 0.02mmol/L, 0.05 mmol/L, 0.1 mmol/L and 0.2mmol/L concentration of L-Arg, the velocity of L-Arg transport in HH group was lower than that in NC group, and in HL group higher than in HH group, and in HP group was much higher than that in HH group and in HL group. (3) Light microscopy showed that vessel well area/total area (WA/TA) and media thickness of pulmonary arterioles (PAMT) were much higher in rats of HH group than those in NC group, WA/TA and PAMT in HP group were obviously improved. CONCLUSION: The above results indicated that there existed a functional disturbance in L-Arg transport of pulmonary artery in rats chronically exposed to hypoxia-hypercapnia, and it was obviously enhanced when liposome was used as L-Arg carrier. Thus, it appears that liposome-L-Arg may have clinical perspective in the treatment of chronic hypoxic pulmonary hypertension.

Expression of MMP-2 mRNA and MMP-9 mRNA in pulmonary arterioles of rats with pulmonary hypertension induced by chronic hypoxia hypercapnia / 中国病理生理杂志

AIM: To investigate the expression of matrix metalloproteinases(MMPs) in pulmonary arterioles of rats with chronic hypoxia and hypercapnia-induced pulmonary hypertension. METHODS: MMP-2, MMP-9 and MMP-2 mRNA, MMP-9 mRNA were observed in pulmonary arterioles by the techniques of immunohistochemistry and in situ hybridization. RESULTS: ①The mean pulmonary artery pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV+S) of hypoxia-hypercapnia groups were higher than those of normal control group ( P

Effects of puerarin on pulmonary vascular structure of chronic hypoxia in rats / 中国药理学通报

AIMTo investigate the effects of puerarin on pulmonary vascular structure in pulmonary hypertension rats induced by chronic hypoxia. METHODSThirty male spragu-dawley rats were randomly divided int o three groups:control group(NC), hypoxia group(HH), hypoxia+puerarin group(HP). Collagen Ⅰ, Ⅲ and collagen I mRNA were observed in pulmonary arterioles by th e technique of immunohistochemistry and in situ hybridization. RESULTS①mPAP was much higher in rats of HH group than that of NC group(P0 05). ②The contents of lung homoge nates SOD and MDA of HP group were obviously higher than those of HH group(P 0 05). CONCLUSIONPuerarin can improve pulmonary vessel remodeling.

Effect of signal transducer and activator of transcription 6 and its mRNA on airway inflammation in a rat asthma model / 中国病理生理杂志

AIM: To study the effect of signal transducer and activator of transcription 6 (STAT6) on airway inflammation of rats with asthma. METHODS: Male Sprague-Dawley rats were randomly divided into control group and asthma group. The lung tissue was sampled from the left lung. Bronchoalveolar lavage fluid (BALF) was collected from the right lung. The concentrations of IL-4 in serum and BALF were measured by sandwich ELISA. STAT6 protein and STAT6 mRNA were observed in the epithelial cells of bronchus by the technique of immunohistochemistry and in situ hybridization. RESULTS: (1) The concentrations of IL-4 in BALF and serum of asthma group were significantly higher than those in control group (P

Changes of vascular endothelial growth factor in chronic pulmonary hypertension rats with different hypoxia and hypercapnia duration / 中国病理生理杂志

AIM: To investigate the changes of vascular endothelial growth factor (VEGF) in the pulmonary circulation of rats with different hypoxia and hypercapnia duration. METHODS: Forty SD rats were randomly divided into normol control group (N), exposed to hypoxia hypercapnia for 2 weeks group (T), for 4 weeks group (F), for 8 weeks group (E). The levels of VEGF were measured and the ultrastructure of pulmonary arterioles was observed by electron microscopy. RESULTS: Mean pulmonary arterial pressure (mPAP), weight ratio of RV to LV+S, the levels of VEGF in serum and lung tissue, the expression of VEGF and VEGF mRNA in group T, F, E were significantly higher than that in group N. With the prolong duration, base of endothelial cell was narrowed, proliferation of smooth muscle cells and collagenous fibers of pulmonary arterioles in rats were increased gradually. CONCLUSIONS: Hypoxia and hypercapnia increase the expression of VEGF mRNA and synthesis of VEGF. VEGF may play an important role in the pathogenesis of hypoxia pulmonary hypertension and reconstruction of pulmonary artery.