Analysis of reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products / 中国临床药理学与治疗学

AIM: To explore the reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products (OIDPs). METHODS: Screening data of 1 432 healthy subjects who participated in clinical trials of OIDPs were collected. The main reasons for the screening failure, gender differences in screening failure rate and the correlation between age and screening failure rate were summarized and analyzed. RESULTS: The screening failure rate was 72.4 % and increased with age. The failure rate was slightly higher in females than in males. Besides abnormal vital signs (17.3%), abnormal laboratory test results (16.5%) and withdrawal of consent (7.6%), poor venous condition (13.9%), positive for cigarette test results (12.6%) and failure in inhalation training (7.1%) were also the other three main reasons affecting the screening success rate. Abnormal vital signs and poor venous conditions were the primary screening failure reasons for males and females, respectively. CONCLUSION: The screening success rate could be improved by informing fully and communicating effectively, selecting young subjects with strong understanding abilities, and enhancing the training skills of investigators.

Safety analysis on bioequivalence studies of orally inhaled drug products in healthy Chinese subjects / 中国临床药理学与治疗学

AIM: To investigate the safety of bioequivalence (BE) studies of orally inhaled drug products (OIDPs) conducted by Phase I clinical Research Center of our hospital. METHODS: The safety data were collected from 482 healthy subjects enrolled in 20 OIDPs BE studies in Wuxi People's hospital from 2017 to 2022. The difference of adverse events (AEs) between test preparation and reference preparation were compared, as well as the influence of gender, age, mechanism of drug action and device type on AE were analyzed. RESULTS: A total of 102 cases of AEs were occurred in 77 subjects (16.0%, 77/482), 87 cases of AEs were related to experimental drugs, all AEs were mild or moderate, and no serious adverse events occurred. There was no difference in the incidence of AE between test preparation and reference preparation. In addition, gender, age, mechanism of drug action and device type had no significant effects on AEs. CONCLUSION: In 20 bioequivalence studies of OIDPs, OIDPs were safe and well tolerated in healthy subjects after dosing, and safety features of generic OIDPs and original drug were basically similar.

Multicenter study on the effect of early screening skills training for autism spectrum disorders in primary care hospitals in Chengdu / 四川精神卫生

ObjectiveTo investigate effect of conducting training of autism spectrum disorder （ASD） early screening skill on improving the ability to early identify ASD of medical staffs in primary care hospitals. MethodsIn September 2021， the training of ASD early screening skills was carried out for medical staffs from 20 primary care hospitals in Chengdu. After training， the training effect was evaluated. The numbers of referrals from primary care hospitals to superior hospitals， confirmed ASD as well as their average diagnostic age of children with ASD before and after training were used as evaluation indicators. ResultsAfter training， the number of children with suspected ASD referred by primary care hospitals was more than that before training ［（16.65±11.60） vs. （3.40±2.23）， t=5.431， P<0.01］， the number of children diagnosed with ASD was more than that before training［（6.85±4.93） vs. （2.45±1.67）， t=4.171， P<0.01］， and the differences were statistically significant. As for the diagnosed age of ASD children， after training， the average age was lower than that before training ［（34.95±11.67） vs. （42.2±14.64）， t=-2.553， P=0.019］. ConclusionTraining of ASD early screening skills for medical staffs in primary care hospitals may help to improve their ability to early screening ASD children.

Endovascular repair of complex aortic arch lesion with application of recanalize left subclaivian artery in intracavitary / 中华胸心血管外科杂志

Objective:To investigate the effect of different ways of reconstruction of left subclavian artery (LSA) in the treatment of complex aortic arch lesions.Methods:The clinical data of 34 patients with complex thoracic aortic disease undergoing intracavitary LSA reconstruction in our center from January 2019 to February 2020 were retrospectively analyzed. The distance of proximal healthy landing zone of all patients, including 29 aortic dissections involving LSA, 3 penetrating aortic ulcer and 2 thoracic aortic aneurysms, was less than 15 mm. Among them, 16 cases were treated with chimney technique, 16 cases were implanted with single branched stent-graft, 2 cases were received with left common carotid artery and LSA in situ fenestration.Results:The operation success rate of all 34 patients was 100%. One case was changed from in situ fenestration to chimney stenting. Followed up for 1-12 months, there were no death, cerebral ischemia, paraplegia and other postoperative complications. CTA review showed that the main and branch stents were in good shape, the patency rate of LSA branch stents was 100% and no endoleak occurred at 1 and 3 months after operation. The muscle strength and arterial blood pressure of bilateral upper limbs of all patients were basically the same.Conclusion:There is no consensus for the treatment of complex aortic arch lesions, so we need to customize the personalized plan and select the appropriate LSA reconstruction method in order to reduce the incidence of complications.

