Research progress on the development of human neutrophil elastase inhibitors / 药学学报

Human neutrophil elastase (hNE) is a serine proteolytic enzyme mainly distributed in neutrophils. When the balance between anti-hNE protein and hNE is broken, excessive release of hNE can cause the occurrence of various diseases. Therefore, inhibition of hNE is a promising therapeutic strategy. In this paper, the structure, action mechanism, physiological function of hNE and the development of hNE inhibitors were briefly summarized, in order to provide information for the related research.

Analysis of coronary angiographic findings in 117 children with Kawasaki disease and coronary artery lesion / 中华实用儿科临床杂志

Objective:To analyze the coronary angiographic (CAG) characteristics of coronary artery lesion (CAL) in children with Kawasaki disease (KD), and to clarify the necessity of CAG in the diagnosis and treatment of KD combined with CAL in children.Methods:It was a retrospective study to analyze the clinical data, electrocardiogram, echocardiography, time and findings of CAG in children with KD and CAL who underwent CAG in Shanghai Children′s Medical Center of Shanghai Jiao Tong University School of Medicine from January 2013 to August 2022.The distribution, type, severity, and prognosis of CAL were analyzed.Results:A total of 117 children with KD and CAL were included in the analysis.The onset age of KD was from 2 months to 12.8 years old, and the age of performing CAG was from 8 months to 18.1 years old.A total of 234 coronary artery lesions were detected in 117 cases.Among them, CAL in the right coronary artery (RCA), left anterior descending branch (LAD), left main coronary artery and left circumflex artery were detected in 96 branches(41.1%), 78 branches(33.3%), 44 branches(18.8%), and 16 branches(6.8%), respectively.Unilateral coronary artery involvement was detected in 43 cases (36.8%), of which LAD was the dominant; while bilateral involvement was detected in 74 cases (63.2%), among which, LAD and RCA were the most involved arteries.Stratified by the degree of coronary involvement, large coronary aneurysms and severe coronary stenosis were most frequently occurred in the RCA and LAD.In contrast, 10 cases (13.6%), 20 cases (24.3%), 55 cases (45.8%) and 37 cases (67.3%) of intraluminal lesions were found in small, medium and large coronary aneurysms, and stenosis or occlusion, respectively.The incidence of intraluminal lesions tended to be higher in the site of severe lesions.CAG showed stenosis or occlusion in a total of 55 cases, and collateral circulation at varying degrees was found in cases of severe stenosis or occlusion.Conclusions:CAL in children with KD are complex and varied.Although clinical symptoms, routine electrocardiogram and cardiac ultrasound may indicate severe CAL.Their applications are limited by the diagnosis of the type (especially stenosis), degree, and extent of CAL, as well as the detection of extracoronary lesions.CAG is of great significance to identify vascular lesions and guide clinical management of KD combined with CAL in children.

Surgical treatment of coronary artery lesions caused by Kawasaki disease / 中华实用儿科临床杂志

Kawasaki disease is an acute self-limiting systemic vasculitis syndrome and usually occurs in children.The small and medium arteries of the whole body are mainly invaded, and marked with coronary arteries.Coronary artery dilation and aneurysm formation mainly occur in the early period.Thrombi, intimal hyperplasia, and calcification could be formed during the later period.Consequently, sometimes, it develops intochronicischemic cardiopathy or myocardial infarction.In that, Kawasaki disease has become the leading cause of acquired heart disease for children in developed countries.Presently, the treatment of coronary artery lesions caused by Kawasaki disease includes drug therapy, and interventional and surgical treatment.However, medications usually fail to solve severe coronary conditions, and only interventional and surgical treatment can we choose.Therefore, the development and indications of interventional and surgical treatment of coronary artery lesions caused by Kawasaki disease were reviewed in this article.

