Corynoxine B targets at HMGB1/2 to enhance autophagy for α-synuclein clearance in fly and rodent models of Parkinson's disease

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Experimental study on rabbit lamellar corneal transplantation with double-layer corneal stromal lens attactched by fibrin sealant / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the biocompatibility of double-layer corneal stromal lens attactched by fibrin sealant(FS)<i>in vivo</i>, and to explore the feasibility of using this material for corneal transplantation.<p>METHODS: Fifteen healthy and clean New Zealand white rabbits were selected for a self-control study. The right eye of the rabbit was used as the experimental eye and the left eye was used as the control eye. The experimental eyes used FS adhesived double-layer corneal stromal lens as the material for lamellar keratoplasty, and the control eyes did not undergo manual intervention. At 7,14, and 28d after surgery, a hand-held slit lamp was used to observe the cornea of the rabbits and then score the biocompatibility. The corneas of both eyes were taken for histopathological examination by HE staining to observe the corneal recovery at the same time.<p>RESULTS: Slit lamp observation results showed that by 28d after the operation, the corneal epithelium of the experimental eyes grew well, the degree of corneal transparency was basically restored, the degree of edema was reduced, the growth of neovascularization to the corneal edge was not aggravated, and no rejection reaction such as epithelial and endothelial rejection lines were seen; The control eyes had clear corneas and smooth corneal epithelium. The results of biocompatibility score showed that the degree of corneal implant edema gradually decreased, the transparency gradually recovered, the rejection reaction was less, and the biocompatibility of corneal implants was better in the experimental eyes after corneal transplantation. There were no differences in the degree of corneal transparency, edema and neovascularization growth between the experimental and control eyes at 28d after surgery(<i>P</i>>0.01). The results of histopathological examination showed that by 28d after corneal transplantation, there were 4-5 layers of corneal epithelial cells covering the surface of the implant in the experimental eyes, the corneal collagen was neatly and regularly arranged, no obvious inflammatory cell infiltration was seen in the implant, the boundary between the two lenses disappeared, the interlayer FS was completely absorbed by the organism, the implant was fused with the implant bed, and no obvious demarcation was seen.<p>CONCLUSION:Using FS pasted double-layer corneal stroma lens as a graft for lamellar keratoplasty has better recovery, less rejection and better biocompatibility, and can be used for lamellar keratoplasty.

Mechanism of Chinese Herbal Monomers Against Cisplatin-induced Resistance of Ovarian Cancer： A Review / 中国实验方剂学杂志

Because the early symptoms of ovarian cancer are not typical and there is a lack of effective screening methods， most patients are diagnosed at an advanced stage， which seriously endangers the health of modern women. Platinum-based chemotherapy after tumor reduction is the first choice for patients with advanced and recurrent ovarian cancer， but almost all patients with recurrent ovarian cancer will eventually develop platinum resistance. Therefore， the search for natural， safe， and effective chemotherapeutic sensitizers has become an urgent and important topic in the study of ovarian cancer. With the increasingly extensive application of traditional Chinese medicine （TCM） in the treatment of cancer， the research on Chinese herbal monomers is also deepening， and the mechanisms of Chinese herbal monomers in intervening in cisplatin （DDP）-induced resistance of ovarian cancer is becoming increasingly clearer. Based on the research status of Chinese herbal monomers available in many Chinese and English databases， it was found that Chinese herbal monomers were involved in the reversal of DDP-induced resistance of ovarian cancer via many routes， mainly through increasing the intracellular drug concentration， reversing the blocked apoptosis， correcting the abnormal intracellular signaling pathway， enhancing DNA damage and inhibiting DNA repair， regulating intracellular autophagy， and suppressing epithelial mesenchymal transition （EMT）. Chinese herbal monomers weaken the resistance of ovarian cancer to DDP from multiple targets and enhance the toxicity of DDP to ovarian cancer cells in vitro and transplanted tumors in vivo. Therefore， Chinese herbal monomers are expected to become natural sensitizers for ovarian cancer chemotherapy with DDP. However， the current studies on Chinese herbal monomers are still confined to the single experimental type， and their action mechanisms and toxic and side effects remain to be further clarified. The application of Chinese herbal monomers for sensitizing DDP chemotherapy still needs to be verified by multi-target， multi-level experimental studies and large-scale clinical studies in the future.

