ObjectiveTo explore the mechanisms of Astragali Radix-Curcumae Rhizoma （HQ-EZ） in alleviating hypercoagulability and inhibiting tumor growth and metastasis by modulating the formation of neutrophil extracellular traps （NETs） via the complement component 5a （C5a）/C5a receptor （C5aR） pathway. MethodForty male C57BL/6 mice were randomized into four groups： Blank， model， HQ-EZ （8.2 g·kg^-1）， and PMX53 （1 mg·kg^-1）. The mouse model of Lewis lung cancer was established in other three groups except the blank group. Mice were administrated with corresponding drugs from day 3 after modeling. Specifically， the HQ-EZ decoction was administrated for 14 consecutive days， while intraperitoneal injection of PMX53 was implemented on days 3， 6， 9， 12， and 15. Mouse body weight and tumor diameter were measured every two days. On the next day of the last administration， lung microCT was performed to observe the tumor metastasis in vivo. Blood samples were collected from the eyeball after anesthetization， and tumor and lungs were collected after the mice were sacrificed. Tumor weight was measured to calculate the tumor growth inhibitory rate. Enzyme-linked immunosorbent assay was employed to measure the levels of C5a， neutrophil elastase （NE）， citrullinated histone-H3 （Cit-H3）， myeloperoxidase （MPO）， matrix metallopeptidase-9 （MMP-9）， NETs， von Willebrand Factor （vWF）， tissue factor （TF）， and P-selectin in the serum and tumor tissue. Terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling was conducted to assess apoptosis in the tumor tissue. Hematoxylin-eosin staining was conducted to observe lung metastasis， and immunofluorescence （IF） was employed to observe the expression of NETs in the tumor tissue. Western blot was employed to determine the protein levels of C5aR， MPO， and Cit-H3 in the tumor tissue. ResultCompared with the blank group， the model group had nodules in the lung， increased areas with low X-ray transmittance， appearance of nodular foci and multiple hemorrhagic foci in the lungs， and darkening lung color. Furthermore， the modeling elevated the serum levels of C5a， NETs and related proteins， vWF， TF， and P-selectin （P<0.01）. Compared with the model group， HQ-EZ and PMX53 reduced the lung metastases， areas with low X-ray transmittance， and nodules in the lungs and lightened the lung color. Compared with the model group， the two drug intervention groups showed flat tumor growth curves， decreased tumor weight （P<0.01）， increased apoptosis of tumor cells （P<0.01）， lowered levels of C5a， NETs and related proteins， vWF， TF， and P-selectin both in the serum and tumor tissue （P<0.05）， and down-regulated protein levels of C5aR， MPO， and Cit-H3 （P<0.05）. ConclusionHQ-EZ inhibited the expression of NETs by suppressing the C5a/C5aR pathway， thereby alleviating hypercoagulability and inhibiting tumor growth and metastasis.

Objective:To explore the relationship between integrin ɑ3(ITGA3)expression and immune cell infiltration in colorectal cancer(CRC).Methods:Bioinformatic methods were used to analyze ITGA3 mRNA expression in pan-cancer and CRC tissues,as well as its associ-ation with CRC prognosis.The correlation between ITGA3 and tumor-infiltrating immune cells was also investigated.In total,233 cases of CRC diagnosed at Shanxi Provincial Cancer Hospital between January and December 2021 were included,and ITGA3,CD8,CD163,FOXP3,PD-L1,CTLA-4,and PD-1 expression in CRC tissues were determined by immunohistochemistry(IHC)to analyze the relationship between ITGA3 and infiltrating immune cells and immune checkpoints.Results:Bioinformatics analysis showed elevated ITGA3 mRNA levels in CRC.High ITGA3 expression was associated with PFS(P＜0.05).Univariate and multifactorial analyses showed that age and stage were significantly cor-related with prognosis(P＜0.05).In addition,ITGA3 upregulation was closely correlated with multiple immune cell infiltration levels in CRC.Furthermore,IHC results showed that ITGA3 expression in CRC tissues was significantly higher than that in adjacent normal tissues(P＜0.05).ITGA3 expression was associated with lymph node metastasis(P＜0.05)and correlated with the expression of immune markers,such as CD8+T-cells,PD-L1,and CTLA-4(P＜0.05).Conclusions:ITGA3 is highly expressed in CRC,which is closely related to immune cell infiltration and may regulate the tumor immune microenvironment,which provides a new idea for clinical treatment and a potential new independent predictive marker.

