Exosomes are extracellular vesicles that facilitate cellular communication by transmitting biomolecules and altering the biochemical characteristics of receptor cells. Mesenchymal stem cell-derived exosomes(MSC-Exos)are lipid bilayer vesicles secreted by mesenchymal stem cells(MSCs). These exosomes have similar functions to MSCs and contain bioactive substances such as proteins, lipids, and nucleic acids. MSC-Exos play a vital role in intercellular communication and are involved in essential physiological processes including immune regulation, tissue damage repair, and angiogenesis promotion. Consequently, they have gained significant attention in research, particularly in the treatment of immune inflammatory diseases, ischemic diseases, and other related fields. This article provides an in-depth analysis of the potential treatment mechanisms for dry eye, focusing on the pathogenesis of the condition, including inflammatory reactions, nerve regeneration, and tissue repair. The objective is to establish a foundation for the application of MSC-Exos in the treatment of dry eye, thereby offering a valuable reference for the future clinical applications.

OBJECTIVE To study the role of phosphatidylinositol-3-kinase （PI3K） on sunitinib-induced myocardial systolic dysfunction. METHODS Using human-induced pluripotent stem cell-derived cardiomyocytes （hiPSC-CMS） as objects， the contractile force of cardiomyocytes was measured by CardioExcyte 96 system， and IC50 of sunitinib was calculated after hiPSC- CMS were treated with sunitinib at different concentrations [0 （control）， 0.5， 1， 3， 5， 10 μmol/L] for 24 hours. The effects of sunitinib （3.14 μmol/L） on the contractile frequency of cardiomyocytes， calcium transient amplitude and calcium transient recovery time course， mRNA expression of myocardial injury markers atrial natriuretic peptide （ANP）， brain natriuretic peptide （BNP） and β-myosin heavy chain （β-MHC） were detected. PI3K activator 3，4，5-triphosphate phos-phatidylinositol （PIP3， 1 μmol/L） and sunitinib were used to intervene in hiPSC-CMs jointly， so as to investigate the role of PI3K in the myocardial systolic dysfunction induced by sunitinib. RESULTS Sunitinib inhibited the contractile force of hiPSC-CMs in a concentration-dependent manner. IC50 of sunitinib was 3.14 μmol/L. After intervention with 3.14 μmol/L sunitinib， the contractile frequency of hiPSC-CMs and calcium transient amplitude were decreased significantly （P＜0.05 or P＜0.01）； the duration of calcium transient recovery was prolonged significantly （P＜0.05）， and mRNA expressions of ANP， BNP and β-MHC were significantly increased （P＜0.01）. After PI3K was activated with PIP3， the contractile force of hiPSC-CMs was increased significantly （P＜0.01）. CONCLUSIONS Activating PI3K activity is a potential molecular mechanism to improve myocardial toxicity induced by sunitinib.

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.
Cellular Senescence/genetics* ; Humans ; Immunoglobulin G/metabolism* ; Interleukin-13/pharmacology* ; Mitochondria/metabolism* ; Sialadenitis/metabolism*

Objective To introduce the construction of clinical research information system of a tertiary grade A comprehensive hospital in Shanghai.Methods Based on the database construction,the structured inpatient medical records,surgical records and ancillary diagnostic report are designed and the application terminal is developed.Results A full-link normalized clinical research information system for research-based cases covering all aspects of clinical research is developed,which can provide customized and structured data.Conclusions The clinical research information system provides convenience for clinical medical research,and its practice has certain reference significance.

