OBJECTIVE:To establish the mesoporous carbon nano-drug delivery system (MCNs) with chemotherapy drugs loaded and holding photothermal and photodynamic combined effect,and study its anti-multidrug-resistant tumor effect in vitro. METHODS:MCNs was prepared by low-concentration hydrothermal route,and the MCNs surface was carboxylated by the mixed acid ultrasound method to made MCNs-COOH (MCNC). The morphology and surface properties were evaluated. Adriamycinc (ADR)was loaded into MCNC to fabricate ADR/MCNC via adsorption method. Drug loading capacity was calculated by UV,and drug release profile was investigated by dialysis method. ADR-resistant human breast cancer MCF-7/ADR cells were chosen,and cell uptake and positioning of ADR/MCNC were observed by confocal laser microscopy;cytotoxicity of ADR/MCNC was detected by MTT method;and intracellular reactive oxygen species(ROS)level under NIR irradiation was measured by flow cytometry. RE-SULTS:The particle size of prepared MCNs was about 90 nm,with carboxyl in surface. The specific surface area was 541.62 m2/g,pore volume was 0.34 cm3/g,and pore size distribution was 2.5 nm,with significant photothermal effect. The drug loading ca-pacity of ADR/MCNC was 47.4%,showing pH/NIR responsiveness release characteristics. It can promote ADR in cell uptake and nuclear accumulation and induce MCF-7/ADR cell to generate ROS under NIR irradiation,with significant inhibitory effect. CON-CLUSIONS:MCNs is prepared successfully,and ADR/MCNC has an effect on anti-multidrug-resistant tumors.

OBJECTIVE:To prepare the Indocyanine green gold nanocages(ICG/Biotin-PEG-AuNC-PCM),and study its anti-tumor activity. METHODS:Polyol reduction method was used to prepare silver nanometer cubes (AgNC) as template,ion ex-change reaction was used to prepare gold nanocages (AuNC) to characterize its morphology,particle size,near infrared (NIR) light and heat properties. Organic solvent evaporation method was conducted to prepare the ICG/Biotin-PEG-AuNC-PCM loaded with ICG,1-tetradecanol(PCM),surface modification of biotin polyethylene glycol mercapto(Biotin-PEG-SH). Its particle size, polydispersity index (PDI) and drug loading were detected,and in vitro cumulative release (Q) within 180 min under 37,40 ℃was investigated. Using adriamycin-resistant human breast cancer cells(MCF-7/ADR cells)as objects,MTT method was used to in-vestigate the antitumor activities of ICG,ICG/PEG-AuNC-PCM and ICG/Biotin-PEG-AuNC-PCM,and half inhibitory concentra-tion(IC50)was calculated. RESULTS:AuNC was cubic with particle size of about 60 nm and good light and heat properties. The particle size of ICG/Biotin-PEG-AuNC-PCM was(105±2.8)nm,PDI was 0.261±0.02(n=3). Drug loading was 1.34×108 g/mol AuNC,Q180 min was about 10%under 37℃and Q20 min was about 80%under 40℃. IC50 of ICG,ICG/PEG-AuNC-PCM and ICG/Bi-otin-PEG-AuNC-PCM on MCF-7/ADR cells was 95.2, 29.3, 16.1 μg/mL, respectively. CONCLUSIONS:ICG/Biotin-PEG-AuNC-PCM is successfully prepared,and the antitumor activity on MCF-7/ADR cells is stronger than ICG.

Objective To evaluate PBL teaching results in medical virology experiment course. Methods Medical students of class 2011 were randomized assigned into PBL group (n=45, 20 five-academic-year students and 25 seven-academic year students) and control group (n=63, 38 five-academic-year students and 25 seven-academic year students). Teaching effectiveness was evaluated by scores of experiment, medical virology examination and final examination. PBL group was surveyed with questionnaire. SPSS statistical software was used and t test was employed to do analysis. Results Scores in medical virology examination were higher in seven-academic-year students in PBL group than in control group and there was no difference in other two examination scores between the two groups. Survey showed that interest motivation, case analysis, experiment design and knowledge grasp-ing in PBL group were highly satisfied. However, evidence-based and generalization ability among seven-academic-year students as well as autonomous learning ability and ability to deduce material among five-academic-year students were not completed satisfied. Conclusions PBL with public health events in medical virology experiment course can develop students' intrinsic motivation, knowledge grasping and public health awareness. However, PBL methods should be adjusted to suit different academic students.

Abstract: Cell death is a fundamental biological phenomenon that is essential for the survival and development of organisms. Cell death can be either a spontaneous programmed process by the host or an accidentally triggered process. According to the different signaling pathway activated by various stimulates, programmed cell death exhibits the lytic or non-lytic morphology. For example, apoptosis, a typical non-lytic form of cell death, exhibits cell shrinkage and induces the formation of apoptotic bodies. Pyroptosis mediated by cysteine-containing aspartate-specific protease-1/11 (caspase-1/11) and necroptosis can induce inflammatory reactions and promote cell lysis to release inflammatory cytokines via triggering the pore-forming mechanism of the cell membrane, representing a typical modes of lytic cell death. In addition, the release of reactive oxygen species caused by the damaged mitochondria may further trigger ferroptosis during the pathogen infection. Programmed cell death can play an immune defensive role by eliminating infected cells and intracellular pathogens and stimulating the innate immune response through the resulting cell corpses. Here, we discuss the molecular mechanisms of five programmed cell death pathways: apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis. We describe their roles in the innate immune defense against bacterial infections and give a brief statement of the interactions between the different programmed cell death, hoping to provide new insights for in-depth study of the pathogenic mechanisms of infectious diseases.