Mechanisms of Guizhi Fulingwan Against Ovarian Cancer： A Review / 中国实验方剂学杂志

Ovarian cancer （OC） is one of the three major gynecological malignancies. Due to its insidious onset at the early stage，most of OC patients are diagnosed at the advanced stage， making it become one of the most deadly gynecological tumors and thus a hot topic in the field of gynecology and oncology. Guizhi Fulingwan is a classic Chinese herbal compound derived from Synopsis of Golden Chamber （《金匮要略》） for the treatment of abdominal mass in women on account of its efficacy in resolving stasis， generating new blood， and eliminating mass. The articles concerning the treatment of OC with Guizhi Fulingwan were searched from such databases as China National Knowledge Infrastructure （CNKI）， PubMed，Wanfang Data Knowledge Service Platform， and Chongqing Weipu Database for Chinese Technical Periodicals （VIP） and collated for expounding its action mechanisms， in order to provide ideas for further research on its pharmacological effects，clinical application， and promotion. Clinically，Guizhi Fulingwan has been proved to control the growth of myoma，correct serological indexes，enhance chemotherapy sensitivity and anti-tumor immunity，reduce postoperative recurrence rate， and improve the quality of life of patients. As revealed by experimental research，Guizhi Fulingwan alleviates the pathological state of animal and cell models by promoting mitochondrial apoptosis and tumor immunity，inhibiting vascular factors，inducing cell cycle arrest， and reversing multidrug resistance. Guizhi Fulingwan exerts a certain therapeutic effect on OC through multi-target and multi-channel mechanisms， reflecting the advantages of traditional Chinese medicine in treating OC.

Effect of Curdione on MDA-MB-231 Cell Cycle and Apoptosis / 中国实验方剂学杂志

Objective:To investigate the effects of curdione on the proliferation， apoptosis and cell cycle of triple negative breast cancer cell line MDA-MB-231. Method:MDA-MB-231 cells were cultured<italic> in vitro</italic> with capecitabine （positive control） and curdione at different concentrations （125， 250， 500， 1 000， and 2 000 μmol·L^-1）， respectively， for detecting their viability using the cell counting kit-8 （CCK-8） at 24 and 48 h. Three effective inhibitory concentrations （250， 500， and 1 000 μmol·L^-1） against cell proliferation were selected for subsequent experiments. The effect of curdione on cell cycle was determined by flow cytometry combined with propidium iodide （PI） staining. After the set-up of high-concentration （2 000 μmol·L^-1） group， the effect of curdione on cell mitochondrial membrane potential was measured by JC-1（5，5，6，6-tetrachloro-1，1，3，3-tetraethylbenzimidazolylcarbocyanine iodide） staining， followed by the detection of cell apoptosis by flow cytometry combined with Annexin V-FITC/PI double staining. The changes in cell cycle status and apoptosis-related protein expression following curdione intervention were assayed by Western blot. Result:Compared with the blank control， curdione at 250， 500， 1 000， and 2 000 μmol·L^-1significantly inhibited the proliferation of MDA-MB-231 cells （<italic>P</italic><0.01）， exhibiting a concentration- and time-response relationship. The half maximal inhibitory concentration （IC₅₀） values at 24 and 48 h were 1 607 and 1 401 μmol·L^-1， respectively. Curdione at 250， 500， and 1 000 μmol·L^-1 arrested cells in G₁ phase. Curdione at 250 μmol·L^-1had no effect on cell mitochondrial membrane potential， which， however， declined significantly in the 500， 1 000， and 2 000 μmol·L^-1groups （<italic>P</italic><0.05， <italic>P</italic><0.01）. Curdione at 250， 500， and 1 000 μmol·L^-1obviously increased the proportion of apoptotic cells （<italic>P</italic><0.05， <italic>P</italic><0.01）. Curdione at each concentration elevated the Bcl-2-associated X protein （Bax）/B-cell lymphoma 2 （Bcl-2） ratio （<italic>P</italic><0.05， <italic>P</italic><0.01）， but did not change the cysteinyl aspartate-specific protease-3 （Caspase-3） expression. The protein expression levels of Caspase-9， cleaved Caspase-9， cleaved Caspase-3， p53， and p21 were up-regulated （<italic>P</italic><0.05）. Conclusion:A certain concentration of curdione inhibits the proliferation of MDA-MB-231 cells， which may be related to its efficacy in arresting cell cycle and inducing apoptosis.