Efficacy and safety of low-dose corticosteroids for acute respiratory distress syndrome: A systematic review and meta-analysis / 世界急诊医学杂志（英文）

@#BACKGROUND: There are conflicting results regarding whether corticosteroids have better efficacy than placebo in acute respiratory distress syndrome (ARDS) patients. Therefore, we aim to further evaluate the efficacy and safety of corticosteroids in adult ARDS patients. METHODS: The databases, including Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, were searched from their inception to May 2, 2020. Randomized controlled trials (RCTs) and observational cohort studies were selected to assess the use of corticosteroids in adult ARDS patients. The quality of the results was judged by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The inverse-variance method with random or fixed effects modeling was used to compute pooled odds ratio (OR), standardized mean difference (SMD), and their 95% confidence interval (CI). RESULTS: Eight eligible RCTs and six cohort studies were included. The use of corticosteroids was associated with reduced mortality (OR 0.57, 95% CI 0.43-0.76, I2=35.1%, P=0.148) in ARDS patients, and the result was confirmed in the included cohort studies (OR 0.51, 95% CI 0.27-0.95, I2=66.7%, P=0.010). The subgroup analysis stratified by the initiation time and duration of corticosteroid use showed that early ARDS and prolonged corticosteroid use had significant survival benefits in the RCTs. The low-dose corticosteroid use was also associated with significantly more ventilator-free days and a reduced rate of new infections in ARDS patients. CONCLUSIONS: The low-dose corticosteroid therapy may be safe and reduce mortality, especially in patients with prolonged treatment and early ARDS.

Research progress of KRAS inhibitors / 药学学报

The RAS (rat sarcoma) gene is one of the important oncogenes, and its mutation is present in about 30% human tumors. KRAS (kirsten rat sarcoma viral oncogene) is one of the three RAS subtypes, and KRAS mutations are more common than the mutations in other two RAS subtypes. In recent years, with the continuous research, new ideas have been provided for the treatment of cancers via targeting-KRAS. Efforts have been made to develop various KRAS inhibitors. Here, based on the mechanism of action, we classified KRAS inhibitors into two categories: inhibitors that directly target KRAS and inhibitors that indirectly act on KRAS. The representative KRAS inhibitors were summarized and introduced in this paper.

Research progress on indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors / 药学学报

Indoleamine 2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in the degradation of tryptophan to kynurenine. IDO1 is highly expressed in some tumor tissues. IDO1 can deplete tryptophan in tumor microenvironment, inhibit T cell function, and mediate the immune escape of tumor cells. Thus, IDO1 is considered a potential target of tumor immunotherapy. Currently, there are several IDO1 inhibitors in clinical research studies. The mechanism of IDO1-mediated tumor immune escape and the structure of IDO1 inhibitors are summarized in this review.

An arthroscopic "inlay" Bristow procedure with suture button fixation: Surgical technique and radiology evaluation / 北京大学学报(医学版)

OBJECTIVE@#To introduce an arthroscopic "inlay" Bristow procedure based on the Mortise-Tenon joint structure concept using suture button fixation, and to evaluate its clinical and radiology results postoperatively with a minimal 3-year follow-up.@*METHODS@#A total of 56 patients who received arthroscopic "inlay" Bristow procedure with suture button fixation between June 2015 to June 2016 were eventually enrolled in this study. Radiological assessment on the 3D CT scan was performed preoperatively, immediately after operation, and postoperatively at the end of 3 months, 6 months and the final follow-up. Complications postoperatively were also recorded.@*RESULTS@#A total of 56 patients were finally included in this study. The mean follow-up time was (36.1±3.7) months. Coracoid grafts (middle point) were positioned at about 4 o'clock (123.8°±12.3°) in the En-face view. In the axial view, 95% (53/56) of the grafts positioning were measured as flush, 5% (3/56) as medial. Bone union rate was 96.4% at the final follow-up. At the end of 3 months, 6 months, and the final follow-up, the length of the coracoid graft was 96.9%±4.9%, 91.9%±6.2%, and 91.6%±6.6% of the immediate postoperative length, respectively. Compared with the immediate postoperative length, the length measured at the end of 3 months shortened not significantly (t=2.12, P > 0.05). The coracoid graft shortened more pronouncedly 6 months postoperatively (t=4.98, P < 0.05) and then remained almost constant over time (t=-0.75, P > 0.05), with all grafted coracoid graft retaining more than 90% of their initial length by the 3-year follow-up. And new bone formation at the junction between the coracoid graft and glenoid neck in the axial view were obviously noted in 25 cases. The quantitative evaluation showed that the glenoid area in En-face view was significantly increased at the final follow-up than that immediately after surgery [(9.72±1.22) cm2 vs. (9.42±1.11) cm2]. No degenerative changes were noted on CT images in all the patients at the final follow-up.@*CONCLUSION@#This study reported a series of "inlay" Bristow procedure with suture button fixation for recurrent shoulder dislocation, providing satisfactory union rate and excellent graft positioning. And using suture button fixation instead of screw can reduce osteolysis and complications related to hardware implantation. Moreover, the bone remodeling between the coracoid process and glenoid could be beneficial to restoring the anterior stability of shoulder joint in a long term follow-up.