Sesamol improves inflammation and insulin resistance in adipose tissue of obese mice by regulating macrophage polarization / 中国临床药理学与治疗学

AIM: To investigate whether sesamol can improve inflammation and insulin resistance in adipose tissue of obese mice by regulating macrophage polarization. METHODS: An obese animal model was established in mice by inducing obesity with high-fat diet. The obese mice were administrated with sesamol (100 mg/kg) for 8 weeks. The mice were sacrificed after the intraperitoneal glucose tolerance test and insulin tolerance test, and the plasma lipid and insulin levels were measured. The expression of P-AKT and P-JNK in adipose tissue of epididymis was detected by Western blotting. F4/80 and Cd11c immunohistochemistry and immunofluorescence staining were performed on the adipose tissue sections. The mRNA expression of cytokines and chemokines in adipose tissue was measured by Real-time fluorescence quantitative PCR. RESULTS: Sesamol treatment reduced body weight and lipid level of obese mice, improved glucose tolerance and insulin resistance. In sesamol treated group, macrophage infiltration in adipose tissue was decreased, P-AKT expression was enhanced, P-JNK expression was reduced, mRNA expression of M1 type of macrophage markers (Cd11c, iNOS, TNF-α and IL-6) was down-regulated, mRNA expression of M2 type markers (chi3l3, Arg1 and Mgl1) was up-regulated. CONCLUSION: Sesamol can alleviate inflammation and insulin resistance in adipose tissue of obese mice. These effects may be associated with inhibition of JNK signal pathway and improvement of polarization imbalance of macrophages in adipose tissue.

Clinical effect of thoracic endovascular aortic repair for Stanford type B aortic dissection / 中国医师进修杂志

Objective To summarize the clinical efficacy of thoracic endovascular aortic repair (TEVAR) in the treatment of Stanford type B thoracic aortic dissection. Methods The clinical data of 80 patients with Stanford type B aortic dissection who had underwent TEVAR in cardiac surgery of the First Affiliated Hospital of University of Science and Technology of China from January 2017 to December 2017 were analyzed retrospectively. Among them, there were 56 males and 24 females. The effect of operation and postoperative complications were observed. The diameters of different aortic levels before and after TEVAR were compared in order to understand the aortic remodeling after TEVAR. Results All 80 patients were operated successfully. A total of 87 stents were implanted, of which 2 stents were placed in 7 patients. Four patients died 30 days after operation, 3 of whom were diagnosed as dissection rupture before operation and underwent emergency TEVAR. The cause of death was massive hemorrhage due to re-rupture of dissection. One patient complicated with massive cerebral infarction before operation died of respiratory failure. Six months after operation, CTA showed that the diameter of the aortic true lumen at the level of the left subclavian artery, the maximum diameter of the tumor and the level of the diaphragm significantly increased: (30.1 ± 3.5) mm vs. (24.4 ± 4.2)mm, (33.4 ± 5.1) mm vs. (24.9 ± 6.2) mm,(26.1±4.9) mm vs. (19.3 ± 3.1) mm; all P values＜0.01, and the false lumen significantly decreased: (3.5 ± 1.7) mm vs. (11.2 ± 5.7) mm, (9.1 ± 2.4) mm vs. (18.3 ± 5.9) mm, (6.2 ± 1.3) mm vs. (14.7 ± 5.2) mm, all P values＜0.01. There was no significant difference in the overall diameter of aorta before and after operation (P > 0.05). Conclusions The treatment of Stanford type B aortic dissection with TEVAR has significantly good short-term clinical efficacy, which is less traumatic and quick to recover. However, the long-term efficacy remains to be observed.