Study Progress of Effect of Traditional Chinese Medicine Monomer in Intervening Ovarian Cancer by Regulating PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

Ovarian cancer is a kind of malignant tumor in female reproductive system with a high incidence. This disease is insidious at its early stage and the symptoms are not typical. Most of the patients have reached advanced stage by the time of diagnosis， seriously threating women's life and health. Many signaling pathways are involved in the formation and development of ovarian cancer， among which the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway is one of the key regulatory pathways. In recent years， traditional Chinese medicine （TCM） has obtained wide attention in treatment of tumors due to its advantages of high safety and less adverse reactions， and more and more attention has been paid to the study of TCM monomers. Molecular biology studies have shown that TCM monomers can play a role against tumor by regulating multiple targets. By reviewing the literature and searching several databases， we found that TCM monomer can play an important role in the growth， proliferation， invasion and migration， apoptosis， autophagy and reversal of drug resistance of ovarian cancer cells by regulating PI3K/Akt signaling pathway. According to the existing studies， TCM monomers have a certain effect on ovarian cancer， but there are still many problems. Although the mechanisms of some TCM monomers have been clarified in the treatment of ovarian cancer， such TCM monomers are only limited to the tumor-bearing nude mice in vivo and experimental studies on in vitro cells， and further studies are needed in the future. In addition， in the future researches， ovarian cancer syndrome differentiation and targeted therapy can be linked to the TCM flavors， efficacy and indications to further develop the advantages of TCM. Based on the current research situation at home and abroad， this paper summarized the research progress of targeted intervention of TCM monomers in ovarian cancer by regulating PI3K/Akt signaling pathway， in order to provide reference for further research of TCM monomers， and provide important ideas for the development of targeted treatment of ovarian cancer with TCM.

Effect of solubilizing strategies on oral absorption of felodipine / 中国药科大学学报

@#As a typical BCS Ⅱ drug, felodipine exhibits low solubility and high permeability. We herein investigated the effects of different solubilization strategies on the oral absorption of felodipine. Firstly felodipine tablets based on 200 μm, 150 μm and 25 μm particle size of bulk drug were prepared. Meanwhile, felodipine solid dispersion and felodipine nanosuspension with average particle size of (168.90 ± 6.22) nm, PDI of 0.11 ± 0.06 were prepared. The absorption rate, apparent permeability coefficient (Papp), absorption quality in duodenum, jejunum, ileum and colon of rats and in vivo pharmacokinetics of the above different felodipine preparations were investigated. The results of rat single-pass intestinal perfusion showed that the absorption of felodipine preparations in duodenum, jejunum and ileum was better than in colon. Felodipine had a wide absorption window in the small intestine, with the best absorption site in the small intestine. Papp of different felodipine preparations was greater than 2.0 × 10-5 cm/s. Thus, the low solubility was the main factor limiting the absorption. In vivo pharmacokinetic experiments demonstrated the solubilization strategies significantly improved the bioavailability. The bioavailabilities of felodipine tablets with particle sizes of 150 and 25 μm, as well as nanosuspension, and solid dispersion were 138.75%, 173.01%, 208.65% and 314.53% that of the tablets with particle size of 200 μm, respectively. Solubilization strategies can significantly improve the gastrointestinal absorption rate and absorption quality of felodipine, and thus improve its bioavailability, which provides some reference for the research on the improvement of oral absorption of BCS II drugs.

