Treatment of Sepsis with Chinese Medicine： A Review Based on NF-κB Signaling Pathway / 中国实验方剂学杂志

Sepsis， a common critical disease in the intensive care unit（ICU）， features high morbidity and mortality. At present， it is mainly tackled with western medicine， which may trigger a series of problems like antibiotic resistance， adverse hormonal reactions， and high cost after a long-term use. Therefore， exploring new efficient， safe， and cheap drugs and treatment modes has become the focus of our research at this stage. By virtue of unique advantages including "the concept of holism and individualized treatment based on syndrome differentiation"， Chinese medicine has accumulated quite rich experience in the prevention and treatment of sepsis. In recent years， research on the regulation of Chinese medicine on nuclear transcription factor-κB（NF-κB） signaling pathway in sepsis has kept emerging. On this basis， this paper reviewed the etiology and pathogenesis of sepsis， syndrome differentiation and treatment， NF-κB signaling pathway， and its intervention with Chinese medicine. It has been found that some single Chinese herbs and their extracts， Chinese herbal compounds， and Chinese herbal injections effectively inhibit the expression of such inflammatory factors as NF-κB-mediated tumor necrosis factor-α（TNF-α）， interleukin-1（IL-1）， and IL-6 as well as the related proteins， reduce the systemic inflammatory response and organ injury， and improve the prognosis by regulating the activation of NF-κB signaling pathway and the immune function of macrophages. However， due to the limitations of objective conditions， some studies also have the problems of fuzzy pro-inflammatory anti-inflammatory balance mechanism， unclear pharmacokinetics and low drug safety evaluation， which need to be further studied and explored in order to provide a new theoretical basis and diagnosis and treatment thinking for the treatment of sepsis with traditional Chinese medicine.

Value of peripheral blood eosinophils in predicting the therapeutic effect of sublingual specific immunotherapy in patients with allergic rhinitis / 中国医师杂志

Objective:To investigate the value of peripheral blood eosinophils (EOS) in predicting the therapeutic effect of sublingual specific immunotherapy (SLIT) in patients with allergic rhinitis (AR).Methods:From January 2018 to June 2020, 200 patients with AR who received SLIT in Dongguan Kanghua Hospital were evaluated for their symptoms before treatment and 6 months after treatment. The curative effect was evaluated according to the improvement of the total symptom score. The number of eosinophils, percentage of eosinophils in peripheral blood were measured before treatment. The correlation between curative effect and EOS count and EOS percentage was analyzed and the value of these two indicators in predicting the efficacy of SLIT was evaluated.Results:Of the 200 AR patients, 178 patients were confirmed to have completed the treatment course of 6months. 126 effective and 52 ineffective, the effective rates were 70.8%. There was a weak correlation between the number of EOS in peripheral blood and the percentage of EOS in peripheral blood before treatment and the efficacy of SLIT ( r=0.168, P=0.048; r=0.250, P=0.001). The area under the curve of peripheral blood EOS count was 0.380, and the percentage of peripheral blood EOS was 0.355, which were all less than 0.5. Conclusions:There was no significant correlation between the number of peripheral blood EOS count and peripheral blood EOS percentage and the efficacy of SLIT , therefore, both of blood EOS count and blood EOS percentage have no value in predicting the efficacy of SLIT.

Prevalence and risk factors of renal function decline in elderly people in a community in Shanghai / 上海预防医学

Objective:To determine the prevalence of renal function decline in the elderly population in a community and risk factors. Methods:Data in the physical examination of the elderly population aged over 60 years old in a community in 2018 were collected and analyzed. Estimated glomerular filtration rate was calculated by modified modification of diet in renal disease （MDRD） formula. Association between renal function decline and risk factors were determined. Results:Among the 9 626 elderly people， the prevalence of renal function decline was 10.71%， which increased with age. Multivariate logistic regression showed that men， age， anemia， abnormal uric acid， hypertension， hyperlipidemia， diabetes， glutamine transaminase， and the history of stroke were the independent risk factors associated with renal function decline. Conclusion:The prevalence of renal function decline in elderly people in a community in Shanghai is relatively high. It is necessary to pay attention to early screening and take effective preventive measures， such as health education， scientific exercise and reasonable diet， chronic disease management and other measures.