Sexual behavior characteristics and influencing factors of gonorrhea patients in Yunnan Province / 中华疾病控制杂志

Objective To investigate the sexual behavior types, condom use and influencing factors of gonorrhea patients in Yunnan Province, and to provide evidence for the adjustment of sexually transmitted disease (STD) prevention and control strategy. Methods A cross-sectional study was carried out to investigate gonorrhea patients in 14 STD clinics in 7 more prevalent prefectures (cities) of Yunnan Province. A questionnaire survey was conducted to investigate the socio-demographic and sexual characteristics of the patients in a one-to-one way. Multiple Logistic regression model was used to analyze the influencing factors of sexual behavior. Results A total of 179 cases of gonorrhea were investigated. The average age was (29.01±8.93) years old. 95.53% (171/179) patients were 40 years old and 88.27% were male patients (158/179). Unmarried patients accounted for 55.31% (99/179). Service and self-employed patients accounted for 34.64% (62/179) and 23.46% (42/179) respectively. The rate of sexual intercourse with opposite sex was 98.32% (176/179), the rate of men who have sex with men was 1.68% (3/179) and the rate of having more than two sexual partners was 27.93% (50/179). The rate of sexual intercourse between temporary partners, spouses/fixed partners and commercial partners were 53.07% (95/179), 37.99% (68/179) and 8.94% (16/179) respectively. Recent sexual activity had lower condom use rate, 17.89% (17/95), 19.12% (13/68) and 18.75% (3/16) respectively. The main ways for gonorrhea patients to make temporary partners were friend introductions or gatherings, accounting for 66.32% (63/95). Condom use in male patients was worse than that in female patients (OR=0.234, 95% CI: 0.084-0.656, P=0.006). Conclusions The patients with gonorrhea were mainly unmarried young adults. The main risk behaviors were unprotected behaviors between heterosexual temporary and spouse/fixed sexual partners. The condom use consciousness was generally low. The promotion of safe sex education for young adults should be further strengthened, with special attention to the use of condoms for temporary sexual behavior and spouse/fixed sexual intercourse.

Thromboxane A2 receptor contributes to the activation of rat pancreatic stellate cells induced by 8-epi-prostaglandin F2α / 中华医学杂志(英文版)

BACKGROUND@#Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α).@*METHODS@#TxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10, 10, 10 mol/L) for 48 h, and SQ29548 (10, 10, and 10 mol/L), a TxA2r-specific antagonist for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10 mol/L) for 2 h, followed by 10 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student's t test.@*RESULTS@#TxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2α significantly increased mRNA levels of α-SMA (10 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t = 10.70, P < 0.001; 10 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t = 10.83, P < 0.001; 10 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t = 11.40, P < 0.001) and collagen I (10 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t = 15.41, P < 0.001) and α-SMA (10 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t = 15.17, P < 0.001; 10 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t = 11.29, P < 0.001; 10 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t = 12.86, P < 0.001). After being treated with SQ29548 (10 mol/L) and then 8-epi-PGF2α (10 mol/L), the mRNA levels of α-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t = 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group.@*CONCLUSIONS@#The results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.

Study on the effect of stilamin in alleviating mitochondrial injury of pancreatic acinar cells in acute pancreatitis / 中华胰腺病杂志