Value of Serum Tumor Marker Isocitrate Dehydrogenase 1 in the Diagnosis of Lung Cancer / 中国医学科学院学报

To investigate the clinical value of serum tumor marker isocitrate dehydrogenase 1(IDH1)in the diagnosis of lung cancer. The general data were collected in lung cancer patients and non-lung cancer patients.The serum level of IDH1 was detected by enzyme-linked immunosorbent assay to evaluate its clinical significance in diagnosing lung cancer. The serum IDH1 level was significantly higher in lung cancer patients than in non-lung cancer patients [(7.12±6.98)ng/ml (2.09±1.83)ng/ml,=11.540,<0.001].The serum IDH1 level in patients with adenocarcinoma or squamous cell carcinoma was significantly higher than that in patients with small cell lung cancer [(7.91±7.26)ng/ml (2.76±2.27)ng/ml, =6.345,<0.001].The sensitivity of IDH1 in detecting lung cancer,stage Ⅰ/Ⅱ lung cancer,and stage Ⅲ/Ⅳ lung cancer was 47.4%,49.1%,and 46.3%,respectively. Serum IDH1 has high sensitivities and specificities in the diagnosis and differential diagnosis of non-small cell lung cancer(squamous cell carcinoma and adenocarcinoma)and small cell lung cancer as well as the auxiliary diagnosis of stage Ⅰ and Ⅱ lung cancer.It is a valuable marker for the auxiliary diagnosis of lung cancer.

On the effects of NLRP3 inflammasome on mice pancreatic β-cell damage induced by advanced glycation end products / 中华内分泌代谢杂志

Objective To explore the role of the pyrin domain-containing 3 ( NLRP3) inflammasome in advanced glycation end products ( AGEs )-induced mice pancreatic β-cell damage. Methods AGEs were administered intraperitoneally for 6 weeks in NLRP3 knockout mice or C57BL/6J mice. Intraperitoneal glucose tolerance test and insulin releasing test were performed. Pancreatic sections were stained with haematoxylin and eosin, or with F4/80 and NLRP3 antibodies. Insulin and pancreatic tissue monocyte chemotactic protein 1 ( MCP-1) as well as interleukin-1β( IL-1β) levels were measured with ELISA kits. Expression of MCP-1 protein was determined by western blot. MIN6 cells and mouse peritoneal macrophages cells were treated with AGEs and different interventions (antioxidant NAC, adenovirus NLRP3 shRNA or NLRP3 knockout). Reactive oxygen species production, NLRP3 mRNA expression, IL-1β secretion, caspase 1 activity, apoptosis and glucose stimulated insulin release were determined. Results Injection of AGEs induced an abnormal response to glucose, enhanced the insulitis score, and increased the levels of pancreatic tissue MCP-1 and IL-1β, as well as raised the expression of NLRP3 and F4/80 in pancreatic islet. Remarkably, co-localization of NLRP3 and macrophage marker F4/80 was observed in islet. The damages were improved in NLRP3 knockout mice. After incubation with AGEs, reactive oxygen species production and cell apoptosis was enhanced, NLRP3 inflammasome activated, with glucose-stimulated insulin release impaired in MIN6 cells. NAC treatment alliviated the above damages, but NLRP3 gene silencing had no effect on ROS level, apoptosis, and insulin secretion. Finally NAC treatment and NLRP3 gene knockout inhibited activation of NLRP3 inflammasome induced by AGEs in mouse peritoneal macrophages cells. Conclusion NLRP3 knockout ameliorates the islet β-cell damage induced by AGEs. These effects were associated with AGEs-induced islets macrophage infiltrating by up-regulation of MCP-1 expression, and AGEs-induced activation of NLRP3 inflammasome in macrophage through ROS pathway, which results in the release of active IL-1βand leads to the lesions of β-cell.