Objective To evaluate the effects of rapamycin combined with rosiglitazone on lung injury in septic rats.Methods One hundred and twenty healthy male Wistar rats were randomly divided into 5 groups (n =6 each):sham operation group (group S); cecum ligation and punture (CLP) group; rapamycin group (group RPM) ; rosiglitazone group (group RGZ) ; rapamycin plus rosiglitazone group (group RPM + RGZ).The rats were anesthetized with intraperitoneal 10% chloral hydrate 100 mg/kg.Sepsis was induced by CLP in groups CLP,RPM,RGZ and RPM + RGZ.At 30 min before CLP,rapamycin 0.4 mg/kg was injected subcutaneously in RPM group,rosiglitazone 0.3 mg/kg was injected via the femoral vein in RGZ group,and rapamycin 0.4 mg/kg was injected subcutaneously and rosiglitazone 0.3 mg/kg was injected via the femoral vein in group RPM + RGZ.While the equal volume of normal saline was given instead in CLP group.Six rats were sacrificed at 2,6,24 and 48 h after CLP in each group,and lungs were removed and cut into sections which were stained with haematoxylin and eosin and examined under microscope.The pathological changes of lungs were scored.The myeloperoxidase (MPO) activity and signal transducer and activator of transcription 3 (STAT3)-DNA binding activity in lung tissues were measured.Results Compared with group S,the pathological scores,MPO activity and STAT3-DNA binding activity were significantly increased in groups CLP,RPM,RGZ,RPM + RGZ (P ＜ 0.05).The pathological scores,MPO activity and STAT3-DNA binding activity were significantly lower in groups RPM,RGZ and RPM +RGZ than in group CLP,and in group RPM + RGZ than in groups RPM and RGZ (P ＜ 0.05).Conclusion Rapamycin combined with rosiglitazone offers additional benefit to attenuating lung injury induced by sepsis over rapamycin or rosiglitazone alone,and inhibition of activation of STAT3 pathway is involved in the mechanism.

Objective To investigate the effects of dexmedctomidine pretreatment and postconditioning on renal ischemia-reperfusion (I/R) injury in rats.Methods Thirty-two male Wistar rats,aged 3-4 months,weighing 220-300 g,were randomly divided into 4 groups ( n =8 each):sham operation group ( group S),I/R group,dexmedetomidine pretreatment group (group Pre) and dexmedetomidine postconditioning group (group Post).The rats were anesthetized with phenobarbital sodium 65 mg/kg.Renal I/R was produced by occlusion of both renal pedicles for 60 min followed by 48 h reperfusion.Dexmedetomidine 50 μg/kg was given intraperitoneally at 30 min before ischemia and at the beginning of reperfusion in Pre and Post groups respectively.The concentrations of serum creatinine and blood urea were determined at 0,24 and 48 h of reperfusion (T1-3).The renal tissues were obtained at the end of reperfusion for microscopic examination and detection of apoptosis by TUNEL assay.Acute kidney tubular necrosis was scored and apoptosis index (AI) was calculated.Results Compared with group S,the concentration of serum creatinine and blood urea at T2.3,and acute kidney tubular necrosis score and AI were significantly increased in I/R,Pre and Post groups ( P ＜ 0.05).Compared with I/R group,the concentration of serum creatinine and blood urea at T2.3,acute kidney tubular necrosis score and AI were significantly decreased in Pre and Post groups ( P ＜ 0.05).Conclusion Both dexmedetomidine pretreatment and postconditioning can attenuate renal I/R injury through inhibition of cell apoptosis in rats.

Objective To analyse the difference of effects of different tidal volume mechanical ventilation strategies in infants with severe congenital heart disease after curative.Methods Sixty-eight cases were chosen from CICU of Anhui Provincial Children's Hospital during Oct 2010 to Jan 2012.Thirty-two cases in A group were used in ventilation strategy by lower tidal volumes (6 ～ 10 ml/kg),36 cases in B group were used in ventilation strategy by larger tidal volumes (10 ～ 15 ml/kg).The time of mechanical ventilation,duration of ICU stay and postoperative complications were compared between the two groups.Results The time of mechanical ventilation of B group was shorter than that of A group [(8.6 ± 2.5) d vs (11.7 ± 3.2) d],duration of ICU stay of B group was shorter than that of A group [(11.4 ± 4.8) d vs (15.6 ± 5.7) d],there were statistical differences between two groups(P ＜ 0.0l).The incidence rate of ventilator associated pneumonia and pneumothorax were 6.3％ and 3.1％ in A group,which were 5.6％ and 5.6％ in B group,there were no statistical differences between two groups (P ＞ 0.05).Conclusion The effects of mechanical ventilation with larger tidal volumes is better than that with lower tidal volumes in infants with congenital heart disease postoperative therapy.