Acute kidney injury(AKI)is a very common critical disease worldwide, especially in pediatric intensive care unit(PICU). There are many pathogenic factors for AKI, among which sepsis is essential to the development of AKI.Sepsis-associated acute kidney injury(SA-AKI) often have sudden onset and poor prognosis.Because there is still a lack of powerful diagnostic tools, resulting in clinical intervention in SA-AKI often lags behind.Therefore, awareness of SA-AKI risk and early identification of injury severity, as well as timely initiation of supportive treatment, remain the main contents of current research.There are hundreds of new biological markers and diagnostic tools for early identification and prognosis of AKI.This review introduced the progress on diagnosis of SA-AKI.The aim is to improve clinicians′ understanding of SA-AKI.

Objective:To investigate the relationships between hyperuricemia and the incidence risk for cardiometabolic abnormity in children.Methods:Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected through stratified cluster sampling at baseline survey. Follow-up investigation was conducted in 2019. Logistic regression model was used to analyze the relationships of uric acid quartiles and change in uric acid levels with incidence risks for cardiometabolic abnormity (hypertension, hyperglycemia and dyslipidemia).Results:A total of 8 807 children (4 376 boys, 4 431 girls) were included in the analysis, the average age of the children was (11.1±3.3) years at baseline survey. The adjusted odds ratios ( ORs) and 95% confidence intervals ( CIs) of incidence risk for hypertension in the third and fourth quartiles of the UA were 1.39 (1.11-1.75) and 1.56 (1.19-1.81), respectively. The ORs and 95% CIs of risk for high LDL-C in the second, third and fourth quartiles were 1.88 (1.16-3.05),1.98 (1.23-3.17) and 2.25 (1.42-3.57). The uric acid level increased by one standard deviation, the risk increased by 17% for hypertension and 27% for high LDL-C. The uric acid level increased by 10 μmol/L, the risk increased by 2.1% for hypertension and 2.9% for high LDL-C. The gender-stratified analysis showed that the similar results. The ORs and 95% CIs were 1.32 (1.09-1.60) and 1.50 (1.05-2.16) for hypertension, 1.90 (1.38-2.60) and 2.96 (1.58-5.52) for high TC, 1.78 (1.26-2.51) and 2.84 (1.60-5.03) for high LDL-C in the groups of newly diagnosed hyperuricemia and persistent hyperuricemia. Conclusions:Higher uric acid level was associated with increased incidence risks for hypertension, abnormal TC and LDL-C. Maintaining optimal uric acid level by children might contribute to the early prevention of cardiovascular diseases.

Objective To evaluate the therapeutic effect of hepatocyte growth factor(HGF) gene modified placenta-derived mesenchymal stem cells( PMSCs) on limb ischemia in a rabbit model.Methods The placental tissue was digested with enzyme, cultured and passaged.The PMSCs were characterized by surface marker expression.These cells were infected with adenoviral( Ad)-HGF and intramuscular injected for treatment of limb ischemia in a rabbit model.The blood supply of the limb was detected by digital subtraction angiography ( DSA ) and the vessel number was evaluated in histopathological HE staining.Results The results showed that Ad-HGF gene transduction increased the vascular endothelial growth factor ( VEGF ) , basic fibroblast growth factor, bFGF ( bFGF ) and HGF expression in PMSCs. Transplantation of HGF-transduced PMSCs resulted in the increase in vessel density and improvement of blood supply in the rabbit limb ischemia model.Conclusion The therapeutic effect of HGF gene engineered PMSCs on ischemia by enhancing angiogenesis in a rabbit model is evaluated.Transplantation of PMSCs with HGF gene therapy may be a promising strategy for the treatment of ischemia diseases.

