Objective:To explore the osteogenic activity of in vitro cultured preosteoblasts treated by magnesium loaded hydrogel core-shell microspheres.Methods:A microfluidics chip device was designed and made to fabricate magnesium loaded hydrogel core-shell microspheres to precisely control the stable release of magnesium ions in vitro,the mechanism of controllable magnesium ion release in the promotion of osteogenic activity of MC3T3-E1 preosteoblasts was systematically investigated.Results:The magnesium loaded hydro-gel microspheres(PLGA/MgO-alginate microspheres)prepared by the microfluidics chip exhibited to be monodisperse with special core-shell structure and could control the stable release of magnesium ions at a concentration of 50 ppm in vitro.The in vitro study showed that it significantly enhanced the activity and proliferation ability of MC3T3-E1 preosteoblasts,promoted their osteogenic differ-entiation and mineralization ability,and increased ALP activity.Conclusion:Magnesium loaded hydrogel core-shell microspheres can promote the osteogenic activity of MC3T3-E1 osteoblasts in vitro.

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

Ginsenoside Rc,a dammarane-type tetracyclic triterpenoid saponin primarily derived from Panax ginseng,has garnered significant attention due to its diverse pharmacological properties.This review outlined the sources,putative biosynthetic pathways,extraction,and quantification techniques,as well as the pharmacokinetic properties of ginsenoside Rc.Furthermore,this study explored the pharmaco-logical effects of ginsenoside Rc against metabolic syndrome(MetS)across various phenotypes including obesity,diabetes,atherosclerosis,non-alcoholic fatty liver disease,and osteoarthritis.It also highlighted the impact of ginsenoside Rc on multiple associated signaling molecules.In conclusion,the anti-MetS effect of ginsenoside Rc is characterized by its influence on multiple organs,multiple targets,and multiple ways.Although clinical investigations regarding the effects of ginsenoside Rc on MetS are limited,its proven safety and tolerability suggest its potential as an effective treatment option.

Purpose: This study aimed to investigate the factors associated with chemoresistance to neoadjuvant chemotherapy (NACT) followed by radical hysterectomy (RH) and construct a nomogram to predict the chemoresistance in patients with locally advanced cervical squamous carcinoma (LACSC). Materials and Methods: This retrospective study included 516 patients with International Federation of Gynecology and Obstetrics (2003) stage IB2 and IIA2 cervical cancer treated with NACT and RH between 2007 and 2017. Clinicopathologic data were collected, and patients were assigned to training (n=381) and validation (n=135) sets. Univariate and multivariate analyses were performed to analyze factors associated with chemoresistance to NACT. A nomogram was built using the multivariate logistic regression analysis results. We evaluated the discriminative ability and accuracy of the model using a concordance index and a calibration curve. The predictive probability of chemoresistance to NACT was defined as > 34%. Results: Multivariate analysis confirmed menopausal status, clinical tumor diameter, serum squamous cell carcinoma antigen level, and parametrial invasion on magnetic resonance imaging before treatment as independent prognostic factors associated with chemoresistance to NACT. The concordance indices of the nomogram for training and validation sets were 0.861 (95% confidence interval [CI], 0.822 to 0.900) and 0.807 (95% CI, 0.807 to 0.888), respectively. Calibration plots revealed a good fit between the modelpredicted probabilities and actual probabilities (Hosmer-Lemeshow test, p=0.597). Furthermore, grouping based on the nomogram was associated with progression-free survival. Conclusion We developed a nomogram for predicting chemoresistance in LACSC patients treated with RH. This nomogram can help physicians make clinical decisions regarding primary management and postoperative follow-up of the patients.

Objective: To establish a standard operation procedure (SOP) for ribosome genotyping (ribotyping) on Clostridioides (C.) difficile, supplement and verify ribotyping typing library, so as to improve the comparability of data between different laboratories and to develop surveillance network of C. difficil in China. Methods: Molecular typing of 54 reference strains from the United States and Europe of C. difficile were performed by using the SOP referencing correspondence from abroad and from our laboratory with a BioNumerics 7.6 software to estimate the reference library of types of C. difficile. Identification of 374 clinical and animal isolates of C. difficile from 13 cities in China between 2010 and 2018, to supplement the library information. Kappa test was used to evaluate the consistency. Results: Results of capillary electrophoresis of reference strains appeared clear and stable, which guaranteed the clustering results being fast and accurate. Results from the supplementary typing showed that there were 84 types of isolates, of which 25 RT types were consistent with reference strains from abroad, while 58 RT types were different from referenced types. In the 40 referenced types, 15 RT types were not found in this study. In the consistency evaluation, the Kappa value was 0.891 and (P<0.01), showing the two Molecular typing as consistent and with close resemblance. Conclusions The result of capillary electrophoresis by applying SOP for ribotyping on C. difficile base on QIAxcel capillary electrophoresis system, appeared clear and stable. The standardized library seemed more easily used for comparability and data sharing between the laboratories.