Clinical Observations on Knife Needle Microinvasive Operation for Cervical Spondylotic Arteriopathy / 上海针灸杂志

Objective To investigate the clinical efficacy of knife needle microinvasive operation for cervical spondylotic arteriopathy. Method Sixty patients with cervical spondylotic arteriopathy were randomized, in order of admission times, to observation and control groups, 30 cases each. The observation group received three-step knife needle microinvasive operation and the control group, single suboccipital deltoid muscle lysis. The therapeutic effects were compared between the two groups of patients. Result In the two groups of patients the score changed significantly at the end of and three months after treatment compared with before and had a tendency towards gradual increase (P<0.05). The score difference values between pre-treatment and post-treatment and between post-treatment and three-month follow-up were significantly higher in the observation group than in the control group (P<0.05). Repeated measurement analysis integrogram showed significant differences in the scores between the two groups. The total efficacy rate was significantly higher in the observation group (96.7%) than in the control group (76.7%) (P<0.05). Conclusion Knife needle microinvasive operation has clinically a marked therapeutic effect on cervical spondylotic arteriopathy.

Correlation between Laryngopharyngeal Reflux and Secretory Otitis Media in Adults / 听力学及言语疾病杂志

Objective To study the correlation between laryngopharyngeal reflux (LPR) and secretory otitis media (SOM).Methods A total of 294 adult patients with reflux-related symptoms were recruited in this study.The patients were evaluated with reflux symptom index (RSI) and reflux finding score (RFS).Tympanometry was conducted to all the patients.The 54 patients with the otitis media effusion with type B tympanograms were tested by auripuncture.Results Among the 294 patients,168 cases showed RSI＜13,in which 128 cases,31 cases and 9 cases had type A,type C,and type B tympanograms,respectively.The other 126 patients showed RSI＞13 in which 52 cases,29 cases and 45 cases had type A,type C,and type B tympanograms,respectively.Among the 294 patiems,172 patients showed RFS＜7,in which 131,32 and 9 cases had type A,type C,and type B tympanograms,respectively.The left 122 patients showed RFS＞7,in which 49,28 and 45 cases had type A,type C,and type B tympanograms,respectively.The ratio of type B tympanograms in the patients with RSI＞13 and RFS＞7 were both significantly higher than those in the patients with RSI＜13 and RFS＜7 (P＜0.05).The RSI scores of patients with type A,C,and B tympanogram were 8.6± 3.8,15.9±7.5,and 23.9±8.6,respectively,and the RFS score were 5.6±2.6,9.6±4.7,and 15.3±6.6,respectively.Compared with type A and C,the patients with type B tympanogram had significantly higher RSI and RFS score (P＜ 0.05).Among the 54 patients of type B tympanograms,those with RSI＜13 were found to have serous fluid,grume fluid,glue fluid as in 6 cases,2 cases,and 1 case,while the patient of the RSI＞ 13 had serous fluid,grume fluid,glue fluid in 13 cases,23 cases,and 9 cases,respectively.The otitis media effusion of the patients with the RSI＜13 were mainly serous,while those with the RSI＞13 were mainly sticky.Conclusion The correlation between LPR and SOM was significant.LPRmay accelerate the progress of SOM.