Research and application of nanometer black phosphorus in phototherapy and drug carrier / 药学学报

The emerging nano-black phosphorus materials have created a new platform for biomedical research. Nano-black phosphorus has the following advantages: black phosphorus can produce singlet oxygen under near-infrared light irradiation, so it can be used as a photosensitizer for photodynamic therapy;black phosphorus has extensive light absorption in the long wavelength region, and this near-infrared photothermal property can be used in photothermal therapy. The high specific surface area and unique fold structure of the black phosphorus nanosheet make it have very high drug loading.This paper mainly reviews the applications of black phosphorus in biological imaging, photothermal therapy, photodynamic therapy, and as a drug carrier in recent years. Based on the photoelectric properties of black phosphorus nanomaterials combined with intelligent drug delivery platform, the synergistic effects of light/heat/chemistry, light/chemistry/gene, and light/chemistry/immunity can be produced, which has a broad application prospect.

Mediating effect of obsessive-compulsive symptoms between attributional style and depressive symptoms in patients with obsessive-compulsive disorder / 上海交通大学学报（医学版）

Objective • To explore the relationship among depressive symptoms, attributional style and obsessive-compulsive symptoms in patients with obsessive-compulsive disorder. Methods • Seventy patients with obsessive-compulsive disorder who met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM- ) were selected. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to evaluate the severity of obsessive-compulsive symptoms, the Beck Depression Inventor- Ⅱ (BDI- Ⅱ ) was used to measure the depressive symptoms, and the Attributional Style Questionnaire (ASQ) was used to measure the attributional style. The correlations among obsessive-compulsive symptoms, depressive symptoms and attributional style as well as the mediating role of obsessive-compulsive symptoms between attributional style and depressive symptoms were analyzed. Results • The globality dimension of negative events in attributional style was positively correlated with obsessive-compulsive symptoms and depressive symptoms (both P<0.05), and obsessive-compulsive symptoms were also positively correlated with depressive symptoms (P=0.000). The mediating effect analysis showed that the mediating role of obsessive-compulsive symptoms between the globality dimension of negative events and depressive symptoms was 0.105 (95%CI 0.031-0.218), with an mediating effect ratio of 44.20%. Conclusion • Obsessive-compulsive symptoms in patients with obsessive-compulsive disorder may play a completely mediating effect between the globality dimension of negative events in attribution style and depressive symptoms.

Establishment and validation of predictive model of pregnancy loss in patients with systemic lupus erythematosus / 上海交通大学学报（医学版）

Objective: To establish and verity predictive model of pregnancy loss in systemic lupus erythematosus (SLE). Methods: A total of 338 SLE pregnant patients admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine from Sept. 2011 to May 2017 (model development group) and 131 SLE pregnant patients admitted from Jun. 2017 to Jun. 2018 (model validation group) were selected. Multivariable Logistic regression model was used to determine the predictive variables and their coefficients of pregnancy loss in model development group. The predictive model was established, the risk score classification was performed, and model validation group was used for external validation. Results: Multivariate Logistic regression analysis showed that unplanned pregnancy (P=0.032), low complement C3 (P=0.002) and 24 h urinary protein ≥ 1.0 g (P=0.000) were the risk factors of the predictive model of SLE pregnancy loss. When the risk score of the model was 0-3, the risk of SLE pregnancy loss was low, and when the risk score is more than 3, it is high risk, with a sensitivity and specificity of 60.5% and 93.3%, respectively. The model was used in the model validation group for external validation, and the prediction accuracy of SLE pregnancy loss was 90.1%. Conclusion: The predictive model of SLE pregnancy loss can help clinicians efficiently screen the high-risk population of SLE pregnancy loss in order to take relevant measures as soon as possible to obtain better pregnancy outcomes.

