Objective To study the clinical features, efficacy and complications of the radiotherapy for cervical cancers in aged women. Methods Basing on the clinical stages, histologic types, differentiation of neoplasms, macroscopic types, sizes of cervical masses and vagina,542 female patients ≥ 60 years of age with cervical cancers were analyzed. The survival rates and sequelae were observed. Results The clinical stages, histologic types and differentiation of tumors in both ≥ 60 and

Fatal anaphylactic shock is common in forensic practice. However, it is difficult to diagnose for lacking specific pathological and morphologic changes in forensic autopsy. The application of some biochemical indicators is of great significance. This paper reviews the biological characteristics of some biochemical indicators and detection methods. The forensic application, problems and prospects of these indicators are also introduced in details. The stable biochemical indicators, IgE, tryptase and chymase, show great potential and advantages in the identification of fatal anaphylactic shock in forensic medicine.

Objective To analyze and evaluate the characteristics of enzyme kinetics of CTX-M-14 type extended-spectrum β-lactamase(ESBL) with Pro167 residue substitution. Methods By molecular cloning and PCR techniques, CTX-M-14 gene was directionally cloned into plasmid pET28a( + ) from a clinical E. coli isolate and formed an expression vector to transform competent E. coli BL21 (DE3 ). Prol67 residue substitutions of P167G, P167Q, P167S and P167T were introduced to CTX-M-14 by site-directed muta-genesis based on overlap extension PCR with the former recombinant plasmid as PCR template, respectively.The wild-type CTX-M-14, recombinant CTX-M-14 protein and its variants were expressed and purified, then their steady-state kinetic parameters (Kcat, Km and Kcat/Km ) against β-lactam antibiotics were determined.Results The kinetic parameters of wild-type and recombinant CTX-M-14 had no statistically significant differences (P>0.1). The 1/Km, Kcat and Kcat/Km values of P167S variant against ceftazidime were 16-fold, 2.87-fold and 43.6-fold higher than those of recombinant CTX-M-14, respectively, and the Kcat/Km value of P167S variant against penicillin, ampicillin, cefazolin, cefuroxime, ceftriaxone, cefotaxime decreased( < 0.05). Compared with the kinetic parameters of recombinant CTX-M-14, the kinetic parameters of P167T variant against ceftazidime had no significant change, but the Kcat values of P167Q and P167G variants decreased dramatically(P<0.01). Conclusion There was no difference between the enzyme activities of wild-type and recombinant CTX-M-14. P167S variant could not only promote the enzyme affinity of CTX-M-14 to ceftazidime but also improve the conversion rate of enzyme-substrate complex in the ceftazidime hydrolysis. The comparison of the kinetic parameters of CTX-M-14 and its variants with Pro167 residue substitution showed that the increased activity of CTX-M ESBL variants against ceftazidime could not be simply explained with the enlarged cavity in active site that may be caused by the replacement of Pro167 residue by smaller amino acids.

OBJECTIVETo explore a new method of alleviating graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) through selected elimination of mouse alloreactive T cells (ARTC) by Fas-Fas ligand (FasL) passway.

METHODSThe Sca-1(+) early hematopoietic cells (EHCs) were isolated from BALB/c mouse (H-2(d)) bone marrow mononuclear cells (BMMC) by using a high gradient magnetic cell sorting system (MACS), then transferred with exogenous mouse FasL (mFasL) gene by retroviral gene transfecting technique. Afterward the transduced EHCs were expanded in vitro for one week followed by coculture with the spleen cells from BAC mouse (H-2(d) x b) as one-way mixed lymphocyte culture (OWMLC) for 6 days, then the cytotoxicity of treated BAC mouse spleen cells against Na(2)(51)CrO(4) labelling spleen cells from BALB/c mouse was observed.