Oridonin inhibits proliferation of Jurkat cells via the down-regulation of Brg1 / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of oridonin on the human acute lymphocytic leukemia cell line Jurkat and its mechanism.</p><p><b>METHODS</b>Jurkat cells were cultured in vitro and treated with various concentrations (0, 1.25, 2.5, 5, and 10 μmol/L) of oridonin for different lengths of time (24, 48, and 72 hours). The proliferation of Jurkat cells was analyzed by MTT assay. The changes in nuclear morphology were evaluated by fluorescence microscopy at 12 hours after treatment with various concentrations of oridonin. The expression levels of Brg1, P53, and C-myc were determined by semi-quantitative Western blot in Jurkat cells treated with various concentrations of oridonin for 24 hours or 5 μmol/L oridonin for various lengths of time (0, 2, 6, 12, and 24 hours). The expression levels of P53 and C-myc and proliferation of Jurkat cells were evaluated after Brg1 expression was knocked down by Brg1-specific siRNA.</p><p><b>RESULTS</b>Compared with the control group, the proliferation of oridonin-treated Jurkat cells was significantly inhibited in a concentration- and time-dependent manner (P<0.05). According to the florescence microscopic analysis, oridonin treatment led to nuclear pyknosis in Jurkat cells. Compared with the control group, Jurkat cells treated with 5 μmol/L oridonin had reduced expression of Brg1 and C-myc but elevated expression of P53. Brg1 knock-down led to a significant reduction in proliferation of Jurkat cells (P<0.05), up-regulated expression of P53, and down-regulated expression of C-myc.</p><p><b>CONCLUSIONS</b>Oridonin can inhibit the proliferation of Jurkat cells, probably via the Brg1 signaling pathway.</p>

Clinical study for the effect of nano-carbon tracer on the dissection of central group lymph nodes in thyroid cancers / 中国现代普通外科进展

Objective:to explore the effect of nano-carbon tracer on the dissection of central group lymph nodes in thyroid cancers.Methods:60 patients with thyroid cancers enrolled from January 2015 to December 2015 in our hospital were selected as research objects.Tracing group contained 30 cases would carry out nano-carbon tracer for the dissection of lymph nodes,while the other 30 patients without using nano-carbon tracer were defined as control group.The number of dissected lymph nodes,the discovery rate of positive lymph nodes and the postoperative parathyroid function were made a comparison between the two groups.Results:the total number of dissected lymph nodes in the tracing group was more than the control group (269 vs 204).The average number of dissected lymph nodes in the tracing group (8.97 ± 1.65/case) was also significantly more than the control group(6.8 ± 1.52/case)(P＜0.05).In the tracing group,the total discovery rate of positive lymph nodes was 40.15％,while the control group was 37.25％.Therefore,the average number of dissected positive lymph nodes in the tracing group (3.6 ± 1.16/case) was significantly more than the control group (2.53 ± 1.17/case)(P＜0.05).Observation of the postoperative adverse reactions,there were fewer patients suffering hypocalcemia or recurrent laryngeal nerve injury in the tracing group compared to the control group.In detail,although the blood calcium levels on the 2nd day after operation in both two groups decreased compared with preoperative baseline values,significantly statistical difference was only observed in the control group with 2.173 ±0.20mmol/L in postoperation vs 2.28 ± 0.06mmol/L in pre-operation (P＜0.05).What's more,the blood calcium level in the tracing group on the 2nd day after operation (2.27 ± 0.19mmol/L) was significantly higher than the control group (2.173 ± 0.20mmol/L)(P＜0.05).Besides,the postoperative PTH levels in both two groups reduced in some degree compared to the preoperative baseline values,but there were no statistical differences (P＞0.05).Conclusion:using nano-carbon tracer during the operation would be benefit for the dissection of positive central group lymph nodes,the recognition of parathyroid glands and reduction of postoperative adverse reactions.