Edaravone Enhances the Viability of Ischemia/reperfusion Flaps / 华中科技大学学报（医学）（英德文版）

The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion (IR) and its mechanism.Forty-eight adult male SD rats were randomly divided into 3 groups:control group (n=16),IR group (n=16),and edaravone-treated IR group (n=16).An island flap at left lower abdomen (6.0 cm×3.0 cm in size),fed by the superficial epigastric artery and vein,was created in each rat of all the three groups.The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h,and then the blood perfusion was restored.From 15 min before reperfusion,rats in the edaravone-treated IR group were intraperitoneally injected with edaravone (10 mg/kg),once every 12 h,for 3 days.Rats in the IR group and control group were intraperitoneally injected with saline,with the same method and frequency as the rats in the edaravone-treated IR group.In IR group and edaravone-treated IR group,samples of flaps were harvested after reperfusion of the flaps for 24 h.In the control group,samples of flaps were harvested 34 h after creation of the flaps.The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined,and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin (HE) staining,apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay,and the apoptotic rate of cells in vascular wall was calculated.The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy (TEM).Seven days after the operation,we calculated the flap viability of each group,and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels.The results showed that the content of MDA,the number ofmulticore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group.The activity of SOD,flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group.All the differences were statistically significant.The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group.It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels,which is related to scavenging oxygen free radicals,reducing the consumption of SOD,reducing the extent of lipid peroxidation and inflammation,and protecting functional structure of vessels in the early stages of reperfusion.

Design, synthesis and evaluation of a novel BRD4 protein inhibitors / 药学学报

Bromodomain-containing proteins (BCPs) can specifically recognize acetylated lysine (KAc) in histones and other substrate proteins. Recently, several kinase inhibitors were found to inhibit bromodomains, such as the PLK1 inhibitor BI-2536 and the JAK2 inhibitor TG101209, which bind to BRD4 with IC50 values of 25 nmol·L-1 and 130 nmol·L-1, respectively. To obtain potent BRD4 inhibitors from inhibitor BI-2536, we used dihydroquinoxalin-2(1H)-one to replace the 7,8-dihydropteridin-6(5H)-one in BI2536. By exploring the structure-activity relationships of the new dihydroquinoxalin-2(1H)-one structures, we obtained a novel phenyl side chain series of BRD4 inhibitors. We identified several potent BRD4 inhibitors, especially compounds 16, 22, 28 and 29, which had IC50 values below 100 nmol·L-1 in fluorescence anisotropy (FA) assays, indicating this series of compounds are worth to fruther investigation.

Establishment and evaluation of a novel mouse model of orthotopic colon cancer in the mesenteric triangle of the cecum / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the feasibility of preparation of a mouse model of orthotopic colon cancer by injecting tumor cell suspension into mesenteric triangle of the cecum.</p><p><b>METHODS</b>Twenty SPF 8-week old BALB/c mice (male:female = 1:1) were used in this study. The mouse caecum was exposed by laparostomy, and suspension of mouse colon adenocarcinoma CT26. WT cells was injected into the mesenteric triangle of cecum for preparation of a mouse model of orthotopic colon cancer.</p><p><b>RESULTS</b>Mouse orthotopic colon cancer was developed by injection of tumor cell suspension into mesenteric triangle of the cecum showing a successful rate of 100%, without intestinal obstruction, and the liver, spleen, diaphragm and mesenteric lymph nodes metastasis rates were high in all the 20 experimental mice.</p><p><b>CONCLUSIONS</b>The establishment of mouse models of orthotopic colon cancer by injection of tumor cell suspension into the mesenteric triangle is a simple, rapid, and easy to master procedure, causing less damage to the colon wall, safe and with less trauma to the mice. This method may provide an ideal mouse model of orthotopic colon cancer for the study of pathogenesis as well as liver metastasis mechanisms of colon cancer.</p>

Progress in the study of small molecule inhibitors of HSP90 / 药学学报

HSP90, which is the biomarker of cell stress and endogenous protective protein, functions as a molecular chaperone. Many client proteins of HSP90, including EGFR, Met, Raf-1, IKK and p53, play important roles in the occurrence and development of tumor. Binding of HSP90 inhibitors triggers the deactivation of HSP90, resulting in client protein degradation, and hence inhibits the tumor growth by blocking multiple targets involved in signaling of tumor proliferation. This review summarizes recent development of small molecule inhibitors bound to N-terminal of HSP90.