Association between circulating vaspin levels and the risk of gestational diabetes mellitus: A systematic review and Meta－analysis / 中华疾病控制杂志

@#Objective To review the existing literature and quantitatively evaluate the association of circulating vaspin levels and the risk of gestational diabetes mellitus ( GDM) ． Methods We systematically searched the PubMed，EMBASE，Web of Science，China National Knowledge Infrastructure，and WanfangData databases up to June 2019． Pooled standardized mean differences ( SMDs) with 95% confidence intervals ( CIs) were calculated using random－ or fixed－effects models based on the heterogeneity of studies． Subgroup analyses，Meta－regression，sensitivity and publication bias were assessed to analyze the heterogeneity and the robustness of the results． All statistical analyses were performed using STATA 12．0． Ｒesults Nine articles ( 11 comparisons) published from 2013 to 2019 were included in our final Meta－analysis，covering a total of 738 patients with GDM and 661 normal pregnant women． There was significant difference in the overall maternal circulating vaspin levels between GDM patients and healthy pregnant women ( SMD= 0．613，95% CI: 0．044－1．182，P= 0．035) ． Subgroup analyses stratified by trimester in which vaspin was measured and whether BMI was matched suggested the similar trend to the overall result． Subgroup analysis according to ethnicity found that circulating vaspin level might not be related to GDM in " European" subgroup; sensitivity analysis by excluding moderate－quality studies and BMI－unmatched studies found that circulating vaspin levels were still related to GDM risk． Conclusions Our Meta－analysis indicated that maternal circulating vaspin levels might be positively correlated with the risk of GDM in Asians．

Association of Gene Mutations with Response to Arsenic-Containing Compound Qinghuang Powder () in Patients with Myelodysplastic Syndromes / 中国结合医学杂志

OBJECTIVES@#To investigate the relationship between gene mutations and response to Compound Qinghuang Powder (, CQHP) in patients with myelodysplastic syndrome (MDS).@*METHODS@#Forty-three MDS patients were genotyped by ultra-deep targeted sequencing and the clinical data of patients were collected and the relationship between them was analyzed.@*RESULTS@#Up to 41.86% of patients harbored genet mutations, in most cases with more than one mutation. The most common mutations were in SF3B1, U2AF1, ASXL1, and DNMT3A. After treatment with CQHP, about 88.00% of patients no longer required blood transfusion, or needed half of prior transfusions.@*CONCLUSIONS@#CQHP is an effective treatment for patients with MDS, especially those with gene mutations in SF3B1, DNMT3A, U2AF1, and/or ASXL1.

Consistency Analysis of Gene Mutation Sites of Bone Marrow Tumor DNA and Circulating Tumor DNA in Patients with Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To analyze the consistency of gene mutation sites between bone marrow DNA (BM-tDNA) and perepheral plasma circulating tumor DNA (PP-ctDNA) in patients with myelodysplastic syndrome (MDS).@*METHODS@#The simultaneous sampled BM and PP from 19 patients (SBPP) was detected by NGS-127 gene panel, and the consistency of VAF between BM-tDNA and PP-ctDNA was analyzed. The peripheral blood cell tumor DNA (PC-tDNA) of 5 out of 19 patients was detected randomly, the consistency of VAF among PC-tDNA，BM-tDNA and PP-ctDNA was analyzed. The non simultaneous sampled BM and PP from 13 patients (NBPP) was detected, and the difference value of VAF between BM-tDNA and PP-ctDNA in SBPP and NBPP was analyzed.@*RESULTS@#The average concentration of PP-ctDNA in SBPP was 0.59 ng/µl and 0.604 ng/µl in NBPP. The median concentration of PP-ctDNA in SBPP and NBPP was 0.330 ng/µl and 0.338 ng/µl, respectively. The study showed a good consistency of VAF between BM-tDNA and PP-ctDNA in the SBPP (R=0.9693, P<0.05), and the consistency of VAF between BM-tDNA and PP-ctDNA in single base replacement (SNP) sites (R=0.9712) was better than that in insertion deletion (Indel) sites (R=0.6813). The results showed a good consistency of VAF between BM-tDNA and PP-ctDNA both in 12 patients before treatment (R=0.9325, P<0.05) and 5 patients (R=0.9875, P<0.05) after treatment. The results also showed that the VAF of PC-tDNA had a good consistency with the VAF of BM-tDNA (R=0.8783) and PP-ctDNA (R=0.8783) (P<0.05). The difference value of VAF between BM-tDNA and PP-ctDNA in SBPP was significantly lower than that in NBPP (P<0.05).@*CONCLUSION@#PP can replace BM as a biological sample for genes mutation detection in patients with MDS due to its stable concentration, high degree of consistency with bone marrow in clinical significant mutation sites and easy collection.

