Objective To construct a glioma targeting delivery system, PAMAM G5 were modified with the oligopeptide of blood brain barrier (BBB) targeting TGN and tumor targeting oligopeptide iRGD to solve the problem of non-specificity in distribution and difficulty in permeating BBB of ATO, in order to have better anti-glioma effect. Methods The physical and chemical properties of nanocarriers were investigated by 1H-NMR and transmission electron microscopy (TEM); The encapsulation efficiency and in vitro release were analyzed by inductively coupled plasma emission spectrum (ICP) and dialysis bag method; The effects of iRGD and TGN on cellular uptake of the carriers were analyzed by laser confocal and flow cytometry. The cytotoxicity of nanocarriers on brain microvascular endothelial cells (HBMEC) and glioma cells (U87), the inhibition effect on U87 cells of drug delivery systems after acrossing the BBB model in vitro were investigated by MTT method. Results The iRGD/TGN-PEG-PAMAM was synthesized successfully. The TEM results showed that iRGD/TGN-PEG-PAMAM was regular in shape and uniform in size. The particle size of iRGD/TGN-PEG-PAMAM/ATO was (24.87 ± 0.84) nm and the potential was (17.26 ± 1.64) mV. The synthesized carrier had less toxicity to HBMEC and U87 cells. The encapsulation efficiency of iRGD/TGN-PEG-PAMAM/ATO delivery system was (71.92 ± 1.17)%. The in vitro release showed that ATO had a slow release trend after entrapment, and it was more favorable for ATO release under acidic conditions. The cell uptake indicated that iRGD/TGN modification was more beneficial for U87 cell to uptake the drug delivery system. The in vitro inhibition effect on U87 cells after acrossing the BBB model showed iRGD/TGN-PEG-PAMAM/ATO had better inhibition effect on U87 cells. Conclusion The iRGD/TGN-PEG-PAMAM/ATO targeting drug delivery system has good inhibition effect on U87 cells effect after acrossing the BBB model in vitro, which provides a new strategy for the treatment of glioma.

Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; Drug Delivery Systems ; Female ; Humans ; Nitriles ; therapeutic use ; Receptor, ErbB-2 ; metabolism ; Survival Rate ; Tamoxifen ; therapeutic use ; Trastuzumab ; Triazoles ; therapeutic use

Objective To evaluate the value of serum E2 levels during COH in predicting IVF-ET outcome. Method Data from 311 IVF-ET cycles received long protocol were collected and analyzed according to E 2 levels 5 days after stimulation:Group A (E2≤500 pmol/L), Group B (500 2 000 pmol/L). Results In groups with E2>1 000 pmol/L, the conditions of oocyte and embryo are higher than E2<1 000 pmol/L. With the increase of E2 levels, period cancellation rate increases. When E2> 2 000 pmol/L, the pregnancy rate become lowest. Conclusion E2 levels among 1 000~1 500 pmol/L during early COH predicts a better pregnancy outcome.

Abstract: Objective　To evaluate the completion and final effect of key parasitic disease prevention and control planning tasks in Hubei Province from 2016 to 2019, summarize the experience, find out the problems, and provide the basis for the next stage of prevention and control. Methods　According to the requirements of the Final Evaluation Plan of the National Plan for the Prevention and Control of Hydatid Disease and Other Major Parasitic Diseases (2016-2020), a retrospective survey method was adopted to collect relevant data on the implementation and safeguard measures of the prevention and control of major parasitic diseases, and population infection status in Hubei Province in 2016-2019. Results From 2016 to 2019, We carried out 2 920 992 person times of publicity and education, 209 times of prevention and control technology training, 7 680 person times of business training, with an average of 52 sessions and 1 920 person times per year. We have allocated 3.445 2 million yuan for the prevention and control of parasitic diseases, including 1.722 2 million Yuan froom provincial government, to achieved full coverage of safe drinking water in rural areas under the current national standards, and 7.687 9 million harmless toilets have been built in rural areas. From 2016 to 2019, we carried out 39 658 person times of monitoring and disease investigation, the infection rate of human liver fluke was 0, and the infection rate of soil transmitted nematode was 0.42%. While the annual infection rates varied, there was no statistically significant difference in infection rate between years (χ2＝2.276, P>0.05), but there were statistically significant differences in the infection rates between various soil nematodes (χ2=112.807, P<0.01). From 2016 to 2019, a total of 5 393 people were detected at 17 monitoring points, with the serum positive rate of 3.93% for paragonimiasis, there was a statistically significant difference in serological positive rate between years (χ2=146.011, P<0.01); a total of 738 stream crabs were collected, and the infection rate of intermediate host was 16.26%, wtih a statistically significant difference in the infection rate of stream crabs between years (χ2=49.731, P<0.01). Conclusions　From 2016 to 2019, we adhered to the prevention and control strategy of "prevention first, prevention and control combined", implemented comprehensively various prevention and control measures, and achieved remarkable results in Hubei Province. The key parasitic diseases have been in a low epidemic situation, meeting the requirements of the prevention and control objectives. But the transmission risk still exists, the next step is to continue to strengthen security and monitoring and consolidate the achievements of prevention and control.