Objective:To investigate the effect of stilamin on mitochondrial injury of acute pancreatitis (AP)-related acinar cells and the possible mechanism.Methods:24 C57BL/6 mice were randomly divided into control group, AP group and AP+ stilamin treatment group (Stilamin group). AP model was prepared by intraperitoneal injection of l-arginine in AP group, 0.4 mg/kg stilamin was intraperitoneally injected at 2 h after modeling in stilamin group, and control group received intraperitoneal injection with saline in the same volume. Histopathological examination of pancreatic tissue was performed routinely. Serum levels of IL-6, IL-10 and TNF- α were detected by ELISA, serum levels of amylase and lipase, and serum levels of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) reflecting oxidative stress were detected by biochemistry method, respectively. Mitotracker red fluorescent labeling was used to detect the number of mitochondria in pancreatic acinar cells, and western blot was used to detect the ND-3 protein expression reflecting the number of mitochondria. The expression levels of mitochondrial fusion protein (Mfn-2) and mitochondrial transcription factor A (TFAM) reflecting mitochondrial function were determined by immunohistochemical staining.Results:Compared with AP group, the pancreatic pathology scores of mice in Stilamin group were significantly decreased [(2.07±0.50) vs (3.93±0.64)], serum amylase and lipase levels were significantly decreased [(1 493±172)U/L vs (1 832±86)U/L, (225.4±83.2)U/L vs (671.0±164.5)U/L]; serum IL-6 and TNF-α levels were greatly decreased, while IL-10 levels were obviously increased [(99.09±39.65)ng/L vs (358.60±139.22)ng/L, (22.75±11.24)ng/L vs (40.83±1.62)ng/L, (15.12±5.03)ng/L vs (9.92±8.73)ng/L]. Mitotracker staining density and expression levels of ND-3, Mfn-2 and Tfam were increased [(71.67±17.62) vs (40.00±10.15), (0.45±0.16) vs (0.11±0.05), 78% vs 54%, 86% vs 47%], and MDA, SOD, and GSH levels were increased [(5.00±1.73)nmol/mg vs (7.33±2.08)nmol/mg protein, (17.33±3.21)U/mg vs (8.67±2.07)] U/mg protein. The ratio of (131.33±20.55)U/mg to (77.33±29.69)U/mg protein was statistically significant (all P<0.05). Conclusions:By protecting the mitochondria number and function of damaged pancreatic acinar cells and reducing the level of oxidative stress, stilamin could alleviate the level of pancreatic tissue damage and inflammatory response in mice with acute pancreatitis.

Sexual and reproductive health knowledge, attitude, and behavior of young migrant workers in Shanghai / 上海预防医学

Objective To evaluate the current status of sexual and reproductive health knowledge and behavior of young migrant workers in Shanghai, which would provide information for the development of intervention measures. Methods A cluster random sampling with self-filled questionnaires was used for survey in two factories of Shanghai.The total number of young migrant workers surveyed was 713.The questionnaire contents included socioeconomic characters, knowledge, attitude and behavior of sex and reproductive health. Results There were 428 males and 285 females ranged from 17 to 24 years old.Eighty-eight percent of them were from rural area of China, and 79.7% of them were unmarried.Their awareness of sexual and reproductive health was low, including misunderstandings of sexually transmitted diseases and HIV transmission pathways, and failure to realize the difference between condom and contraceptive pills.Only 46.5% of the males and 31.5% of the females answered correctly about the role of contraceptive pills.Their sexual attitude was open on premarital sex and cohabitation.Males were more tolerant than women; 59.1% of the males thought they could have sex before marriage if they got consent, which was much higher than females (39.6%, P < 0.01).While the rate of premarital sex was high (64.0% in males and 56.1% in females), sexual safety awareness was not strong.The rate of condom use was only 20%, and 12.4% of the females had unwilling pregnancy and abortion. Conclusion The sexual and reproductive health status in young migrant workers need to be improved by strengthening health education and health promotion.

Synthesis of benzimidazole and benzothiazole derivatives as a sirtuins 2 inhibitor / 药学学报

A series of novel benzimidazole and benzothiazole derivatives were designed and synthesized as inhibitors of SIRT1-SIRT3. The target compounds were synthesized from potassium O-ethyldithiocarbonate through a three-step route. The structures of the obtained compounds were elucidated by 1H NMR and HR-MS. Of all compounds, six showed potent SIRT2-inhibitory activities with IC50 values ranging from 2.8 to 21.2 μmol·L-1. Among them, compound 10c displayed the most potent SIRT2-inhibitory activities (IC50 = 2.8 μmol·L-1), with more than 35-fold selectivity over SIRT1 and SIRT3 (IC50>100 μmol·L-1).

