Objective:To identify XMA09,a broadly neutralizing antibody against severe acute respiratory syndrome coronavi-rus 2(SARS-CoV-2),and to explore the potential mechanism of XMA09 to broadly neutralize variants of SARS-CoV-2,so as to pro-vide a reference for vaccine design and broadly neutralizing antibody screening against SARS-CoV-2.Methods:XMA09 protein was expressed and purified by ExpiCHO expression system and Protein A chromatography column.The key amino acid sites on receptor binding domain(RBD)recognized by XMA09 were identified by Cryo-EM,and the affinity of XMA09 to Spike protein of SARS-CoV-2 and its variants was detected by indirect ELISA and Surface Plasmon Resonance(SPR).The pseudovirus neutralization assay based on vesicular stomatitis virus(VSV)was used to detect the neutralization ability of XMA09 to wild-type and variants of SARS-CoV-2.Results:In this study,it was found that the epitopes recognized by XMA09 were conservative,who has an excellent binding ability to Spike protein of many kinds of variants,and could neutralize the variants of concern(VOCs),including the widespread BA.4/5.Conclusion:XMA09 is a broadly neutralizing antibody,which has the potential to be used as a therapeutic antibody against SARS-CoV-2,and can provide reference for broad-spectrum vaccine design and antibody drug development against SARS-CoV-2.

The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy of triple negative breast cancer. BL-RD was composed of phospholipids, apolipoprotein A1 mimetic peptide (PK22), targeting peptide-conjugated cytotoxic mertansine (RM) and photodynamic agents of DiIC18(5) (DiD). The counterpart biomimetic lipoprotein system without RM (termed as BL-D) was fabricated as control. Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells. After intravenous injection, they can be specifically accumulated at tumor sites. When comparing to the counterpart BL-D, BL-RD displayed superior capability to permeate across the tumor mass, extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor, thus producing noticeable depression of the tumor growth. Taken together, BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.

Objective To study the changes of maternal serum lipid,free fatty acid levels and the neonatal arterial blood gas,lactic acid and myocardial enzyme levels in the patients with early-onset pre-eclampsia(EOPE) combine with gestational diabetes mellitus(GDM).Methods One hundred and fifty cases EOPE patients were divided into EOPE+GDM group(observation group,n=67) and normal glucose tolerance EOPE group(control group,n=83) according to international association of diabetic pregnancy study group standard.The maternal BMI,serum lipid(TC,TG,LDL-C,very low density lipoprotein cholesterol(VLDL-C)),free fatty acid(FFA),HbA1c levels and the blood routine and biochemical tests were compared between two groups.The neonatal peripheral arterial blood-gas,lactate(LAC) and myocardial enzymes(creatine kinase(CK),lactate dehydrogenase(LDH),creatine kinase isoenzyme(CK-MB)) levels within 1 h after birth were measured and compared between two groups.Pearson correlation analysis was used to explore the impact of maternal glucose/lipid metabolic index,the birth condition on the neonatal LAC and CK-MB levels in EOPE patients.Results (1)In observation group,the patients had significantly higher BMI((32.66±4.23) kg/m2 vs.(29.98±5.44) kg/m2,t=4.904),TC((7.28±1.34) mmol/L vs.(6.65±0.76) mmol/L,t=5.760),TG((4.10±1.26) mmol/L vs.(3.51±0.71) mmol/L,t=4.199),LDL-C((4.85±1.24) mmol/L vs.(3.77±0.82) mmol/L,t=5.292),VLDL-C((1.91±0.37) mmol/L vs.(1.26±0.48) mmol/L,t=4.498),HbA1c((5.95±0.41)% vs.(5.20±0.37)%,t=8.821) levels than control group(P<0.05),and the patients had significantly elevating levels of LAC((5.76±3.32) mmol/L vs.(3.89±1.53) mmol/L,t=5.348) and CK((419.03±198.29) U/L vs.(323.22±154.38) U/L,t=6.632),CK-MB((218.97±86.74) U/L vs.(142.18±60.12) U/L,t=5.562),LDH((723.22±180.16) U/L vs.(584.57±139.81) U/L,t=4.987)(P<0.05).(2)Stepwise multiple regression showed that in patients with early-onset preeclampsia,maternal HbA1c(β=70.821,t=5.461),FFA levels(β=88.590,t=4.990),the gestational age (β=-8.776,t=-4.901) and the neonatal LAC levels(β=5.948,t=4.047) were the independent factors of newborn's CK-MB level.Conclusion In patients with early-onset preeclampsia combine with GDM,the disorders in glucose and lipid metabolism are more severe.And the metabolic disturbance will further interfere with the perinatal material metabolism,resulting in the elevating levels of lactic acid and the potential myocardial injury in neonates.