Progress of transcranial direct current stimulation for treatment of obsessive-compulsive disorder / 上海交通大学学报（医学版）

Obsessive-compulsive disorder is a disabling disease with symptoms of repeated and persistent unwanted intrusive thoughts and compulsive behaviors. The current first-line treatment methods mainly include psychopharmacology, psychotherapy, and the combination of both, but nearly 40% patients still show no response to conventional treatment. Among the recently developed treatments, non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), are expected to alleviate the symptoms of various psychiatric disorders and improve cognitive function. tDCS has been applied to the treatment of depression, schizophrenia, generalized anxiety disorder and other mental diseases, and has achieved definite clinical effect. However, there are few studies about tDCS applying to the obsessive-compulsive disorder, especially in the number of randomized controlled trials. Most of the studies are open trials and case reports, and the results are inconsistent. By reviewing the effect of tDCS in treating obsessive-compulsive disorder patients in existing reports, the possibility of applying tDCS widely to treating obsessive-compulsive disorder in the future is analyzed.

Analysis of risk factors for diabetic retinopathy without proteinuria in type 2 diabetic patients / 医学研究生学报

Objective　To analyze risk factors for diabetic retinopathy without proteinuria in type 2 diabetic patients．　Methods　The clinical data of type 2 diabetic patients were retrospectively analyzed. These patients were divided into two groups based on the results of fundus examination. Basic clinical data were compared in simple diabetic retinopathy (DR, without albuminuria and DPN) group including 169 cases and non-diabetic retinopathy (NO-DR, without microvascular complications) group including 208 cases. Logistic regression analysis was used to analyze the risk factors of DR. Among DR, 60 patients were mild non-proliferation DR (NPDR), 82 patients were moderate NPDR, 20 patients were severe NPDR and 7 patients were proliferation DR (PDR). Severe NPDR and PDR were combined into severe DR group. The correlation between risk factors and DR staging were analyzed by Pearson correlation analysis.　Results　The results showed that duration of diabetes, HbA1c, systolic blood pressure, diastolic blood pressure, postprandial blood glucose, triglyceride, serum creatinine, cystatin C and ratio of statin were higher in DR group, but age at onset of diabetes, CKD-EPI formula estimated GFR, fasting c-peptide and postprandial c-peptide were lower in DR group than that in NDR group (P<0.05). Logistic regression analysis showed that young age at onset of diabetes (OR:0.914, P≤0.001), hypertriglyceridemia (OR:1.369, P<0.05), high systolic pressure (OR:1.041, P<0.01) and reduced GFR (OR:0.912, P≤0.001) were the risk factors of DR. Pearson correlation analysis demonstrated that GFR was negatively correlated to DR staging (r=-0.513, P<0.001), TG (r=0.110，P<0.033) and SBP (r=0.231, P<0.001） were positive correlated to DR staging.　Conclusion　In addition to the traditional factors, simple diabetic retinopathy in type 2 diabetic patients was related to young age at onset of diabetes, high systolic pressure, hypertriglyceridemia and reduced eGFR. eGFR decline occurred before the proteinuria and associated with the development of DR was a predicted factor of DR.

Chemical profiling from water extract of Wikstroemia indica by UPLC-Q-TOF-MS/MS / 中国中药杂志