Objective To clarify the role of syk kinase in inflammasome activation in mouse peritoneal macrophages during Listeria monocytogenes (LM) infection. Methods Murine peritoneal macrophages were randomly divided into BAY treatment group, SB treatment group, WO treatment group, no treatment group and negative control group (NI). There were three wells in each group. The syk inhibitor BAY 117082, P38MAPK inhibitor SB203580 and PI3K inhibitor wotamine were used to treat murine peritoneal macrophages for 1h in BAY treatment group, SB treatment group and WO treatment group. Murine peritoneal macrophages were infected with LM for 24 h except NI group. The protein level of interleukin (IL)-18 in the supernatant was detected by ELISA kit. The activation condition of key molecule ASC in the infected-macrophages cyto-plasm was observed under fluorescence microscope. The phosphorylation levels of syk protein kinase at different time points during LM infection were determined by Western blot assay. Results There was no significant difference in IL-18 protein level before and after BAY treatment in NI group (P>0.05). The IL-18 protein level was significantly lower after LM infec-tion in BAY treatment group compared with that in no treatment group (P<0.05). In contrast, there was no significant differ-ence in IL-18 production between SB treatment group, WO treatment and no treatment group (P>0.05). Meanwhile, the per-centage of ASC-speck positive cells was obviously diminished in BAY treatment group compared with that in no treatment group (P<0.01). The phosphorylation levels of syk were significantly increased in 5 min, 15 min and 30 min post-infection. Conclusion Syk kinase signaling is involved in the inflammasomes activation upon Listeria monocytogenes infection in mu-rine macrophages.

Objective To investigate the expressions of spleen tyrosine kinase (Syk), c-Jun amino terminal kinase (JNK) and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the heart tissue in SD rat model of diabetic cardiomyopathy, and to explore the relationship between Syk, JNK and NLRP3. Methods Clean male SD rats were randomly divided into the control (Ctrl) group and diabetic cardiomyopathy model (DCM) group. Rats of DCM group were treated with a single intraperitoneal injection of streptozotocin (STZ), while rats of Ctrl group were injected with the same dose of citrate buffer. The random blood glucose level and body weight were monitored every week until 20 weeks after STZ or citrate buffer injection, then all the rats were killed and their hearts were obtained. Rat H 9c2 cardiomyocytes were randomly divided into normal glucose treatment (NG) group, high glucose treatment (HG) group, Syk inhibitor control (BAY) group and Syk inhibitor high glucose (HG+BAY) group. The Syk and JNK phosphorylations and NLRP3 protein expression were detected by Western blot assay in the heart tissue of SD rats and H9c2 cardiomyocytes. The NLRP3, cysteine-containing aspartate specific protease 1(caspase-1) and interleukin (IL)-1β expressions at mRNA level were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results The random blood glucose level was significantly increased (P<0.05) and the body weight was significantly decreased (P<0.05) in DCM group compared with those of Ctrl group. The expressions of cardiac p-Syk, p-JNK and NLRP3 at protein level were significantly increased in DCM group compared with those of Ctrl group (P<0.05). Furthermore, the mRNA levels of NLRP3, caspase-1 and IL-1β were significantly up-regulated (P < 0.05). BAY treatment significantly inhibited the high glucose-induced NLRP3, caspase-1 and IL-1β mRNA expressions and p-JNK, NLRP3 protein expressions in H9c2 cardiomyocytes (P < 0.05). Conclusion JNK phosphorylation and NLRP3 inflammasome activation induced by Syk play an important role in the pathogenesis of diabetic cardiomyopathy.

Objective To explore the safety and cosmetic effect of nipple-sparing modified radical mas tectomy and immediate tissue expander implantation with single circumaereolar incision.Methods 30 patients were enrolled in Peking Union Medical College Hospital between Jan.2014 and Dec.2015.All the patients were categorized according to surgical incision (single circumaereolar incision group vs double incisions group).Data on clinicopathological parameters,average hospital stay,complications and overall cosmetic effect were retrospectively collected.Data was performed with Chi-square test,Fisher exact test and t-test.Statistical significance was defined as P＜0.05.Results 19 patients were enrolled in single circumaereolar incision group,and 11 patients in double incisions group.There was no significant difference for operation duration (P=0.093) and average hospital stay (P=0.339).After follow-up for 19.1 months,ranging from 8 to 31 months,no patients developed seroma or arm lymphedema.There was no statistical significance between the two groups in terms of sensation in nippleaereolar area (P=0.973),bilateral symmetry (P=0.650) and overall cosmesis (P=0.483).Conclusion single circumaereolar incision nipple-sparing modified radical mastectomy and immediate tissue expander implantation can be one of the preferable surgical procedures with benefits of minimal invasiveness,reliable oncological safety and decent cosmetic effect.