Objective To compare the outcomes of in-vitro maturation (IVM) and in-vitro fertilization (IVF) after early follicular phase gonadotropin-releasing hormone agonist (GnRH-a)down-regulation in infertile patients with polycystic ovary syndrome (PCOS).Methods From July 2010 to December 2012,72 infertile patients with PCOS undergoing assisted reproductive technology treatment in the Affiliated First Hospital of Wenzhou Medical University were enrolled in this study.The patients were divided into 2 groups,which were patients with early follieular phase down-regulation IVM (36 cases) at IVM group and early follicular phase down-regulation long protocol IVF (36 cases) at IVF group.The laboratory parameters and clinical outcomes were compared between two groups.Results (1) Lab parameters:a total of 442 oocytes were retrieved in group IVM,and 560 were in group IVF.The rate of mature oocytes of 83.8％ (469/560) and high-quality embryos of 70.9％ (212/299) at group IVF were significantly higher than that of group IVM [54.1％ (239/442) and 50.7％ (73/144),retrospectively,P ＜0.01].In group IVM,the average duration of gonadotropin (Gn) was (2.8 ± 1.5) days and the average dosage of Gn was (285 ± 169) U,which were significantly lower than (11.0 ± 1.0) days and (1499 ±165) U in group IVF (P ＜0.01).The mean number of oocytes retrieved 12.8 ± 2.5,fertilization rate of 64.8％ (155/239),and implantation rate of 31％ (23/74) in group IVM and 15.6 ±3.1,65.5％ (307/469),31％ (23/74) in group IVF,which did not reach statistical difference (P ＞0.05).(2) Clinical outcomes:the clinical pregnancy rate (17/31,55％) of IVF group was not significantly higher than that 44％ (14/32) at IVM group (P ＞ 0.05).The abortion rate was 1/17 at Group IVF and 1/14 in group IVM,which did not show statistical difference.Women at IVM group has no ovarian hyper-stimulation syndrome (OHSS) cycle,group IVF has 31％ (11/36) cycles presented moderate and severe OHSS.Conclusions Infertile patients with PCOS undergoing IVM and IVF treatment after early follicular phase GnRH-a down-regulation can get satisfactory laboratory and clinical outcome.In addition to short treatment cycle,IVM can also avoid the occurrence of OHSS completely,but it has a rising trend in the abortion rate.IVF has a high incidence of OHSS,meanwhile,it increases the dosage of gonadotropins.

ObjectiveTo compare clinical and laboratory outcomes of in vitro maturation (IVM) with in vitro fertilization-embryo transfer (IVF-ET) in treatment of infertility associated with polycystic ovary syndrome (PCOS).MethodsFrom Jan.2007 to Dec.2010,infertile patients with PCOS underwent 701 cycles in First Affiliated Hospital of Wenzhou Medical College were studied retrospectively.Those were divided into 293 cycles of IVM group and 408 cycles of IVF/intra-cytoplasmic sperm injection ( ICSI ) group.The average transplantation rate,mean number of retrieval oocytes,maturation rate,fertilization rate,cleavage rate,high quality embryo rate,embryo implantation rate,pregnancy rate per transfer,pregnancy outcomes and incidence of ovarian hyperstimulation syndrome (OHSS) of the two methods of treatment were compared between two groups.ResultsThere were 275 cycles in IVM group and 342 cycles in IVF/ICSI group established embryo transfer.The transplantation rate was 93.9％(275/293)in IVM group and 83.8％ (342/408) in IVF/ICSI,which reached statistical difference (P ＜ 0.01 ).The maturation rate of 56.64％,cleavage rate of 88.08％,high quality embryo rate of 38.72％ and embryo implantation rate of 17.8％ in IVM group were significantly lower than 91.09％,94.91％,51.50％ and 25.4％ in IVF/ICSI group (all P ＜ 0.01 ).The clinical pregnancy rate per transfer were 37.8％ (104/275) in IVM group and 44.2％ (151/342) in IVF/ICSI group,which did not show statistical difference (P＞0.05).The mean number of oocytes ( 12.9 ±6.5 vs.12.9 ±7.9) and fertilization rate (76.52％ vs.70.75％ ) didn't show significant difference between IVM group and IVF/ICSI group ( P ＞ 0.05 ).The 21.3％ ( 87/408 ) cycles presented mild to moderate OHSS and 2.0％cycles(8/408)presented severe OHSS in IVF/ICSI group.While,no OHSS cycles were observed in IVM group.Conclusion IVM could get similar clinical pregnancy rates compared with IVF/ICSI in patient with PCOS,however,it can avoid occurrence of OHSS.

