eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Objective : To explore the role of semaphoring 6d(SEMA6D) in the malignant progression of triple-negative breast cancer(TNBC). Methods : Bioinformatics and Immunohistochemistry(IHC) were used to analyze the expression level of SEMA6D in TNBC and paracancer non-tumor tissues and its relationship with patients′ clinicopathological features. MDA-MB-231 cell line stably knocking down the expression of SEMA6D was constructed, and the effects of SEMA6D on migration and invasion of TNBC cells were investigated by Wound-healing assays and Transwell assays. cBioPortal and GEPIA2 databases were used to screen out the gene negatively associated with it, namely aurora kinase A(AURKA). Bioinformatics and IHC were used to analyze the expression level of AURKA in TNBC and paracancer non-tumor tissues and its relationship with patients' clinicopathological features. Western blot assay was used to analyze the expression of AURKA and the effect of epithelial-mesenchymal transition(EMT) makers Claudin-1, N-cadherin and Vimentin after knocking downSEMA6D. Results: Bioinformatics analysis and IHC results showed that the expression of SEMA6D in TNBC tissues was significantly lower than that in paracancer non-tumor tissues(bothP<0.05). The expression of AURKA in TNBC tissues was significantly higher than that in paracancer non-tumor tissues(bothP<0.05), SEMA6D and AURKA were significantly negatively correlated in TNBC(P<0.01). Both low expression of SEMA6D and high expression of AURKA were positively correlated with tumor size, tumor histological grade, clinical stage and lymph node metastasis in TNBC patients(allP<0.05). The knockdown ofSEMA6Dsignificantly promoted the migration and invasion ability of TNBC cells(bothP<0.01). Western blot results showed that the knockdown ofSEMA6Dupregulated AURKA expression, promoted the expression of N-cadherin and Vimentin, and inhibited the expression of Claudin-1 in tumor cells. Conclusion Down-regulation of SEMA6D expression in TNBC may be involved in the malignant progression of TNBC through up-regulation of AURKA expression and promotion of EMT.

Objective : To explore the expression of prohibitin2(PHB2) in breast cancer and its effect on the biological behaviors of tumor cells. Methods : Immunohistochemistry was used to detect the expression of PHB2 protein in breast cancer tissues and its relationship with clinicopathologic features. Breast cancer stable transient cell lines were constructed with knockdown and overexpression ofPHB2, respectively. The effects of PHB2 on cell proliferation, migration and invasion ability were detected by clone formation assay, scratch assay and Transwell assay. Western blot(WB) was used to detect the effects of PHB2 on the expression of epithelial-mesenchymal transition(EMT)-related markers, including E-cadherin, N-cadherin, Snail family transcriptional repressor 1(Snail) protein, Vimentin, and Claudin-1. The effect of PHB2 on tumorigenicityin vivowas detected by subcutaneous tumor formation assay in nude mice. Results: The result of immunohistochemical showed that PHB2 was highly expressed in breast cancer and the expression of PHB2 was significantly positive correlated with tumor size, human epidermal growth factor receptor-2(HER-2) status and proliferation index Ki-67 levels(P<0.05). Clone formation assay, scratch assay and Transwell assay revealed that knockdown ofPBH2significantly inhibited the proliferation, migration and invasion ability of breast cancer cells(P<0.01), while the overexpression ofPHB2significantly promoted cell proliferation, migration and invasion(P<0.01). The result of subcutaneous tumor formation experiment in nude mice revealed a significant decrease in tumor volume and weight in knockdownPHB2mice(P<0.000 1), whilePHB2overexpression tumors significantly increased in volume and weight(P<0.001).WB assay showed that the protein expression of epithelial marker E-cadherin increased, while the expressions of mesenchymal markers N-cadherin, Snail and Vimentin decreased significantly afterPHB2knockdown with them in control cells(P<0.01). The expression of Claudin-1 decreased, while the expressions of N-cadherin, Snail and Vimentin increased significantly inPHB2overexpression cells(P<0.05). Conclusion PHB2 is highly expressed in breast cancer and promotes multiple malignant biological behaviors in tumor cells, suggesting PHB2 may be a potential target for breast cancer diagnosis and treatment.

Purpose To explore the expression of autoph-agy-related 7(ATG7)in breast cancer and its effect on the breast cancer development.Methods Immunohistochemistry(IHC)was used to detect ATG7 protein expression in breast cancer tissues and the relationship between ATG7 and clinico-pathological features was analyzed.ShRNA was used to interfere with the expression of ATG7 in breast cancer cell line MCF-7.Puromycin was used to screen for stably transfected cells and Western blot was used to detect transfection efficiency.The effect of ATG7 knockdown cells on proliferation ability was de-tected by CCK8 and clone formation experiments.The effect of ATG7 knockdown cells on tumorigenicity in vivo was detected by subcutaneous tumor formation experiment in nude mice.Results IHC showed that ATG7 expression in breast cancer tissues was mainly localized in cytoplasm,and its expression was significant-ly correlated with tumor size and Ki67 expression(P＜0.05).ATG7-shRNA significantly interfered with ATG7 expression in breast cancer cells MCF-7.CCK8 and clone formation experi-ments showed that ATG7 knockdown promoted the cell prolifera-tion compared with the control group.The experiment of subcu-taneous tumor formation in nude mice showed that the tumor for-mation ability of mice was significantly increased after ATG7 knockdown compared with the control group.Conclusion ATG7 may inhibit the proliferation capacity of breast cancer and could be a potential target for breast cancer therapy.