Pedicle subtraction osteotomy for repairing thoracolumbar degenerative kyphosis:correlation of spino-pelvic parameters / 中国组织工程研究

BACKGROUND:Thoracolumbar degenerative kyphosis could experience severe lumbar back pain due to sagittal plane imbalance, thereby affecting quality of life. Thus, it is very important to reconstruct spino-pelvic profile in these patients. OBJECTIVE:To explore the relationships between life quality and spino-pelvic parameters fol owing pedicle subtraction osteotomy for thoracolumbar degenerative kyphosis and the clinical significance. METHODS:Between May 2010 and October 2014, 59 patients with thoracolumbar degenerative kyphosis undergoing L2 pedicle subtraction osteotomy in Cangzhou Hospital of Integrated Traditional and Western Medicine were retrospectively reviewed. Anteroposterior and lateral X-ray films of al patients during standing were photographed before and after surgery. The pre-and post-operative thoracic kyphosis, lumbar lordosis, sagittal imbalance, T1 pelvic angle, pelvic incidence, sacral slope and pelvic tilt were measured in al patients. The patients’ quality of life was evaluated using SF-36 preoperatively and postoperatively. RESULTS AND CONCLUSION:(1) Significant differences were observed in the improvement of thoracic kyphosis, lumbar lordosis, pelvic tilt, sacral slope and sagittal imbalance (P<0.01). With respect to SF-36, postoperative SF-36 score was higher than preoperative postoperative SF-36 score (P<0.01). (2) The alteration of lumbar lordosis showed significant correlation with the change of pelvic tilt, sacral slope and sagittal imbalance. The change of pelvic tilt exhibited cardinal correlation with the change of sacral slope, body pain and general health. The improvement of sagittal imbalance significantly correlated with the improvement of lumbar lordosis, body pain and general health. The improvement of T1 pelvic angle significantly correlated with the improvement of lumbar lordosis, sagittal imbalance, body pain and general health. (3) Pedicle subtraction osteotomy can effectively restore spino-pelvic sagittal profile, improve the life quality and relieve pain for the patients with thoracolumbar degenerative kyphosis.

Facilitating the measurement of circulatory hydrogen sulfide with fluorescence probe-coated microplates / 北京大学学报(医学版)

Objective:The hydrogen sulfide (H2 S) role in pathogenesis of various diseases were wildly addressed in recent decade.The circulatory (plasma or serum) and biological fluid H2S measurement is still an enormous issues due to the technical limitation.This paper aimed to develop a novel measurement method based on fluorescence probe.Methods:Firstly,20 μL ethanol was used to dissolve 100 pmol fluorescence probe,then added in a 96-well plate.An equal volume of ethanol was also added to the blank well of the plate.The plate was placed in a dark room for about 1 h until the fluorescence probe was evenly coated in the 96-well microplate and dried.The plate was frozen at-20 ℃ for later use.Secondly,the plasma or serum sample was added with saturated ammonium sulfate buffer (pH 7.8) and then centrifuged to remove the proteins.The equal volume supernatant liquid was added to the probecoated well and the probe-uncoated well.The plate was incubated in a dark environment at 37 ℃ for 2 h.Finally,after incubation,the fluorescence density was acquired at λEx/λEm 340/445 nm in a microplate reader.The differences of the fluorescence density values between the probe-coated well and probeuncoated well were counted and H2S concentration of plasma/serum was calculated by standard curve with NaHiS.Results:The method had high sensitivity (from 0.3 to 100 μmol/L) and specificity for measuring H2S as compared with other biologically relevant reactive sulfur species and sulfur-containing amino acid.Serum H2S concentrations were assayed in 188 health volunteers using this method [(12.1 ±3.5) μmol/L,95％ CI:4.6-19.8 μmol/L],and the frequency distribution showed a normal tendency(one-sample Kolmogorov-Smirnov test,P ＞ 0.1).The serum H2S concentrations in 30 hypertension patients were decreased compared with 22 age-and gender-matched health individuals (paired-samples t test,t =9.937,P ＜ 0.001).There were no differences of H2S concentration in serum [(19.66 ±2.32) μmol/L] or plasma [(18.67 ±2.07) μmol/L],between the samples acquired from artery [(19.34 ±0.51) μmol/L] or vein [(18.99 ±0.50) μ mol/L] of male Wistar rats (repeated measurement of ANOVA,P =0.38).One week frozen samples did not affect the detection.The values of the repeated measurement did not differ (two-way ANOVA,P ＞ 0.05).Conclusion:The present method is easily performed with high sensitivity,specificity and repeatability for circulatory H2S.It is also quick and may apply for large samples.