Clinical implications of circulating miRNA-101 expression level in patients with newly diagnosed type 2 diabetes mellitus / 中国临床药理学与治疗学

AIM:To investigate the serum miRNA-101 expression level in patients with newly diagnosed type 2 diabetes mellitus (T2DM),and to evaluate the clinical implications of miRNA-101 expression level variation.METHODS:qRT-PCR was used to determine the serum miRNA-101 expression level.Pearson correlation analysis was performed to observe the relationship between two variables.Multiple stepwise linear regression analysis was used to assess the association of serum miRNA-101 level and other parameters.RESULTS:Serum miRNA-101 level in patients with newly diagnosed T2DM was significantly higher than that in control subjects (P ＜ 0.05).The serum level of miRNA-101 was positively correlated with the glycosylated hemoglobin A1c (HbA1c,P ＜0.05).Multiple linear regression analysis revealed that the circulating miRNA-101 was in significant positive correlation with HbA1c (P ＜ 0.05) after adjustment for age,sex and body weight.CONCLUSION:Enhanced circulating miRNA-101 level in newly diagnosed T2DM patients may be associated with elevation of HbA1 c.

α2-macroglobulin alleviates X-ray induced obstacle on osteogenic differen-tiation of human bone marrow mesenchymal stem cells / 中国病理生理杂志

AIM:To evaluate the effect of α2-macroglobulin(α2M) against X-ray induced obstacle on osteo-genic differentiation of human bone marrow mesenchymal stem cells(hBMMSCs). METHODS:hBMMSCs were cultured in vitro. The 4th generation of hBMMSCs was irradiated with 8 Gy X-ray,then induced osteogenic differentiation and trea-ted with different concentrations of α2M(0.5 and 1.0 g/L). The alkaline phosphatase(ALP) activity and the mRNA ex-pression of runt-related transcription factor-2 (RUNX2) were detected on day 7 after osteogenic induction. The protein ex-pression of osteoglycin (OGN) was evaluated by Western blot on day 14 after osteogenic induction. The formation of calci-um nodules was detected by alizarin red staining on day 21 after osteogenic induction. The activity of superoxide dismutase (SOD) and the protein expression of MnSOD of irradiated hBMMSCs with 8 Gy X-ray were determined at 24 h after α2M treatment. RESULTS:Compared with 8 Gy X-ray group,the activity of ALP,the mRNA expression of RUNX2,the pro-tein expression of OGN and MnSOD,as well as SOD activity were higher than those in the hBMMSCs treated with α2M at 0.5 and 1.0 g/L after 8 Gy X-ray irradiation,and the calcium nodules were also increased. CONCLUSION:α2M signifi-cantly improves the osteogenic differentiation ability,the SOD activity and MnSOD protein expression of hBMMSCs after ra-diation injury.

Antiviral activity of minicircle DNA-mediated shRNA in HBV transgenic mice / 解放军医学杂志

Objective To investigate whether minicircle DNA-mediated shRNA can inhibit the replication and expression of HBV in HBV transgenic mice.Methods First,a universal plasmid shRNA,pU6-shRNA HBV and a minicircle shRNA vector pMC-U6-shRNA HBV targeting HBV gene was prepared by molecular cloning technique.Then,the HBV transgenic mice were divided into three groups and the pMC-U6-shRNA HBV,pU6-shRNA HBV and control vector pU6-control were transfected into them respectively by hydrodynamic injection (HDI).Sera were collected at different time points after injection.The changes of HBV DNA and HBsAg in serum of transgenic mice were detected by real-time PCR and chemiluminescence microparticle immunoassay (CMIA).Immunohistochemistry was used to analyze the expression of HBcAg in the liver of transgenic mice.Results Compared with pU6-control group,HBsAg and HBV DNA in serum of transgenic mice were significantly inhibited by pU6-shRNA HBV and pMC-U6-shRNA from day 7 to day 21 after HDI (P＜0.05).After that,the serum HBsAg and HBV DNA recovered and returned to the control level on the 35th day in pU6-shRNA HBV group.However,pMC-U6-shRNA HBV still maintained a strong inhibitory effect in vivo until 35 days post-injection compared with the other two groups (P＜0.05).Immunohistochemical results also suggest that pMC-U6-shRNA HBV could more significantly inhibit HBcAg expression than pU6-shRNA HBV in mouse liver tissue.Conclusion The minicircle DNA-based shRNA vector pMC-U6-shRNA HBV is of longer inhibitory effect on HBV replication and gene expression in HBV transgenic mice than pU6-shRNA HBV.Minicircle DNA is superior to pRNAT-U6.1/Neo for shRNA delivery in vivo.