Objective To investigate the application effect of the sandwich teaching method in the course of Surgical Nursing . Methods Two classes of the students majoring in nursing were randomly divided into control group and observation group, with 36 students in each group. The students in the control group received the traditional teaching method, and those in the observation group received the sandwich teaching method . The teaching effect was compared between the two groups by theoretical assessment and questionnaire survey. SPSS 24.0 was used for analysis of variance and the t-test. Results Compared with the control group, the observation group had significantly higher scores of course assessment, learning atmosphere, and learning initiative. The observation group also had significantly higher good rates of learning atmosphere and learning initiative than the control group(P<0.05). Conclusion The sandwich teaching method can significantly improve students' abilities of communication and problem solving, arouse their enthusiasm of learning, and increase the interestingness of classroom, and therefore, it has a practical value in teaching.

Misuse and abuse of veterinary antimicrobial agents have led to an alarming increase in bacterial resistance, clinical treatment failure, and drug residues. To address these problems, consistent and appropriate dosage regimens for veterinary antimicrobial agents are needed. Pharmacokinetics/Pharmacodynamics (PK/PD) models have been widely used to establish rational dosage regimens for veterinary antimicrobial agents that can achieve effective prevention and treatment of bacterial diseases and avoid the development of bacterial resistance. This review introduces building methods for PK/PD models and describes current PK/PD research progress toward rational dosage regimens for veterinary antimicrobial agents. Finally, the challenges and prospects of PK/PD models in the design of dosage regimens for veterinary antimicrobial agents are reviewed. This review will help to increase awareness of PK/PD modeling among veterinarians and hopefully promote its development and future use.
Anti-Infective Agents ; Bacterial Infections ; Drug Residues ; Humans ; Treatment Failure ; Veterinarians

Objective To evaluate the effectiveness of comprehensive prevention and control measures on coal-burning-borne endemic tluorosis in Xishui,on residents healthy behavior and situation of the disease.Methods In 2013,five towns were selected according to their location of east,south,west,north and centre.Three villages and one elementary school in each town were chosen,and 20 families' related behavior and fluorine prevention knowledge questionnaire in each village were surveyed.All the students from one class aged 8-12 of grade 3-6 in each school were selected,according to the Diagnosis of Dental Fluorosis,dental fluorosis was examined and fluorine knowledge questionnaire was surveyed.At the same time,the detection rate of dental fluorosis of children aged 8-12,information of the knowledge about prevention and cure of fluorosis and related behavior of target groups in 2007,and the urinary fluoride contents of children aged 8-12 in 2000 were collected.Analysis and comparison of the data in 2000,2007 and 2013 were done.Results After the intervention,the witting rates of students and family householders 90.95％ (11 773/12 945),84.27％ (3 792/4 500),were significantly higher than those of before the intervention [19.29％ (1 039/5 385),26.27％ (394/1 500),x2 =9 279.14,1 794.22,all P ＜ 0.01].Proper utilization rate of cooking stove was 100.00％ (37/37),iron stove utilization rate was 99.64％ (279/280),dry chili correct rate was 100.00％ (299/299) and before the intervention,these values were 3.20％ (43/1 345),90.28％ (1 207/1 337)and 62.14％ (855/1 376),respectively,and the differences were statistically significant (x2 =601.12,27.28,27.28,all P ＜ 0.01).Children's dental fluorosis detection rate was 24.21％ (206/851),compared with that of before the intervention,61.62％ (2 150/3 489),the difference was statistically significant (x2 =385.93,P ＜ 0.01).Children's urine fluoride was (0.51 ± 0.29) mg/L,and before the intervention [(1.55± 1.59) mg/L],the difference was statistically significant (t'=10.25,P ＜ 0.01).Conclusions The effect of comprehensive prevention and control measures against coal-burning-borne endemic fluorosis in Xishui are remarkable.The residents health related behavior has been formed and the condition is reduced markedly.

Objective To investigate the radiosensitization of artesunate on nude mouse transplanted with HeLa cells,and to explore its possible mechanisms.Methods HeLa cells were inoculated into the nude mice to establish tumor model.Mice were randomly divided into 4 groups as blank control,artesunate group,radiation group and artesunate + radiation group when average volume of tumor were about 5 mm × 5 mm× 5 mm.During the term of treatment,the volume of tumors were measured every 2days.After 14 days treatment,the mice were killed and tumor tissues were harvested for flow cytometry to detect the alteration of cell cycle.Meanwhile,the pathological change of the tumor tissue was observed with HE staining method,and the change of expression of cycle regulatory protein Cyclin B1,Cdc2 and Wee1 were detected by Western blot.Results The growth of tumor was significantly inhibited by artesunate combined with radiation and its inhibition rate was 72.34％.Flow cytometry results showed that the percent of cells in G1 phase increased and G2 phase decreased in the artesunate + radiation group compared with those in irradiation group ( t =4.41,4.12,P ＜ 0.05 ).The expression level of Cyclin B1 was obviously increased while that of Wee1 decreased in the artesunate + radiation compared with irradiation group.There was no difference in the expression of Cdc2 among the four groups.Conclusions Artesunate can dramatically increase the radiosensitivity of transplanted tumor of HeLa cells.The possible mechanism might be related to the decreasing G2 phase by regulating the expression of Cyclin B1 and Wee1.

ObjectiveTo explore the effects of hyperbaric oxygen (HBO) on severe brain injury. Methods60 patients with severe brain injury were divided into control group and treatment group. They were treated with neurosurgical conventional therapy, and HBO for treatment group in addition. They were assessed with Glasgow Coma Scale (GCS) before and after treatment, and Glasgow Outcome Scale (GOS) 3 and 6 months after treatment. ResultsCompared with control group, there is significant improvement in GCS (P<0.05) and GOS (P<0.05) in treatment group. ConclusionHBO has immediate and long-term efficiency on severe brain injury.