Purpose To study the clinical features, immunophenotypes and prognostic factors of primary breast diffuse large B-celllymphoma (PBDLBCL). Methods The clinical pathological data of 49 cases of PBDLBCL during January 2006 to December 2016 were retrospectively analysed, and the basic clinical and pathologic data, pathologic types and the immunohistochemical slides by EnVision method for staining were summarized. Results 47 cases were women and 2 cases were men. The age ranged from 24 to 79 year old with the median age of 48 year old. On microscopic observation, tumor cells were large to medium-sized which characterized as diffuse infiltration between the lobules of mammary gland, around the duct, interstitial and fat tissue, some were single file cord pattern. The immunophenotype showed 37 cases were of non-GCB, 12 cases were GCB type. Ki-67 index were greater than 40％. According to Ann Arbor staging, 16 cases were stage I EA, 28 cases were stage Ⅱ EA, 5 cases were stage Ⅳ E. IPI score: 30 cases with 0 ～1 score, 10 cases with 2 score, 9 cases with 3 score. Patients were followed up from 5 to 146 months, The 3-year overall survival (OS) rate was 51.2％ and 5-year OS rate was 36.7％, Single factor analysis showed that there were statistically significant difference in clinical stage, levels of LDH, IPI score, BCL-2 protein expression, and BCL-6 protein expression in 3 and 5 years of OS rate. The multiple factor analysis of Cox regression showed that the increase of IPI risk classification was the independent adverse prognostic factor of primary breast diffuse large B-cell lymphoma. Conclusion The diagnosis of PBDLBCL is confirmed by pathological biopsy and immunohistochemical markers. The immunophenotype was mainly non-GCB type. Comprehensive treatment including surgery, chemotherapy and radiotherapy is appropriate. The prognosis should be comprehensively evaluated by multiple factors. IPI increase risk classification is the independent adverse prognostic factor.

OBJECTIVETo investigate osthole effect on femoral tissue resorption activity of rat in vitro.

METHODSSix SD rats weighted (80 ± 5) g were used to isolate and culture femoral tissue (diaphyses and metaphysis) in vitro. The cultured tissue were devided into control group, estradiol group and osthole group. The femoral tissue was treated with final concentration of 1 x 10(-5) mol/L osthole and 1 x 10(-8) mol/L estradiol culture in vitro at 48 hours after cultured. Tartrate-resistant acid phosphatase (StrACP) activity, glucose and Lactic acid content, StrACP, MCSF (Macrophage colony stimulating factor) and CTSK (Cathepsin K) mRNA was detected by Real-Time RT-PCR were detected.

RESULTSConcetration of Alkaline phosphatase activity were 2226 and 2498 in 1 x 10(-5) mol/L osthole and 1 x 10(-8) mol/L estradiol respectively. As compared with control group, the activity of StrACP of 1 x 10(-5) mol/L osthole and 1 x 10(-8) mol/L estradiol were inhibited at 6, 9, 12 days (P < 0.05); under treatment of in l x 10(-5) mol/L osthole, the content of Lactic acid were increased and the content of glucose were decreased at 3, 6, 9 days (P < 0.05); StrACP, MCSF and CTSK mRNA expression level were inhibited at 6, 9 days (P < 0.05).

CONCLUSIONOsthole can inhibit bone resorption and raise the level of nutrition metabolism of femurs tissue.