BACKGROUND: It remains poorly understood whether anterior column quadrilateral wing plate exists to solve intraoperative multiple plastic and quadrilateral in vivo shift for treating acetabular anterior column and acetabular quadrilateral body fractures.OBJECTIVE: To figure out the promising application on measurement of anatomical character parameters when designing acetabular anterior column and acetabular quadrilateral body using Mimics software. METHODS: 60 pelvic CT scan data were collected and three-dimensionally reconstructed by Mimics software. The following anatomical character parameters were measured, including the angle between plane of arcuate line of true pelvis and plane of quadrilateral surface, the four boundary lines of quadrilateral body, and the thickness of substance of bone in quadrilateral region. The projection curve on quadrilateral surface of acetabular margin and dangerous zone for screw placement were both drew. Above all, the study attempted to find out the proper safe entry point of quadrilateral screw and to measure their leaning inside angles.RESULTS AND CONCLUSION: (1) The angle between plane of arcuate line of true pelvis and plane of quadrilateral surface was not significantly different between males and females. (2) The minimum thickness of quadrilateral body in males was larger than that in females. (3) The maximum leaning angle flapper plate screw P1 and P2 for quadrilateral body was significantly smaller in males than in females, but that of screw P3 was not significantly different between males and females. (4) The application of Mimics software made it easier, more intuitive and more practical for the design or development of new plate for acetabular anterior column and acetabular quadrilateral body. The common points and difference between acetabular anterior column and acetabular quadrilateral body could be specifically described by the new anatomical character parameters, which are defined by bone surface features of pelvis.

Objective To explore the influence on intraoperative hemorrhage and relative complications of temporary balloon occlusion of the abdominal aorta in cesarean section for the pernicious placenta previa and placenta accreta.Methods One hundred and thirty-four cases of pernicious placenta previa and placenta accrete from January 2011 to January 2016 were analyzed retrospectively.Before the cesareans,temporary balloon occlusion in abdominal aorta was carried out in 69 patients (observation group).The other 65 patients didnt get the balloon occlusion in abdominal aorta (control group).The situation during and after the operation and relative complications were compared.Results The operation duration [(65.2 ± 6.3)min vs (93.2 ±8.8)min],postpartum hemorrhage [(923.2 ± 188.6)ml vs (2 791.8 ±336.2)ml],intraoperative blood transfusion [(423.7 ±59.3)ml vs (1 581.6 ±68.3)ml],the prothrombin time during the operation [(9.3 ± 1.1) s vs (12.4 ± 1.5) s],the hysterectomy rate [0 vs 7.7％ (5/65)],hospitalization time [(5.2 ±0.9)d vs (6.8 ± 1.1)d],and the rate of transferring to intensive care unit [1.4％ (1/69) vs 12.3％ (8/65)] in the observation group were lower than control group,with a statistical significant difference (P ＜ 0.05).There was no significant difference between two groups in Apgar score and birth weight of the neonate (P ＞ 0.05).Conclusions Temporary balloon occlusion of the abdominal aorta in cesarean section is a safe and effective technique,which can reduce the relative complications,such as the volume of bleeding and the risk of hysterectomy.

OBJECTIVE:To provide reference for the further improvement of the drug purchasing system in Chongqing city. METHODS:30 primacy medical and health institutions in Chongqing were selected to collect the data about cost changes and busi-ness development in above-mentioned institutions from 2009 to 2013,the purchasing price,use and supply of essential medicines were collected via Chongqing Municipal Health and Family Planning Commission to evaluate and analyze the effects and existing problems of drug purchasing system,and suggestions were put forward. RESULTS:Compared with 2009,the non-essential drugs’ prices fell an average of 28.00%in 2013,prices of 307 varieties in National Essential Medicine System(2009 edition)fell an aver-age of 32.97%,205 varieties in supplementary list of local prices fell an average of 43.78%. The proportion of sales amount(not including Chinese herbal medicine)in primacy medical and health institutions increased from 76.48% in 2010 to 92.07% in 2013, the average rate of essential medicines increased from 6.84% to 28.12%. Compared with 2009,the average drug cots and inpatient drug costs decreased 16.78% and 25.85% in 2013,the proportion of drugs decreased from 56.32% in 2009 to 49.70% in 2013. CONCLUSIONS:Generally speaking,the implementation of drug purchasing system in Chongqing is successful,but also exists some problems,such as imperfect pricing mechanism,difficult supply of low-cost drugs,slow rise of average outpatient costs in primacy medical and health institutions and irrational drug use. It is suggested to improve it from aspects of perfecting drug pricing mechanism,optimizing logistics and distribution,strengthening the role of the medical insurance institutions,regulating medication overuse and improving compensation policy of medical institutions.