Objective: To investigate the effect of cinobufacin combined with As₂O₃ on the angiogenesis of subcutaneous transplantation tumor in colorectal carcinoma BALB/C nude mice. Methods: The colorectal carcinoma transplantation tumor model of BALB/C nude mice was established and divided into 4 groups, 5 mice in each group. The growth state of nude mice was observed by injecting the corresponding reagents into the tumor in As₂O₃ group, cinobufacin group, cinobufacin combined As₂O₃ group and the blank control group (replaced by phosphate buffer), respectively. The nude mice were killed two weeks later, and the tumor tissues, liver and kidney tissues and orbital vein blood were taken. The tumor volume inhibition rate and mass inhibition rate of nude mice were calculated. The histomorphology of tumor, liver and kidney and blood routine were detected. The expressions of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), fibroblast growth factor-basic (b-FGF) and CD105 in transplanted tumor tissues were detected by using immunohistochemistry method, and the microvascular density (MVD) of transplanted tumor in nude mice was evaluated. Western blot method was used to detect the protein expression levels of VEGF, EGFR and b-FGF. Results: After 2 weeks of administration, the tumor volume and tumor mass in As₂O₃ group, cinobufacin group and cinobufacin combined As₂O₃ group were lower than those in the blank control group. The volume inhibition rate was 16%, 17%, 72%, and the mass inhibition rate was 31%, 33%, 78%, respectively, and the difference was statistically significant (all P < 0.01); there was no statistical difference between As₂O₃ group and cinobufacin group in the tumor volume and tumor mass (P > 0.05), and cinobufacin combined As₂O₃ group had the most obvious therapeutic effects (all P < 0.05). The immunohistochemistry method showed that the expressions of VEGF, EGFR, b-FGF and MVD were decreased in As₂O₃ group, cinobufacin group and cinobufacin combined As₂O₃ group compared with the blank control group, and there were statistical differences of the four groups (all P < 0.05). There was no statistical difference of the marker changes in As₂O₃ group and cinobufacin group (all P > 0.05), and cinobufacin combined As₂O₃ group had the most significant decrease in the marker changes, and there was a significant difference compared with the other groups (all P < 0.05). Western blot showed that compared with the blank control group, the other three groups could downregulate the protein expressions of VEGF, EGFR and b-FGF in the transplanted tumor of nude mice. And the decreasing expression of each protein in cinobufacin combined As₂O₃ group was the most significant. Pathomorphology examination showed that the histomorphology of liver and kidney of the four groups of nude mice was normal. Blood routine examination showed that compared with the blank control group, the white blood cell count of nude mice in other groups was decreased, and the difference was statistically significant (all P < 0.05). The white blood cell count of cinobufacin combined As₂O₃ group was decreased most significantly; there was no statistically significant difference in hemoglobin and platelet count among the four groups (all P > 0.05). Conclusions Cinobufacin and As₂O₃ show synergistic effects in the tumor angiogenesis and inhibition of transplantation tumor growth of colorectal cancer BALB/C nude mice. Moreover, cinobufacin and As₂O₃ have no obvious toxicity to the hepatic, kidney and hematopoietic tissues.

Personalized information service has become an important interest in medical library due to the rapid development of Internet technology. The SOA framework-based personalized information service system architecture was proposed by analyzing the contents and characteristics of personalized information service in medical library, which is characterized by standards, loose couple, low cost modification and operating maintenance, and can thus ensure both personalized information service and daily professional activities in medical library.

Purpose To observe the effects of midkine ( MK) on human breast cancer cell line MDA-MB-231 angiogenesis in vitro, and to explore its mechanism. Method shRNA interference was performed to silence the expression of MK in MDA-MB-231 cells, and Western blot was used to identify the expression of MK and EPCR. After MK and EPCR knockdown, or treated with anti protease-activated receptor 1 (PAR1) antibody, the culture medium of MDA-MB-231 cells were collected and the conditioned medium were pre-pared. Human umbilical vein endothelial cells ( HUVECs) were cultured with conditioned medium, and the endothelial cells prolifera-tion was detected by CCK-8 assay, cell migration was detected by transwell method, vasculogenic activity was assessed by Matrigel-based tube formation assay. Results After knockdown of MK, the protein level of EPCR was decreased in MDA-MB-231 cells. Com-pared with control, knockdown of MK and EPCR decreased the proliferation, migration and angiogenesis ability of HUVECs significant-ly (P<0. 05), and the effect of EPCR knockdown group was stronger than MK knockdown group (P<0. 05). After treated with anti-PAR1 antibody, the proliferation, migration and angiogenesis ability of HUVECs were decreased compared with control and EPCR knockdown group (P<0. 05). Conclusion MK promotes human breast cancer cell line MDA-MB-231 angiogenesis through EPCR /PAR1 signaling pathway in vitro.