Isolation and diversity analyses of endophytic fungi from Paris polyphylla var. yunnanensis / 中国中药杂志

The paper is aimed at studying the diversity of endophytic fungi community from Paris polyphylla var. yunnanensis, and to provide a scientific basis for the utilization value of the endophytic fungi as bioactive material resources. In the present study, endophytic fungi were isolated from roots, rhizomes and leaves of wild P. polyphylla var. yunnanensis collected from Baoshan, Heqing county and Songming city of Yunnan province, and identified and classified by morphological methods together with its ITS sequence analysis. Seven and forty-nine strains of endophytic fungi were isolated from P. polyphylla var. yunnanensis. They were identified belonging to 41 genus. In these 41 genus, 3 genus exist in root only, 12 genus only exist in rhizome and 8 genus only exist in leaf. There was difference in endophytic fungi isolated from different sample sites. Endophytic fungi diversity from rhizomes of Heqing site was the highest. Endophytic fungi similarity coefficient was low among different sites and tissues. Based on these results, it is reasonable to propose that endophytic fungi of P. polyphylla var. yannanensis from different tissue and different sample sites has a certain difference which is possibly relate to their different habitats, different structure and composition of each tissue.

Progress in the fragment-based drug discovery / 药学学报

As an extension of the structure-based drug discovery, fragment-based drug discovery is matured increasingly, and plays an important role in drug development. Fragments in a small library, with lower molecular mass and high "ligand efficiency", are detected by SPR, MS, NMR, X-ray crystallography technologies and other biophysical methods. Then they are considered as starting points for chemical optimization with the guidance of structural biology methods to get good "drug-like" lead and candidate compounds. In this article, we reviewed the current progress of fragment-based drug discovery and detailed a number of examples to illustrate the novel strategies.

To take advantage of tumor hospital resources for clinical epidemiological study / 中华医学科研管理杂志

The tumor hospital has its unique resources superiority.To collect and utilize the information from tumor patients,information from their diagnosis and treatment,and biological specimens,through clinical epidemiology methods and design,would facilitate the deep development in the management and research at tumor hospitals in the new circumstances.Nantong Tumor Hospital,a first rate 3A hospital,and also one of the earliest-run specialized tumor hospitals in prefecture-level cities,possesses own basis for clinical epidemiological research,medical follow-up,and application of biobanking.In this paper we report the specific work plan and work contents,including:to establish a hospital-based cancer registry system for serving clinical epidemiology; to set up a follow-up system for clinical cases with tumor,in order to assess the effect of factors on tumor treatment and to analyse their survival rates; to build a biobank of tumor cases with perfect epidemiological information and background,fitting in with the needs of the development of translational medicine.The bottleneck problems in the work are also discussed.

Research progress of sodium-glucose co-transporter 2 inhibitors for treatment of type 2 diabetes / 药学学报

Sodium-glucose co-transporters are a family of glucose transporter found in the intestinal mucosa of the small intestine (SGLT-2) and the proximal tubule of the nephron (SGLT-1 and SGLT-2). They contribute to renal glucose reabsorption and most of renal glucose (about 90%) is reabsorbed by SGLT-2 located in the proximal renal tubule. Selectively inhibiting activity of SGLT-2 is an innovative therapeutic strategy for treatment of type 2 diabetes by enhancing urinary glucose excretion from the body. Therefore SGLT-2 inhibitors are considered to be potential antidiabetic drugs with an unique mechanism. This review will highlight some recent advances and structure-activity relationships in the discovery and development of SGLT-2 inhibitors including O-glycoside, C-glycoside, C, O-spiro glycoside and non glycosides.