Clinical study for the effect of nano-carbon tracer on the dissection of central group lymph nodes in thyroid cancers / 中国现代普通外科进展

Objective:to explore the effect of nano-carbon tracer on the dissection of central group lymph nodes in thyroid cancers.Methods:60 patients with thyroid cancers enrolled from January 2015 to December 2015 in our hospital were selected as research objects.Tracing group contained 30 cases would carry out nano-carbon tracer for the dissection of lymph nodes,while the other 30 patients without using nano-carbon tracer were defined as control group.The number of dissected lymph nodes,the discovery rate of positive lymph nodes and the postoperative parathyroid function were made a comparison between the two groups.Results:the total number of dissected lymph nodes in the tracing group was more than the control group (269 vs 204).The average number of dissected lymph nodes in the tracing group (8.97 ± 1.65/case) was also significantly more than the control group(6.8 ± 1.52/case)(P＜0.05).In the tracing group,the total discovery rate of positive lymph nodes was 40.15％,while the control group was 37.25％.Therefore,the average number of dissected positive lymph nodes in the tracing group (3.6 ± 1.16/case) was significantly more than the control group (2.53 ± 1.17/case)(P＜0.05).Observation of the postoperative adverse reactions,there were fewer patients suffering hypocalcemia or recurrent laryngeal nerve injury in the tracing group compared to the control group.In detail,although the blood calcium levels on the 2nd day after operation in both two groups decreased compared with preoperative baseline values,significantly statistical difference was only observed in the control group with 2.173 ±0.20mmol/L in postoperation vs 2.28 ± 0.06mmol/L in pre-operation (P＜0.05).What's more,the blood calcium level in the tracing group on the 2nd day after operation (2.27 ± 0.19mmol/L) was significantly higher than the control group (2.173 ± 0.20mmol/L)(P＜0.05).Besides,the postoperative PTH levels in both two groups reduced in some degree compared to the preoperative baseline values,but there were no statistical differences (P＞0.05).Conclusion:using nano-carbon tracer during the operation would be benefit for the dissection of positive central group lymph nodes,the recognition of parathyroid glands and reduction of postoperative adverse reactions.

Case-control study on superior labrum from anterior to posterior repair and biceps tenodesis for the treatment of type II SLAP injury / 中国骨伤

<p><b>OBJECTIVE</b>To compare clinical outcomes of superior labrum from anterior to posterior (SLAP) repair and biceps tenodesis in treating type I SLAP injury.</p><p><b>METHODS</b>From March 2009 to March 2012, 38 patients with type II SLAP injury were treated with SLAP repair and biceps tenodesis, and all patients were unilateral SLAP injury. Sixteen patients treated with biceps tenodesis included 8 males and 7 females with an average age of (49.3±3.7) years old (ranged, 45 to 54); 10 cases were on the left side and 6 cases on the right side; 10 cases were caused by falling down, 2 cases were caused by throwing damage and 4 cases were caused by daily life damage; the time from injury to operation were from 3 to 8 weeks. Twenty-two patients treated with SLAP repair included 14 males and 8 females with an average age of (49.0±2.8) years old (ranged, 44 to 56); 13 cases were on the left side and 9 cases were on the right side; 14 cases were caused by falling down, 5 cases were caused by throwing damage and 3 cases were caused by daily life damage; the time from injury to operation were from 3 to 7 weeks. Preoperative, postoperative at 6 months, 1 year and 2 years' UCLA and SST score were compared between two groups.</p><p><b>RESULTS</b>There was no significant differences in UCLA and SST score between two groups before operation. At 6 months after operation, UCLA and SST score in biceps tenodesis group was higher than SLAP group, and action,range of anteflexion, strength of anteflexion, degree of satisfaction in biceps tenodesis group was higher than SLAP group. There was no significant meaning in SST and UCLA score between two groups at 1 and 2 years after operation.</p><p><b>CONCLUSION</b>Short-term efficacy of biceps tenodesis for SLAP injury is better than SLAP repair, but long-term efficacy is fairly.</p>