OBJECTIVETo explore the technical feasibility, safety, and short-term clinical efficacy of right-to-lateral approach in laparoscopic-assisted radical gastrectomy.

METHODSClinicopathological data of 178 gastric cancer patients undergoing laparoscopic-assisted radical gastrectomy, including 92 patients with right-to-lateral approach(R-LG group) and 86 cases with left-to-lateral approach (L-LG group), in our department from October 2010 to September 2013 were analyzed retrospectively. Short-term efficacy and complication morbidity were compared between R-LG group and L-LG group according to body mass index (BMI).

RESULTSFor those patients with BMI ≥ 24 kg/m², the R-LG group (35 cases) had shorter mean operation time, less intraoperative blood loss, shorter painkiller used time than L-LG group (31 cases)[(227 ± 17) min vs. (262 ± 23) min, (73 ± 9) ml vs. (84 ± 8) ml and (2.1 ± 0.1) d vs. (2.6 ± 0.4) d, all P<0.05]. The average time to ambulation and recovery time of peristalsis in the R-LG group were faster than those in L-LG group [(2.2 ± 0.2) d vs. (2.8 ± 0.6) d and (3.6 ± 0.3) d vs. (4.2 ± 0.5) d, all P<0.05]. The R-LG group had more dissected lymph nodes per patient (35 ± 4) than the L-LG group (30 ± 5) with significant difference (P<0.05). There were no significances in postoperative hospital stay, postoperative complication morbidity and hospitalization expenses between R-LG and L-LG group (all P>0.05). For those patients with BMI<24 kg/m², there were no significant differences in all above parameters between R-LG group (57 cases) and L-LG group (55 cases). No mortality and recurrence was observed during follow-up of 3 to 24 months.

CONCLUSIONRight-to-lateral approach in laparoscopic-assisted radical gastrectomy is a safe and feasible procedure, especially for the obesity patients, which can shorten the operation time, decrease intraoperative blood loss, lead to a faster postoperative recovery and harvest more lymph nodes as compared to L-LG procedure.

Body Mass Index ; Gastrectomy ; Humans ; Laparoscopy ; Length of Stay ; Lymph Node Excision ; Obesity ; Operative Time ; Postoperative Complications ; Postoperative Period ; Retrospective Studies ; Stomach Neoplasms ; surgery

Background Studies have determined that nucleotide binding oligomerization domain 2 (NOD2) plays a key role in innate immune response.However,whether NOD2 participates in the nature defense of fungal keratitis is unclear.Objective This study was to investigate the expression and significance of NOD2 on cornea in the initial of Aspergillus fumigatus keratitis (AFK) in rats.Methods Seventy-two adult clean Wistar rats were randomized into the normal control group,only corneal epithelial scraped group and AFK model group,and the AFK models were established by incubating Aspergillus fumigatus to cornea after corneal epithelium was scraped.All the operations were performed in the right eyes of rats.Reverse transcription PCR (RT-PCR) was carried out to detect the expression of NOD2 mRNA in corneal epithelium 4,8,16,24 hours after operation.Twenty-four hours after operation,the expression of NOD2 protein in rat corneas was examined by immunochemistry and immnunofluorescence technology.Also,the rat corneas were obtained for regular histopathological examination.The use and care of the animals complied with Institutional Animal Care and Use Committee Guidebook by NIH.Results All the models were made successfully.RT-PCR revealed that a fewer NOD2 mRNA were expressed on cornea in the normal control group,but the expressing levels of NOD2 mRNA were increased in the only corneal epithelial scraped group and AFK model group.Compared with only corneal epithelial scraped group,the elevated values of NOD2 mRNA expression in the AFK model group were statistically significant at 4,8,16 and 24 hours after operation (t =-0.409,-0.439,-0.534,-0.618,all at P=0.000).The histopathological examination displayed that the cornel tissue had intact structure in the normal control group,and partly corneal epithelial deficiency,slight corneal swelling and fewer neutrophil granulocytes were seen in the only corneal epithelial scraped group.However,corneal ulcer,severe corneal edema and a lot of neutrophil granulocytes were exhibited in the AFK model group.Immunochemistry and immnunofluorescence staining evidenced that weaker expression of NOD2 was visualized in the corneal epithelial and endothelial layers,and obviously enhanced staining was seen in the AFK model group.The expressing levels (absorbancy) were 0.045 ± 0.005,0.050 ± 0.005 and 0.092 ± 0.006 in the normal control group,only corneal epithelial scraped group and AFK model group,respectively,showing a significant increase in the AFK model group compared with the only corneal epithelial scraped group (t =0.042,P =0.000).Conclusions Expression of NOD2 is upregulated in the corneas with AFK,suggesting that NOD2 participates the natural defense in the initial of fungal keratitis.NOD2 may play an important role in the process of anti-fungal innate immune response in cornea.