The lack of effective in vitro infection model for hepatitis E virus (HEV) has greatly hindered the quantitative analysis of neutralizing titers of anti-HEV antibodies and human sera, thus impeding further studies of HEV-stimulated antibody responses and the immunological mechanisms. In order to improve this situation, the infection of HepG2 cells that are inefficient for HEV replication was continuously monitored until the viral load reached the limit of detection on day 13, the results of which confirmed the feasibility of using this cell line to establish the infection model. Then, neutralization assays of five anti-HEV murine monoclonal antibodies and serum samples collected from four HEV vaccine recipients (collected before and after vaccination) were performed by 96 multi-channel parallel infections, nucleic acid extraction, and qPCR. The results showed that the cell model can be applied for quantitative evaluation of the neutralizing capacity of different antibodies and antiserum samples from HEV vaccine recipients. In this study, we have successfully established a high-throughput in vitro HEV replication model, which will prove to be useful for the evaluation of HEV vaccines and studies of HEV epitopes.
Animals ; Antibodies, Viral ; analysis ; immunology ; Hepatitis Antibodies ; analysis ; immunology ; Hepatitis E ; immunology ; virology ; Hepatitis E virus ; chemistry ; immunology ; physiology ; High-Throughput Screening Assays ; methods ; Humans ; Mice ; Mice, Inbred BALB C ; Neutralization Tests ; methods ; Virus Replication

Nanoporous ZnO was used as a carrier to prepare drug solid dispersion, the mechanism of which to improve the drug dissolution was also studied. Nanoporous ZnO, obtained through chemical deposition method, was used as a carrier to prepare indomethacin and cilostazol solid dispersions by melt-quenching method, separately. The results of scanning electron microscope, surface area analyzer, fourier transform infra-red spectroscopy, differential scanning calorimeter and X-ray diffraction showed that drugs were implanted into nanopores of ZnO by physical adsorption effect and highly dispersed into nanopores of ZnO in amorphous form, moreover, these nanopores strongly inhibited amorphous recrystallization in the condition of 45 degrees C and 75% RH. In addition, the results of the dissolution tested in vitro exhibited that the accumulated dissolutions of indomethacin and cilostazol solid dispersions achieved about 90% within 5 min and approximately 80% within 30 min. It was indicated in this study that the mechanism of drug dissolution improvement was associated with the effects of nanoporous ZnO carrier on increasing drug dispersion, controlling drug in nanopores as amorphous form and inhibiting amorphous recrystallization.

Polymeric micelles which are self-assembled from amphiphilic copolymers are thermodynamically stable, and they can solubilize hydrophobic drugs by the hydrophilic core. Many excellent active compounds are confined because of general low oral bioavailability due to poor solubility. Take into account from the two points above, polymeric micelles may be used as proper oral carrier to improve the dissolubility of hydrophobic drugs, and enhance the permeation though gastrointestinal tract, therefore, the pharmacodynamics is elevated. Meanwhile, the segments in copolymers are multivariate, so many kinds of micelles can be obtained, such as, pH- or thermo- sensitive as well as mucoadhesive ones. The modified micelles can alter drug release profiles while solubilizing them, that is why the oral bioavailability increase further. In this review, recent progress of polymeric micelles used in oral administration is summarized, and the prospect of polymeric micelles' application in this field is also evaluated.

Background and purpose:Surgical treatment of breast cancer traditionally has resected including the nipple-areola complex (NAC), because this area had a significant probability of containing occult tumors. The purpose of this study was to investigate the involvement of NAC in breast cancer and evaluate the feasibility of nipple-Areola complex-sparing mastectomy. Methods:168 cases of specimen of NAC collected from breast cancer with 5 mm subareola tissue preserved were sent to pathological examination in order to observe the tumor involvement of nipple, areola, subareola tissue respectively. Results:Tumor involved with nipple, areola and subareola tissue in 3 cases,areola and subareola tissue in 10 cases, and subareola tissue only in 13 cases.The tumors were all located superficially and centrally to the breast in all cases with nipple and areola involvement except sub areola tissue. The factors relative to the involvement of NAC included the location of the primary tumor, alteration of local skin of nipple- areola(?2=9.672,P=0.002), median tumor size(?2=7.141,P=0.008), positive axillary lymph node(?2=6.081,P=0.014) and clinical pathological stage(?2=10.142,P=0.006). Conclusion:If no clinical sign of NAC is found for the patients with tumor distance from areola edge ≥2.5 cm or tumor size≤5 cm, surgery with NAC preservation appears to be safe for the patients with breast cancer.