OBJECTIVE To explore the in vitro and in vivo inhibitory effects and mechanism of metformin on the malignant biological behavior of esophageal squamous cell carcinoma （ESCC） cells by the hypoxia inducible factor-1α （HIF-1α）/interleukin-8 （IL-8） signaling pathway. METHODS Human ESCC TE1 cells were assigned into blank group， metformin low-， medium-， and high-dose groups （0.5， 1， 2 mmol/L）， IDF-11774 （HIF-1α inhibitor） group （20 μmol/L）， and high-dose metformin+HIF-1α activator dimethyloxalylglycine （DMOG） group. After 24 h treatment， cell proliferation [measured by the positive rate of 5-ethynyl- 2′-deoxyuridine （EdU） and optical density at 450 nm （OD450 value）]， apoptosis， invasion and migration as well as mRNA expressions of proliferating cell nuclear antigen （PCNA）， Bcl-2 interacting mediator of cell death （Bim）， migration and invasion enhancer 1 （MIEN1）， and matrix metalloproteinase-9 （MMP-9）， and protein expressions of HIF-1α and IL-8 in the cells were detected. The xenograft tumor model of nude mice was established. Thirty nude mice were randomly divided into blank group， metformin low-， medium-， and high-dose groups （i.g. administration of metformin 62.5， 125， 250 mg/kg+i.p. administration of equal volume of normal saline）， IDF-11774 group （i.g. administration of 50 mg/kg IDF-11774+i.p. administration of equal volume of normal saline） and high-dose metformin+DMOG group （i.g. administration of metformin 250 mg/kg+i.p. administration of DMOG 250 mg/kg）， with 5 mice in each group. They were given relevant medicine， once a day， for 4 consecutive weeks； the mass and volume of the tumor and protein expressions of HIF-1α and IL-8 in the tumor tissue were determined. RESULTS The EdU positive rate， OD450 value， cell invasion number， scratch healing rate， mRNA expressions of PCNA， MIEN1 and MMP-9， protein expressions of HIF-1α and IL-8， as well as the mass and volume of transplanted tumors and protein expressions of HIF-1α and IL-8 in tumor tissues were decreased by metformin in concentration/dose-dependent manner （P＜0.05）. Additionally，metformin increased the apoptosis rate and mRNA expression of Bim in cells （P＜0.05）. The trend of changes in corresponding indicators in the IDF-11774 group was consistent with that in the metformin groups， whereas DMOG could significantly attenuate the aforementioned effects of high-concentration/high-dose metformin （P＜0.05）. CONCLUSIONS Metformin can inhibit the proliferation， invasion， migration of TE1 cells， and tumor growth of nude mice， and induce cell apoptosis， the mechanism of which may be related to the inhibition of HIF-1α/IL-8 signaling pathway.

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Objective To investigate the effect of the humanized care on the blood glucose, blood lipid and diabetic ketoacidosis control of type 1 diabetes patients outside the hospital. Methods Fifty type 1 diabetes patients were enrolled in this study, aged from 18 to 30 years old, outside the hospital. The duration of this study was from Mar 2009 to Jan 2016.The clinical and laboratory data of patients,including HbA1c,LDL-C,HDL-C,TG and diabetic ketoacidosis were collected and analyzed. Results About 60.0% and 80.0% of type 1 diabetes pa-tients achieved the goals of contorlling glycemia (HbA1c < 6.5%) and dyslipidemia (LDL-C < 2.6 mmol/L) respec-tively, after receiving the humanized care outside the hospital, while only 32.0% and 22.0% of type 1 diabetes pa-tients achieved these goals before.Moreover,after receiving the humanized care outside the hospital,only 16.0% of type 1 diabetes patients suffered from diabetic ketoacidosis which was 40.0% before.Conclusions The humanized care outside the hospital can help patients to acheive the goals of contorlling glycemia and dyslipidemia among the type 1 diabetes.Besides,it contributes to reduce the incidence rate of the diabetic ketoacidosis.