Objective To analyze the effects of quality supervision and continuous improvement system on optimizing in-hospital diagnosis and treatment process in patients with acute ischemic stroke (AIS).Methods From September 2013 to May 2016,424 consecutive patients with AIS treated with intravenous thrombolysis and/or endovascular therapy in Changhai Hospital,the Second Military Medical University were enrolled retrospectively.They were analyzed according to the annual running process (the first year[from September 2013 to August 2014],the second year[from September 2014 to August 2015],and the third year[from September 2015 to May 2016]).The spend time and delay (DTN>60 min,DTP>90 min) rate of each treatment process in the first,second,and third year (time from door-to-imaging[DTI],door-to-needle[DTN],imaging-to-needle (ITN),door-to-groin puncture (DTP) and imaging-to-groin puncture (ITP) were compared.Taking the time periods (>median) of having significant differences of the spend time of the treatment processes as the dependent variables in the first,second,and third year,the influence of the years and treatment modalities on delay was observed.The difference of constituent ratio of the reasons for delay in intravenous thrombolysis and endovascular therapy (objective reasons/other reasons) in different years were analyzed.Results (1) DTIs were 23.0 (11.0,42.0) min,22.0 (10.1,39.0) min,and 13.0 (6.0,27.0) min,respectively,and DTNs were 50.0 (30.0,77.1) min,45.0 (30.0,70.2) min,and 36.0 (24.0,57.0) min,respectively in the first,second,and third year.The spending time was shortened year by year.There were significant differences among the different years (all P<0.01).The spending time of DTP had a tendency to be shortened,but there were significant differences among different years (P=0.06).There were no significant differences between the spending time of ITN and ITP (all P>0.05).(2) The DTN delay rates were 33.3% (40/120),20.7% (29/140),and 8.1% (9/111),respectively in the first,second,and third year.There were significant differences among the 3 years (x2=22.111,P<0.01).There were no significant differences among the DTP delay rates (P=0.08).(3) Multivariate Logistic regression analysis showed that taking the first years as a reference,the risk of DTI delay was reduced in the third year (OR,0.174,95%CI 0.101-0.298,P<0.01),the risks of DTN delay were reduced in the second and third year (OR,0.564,95%CI 0.338-0.941;OR,0.180,95%CI 0.101-0.320,all P<0.05).For simple intravenous thrombolysis,bridging therapy was a protective factor for the improvement of treatment efficiency in the DTI process (OR,0.530,95%CI 0.297-0.943,P=0.031).Compared with the bridging therapy,the direct endovascular therapy was a protective factor for DTP treatment (OR,0.427,95%CI 0.202-0.901,P=0.025).The remaining independent variables were not associated with the occurrence of DTN and DTP delay (all P>0.05).(4) During the three years,the delay of intravenous thrombolysis was mainly due to objective reasons.The constituent ratio of other reasons caused delay of intravenous thrombolysis was decreased year by year.There was no other reasons for delay in the third year).There was no significant difference in the constituent ratio of the delay reasons in endovascular treatment (x2=3.622,P=0.164).Conclusion Under the existing process and resource allocation,setting the DTN target time and implementing continuous quality improvement are conducive to the effective implementation of brain CT scan and continuous optimization of intravenous thrombolysis in the processes in AIS patients with the first diagnosis.

This paper introduced the design and application of the performance appraisal scheme for the interventional operation platform.The comparison of interventional operations before and after the means of performance management in place, presented the effective role of performance management in interventional operation platform, and analyzed the motivation effect of performance management on the enthusiasm of interventional operators.The authors recommend performance appraisal and incentive compensation mechanism to motivate the clinical use of the platform, and greater application of such a common platform, for perfection of surgery performance management.

BACKGROUND: A large number of experiments in vivo and in vitro have shown that mesenchymal stem cells may obviously inhibit the lymphocytes and other immunocytes.OBJECTIVE: To investigate the effect of human umbilical cord mesenchymal stem cell transplantation on the immune function and prognosis of patients suffering decompensated liver cirrhosisn due to hepatitis B.METHODS: 118 patients with decompensated cirrhosis due to hepatitis B were randomly divided into control group (n=59) and observation group (n=59). The two groups all received normal medical treatment, and in addition, the observation group also received human umbilical cord mesenchymal stem cell transplantation. (4.0-4.5)×108 stem cells were transplanted twice by intervention via proper hepatic artery (10 mL) and intravenous infusion (10 mL) within 1 week after admission. The levels of serum interleukin-6, tumor necrosis factor-α, interleukin-10, transforming growth factor-β and the percentage of lymphocyte subsets in the peripheral blood were determined in the two groups before and 1, 4 weeks after treatment. The model for end-stage liver disease (MELD) score and Child-Pugh score of 118 patients after treatment for 12 weeks were observed and recorded, and liver failure, complications and survival during follow-up period in the two groups were observed. RESULTS AND CONCLUSION: After treatment for 1 and 4 weeks, the levels of serum interleukin-6 and tumor necrosis factor-α in the observation group were significantly lower than those in the control group (P < 0.05 or P <0.001), but the levels of serum interleukin-10 and transforming growth factor-β in the observation group were significantly higher than those in the control group (P < 0.05 or P < 0.001). After treatment for 1 week, the percentagesof CD3+CD4+T cell and CD4+CD25+Treg cells in the observation group were significantly higher than those in the control group (P < 0.001), but the percentages of CD3+CD8+ T cells and CD3-CD19+ B cells were significantly lower than those in the control group (P < 0.05 or P < 0.001). After treatment for 4 weeks, the percentages of CD3+ T cell ,CD3+CD4+ T cells and CD4+CD25+ Treg cells in the observation group were significantly higher than those in the control group (P < 0.05 or P < 0.001), but the percentages of CD3+CD8+ T cell and CD3-CD19+ B cells were significantly lower than those in the control group (P < 0.05 or P < 0.001). After treatment for 12 weeks, the MELD and Child-Pugh scores in the observation group were significantly lower than those in the control group (P < 0.05).During the follow-up period, none of the cases in the observation group developed liver failure, but five cases in the control group did. In addition, the incidence of complications and cumulative mortality in the observation group were significantly lower than those in the control group (P < 0.05). These results show that the human umbilical cord mesenchymal stem cell transplantation may alleviate liver inflammation and improve liver function, and then may reduce the incidence of hepatic failure and mortality for patients with decompensated cirrhosis due to hepatitis B.