Effects of vinpocetine on inflammation of brain in rats with intracerebral hemorrhage / 中国病理生理杂志

AIM:To investigate the effects of vinpocetine on inflammation of brain in intracerebral hemorrhage ( ICH) rats and to explore the underlying mechanisms .METHODS:All rats were randomly divided into sham group , ICH group, ICH with low dose of vinpocetine treatment group , ICH with medium dose of vinpocetine treatment group , and ICH with high dose of vinpocetine treatment group .Except sham group , the rats in other groups were injected with type VII col-lagenase to establish ICH model , and then the rats in vinpocetine treatment groups were received vinpocetine at 0.5, 1.0 or 1.5 mg/kg by intraperitoneal injection once a day for 7 days.After corresponding treatment , the impairment of neurological function in the rats was scored and the water content of the brain tissues was measured .Moreover, the activity of myeloper-oxidase (MPO) was determined by ELISA, and the protein expression of Toll-like receptors 4 (TLR4), nuclear factor-κB (NF-κB), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molcule-1 (VCAM-1) in the brain tissues was determined by Western blot .RESULTS: Compared with ICH group , vinpocetine treatment significantly de-creased the scores of the impairment of neurological function and the water content of the brain tissues .Moreover, the activ-ity of MPO and the protein expression of TLR4, NF-κB, ICAM-1 and VCAM-1 were also reduced after vinpocetine treat-ment (P<0.05).CONCLUSION:Vinpocetine improves neurological function in ICH rats via suppression of inflamma -tion by inhibiting NF-κB signaling and expression of ICAM-1 and VCAM-1.

Analysis of gastric gastrointestinal stromal tumors in Shandong Province: a midterm report of multicenter GISSG1201 study / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.</p><p><b>METHODS</b>Clinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.</p><p><b>RESULTS</b>Among 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.</p><p><b>CONCLUSIONS</b>The choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.</p>

Flavonoids from leaves of Psidum littorale / 药学学报

We investigated the chemical constituents of the leaves of Psidum littorale, which include 16 flavonoids, including seven flavonols, six flavonoid glycosides and three flavonones. The compounds were isolated by silica gel column chromatography. Their structures were elucidated on the basis of spectral analysis and by comparison with published data. Seven flavonols were kaempferol (1), isorhamnetin (2), myricetin-3,7,3'-trimethyl ether (3), laricitrin (4), quercetin (5), myricetin (6) and quercein-3,4'-dimethyl ether (7), six flavonoid glycosides were guaijaverin (8), hyperoside (9), 5,4'-dyhydroxy-3,7,5'-methoxyflavone-3'-O-β-D-glucoside (10), laricitrin-3-O-xyloside (11), myricetin-3-O-α-L-rhamnopyranoside (12) and myricetin-3-O-β-D-xyloside (13). Three flavonones were 4'-O-methyldihydroquercetin (14), dihydroapigenin (15) and ampelopsin 4'-O-β-D-glucopyranoside (16). Compound 10 is a new chemical, compounds 2-4, 7, 10-16 were first isolated from this plant. 1H NMR and 13C NMR data of compound 11 were not reported in literature.

Anti-HIV-1 activities of pine cone extract from Pinus kesiya var. langbianensis in vitro / 中草药

Objective: To investigate the anti-HIV-1 activity and mechanism of pine cone extracts from Pinus kesiya var. langbianensis in vitro. Methods: The cytotoxicity of pine cone extract from P. kesiya var. langbianensis was examined by MTT assay; Syncytium formation inhibition assay, p24 assay, and the HIV-1-induced MT-4 cell death assay were used to evaluate the anti-HIV-1 activity of pine cone extract from P. kesiya var. langbianensis. HIV DNA species detection assay, cell fusion assays, and time of addition assay were used to determine the mechanisms of the extracts. Results: Pine cone extract from P. kesiya var. langbianensis named SMS-F showed the good inhibition on HIV-1 in C8166 cells with TI value above 436.46 and 558.61, respectively. HIV-1 DNA species detection showed that ssDNA and late-RT were lower in the SMS-F treated group than those in the control group. The result implied that the mechanism of SMS-F might target the early stage of HIV-1 replication. SMS-F blocked the cell to cell fusion with EC50 value 71.03 μg/mL and could not inhibit the replication of HIV-1 after entering the cell, which confirmed SMS-F targeting the HIV entry stage. Conclusion: Pine cone extract from P. kesiya var. langbianensis shows the good inhibition on HIV-1 targeting the viral entry stage.