BACKGROUND:The tensile and stress-relaxation mechanical properties of sciatic nerve injury after repaired with autologous nerve and poly(lactic acid-glycolic acid) (PLGA) scaffold are rarely reported. OBJECTIVE:To analyze the tensile and stress relaxation characteristics of sciatic nerve injury after the transplantation of autologous nerve and PLGA scaffold. METHODS:Sixty sciatic nerves were extracted from the fresh cadavers dead within 24 hours, processed into 35 mm samples, and were then randomly divided into three groups. The nerve samples in control group received no intervention;the nerves in artificial and autologous groups were modeled into 20 mm defects, followed by repaired with PLGA scaffold and autologous nerve, respectively. Afterwards, the tension and stress-relaxation tests were performed in each group. RESULTS AND CONCLUSION:The stress in each group descended fast at the first 600 seconds, then descended slowly and was closed to the horizontal level until 7200 seconds, and the stress-relaxation curves in each group were in logarithmic decrease. The order of the elastic limit load, elastic limit stress, maximum load, maximum stress, elastic limit strain and maximum strain during tension was as follows:control group>artificial group>autologous group (P<0.05). Our results indicate that the PLGA scaffold holds good tension and stress-relaxation properties, which meets the mechanical requirements of the biomaterials used for sciatic nerve repair.

Objective To learn the clinical features of severe pneumonia in northeast sichuan ,and to improve the diagnosis and treatment level .Methods Basic disease or concomitant diseases and it′s clinical features were retrospective analyzed in different age patients with severe pneumonia in 2011 .Results (1)basic diseases and fatality cases /deteriorated cases were increased in elderly patients with the increase of age .There were 4 patients infected with HIV (3 cases under 65 years old ,1 case over 70 year old) .(2) onset pattern was given first place to suffer from cold ,but 40% were showed for symptoms of nervous system ,heart disease and other respiratory system ;(3)The main respiratory failure types of severe pneumonia is Ⅰ (about 70% ) ,30% of patients needed support of machine ventilation ;(4)community pneumonia were main type(75% );detection rate of Fungal infections and G -bacteria were 25% -30% ,normal bacteria (Streptococcus and Neisser bacteria )were over 1/3 ,Staphylococcus aureus were about 10% ;(6) More than 70% of the patients with different degree of hypoalbuminemia ;(7)Cure accounts for 2/3 ,poor prognosis accounted for 1/3 ,in which death and voluntary discharge were each 16 .6% ,ventilator-dependent ,multi-organ failure ,infections and some com-plex social factors were the prognostic factors .Conclusion Understanding the features and treatment difficulty of the local commu-nity acquired pneumonia is helpful to improve the timely diagnosis ,treatment and rescue level of patients with severe pneumonia .

Objective To observe the clinical effect of non-invasive positive pressure ventilation(NIPPV) in the treatment of chronic obstructive pulmonary disease at acute exacerbation phase(AECOPD) combined with typeⅡrespiratory failure.Methods Fifty-three patients of therapeutic group were treated with NIPPV,as well as conventional therapeutic managements,such as antibiotic,pacifying gasp,eliminating phlegm,taking respiratory stimulants,and receiving continual low-flow oxygen.Whereas,53 controls only received conventional intervention.Results There was no significant difference between the 2 groups before the treatment,but significance was found in pH value,PaCO2,PaO2,HR and RR in them.The therapeutic group showed significantly improvement in PaCO2,RR and PaO2 compared with control group.Conclusion NIPPV intervention can effectively lower PaCO2 and RR,improve PaO2,shorten the course of hospitalization.

Objective: To observe the effect of Ruxiankang (RXK) Capsule (Radix Bupleuri, Poria, Rhizoma Atractylodis macrocephalae, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Cyperi, etc.) on mammary gland and sex hormone of rat with mastoplasia. Methods: After benzoate estradiol and progestogen were injected into rats for 30 days the mastoplasia model was made, the model rats were treated with tamoxifen and RXK Capsule for 30days, and injected estradiol at the same time. Results: RXK Capsule and tamoxifen could significantly inhibit HMG rat's mammary gland swell, reduce quantity of lobule alveolus in mammary glands and secretion ( P