RESULTSThe Sca-1(+) EHCs were successfully isolated by MACS, with a purity of (89.0 +/- 6.1)%. After transferred with exogenous mFasL gene and expanded for one week, the transferred EHCs in the 6 day OWMLC with the spleen cells from BAC mouse at a ratio of five to one resulted in an obvious inhibition of the BAC mouse spleen cells cytotoxicity against the BALB/c mouse spleen cell at different effector/target ratios as compared to the control group (P < 0.01).

CONCLUSIONThe higher exogenous mFasL-expressing mouse EHCs can deplete ARTC against their own major histocompatibility complex (MHC) antigens in vitro.

Animals ; Antigens, Ly ; immunology ; Fas Ligand Protein ; Female ; Graft vs Host Disease ; immunology ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; cytology ; immunology ; Membrane Glycoproteins ; genetics ; immunology ; Membrane Proteins ; immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Signal Transduction ; Spleen ; cytology ; immunology ; T-Lymphocytes ; immunology ; Transfection

Objective:To investigate the effectiveness of multimodal magnetic resonance imaging (MRI)-based radiomics models in the auxiliary diagnosis of neonatal cerebral white matter lesion (WML).Methods:Clinical and MRI imaging data were collected from 91 children diagnosed with WML in Dalian Women and Children′s Medical Center from April 2018 to December 2021, including 58 cases in the good prognosis group and 33 cases in the poor prognosis group. The region of interest (ROI) was drawn for the lesion of each sequence image (T 1WI, T 2WI, DWI and SWI). Three models, T 1WI+T 2WI (model 1), T 1WI + T 2WI + DWI (model 2) and T 1WI + T 2WI + SWI (model 3), were created. Resample of the ROI, pre-processing of images and extraction of features were performed by using PyRadiomics, and the extracted features were standardized on the Dr.Wise research platform. A logistic regression classifier was used to create the radiomics model and 5-fold cross-validation was carried out 10 times. Key features were screened, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive ability of the models. And DeLong was used to compare the effectiveness of different models. Results:The AUC values of model 2 (0.95) and model 3 (0.93) in the validation set were higher than that of model 1 (0.90). The accuracy, sensitivity and specificity of model 1, model 2, and model 3 were (86%, 89% and 87%), (79%, 88% and 88%) and (90%, 90% and 86%), respectively. The differences between model 1 and model 2 by DeLong′s test was statistically significant ( P<0.05), whereas there was no statistically significant differences between model 3 and model 1 or between model 3 and model 2 ( P>0.05). Conclusions:Multimodal MRI-based radiomics model was proved to be an effective tool in the auxiliary diagnosis of neonatal WML.

Objective To explore the diagnostic value of thin prep cytology test(TCT) in central lung cancer. Methods All 127 patients suspected central lung cancer were detected by transbronchial needle aspiration(TBNA). The patients were randomly assigned into two groups, the group of conventional smear,CS (62 cases) and the group of CS+TCT(65 cases). The sensitivity and specificity of two methods were compared. Results The sensitivity and specificity of CS were 75.9%and 100.0% respectively. The sensitivity and specificity of CS+TCT were 96.2% and 100.0% respectively. The sensitivity of CS+TCT was significantly higher than sensitivity of CS in diagnosis of lung cancer (P=0.000046<0.01). Conclusion Combination of CS and TCT techniques can improve the TBNA diagnostic sensitivity of lung cancer. TBNA-TCT detection methods should be applied to clinical activites.