Objective To observe the clinical effect of the club exercise designed ourselves on the prevention of should-hand syndromeafter stroke. Methods 100 stroke patients in early stage, whose motor function of upper limb were lower than Grade Ⅲ evaluated byBrunnstrom assessment and without shoulder pain and swelling of hand, were randomly divided into control group (n=50) and observationgroup (n=50). All of them received routine rehabilitation therapy, and the observation group received club exercise in addition. The incidenceof shoulder pain, the active range of motion of shoulder, the motor function of upper limb and activities of daily living (ADL) of 2groups were evaluated before and 2 courses (60 d) after treatment. Results There was no statistical difference between 2 groups before thetreatment (P>0.05). After 2-course treatment, the incidence of shoulder pain was significantly lower in the observation group than in the controlgroup (P<0.001), the active range of motion of shoulder, motor function of upper limb and ADL were significantly better in the observationgroup than in the control group (P<0.001). Conclusion The club exercise can prevent the pain of shoulder joint, increase the activerange of motion of shoulder joint and improve the motor function of upper limb and ADL in patients after stroke.

Objective To establish a stable and efficient method of culturing imDCs in vitro,and to explore the effect of GW5074, which blocks ERK1/2 signal pathway in the process of imnature dentritic cells (imDCs) on inducing differentiation of the na(i)ve allogeneic CD4+ T cells into Treg cells in vitro. Methods The imDCs and mature DCs (mDCs) were isolated and cultured from the peripheral blood mononuclear cells (PBMC) derived from a healthy adult male volunteer, and they were identified by cell morphology, cell surface marker and cell functions respectively. Na(i)ve CD4+ T cells were isolated from newborn umbilical vein blood and were divided into 5 groups to be cultured: (1) Blank control group: Na(i)ve CD4+ T cells were cultured alone;(2) Positive control group: The irrDCs were Middle-concentration GW5074 group;(5) High-concentration GW5074 group. In the last three groups, imDCs and na(i)ve CD4+ T cells were co-cultured, the same as the positive control group, but these groups were added by GW5074 dilution at the concentrations of 8, 24, and 40μmol/Lrespectively. After co-culture for 5 days, the transformation ratio from naive CD4+T cells to Treg T cells was detected by flow cytometry. Results On the surface of imDCs, there was stronger pression of CD1a, but weaker expression of CD80 and CD83. On the contrary, on the surface of mDCs, there was weaker expression of CD1a, but stronger expression of CD80 and CD83. The stimulation index in imDCs group and mDCs group was 1.12±0.03 and 2.85±0. 07 respectively. The transformation ratio of Treg T cells in blank control group, positive control group, low-concentration GW5074 group, middle-concentration GW5074 group and high-concentration GW5074 group was (5. 81±1.36)%, (35.73±2.07)%, (22.53±2.11)%, (11.55±1.73)%, and (4.97±1.83)%respectively. One-way ANOVA analysis revealed that there was no significant difference between high-concentration GW5074 group and blank control group, P＞0. 05, but significant difference between the remaining groups, P＜0.01. Conclusion High purity of imDCs can be obtained from PBMC by induction with rhGM-CSF and rhIL-4. ERK1/2 signal pathway plays a role in inducing the immune tolerance. GW5074 can inhibit differentiation of na(i)ve CD4+ T cells into Treg T cells.

Objective To evaluate physiologic ability and surgical stress (E-PASS) for predicting postoperative complications in patients undergoing elective colonic surgery. Methods The clinical data of 158 patients with colonic cancer who were admitted to the West China Hospital from August to October, 2009 were retrospectively analyzed. E-PASS was applied to evaluate the surgical risk. Three indexes of the E-PASS system,including preoperative risk score (PRS), surgical stress score (SSS) and comprehensive risk score (CRS) were compared with actual postoperative outcomes. Correlation between PRS, SSS, CRS and postoperative risks was analyzed using multiple linear regression analysis. Results Of the 158 patients, 27( 17.1% ) had postoperative complications, and the predictive value was 19.4% ± 2.0% according to the E-PASS. Dukes stages, physical performance indexes, severe heart disease, severe pneumonia disease, length of operation time were correlated with the incidence of complications (r = 0. 193, 0. 410, 0. 183, 0. 174, 0. 198, P ＜ 0.05). PRS, CRS and SSS had good predictive effect on postoperative risks (r = 0. 299, 0. 349, 0. 183, P ＜ 0. 05 ). Conclusions E-PASS system is a relatively simple, fast and user friendly tool for predicting the risk of short-term postoperative complications.