The Hug-up Test: A New, Sensitive Diagnostic Test for Supraspinatus Tears / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The supraspinatus tendon is the most commonly affected tendon in rotator cuff tears. Early detection of a supraspinatus tear using an accurate physical examination is, therefore, important. However, the currently used physical tests for detecting supraspinatus tears are poor diagnostic indicators and involve a wide range of sensitivity and specificity values. Therefore, the aim of this study was to establish a new physical test for the diagnosis of supraspinatus tears and evaluate its accuracy in comparison with conventional tests.</p><p><b>METHODS</b>Between November 2012 and January 2014, 200 consecutive patients undergoing shoulder arthroscopy were prospectively evaluated preoperatively. The hug-up test, empty can (EC) test, full can (FC) test, Neer impingement sign, and Hawkins-Kennedy impingement sign were used and compared statistically for their accuracy in terms of supraspinatus tears, with arthroscopic findings as the gold standard. Muscle strength was precisely quantified using an electronic digital tensiometer.</p><p><b>RESULTS</b>The prevalence of supraspinatus tears was 76.5%. The hug-up test demonstrated the highest sensitivity (94.1%), with a low negative likelihood ratio (NLR, 0.08) and comparable specificity (76.6%) compared with the other four tests. The area under the receiver operating characteristic curve for the hug-up test was 0.854, with no statistical difference compared with the EC test (z = 1.438, P = 0.075) or the FC test (z = 1.498, P = 0.067). The hug-up test showed no statistical difference in terms of detecting different tear patterns according to the position (χ2 = 0.578, P = 0.898) and size (Fisher's exact test, P > 0.999) compared with the arthroscopic examination. The interobserver reproducibility of the hug-up test was high, with a kappa coefficient of 0.823.</p><p><b>CONCLUSIONS</b>The hug-up test can accurately detect supraspinatus tears with a high sensitivity, comparable specificity, and low NLR compared with the conventional clinical tests and could, therefore, improve the diagnosis of supraspinatus tears in clinical settings.</p>

Screening and target gene mapping of differentially expressed microRNAs in the degenerative intervertebral disc of degenerative scoliosis patients / 中国组织工程研究

BACKGROUND:MicroRNAs (miRNAs) play an important role in many diseases. To analyze the miRNA expression profile in degenerative scoliosis patients is helpful for classifying its pathogenesis. OBJECTIVE: To compare miRNAs expression profile in the intervertebral disc tissue between degenerative scoliosis patients and healthy controls, and to investigate its role in the pathogenesis of degenerative scoliosis. METHODS:Degenerative nucleus pulposus tissues from 48 patients with degenerative scoliosis (male 36, female 12; 58-69 years old) and normal nucleus pulposus tissues from 36 patients with lumbar fractures were harvested to isolate, culture and identify nucleus pulposus cels folowed by total RNA extract. Differentialy expressed miRNAs were screened by microRNA microarray analysis and validated by real-Time qPCR. Target genes of highly expressed microRNAs were predicted by analyzing information from MicroCosm v5, TargetScan 5.1 and microRNA.org databases. Biological signal pathways associated with the target genes were analyzed, and qPCR was used to validate the screening results. RESULTS AND CONCLUSION:Nineteen differentialy expressed miRNAs were identified. The miR-98 was highly expressed in degenerative nucleus pulposus tissue, and the fold change was 6.368. Predicted miR-98 target gene was interleukin-10, which was involved in JAK-STAT signaling pathway and located in upstream of this pathway. In degenerative nucleus pulposus cels of degenerative scoliosis patients, miR-98 was highly expressed, and the corresponding target gene was interleukin-10. These results indicate that JAK-STAT signaling pathway may play an important role in the pathogenesis of degenerative scoliosis.