Objective:To identify the factors associated with long-term survival and guide the decision for primary surgery in patients with advanced high-grade serous ovarian cancer(HGSOC).Methods:In this case-control study, clinical parameters, including surgical and non-surgical associated factors, were collected and compared between the patients with short-term (<2 years) and long-term (>5 years) survival who all underwent primary debulking surgery (PDS) followed by carboplatin and paclitaxel chemotherapy from January 2004 to December 2016. Univariate analysis was examined by chi-square test and multivariate analysis was performed by logistic regression analysis.Results:There were 95 cases long-term survival (LTS group) and 77 cases short-term survival (STS group) in 698 newly diagnosed HGSOC patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲc and Ⅳ who met include and exclude criteria. (1) Univariate analysis showed that the proportion of complete cytoreduction with no visible residual disease (R0) at PDS and platinum sensitivity in LTS group were significantly higher than those in STS group ( P<0.01). The surgical complexity score (SCS), the preoperative serum CA 125 level and the ascites volume in the LTS group were significantly lower than those of the STS group (all P<0.05). In the LTS group, the preoperative incidence of lesions in retrograde peritoneum of the bladder, serosal and mesangial membrane of the small intestine, upper abdominal peritoneum and liver parenchyma were significantly lower than those in the STS group (all P<0.05). Multivariate logistic regression analysis showed that platinum sensitivity ( OR=0.016, 95% CI: 0.004-0.063, P<0.01), ascites volume >500 ml ( OR=3.193, 95% CI: 1.285-7.930, P=0.012), and SCS ≥8 ( OR=17.433, 95% CI: 2.281-133.25, P=0.003) were independent factors affecting long-term survival ( P>0.05). (2) Totally 37 of 95 in long-term survival and 16 of 77 in short-term survival achieved R0 cytoreduction at PDS. Univariate analysis showed that preoperative serum CA 125 level, preoperative lesion score, preoperative lesion (DS) score, ascites volume, platinum sensitivity,and SCS were significantly correlated with the R0 PDS (all P<0.05). Multivariate analysis showed that ascites volume >500 ml ( OR=5.199, 95% CI: 2.015-13.409, P=0.001), DS >2 ( OR=15.264, 95% CI: 5.843-39.874, P<0.01) and SCS ≥4 ( OR=4.176, 95% CI: 1.618-10.777, P=0.003) were independent factors associated with R0 cytoreduction. In patients with DS ≤2 or SCS <4, but not those with DS >2 or SCS ≥4, R0 cytoreduction was significantly associated with long-term survival. Conclusion:The intrinsic biology of tumor is the factor influencing long-term survival of advanced HGSOC patients, and those who present with wide intraperitoneal metastases and need to remove multiple organs may not benefit from R0 cytoreduction.

Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (±)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain.

ObjectiveTo observe the effect of Banxia Xiexintang containing intestinal absorption solution （BXCIAS） on migration and invasion of polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） in gastric cancer microenvironment. MethodThe complex solution （containing 0.63 g·mL^-1 crude drug） was prepared. Gastric cancer cells were subjected to non-contact co-culture with PMN-MDSCs in Transwell chamber to create gastric cancer microenvironment. Cell counting kit-8 （CCK-8） assay was used to screen the optimal intervention concentration and time of BXCIAS on PMN-MDSCs for subsequent experiment. The blank group， model group， FAK inhibitor group， and BXCIAS groups （26%， 18%， and 10%） were designed. Scratch assay and Transwell assay were employed to detect the migration and invasion ability of PMN-MDSCs， and enzyme-linked immunosorbent assay （ELISA） to measure the expression of vascular endothelial cell growth factor （VEGF） and matrix metalloproteinase-9 （MMP-9） in tumor microenvironment. The expression levels of PMN-MDSCs pathway-related proteins FAK， phosphorylated （p）-FAK， protein tyrosine kinase （Src）， and p-Src were detected by Western blot. ResultThe inhibition rates of PMN-MDSCs by 5%， 50%， 75%， and 100% BXCIAS at 48 h were higher than those at 24 h （P<0.05， P<0.01）. The inhibition rate of PMN-MDSCs by 50% BXCIAS at 72 h was lower than that at 48 h （P<0.01）， and the inhibition rates by 5% and 100% BXCIAS at 72 h were higher than those at 48 h （P<0.05， P<0.01）. There was no significant difference in the inhibition rate by other concentration levels at 48 h. The half-maximal inhibitory concentration （IC₅₀） at 48 h was 18.09%， indicating that 18% BXCIAS and 48 h were the optimal concentration and time， respectively. The migration distance of PMN-MDSCs was large （P<0.01）， and the number of migrating and invading cells increased （P<0.01） in the mode group compared with those in the blank group. Compared with model group， FAK inhibitor and BXCIAS at different concentration decreased the migration distance of PMN-MDSCs （P<0.01）， and the number of migrating and invading cells （P<0.01）， especially the 26% BXCIAS （P<0.01）. The expression of PMN-MDSCs pathway-related proteins FAK， p-FAK， Src and p-Src （P<0.01） and the expression of VEGF and MMP-9 （P<0.01） were higher in the model group than in the blank group. Compared with model group， FAK inhibitor and BXCIAS （26%， 18%， 10%） decreased the expression of FAK， p-FAK， and Src （P<0.01）， and FAK inhibitor and 18% BXCIAS reduced the expression of p-Src （P<0.01）， and the expression of VEGF and MMP-9 （P<0.01）. ConclusionBXCIAS can inhibit the migration and invasion of PMN-MDSCs by down-regulating the expression of FAK， p-FAK， Src， and p-Src proteins in the FAK signaling pathway of PMN-MDSCs in gastric cancer microenvironment.