Acid Phosphatase ; metabolism ; Animals ; Bone Resorption ; prevention & control ; Coumarins ; pharmacology ; Estradiol ; pharmacology ; Femur ; drug effects ; Glucose ; analysis ; Lactic Acid ; analysis ; Male ; Rats ; Rats, Sprague-Dawley

Abstract: Objective　To analyze the etiological characteristics and drug resistance of patients with bloodstream infection (BSI) in the bacterial resistance monitoring network in Hainan Province from 2018 to 2020, so as to provide laboratory data for clinical diagnosis and treatment. Methods　The clinical data of the subjects were collected, and the etiological characteristics of BSI patients and drug resistance of commonly used drugs in clinical treatment were analyzed retrospectively. SPSS 26.0 software was used for statistical analysis. Results　A total of 877 strains were isolated, including Gram-negative bacteria (584 strains, 66.6%), Gram-positive bacteria (239 strains, 27.2%) and fungi (54 strains, 6.2%); male patients (591 cases, 67.4%), female patients (286 cases, 32.6%); inpatients (780 cases, 88.9%), outpatient and emergency patients (97 cases, 11.1%); the main primary diseases of BSI patients were hypertension, cerebral infarction and type 2 diabetes, and the main primary infections were pulmonary infection and urinary system infection. Intensive care unit (25.2%, 221 cases), emergency department (10.9%, 96 cases), oncology department (9.1%, 80 cases), nephrology department (6.8%, 60 cases) and hepatobiliary and pancreatic surgery department (4.3%, 38 cases) had the highest proportion of pathogenic bacteria. Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, coagulase-negative Staphylococcus, Viridans group streptococci and Candida albicans were the most frequently isolated pathogens. The detection rates of carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii were 3.4%, 15.2% and 36.4% respectively. The carbapenem-resistant Escherichia coli was not checked out. The detection rates of methicillin resistant Staphylococcus aureus and methicillin resistant coagulase negative Staphylococcus were 18.5% and 79.1% respectively. Conclusions　Gram-negative bacteria are the most common pathogens of BSI, and inpatients are the main source of BSI. Age, underlying diseases and primary infection are the risk factors of BSI. Clinical laboratories should strengthen the etiological monitoring of high-risk patients with BSI, and the resistance analysis of common antibiotics can provide a basis for the rational use of antibiotics in clinical practice.

In order to solve the problem of selection and in vivo delivery problem in siRNA treatment, hepatitis B virus (HBV) HBx gene which could be targeted by siRNA was studied. The siRNA expression plasmid which specific inhibits HBx expression was obtained by in vitro selection via a dual-luciferase plasmid including HBx-Fluc fusion protein expression domain. The selected siRNA expression plasmid was then encapsulated in PEG-modified cationic liposome, which was devoted into pharmacodynamic studies at both cellular and animal level. The results illustrated that the cationic liposome which encapsulated siRNA expression plasmid could effectively inhibit HBx gene expression both in vitro and in vivo.
Cations ; Gene Expression Regulation, Viral ; drug effects ; Hepatitis B virus ; genetics ; Liposomes ; chemistry ; Plasmids ; RNA, Small Interfering ; chemistry ; Trans-Activators ; genetics ; metabolism

Carcinoma, Hepatocellular ; genetics ; Hepatitis B virus ; genetics ; Humans ; Liver Neoplasms ; genetics

Objective To investigate the clinical and electrophysiological features and treatments for thallium poisoning. Methods Twelve cases of thallium poisoning patients were from hospital 307 of PLA between June 2012 and October 2017 and their data were retrospectively analyzed. Twelve sex-and age-matched healthy subjects were selected as control group. Result The clinical manifestations of thallium poisoning were mainly symptoms of nervous and gastrointestinal systems as well as hair loss. Thallium poisoning compromised function of motor nerves including the prolonged distal latency of ulnar and common peroneal nerve, the decreased amplitude and slowed nerve conduction velocity of common peroneal nerve and tibial nerve, which were statistically different from control group (P<0.05). Thallium poisoning also impaired function of sensory nerve including the prolonged distal latency and decreased amplitude of median , ulnar and sural nerve, the slowed nerve conduction velocity of median , ulnar, radial and sural nerve which were statistically different from control group (P<0.05 or P<0.01 ). Electroencephalogram (EEG) of 7 cases revealed mild abnormality EEG in 6 cases and moderate abnormality EEG in one case. Patients received potassium supplementation, diuresis, oral Prussian blue, intramuscular injection of sodium dimercaptopropanesulfonate and other treatment. Severe cases had good outcome after hemoperfusion and plasma exchange. Conclusions Thallium poisoning is rare in clinic and typical clinical features and electrophysiological examination are helpful to the diagnosis and differential diagnosis of diseases. Timely increasing thallium excretion and symptomatic support treatment can effectively improve the prognosis of the patients.