Aiming at the technical characteristics and transforming difficulties for patents in medical health industry,this paper makes proposition on establishing a service system for patent transformation in healthcare system and accelerating the transformation and clinical application of medical technologies through the enhancement of technical service platform construction,strengthening of professional staff capabilities,and the improvement of patent values assessment.

BACKGROUND:Valgus knee deformity is rare in the clinic. The therapeutic effects of artificial knee arthroplasty are worse than varus knee deformity. There is no unified opinion for replacement approach, soft tissue release method and procedure and prosthetic choice at present.
OBJECTIVE:To summarize case data and to observe clinical effects of total knee arthroplasty for valgus knee deformity.
METHODS:Clinical data of 37 cases of valgus knee deformity (42 knees) undergoing total knee arthroplasty, who were treated by the same group of physicians in the First Department of Orthopedics, Gansu Provincial Hospital of Traditional Chinese Medicine from January 2010 to December 2012 were retrospectively analyzed. There were 11 males (13 knees) and 26 females (29 knees), at the age from 56 to 78 years, with an average age of 63.7 years. The differences in range of motion, femorotibial angle and Hospital for Special Surgery knee score were compared before and after replacement. Clinical effects of total knee arthroplasty for valgus knee deformity were evaluated.
RESULTS AND CONCLUSION:The postoperative fol ow-up lasted from 6 to 36 months. Knee joint range of motion increased from preoperative 68.5° to an average of postoperative 108.5°. Femorotibial angle reduced from preoperative 16.82° to postoperative 5.62° on average. The average Hospital for Special Surgery knee score increased from preoperative 39 points to postoperative 88 points (P<0.05). These results suggested that the curative effect of total knee arthroplasty for valgus knee deformity is proved. Total knee arthroplasty is an effective way to improve deformity.

Objective To observe the expression of retinol-binding protein 4 (RBP4) and phosphatidylinositol 3 kinase (PI3K) in insulin resistant (IR) rats and the role of pioglitazone intervention. MethodsThirty-five male Wistar rats in SPF level were randomly divided into control fed with normal diet (n= 11 ) and IR model fed with high fat sucrose diet (HFSD) (n= 24). The IR rats were then randomly divided into two subgroups, namely IR fed with HFSD(n = 12) and pioglitazone intervention (n= 12) given a daily dose of 20 mg · kg 1 · d-1 pioglitazone and HFSD (IR +Pio group )for 8 weeks.All rats were killed after 16 weeks and the levels of serum TG, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), fasting blood-glucose (FBG), fasting serum insulin (FIns) and insulin resistance index (HOME-1R) were measured.Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were employed to detect the level of serum RBP4 and the mRNA expression of RBP4 in the epididymis adipose tissues, respectively. Immunohistochemistry was used to detect the protein expression of PI3K in skeletal muscles while UV spectrophotometer was employed to measure level of serum AOPP. The ratio of visceral fat weight of mesentery, epididymis and peritoneum in abdominal cavity to body weight (BW) was calculated. Results(1) the level of BW, TG, LDL-C, FINS and the ratio of visceral fat weight to BW were higher in IR group than in control group, but HDL-C decreased significantly. After the intervention of pioglitazone, the level of BW,TG, LDL-C, FINS, and the ratio of visceral fat weight to BW in IR+Pio group were lower and HDL-C increased significantly than those in IR group.(2) The level of RBP4 from serum and epididymis adipose and serum AOPP were higher in IR group than in control and lower significantly in IR+Pio group than in IR group (all P＜0.05). (3) The expression of PI3K in skeletal muscles were lower in IR group than in NC group, and increased after the invention of pioglitazone. (4) FIns, the ratio of visceral fat weight to BW and LDL-C were positively correlated with RBP4 while HDL-C and PI3K negatively correlated with RBP4. Conclusions(1) The increased RBP4 can lead to metabolic disturbances and oxidative stress in IR rats.(2) RBP4 may decrease the insulin sensibility by weakening insulin signal transduction. (3) Pioglitazone can ameliorate insulin resistance by decreasing the level of RBP4 and serum AOPP and increasing the level of PI3K in skeletal muscles of IR rats.