Effect of sesamin on expression of inducible nitric oxide synthase and nitrotyrosine in rat liver tissue with metabolic syndromic hepatic steatosis / 中国病理生理杂志

AIM: To study the effect of sesamin on expression of inducible nitric oxide synthase(iNOS)and nitrotyrosine(NT)in rat liver tissue with metabolic syndromic hepatic steatosis. METHODS: The rat model of metabolic syndromic hepatic steatosis was induced by operation of two kidneys with one clip(2K1C)and high-fat. The rats taken from that successful model were randomly divided into model group and sesamin(120, 60, and 30 mg·kg~(-1)·d~(-1))groups. In addition, the sham-operated group was set up. The rats in treated group were given sesamin intragastrically everyday for 8 weeks. The levels of blood lipids(TC, TG and FFA)in serum were detected. The activity of SOD and MDA level in the liver homogenate were determined. The expressions of iNOS and NT proteins were detected by Western blotting analysis. The histopathological changes were observed by HE staining in the liver tissues. RESULTS: Compared to model groups, sesamin(120, 60 mg·kg~(-1))significantly inhibited the elevation of serum TC, TG, FFA, and MDA in liver homogenate(P<0.05), and increased the activity of SOD(P<0.05). It also decreased the protein expression of iNOS and NT(P<0.05), and ameliorated the degree of hepatic steatosis. CONCLUSION: Sesamin prevents and cures the metabolic syndromic hepatic steatosis. The mechanism is probably mediated through decreasing the protein expression of iNOS and NT, and alleviating the oxidative stress in addition to regulating the lipid metabolism.

Effect of penehyclidine hydrochloride on oleic acid-induced acute lung injury in rats: A comparison between inhalation and intravenous therapy / 第二军医大学学报

Objective: To compare the therapeutic effects of penehyclidine hydrochloride on rat with oleic acid (OA)-induced acute lung injury (ALI) when given via inhalation and intravenous injection. Methods: Forty male Sprague-Dawley rats were randomly divided into 4 equal groups: normal control group(group I), ALI group(group II), penehyclidine hydrochloride inhalation group(group III), and intravenous penehyclidine hydrochloride group (group IV). The blood pressure (BP), pulmonary artery pressure (PAP), and airway pressure (Paw) were determined every 60 min during the experiment and the artery blood gas analysis and mixed venous blood gas analysis were performed. The wet to dry lung weight ratio (W/D) and the serum concentration of tumor necrosis factor alpha (TNF-α) were determined 240 min after the experiment in each group. Results: The OA-induced increase of PAP, Paw and decrease of PaO2/FiO2 were improved in the group III and group IV compared with those in the group II(P<0.05 for group III). The W/D and serum TNF-α concentration were lower in the group III and group IV compared with those in the group II (P<0.05 for group III). Conclusion: Penehyclidine hydrochloride can relieve the symptoms of OA-induced ALI. Inhalation approach is more effective than intravenous injection when the same dose of penehyclidine hydrochloride is given.

Therapeutic effect of inhaled aerosolized versus intravenous milrinone on oleic acid-induced acute lung injury in rats / 中华麻醉学杂志