Synthesis and LAR inhibition of 7-alkoxy analogues of illudalic acid / 药学学报

To obtain higher potency and specificity, a series of 7-alkoxy analogues of illudalic acid was synthesized on the base of structure-activity relationship (SAR). All of these compounds exhibited submicromolar inhibition of the enzyme when tested against human leukocyte common antigen-related phosphatase (LAR) (for example, for 15e, IC50 = 180 nmol x L(-1)). They represent the most potent small-molecule inhibitors of LAR so far. These analogues also display excellent selectivity for LAR over other protein tyrosine phosphatases (PTPs) except for the highly homologous PTPsigma. The compound 15f is of 120-fold selectivity for LAR versus PTP-1B inhibition. The development of potent enzyme-specific inhibitors is so important that they may serve both as tools to study the role of LAR and as therapeutic agents for treatment of type II diabetes.

Effect of hypoxia on the expressions of hypoxia-inducible factor-1α,glucocorticoid receptor and opiomelanocortin genes in AtT-20 cells / 中华神经医学杂志

Objective To investigate the effect of CoCl2-induced hypoxia on the expressions of hypoxia-inducible factor-1α(HIF-lα),glucocorticoid receptor(GR)and opiomelanocortin(POMC)in AtT-20 cells.Methods AtT-20 cells were exposed to different concentrations(25,50,100,and 200 μmol/L)of CoCl2 to induce hypoxia.MTT assay was employed to assess the changes in the cell proliferation after the exposure,and real-time PCR and Western blotting were performed to detect the expressions of HIF-1α,GR and POMC genes at both the mRNA and protein levels.Results Compared with the cells in normoxic conditions,the AtT-20 cells exposed to CoCl2 treatment at 25,50,and 100 μmol/L for 24 and 48 h showed obviously enhanced cell proliferation.CoCl2 significantly increased the mRNA and protein expressions of HIF-1α,GR and POMC genes in a dose-dependent manner(P＜0.05).Conclusion CoCl2-induced hypoxia up-regulates the mRNA and protein expressions of HIF-1α,GR and POMC genes in AtT-20 cells.

Construction and characterization of mutants in the neurofibromatosis type 2 tumor suppressor gene / 中华神经医学杂志

Objective To construct the eukaryotic expression vector of mutants in the neurofibromatosis type 2 (NF2) tumor suppressor gene and observe its expression in rat schwannoma cell line RT4. Methods Site-directed mutagenesis was performed to induce the mutation of the codons for the residue Ile 546 in pEGFP-N1-NF2 into Met to construct the muton of pEGFP-N1-NF2~(△Ⅱe546Met). After lipofectin-mediated transient transformation of RT4 with the plasmids containing the mutation and the one without mutation, respectively, the mRNA and protein expression levels of NF2 were determined using fluorescence imaging and Western blotting. The cell proliferation was determined by the MTT assay. Results DNA sequence analysis confirmed the success of site-directed mutagenesis and Western blotting showed that pEGFP-NF2 protein could be expressed in the RT4 cells. The RT4 cell inhibition rate in the pEGFP-N1-NF2~(△Ⅱe546Met) transfection group was statistically lower than that in the pEGFP-N1-NF2 transfected group (P<0.05).Conclusion The recombinant plasmids pEGFP-N1-NF2~(△Ⅱe546Met) has been successfully constructed with efficient expressions in RT4.