In this study,a method using ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS) was established to identify complicated chemical constituents of Wikstroemia indica. Chromatographic separation was performed on an AcclaimTMRSLC 120-C18 column( 2. 1 mm×100 mm,2. 2 μm) using gradient elution with 0. 2% ammonium formate buffer salt solution( A)-0. 2% ammonium formate buffer salt solution methanol( B) as mobile phase. The column temperature was maintained at 30 ℃. The analytes were determined by positive and negative ion modes with electro-spray ionization source. A total of 52 compounds( including eleven coumarins,thirteen flavonoids,ten lignans,two amides,four phenolic acids,six sesquiterpenes and six other compounds) were identified or tentatively characterized from the water extract of W. indica by comparing their retention times and MS spectra with those of authentic standards or literature datas. Three compounds were found for the first time from W.indica namely isomer of indicanone,β-hydroxypropiovanillone and epiprocurcumenol. Furthermore,the fragmentation rules of some compounds were speculated and summarized. In addition,the cleavage pathways of guaiane sesquiterpenes were described for the first time,which can provide reference for studying the fragmentation pathways of similar compounds. This study provides an easy way to identify chemical constituents of traditional Chinese medicine and a basis for the further study on chemical fundamentals of W. indica.

Salvianolic acids improve liver lipid metabolism in ovariectomized rats via blocking STAT-3/SREBP1 signaling / 中国天然药物

Postmenopausal women, who have reduced circulating estrogen levels, are more prone to develop obesity and related metabolic diseases than premenopausal women. The absence of safe and effective treatments for postmenopausal obesity has changed the focus to natural products as alternative remedies. Total salvianolic acids (TSA) are the major water-soluble ingredients of Danshen. Salvianolic acid (SA) is the major constituent of the TSA. Salvianolic acids, including TSA and SA, are widely used in traditional Chinese medicine. In the present study, ovariectomized rats and LO2 cells were used to study the effects of salvianolic acids on body weight gain and hepatic steatosis. Salvianolic acids reduced ovariectomy (OVX)-induced body weight gain, attenuated the expressions of hepatic lipogenic genes, such as sterol regulatory element binding protein (SREBP)1, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD)1, and decreased the liver triglyceride (TG) and total cholesterol (TC). For the molecular mechanisms, OVX and high glucose-induced phosphorylation of signal transducer and activator of transcription (STAT)-3 was inhibited by salvianolic acids treatment. In LO2 cells, inhibition of STAT-3 by siRNA attenuated the increased expression of SREBP1 and TG induced by high glucose. Salvianolic acids reduced the upregulation of SREBP1 and TG induced by high glucose in LO2 cells. In conclusion, these findings illustrated that salvianolic acids markedly alleviated the lipid metabolism disorders and protected against the postmenopausal obesity. The underlying mechanism was probably associated with the regulation of STAT-3 signaling.

Salvianolic acids improve liver lipid metabolism in ovariectomized rats via blocking STAT-3/SREBP1 signaling / 中国天然药物

Postmenopausal women, who have reduced circulating estrogen levels, are more prone to develop obesity and related metabolic diseases than premenopausal women. The absence of safe and effective treatments for postmenopausal obesity has changed the focus to natural products as alternative remedies. Total salvianolic acids (TSA) are the major water-soluble ingredients of Danshen. Salvianolic acid (SA) is the major constituent of the TSA. Salvianolic acids, including TSA and SA, are widely used in traditional Chinese medicine. In the present study, ovariectomized rats and LO2 cells were used to study the effects of salvianolic acids on body weight gain and hepatic steatosis. Salvianolic acids reduced ovariectomy (OVX)-induced body weight gain, attenuated the expressions of hepatic lipogenic genes, such as sterol regulatory element binding protein (SREBP)1, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD)1, and decreased the liver triglyceride (TG) and total cholesterol (TC). For the molecular mechanisms, OVX and high glucose-induced phosphorylation of signal transducer and activator of transcription (STAT)-3 was inhibited by salvianolic acids treatment. In LO2 cells, inhibition of STAT-3 by siRNA attenuated the increased expression of SREBP1 and TG induced by high glucose. Salvianolic acids reduced the upregulation of SREBP1 and TG induced by high glucose in LO2 cells. In conclusion, these findings illustrated that salvianolic acids markedly alleviated the lipid metabolism disorders and protected against the postmenopausal obesity. The underlying mechanism was probably associated with the regulation of STAT-3 signaling.