Objective To compare the therapeutic effect of inhaled aerosolized and intravenous milrinone,a phosphodiesterase-3 inhibitor in rats with oleic acid-induced acute lung injury (ALI) .Methods Forty male SD rats weighing 300-350 g were randomly divided into 4 groups (n=10 each) : group Ⅰ normal control: group Ⅱ ALI; group Ⅲ milfinone inhalation and group Ⅳ intravenous milrinone.The animals were anesthetized with intraperitoneal 2% pentobarbital 40 mg/kg,tracheostomized and mechanically ventilated (FiO2 30%,VT 10 ml/kg,RR 80 bpm,I:E=1:2).The chest was opened and the heart was exposed.Pulmonary artery was catheterized via fight ventricle.MAP,CVP,airway pressure and pulmonary artery pressure (PAP) were monitored.ALI was induced with 10% oleic acid 2 ml/kg administered through fight external jugular vein in group Ⅱ,Ⅲ and Ⅳ.In control group 0.1% BSA solution 2 ml/kg was administered iv instead of oleic acid.In group Ⅲ at 30 min after oleic acid administration aerosolized milrinone 1 mg/ml was inhaled 4 times at 60 min interval.Each time milrinone was inhaled for 10 min.In group Ⅳ at 30 min after oleic acid administration a bolus of 10 μg/kg milrinone was given iv followed by 10 min milrinone infusion at 1 μ·kg-1·min-1.The same procedure was repeated 4 times at 60 min interval.MAP and PAP were recorded and blood samples were taken from carotid artery and pulmonary artery for blood gas analysis at the 1st,2nd,3rd and 4th treatment.PaO2/FiO2 and Qs/Qt were calculated.The animals were sacrificed by exsanguination after the 4th treatment.The lungs were removed.The left lung was lavaged.Neutrophil count and protein content in broncho-alveolar lavage fluid (BALF) were determined.W/D lung weight ratio and lung myeloperoxidase (MPO) activity were measured.The uhrastructure of the lung was examined with electron microscope.Results The MAP was significantly lower after oleic acid adminstration in group Ⅳ than in other 3 groups.PaO2/FiO2 was significantly decreased and Qs/Qt increased by iv oleic acid in group Ⅱ ,Ⅲ and Ⅳ.PAP was significantly increased after iv oleic acid in group Ⅱ ,Ⅲ and Ⅳ but was significantly lower in group Ⅲ and Ⅳ than in group Ⅱ .The neutrophil count and total protein content in BALF,W/D ratio and lung MPO activity were significantly increased in group Ⅱ ,Ⅲ and Ⅳ as compared with control group(Ⅰ) and were significantly higher in group Ⅳ than in group Ⅲ.The lung damage induced by oleic acid was less serious in group Ⅲ and Ⅳ than in group Ⅱ .Conclusion Inhaled aerosoLized milrinone has better therapeutic effect than intravenous milrinone in rats with oleic acid-induced ALI and is safer.

Expression of specific antibodies against platelet glycoproteins in patients with mds and its significance / 中国实验血液学杂志

The aim of this study was to find platelet specific autoantibodies against glycoproteins in myelodysplastic syndrome (MDS) and to explore its role in pathogenesis of MDS. The plasma autoantibodies against GP IIb/IIIa and GP Ib/IX were measured by using a modified monoclonal antibody specific immobolization platelet antigens assay (MAIPA). Absorbance greater than mean value plus tripled standard deviation recorded from the normal controls were regarded as positive. The results indicated that the total positive rate in patients with MDS was 16.67% (5/30), the total positive rate in patients with ITP was 46.67% (14/30), the difference between MDS group and ITP group was significant (P < 0.05). It is concluded that partial patients with MDS have plasma specific autoantibodies against platelet GP II b/III a and GP Ib/IX, indicating correlation of thrombocytopenia of patients with immune factors and the autoantibody-mediated platelet destruction may be involved in the pathogenesis of MDS. It provides a new basis for immunosuppression therapy for MDS.

Effect of NF?B family proteins on growth and drug-resistance of human ovarian cancer cell lines / 中国癌症杂志

Purpose:To investigate the relationship between the expression of NF?B family proteins in ovarian cancer cell lines with chemotherapy resistance of ovarian cell lines. Methods:First, 13 ovarian cancer cell lines were cultured, and then protein was extracted separately from cytoplasm and nucleus. Using Western blotting and MTT chemosensitive testing, the relationship between the expression of NF?B family proteins in ovarian cancer cell lines with chemotherapy resistance of ovarian cell was observed.Results:It was found that the expression of positive rate of P65, P50 and IKB in cytoplasm was 76.9%, 81.8% and 84.6% respectively, and the significant positive expression of P65 and P50 was also found in the nucleus, with a rate of 15.3%, 45.5% respectively. In OV MZ 5 and OV MZ 2774, the expression of P65 was positive and their IC 50 reached a significant value. Conclusions:It was concluded that P50 and P65 affected the growth and development of ovarian cancer cells with the effect of P50 being more obvious. P65 had a close relationship with the chemotherapy resistance of ovarian cancer cells, and thus P65 could be expected to be a new marker in the observation of prognosis.