ObjectiveTo observe the effect of Banxia Xiexintang （BXT）-containing intestinal absorption solution on the apoptosis of polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） in gastric cancer microenvironment. MethodBXT-containing intestinal absorption solution was prepared， and gastric cancer cells and PMN-MDSCs were non-contact co-cultured in Transwell chamber to establish gastric cancer microenvironment. Cell counting kit-8 （CCK-8） assay was used to screen the optimal intervention concentration and time of 0-100% BXT-containing intestinal absorption solution prepared by 0.63 g·mL^-1 reconstitution solution. Cells were classified into blank group， model group， oxaliplatin group （10 mg·L^-1）， and BXT （26%， 18%， 10% BXT-containing intestinal absorption solution） group， and the apoptosis of PMN-MDSCs was detected by flow cytometry. The expression of apoptosis-related B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteine-aspartic acid protease-3 （Caspase-3） in PMN-MDSCs was detected by Western blot. ResultAfter treatment for 24 h and 48 h， the PMN-MDSCs-inhibiting rate was increased by 5%， 50%， 75%， and 100% BXT-containing intestinal absorption solution compared with that in the blank group （P<0.05， P<0.01）. At 72 h， the PMN-MDSCs-inhibiting rate by 50% BXT-containing intestinal absorption solution was lower than that at 48 h （P<0.01）， and the PMN-MDSCs-inhibiting rate by 5%， 75%， and 100% BXT-containing intestinal absorption solution showed no significant difference from that at 48 h. Moreover， the half-maximal inhibitory concentration （IC₅₀） at 48 h was 18.40%. Thus， 18% BXT-containing intestinal absorption solution and 48 h were the optimal intervention concentration and time. The survival rate of PMN-MDSCs in model group was higher than that in the blank group （P<0.05）， and the apoptosis rate was lower than that in the blank group （P<0.05）. Compared with model group， BXT containing intestinal absorption solution lowered the survival rate and raised apoptosis rate of PMN-MDSCs （P<0.05）， particularly the 26% BXT-containing intestinal absorption solution （P<0.05）. The expression of Bax and Caspase-3 in PMN-MDSCs was lower in the model group than in the blank group （P<0.05）， and the expression of Bcl-2 was higher in the model group than in the blank group （P<0.05）. The expression of Caspase-3 in PMN-MDSCs increased （P<0.05） and the expression of Bcl-2 decreased （P<0.05） in oxaliplatin group and BXT group compared with those in the model group. The expression of Bax rose in oxaliplatin group and BXT group （10% BXT-containing intestinal absorption solution） （P<0.05）. ConclusionBXT can induce the apoptosis of PMN-MDSCs by regulating the expression of apoptosis-related proteins Bax， Caspase-3， and Bcl-2 in gastric cancer microenvironment.