Clinical, Laboratory and Imaging Features of High Altitude Pulmonary Edema in Tibetan Plateau / 中国医学科学杂志(英文版)

Objective To analyze characteristics of high altitude pulmonary edema (HAPE) in Chinese patients.Methods We performed a retrospective study of 98 patients with HAPE. We reviewed the medical records and summarized the clinical, laboratory and imaging characteristics of these cases, and compared the results on admission with those determined before discharge.Results Forty-eight (49.0%) patients developed HAPE at the altitude of 2800 m to 3000 m. Ninty-five (96.9%) patients were man. Moist rales were audible from the both lungs, and moist rales over the right lung were clearer than those over the left lung in fourteen patients. The white blood cells [(12.83±5.55) versus (8.95±3.23) ×10 /L, P=0.001)] as well as neutrophil counts [(11.34±3.81) versus (7.49±2.83)×10 /L, P=0.001)] were higher, whereas the counts of other subsets of white blood cells were lower on admission than those after recovery (all P<0.05). Serum levels of alkaline phosphatase (115.8±37.6 versus 85.7±32.4 mmol/L, P=0.020), cholinesterase (7226.2±1631.8 versus 6285.3±1693.3 mmol/L, P=0.040), creatinine (85.2±17.1 versus75.1±12.8 mmol/L, P=0.021), uric acid (401.9±114.2 versus 326.0±154.3 mmol/L, P=0.041), and uric glucose (7.20±1.10 versus 5.51±1.11 mmol/L, P=0.001) were higher, but carbondioxide combining power (COCP, 26.7±4.4 versus 28.9±4.5 mmol/L, P=0.042) and serous calcium (2.32±0.13 versus 2.41±0.10 mmol/L, P=0.006) were lower on admission. Arterial blood gas results showed hypoxemia and respiratory alkalosis on admission. Conclusions In the present research, men were more susceptible to HAPE than women, and in the process of HAPE, the lesions of the right lung were more serious than those of the left lung. Some indicators of routine blood test and blood biochemistry of HAPE patients changed.

Comparative study of degenerated versus non-degenerated nucleus pulposus cells in inducing mesenchymal stem cells differentiation / 医学研究生学报

Objective Normal nucleus pulposus cells (nNPCs) can induce the differentiation of mesenchymal stem cells (MSCs).However, the inductive effect of degeneration nucleus pul-posus cells ( dNPCs ) on MSCs has not been determined .This study aimed to compare nNPCs with dNPCs in inducing MSCs into nucleus pulposuslike cells. Methods MSCs (cell line) were co-cultured with NPCs (cell line/isolated from patients with intervertebral disc degeneration) in 3D in vitro.The cells were divided into 5 groups:nNPCs control group, dNPCs control group, MSCs control group, nNPCs-MSCs group (MSCs induced by nNPCs), dNPCs-MSCs group (MSCs induced by dNPCs).After co-cultured for 7 days, the expression level of aggrecan (ACAN), type II collagen (COL-2), SOX-9, matrix metalloproteinase-1 (MMP-1) and MMP-3 in all the 5 groups'cellswere detected by RT-PCR and Western-blot. Results The RT-PCR results showed the expression of ACAN , COL-2 and SOX-9 in nNPCs-MSCs group was higher than that in dNPCs control group and dNPCs -MSCs group (all P<0.05).The expression of MMP-1 and MMP-3 in nNPCs-MSCs group and dNPCs-MSCs group was lower than that in dNPCs control group ( all P<0.01) , but there was no difference when compared with nNPCs control group and MSCs control group (all P>0.05).Western-blot analysis showed that the expression of ACAN , COL-2 and SOX-9 in nNPCs-MSCs group was higher than that in dNPCs control group and dNPCs-MSCs group (all P<0.05).The expression of MMP-1 and MMP-3 in nNPCs-MSCs group and dNPCs-MSCs group was lower than that in nNPCs control group and dNPCs control group ( all P<0.01) , but there was no difference compared with MSCs control group ( all P>0.05) . Conclusion Both nNPCs and dNPCs could induce the differentiation of MSCs into nucleus pulposus cells .After co-cultured with nNPCs, the expression level of ACAN, COL-2 and SOX-9 of MSCs was similar to that of nNPCs, which was superior to the induc-tion of MSCs by dNPCs under the same culture conditions .