Orf1/SpcS chaperones ExoS for type three secretion by Pseudomonas aeruginosa / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Pseudomonas aeruginosa is a ubiquitous and opportunistic pathogen that uses the type III secretion system (TTSS) to inject effector proteins directly into the cytosol of target cells to subvert the host cell's functions. Specialized bacterial chaperones are required for effective secretion of some effectors. To identify the chaperone of ExoS, the representative effector secreted by the TTSS of P. aeruginosa, we analyzed the role of a postulated chaperone termed Orf1.</p><p><b>METHODS</b>By allelic exchange, we constructed the mutant with the deletion of gene Orf1. Analysis of secreted and cell-associated fractions was performed by SDS-PAGE and Western blotting. Using strain expressing in trans Orf1, tagged by V5 polypeptide and histidine, protein-protein interaction was determined by affinity resin pull-down assay in combination with MALDI-TOF. The role of Orf1 in the expression of exoS was evaluated by gene reporter analysis.</p><p><b>RESULTS</b>Pull-down assay showed that Orf1 binds to ExoS and ExoT. Secretion profile analysis showed that Orf1 was necessary for the optimal secretion of ExoS and ExoT. However, Orf1 had no effect on the expression of exoS.</p><p><b>CONCLUSION</b>Orf1 is important for the secretion of ExoS probably by maintaining ExoS in a secretion-competent conformation. We propose to name Orf1 as SpcS for "specific Pseudomonas chaperone for ExoS".</p>

Expression of free fatty acid receptor GPR40 in adult monkey hippocampus after ischemia / 中华神经医学杂志

Objective To investigate the expression of free fatty acid receptor GPR40 and evaluate the possible function of GPR40 in the adult monkey hippocampus after ischemia. Methods According to the post-ischemic adult monkey model of Yamashima, a total of 24 adult monkeys were randomly divided into 4 groups: sham-operated group (control) and post-ischemic day 4, 9, 15 (d4, d9,d15). The expression of free fatty acid receptor GPR40 was detected at the protein level by immunoblotting and immunohistochemistry in the adult monkey hippocampus. Results Immunoblotting analysis showed the expression of GPR40 was decreased in CA1 and increased in DG after ischemia (posfischemic group vs control, P＞0.05). Immunohistochemistry data revealed that the double stained cells of GPR40 and NeuN were also decreased by 50% (d15) in CA1 and had no significant changes in DG after ischemia. Interestingly, the co-labeled cells of GPR40 and GFAP were increased 2.5 folds (d4) in post-ischemic SGZ. Conclusions There is the different expression of GPR40 in adult monkey hippocampal CA1 and DG regions after ischemia. Co-labeled cells of GPR40 and GFAP are increased in post-ischemic SGZ, which indicates that polyunsaturated free fatty acid such as DHA, a ligand of GPR40, may alleviate neuronal injury in post-ischemic hippocampus.

Effects of exogenous FHIT gene on proliferation and apoptosis of human glioma cell line U87 / 上海第二医科大学学报

Objective To investigate the effects of exogenous fragile histidine triad(FHIT) gene on apoptosis of human glioma cell line U87. Methods By the method of liposome transfection,plasmids pcDNA3.1/myc-His(-)B-FHIT and pcDNA3.1/myc-His(-)B were transfected into glioma cell line U87.U87 cells were divided into three groups: U87-FHIT group,U87 cells transfected by plasmids pcDNA3.1/myc-His(-)B-FHIT;U87-vector group,U87 cells transfected by plasmids pcDNA3.1/myc-His(-)B;and blank control group,U87 cells without transfection.The expression of exogenous FHIT protein was detected by Western blot and immunofluorescence staining.The effects of FHIT on the growth characteristics of U87 were observed by MTT and flow cytometry. Results Growth inhibitory rate and apoptosis rate of the cells in U87-FHIT group were significantly higher than those in U87-vector group and blank control group(P

Research on tumor suppressor gene FHIT / 上海第二医科大学学报

Fragile histidine triad(FHIT) gene is a tumor suppressor gene that locates on chromosome 3p14.2.FHIT can induce cell apoptosis and inhibit cell growth by activating caspase,inhibiting PI3K-Akt-survivin signal pathway and phosphorylation of I?B-?,and binding with microtube.The inactivation of FHIT is closely related with carcinogenesis.The advances in research on the structure,biological function,relationship between inactivation and carcinogenesis,and gene therapy of FHIT are reviewed in this paper.