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Src homology phosphotyrosyl phosphatase 2 (SHP2) is a protein tyrosine phosphatase encoded by PTPN11, which catalyzes the dephosphorylation of protein tyrosine. As a convergence node, SHP2 mediates multiple signaling pathways such as rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular regulated protein kinases (ERK), phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT), janus kinase (JAK)-signal transducer and activator of transcription (STAT) and programmed death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1). It can not only regulate the growth and proliferation of tumor cells, but also mediate the immune escape of tumor cells by influencing the tumor microenvironment. Given its dual biological functions in tumor immune regulation, SHP2 is a promising target for cancer immunotherapy. To date, several SHP2 allosteric inhibitors have been advanced into clinical trials for tumor immunotherapy with single or combination therapeutic strategies. Additionally, SHP2 activators also showed therapeutic potential in the field of tumor immune modulation. In this paper, we reviewed the dual function of SHP2 in both tumor and immune cells. Besides, the challenges and prospects of SHP2 modulators in cancer immunotherapy were also briefly discussed, aiming to explore new horizon of SHP2 modulators for tumor immunotherapy.
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Objective To develop an indicator system for the ability of main caregivers of premature in Neonatal Intensive Care Unit (NICU). Methods Delphi method was used to design index system and 16 experts were invited to participate the study. The questionnaire was consulted by emails and we took two rounds of consultation. Results The two rounds of consulting experts enthusiasm coefficients was 100% and the overall authority coefficients was 0.813 and 0.819. In the evaluation index system, there were 8 first grade indexes and 42 second grade indexes, including 11 items of basic care ability , 6 items of feeding and nutrition, 5 items of early itervention, 8 items of common symptoms and sign, 1 item of emergency, 5 items of safety prevention, 4 items of special care and 2 items of parentage. Conclusions The ability of main caregivers of premature in NICU evaluation index system which is designed using Delphi method is scientific and reliable. The results would have important significance to evaluate the level of main caregivers of premature in NICU.
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BACKGROUND: Caspofungin, a novel echinocandins systemic antifungal agent, has been shown to exert broad-spectrum antibacterial effect on deep fungal infections, which is superior to or equivalent with the role of amphotericin B, but there is no report on its application for preventing fungal infection after renal transplantation.OBJECTIVE: To analyze the difference in high risk factors of fungal infection after kidney transplantation using donation after cardiac death donors and living-related donor kidney transplantations, and to explore the feasibility and safety of caspofungin to prevent fungal infection after kidney transplantation using donation after cardiac death donors.METHODS: This was a prospective, single-center, controlled trial finished at the Department of Kidney Transplantation,the First Affiliated Hospital of Zhengzhou University, Henan Province, China. Totally 188 patients undergoing primary kidney transplantation without history of fungal infection and use of antifungal drugs between January 2012 and August 2013 were enrolled, including kidney transplantation with donation after cardiac death donors (n=102, trail group), and kidney transplantation with living-related donors (n=86, control group). The CYP3A5 genotype was determined preoperatively. All patients received tacrolimus+mycophenolate mofetil+prednisone triple immunosuppression after transplantation. The trial group was subjected to caspofungin therapy for 2 weeks. The risk factors for fungal infection in the two groups were compared, and the effects of caspofungin on the tacrolimus concentration, tacrolimus concentration/dose were detected in the recipients with same CYP3A5 genotype recipients at 1 and 2 weeks, and 1, 3 and 6 months postoperatively. The liver and kidney function, adverse events and fungal infections were recorded at different time points. This trial was registered with the Chinese Clinial Trial Registry (Regitration number:ChiCTR-OON-17013342).RESULTS AND CONCLUSION: The survival rate of patient/kidney was 98.4% and 97.3% respectively, 97 cases in the trial group and 86 controls competed 6-month follow-up. Preoperative hemodialysis time, hemoglobin value, cold ischemia time, warm ischemia time, intraoperative blood transfusion volume, time of central venous catheter kept in situ,methylprednisolone usage, ATG usage, serum creatinine reduced level at 1 week, thrombocytopenia and duration of postoperative body temperature > 38 ℃ were the risk factors for fungal infection in the trail group relative to the control group. The fungal infection rate in the trial and control groups was 0% and 2.3%, respectively, at 6 months of follow-up.The serum creatinine level in the trail group was significantly higher than that in the control group at 1 month postoperatively (P < 0.05), and the level showed no significant difference between two groups at other time points (P >0.05). After 2 weeks of caspofungin treatment, the concentrations of tacrolimus and tacrolimus concentration/dosage did not differ significantly in different CYP3A5 genotype recipients (P > 0.05). Caspofungin might induce some adverse reactions, especially electrolyte disturbance with an incidence of 21.6%, but there was no significant difference between two groups (P > 0.05). These findings imply that kidney transplantation using donation after cardiac death donors presents with various risk factors for fungal infection compared with living-related donor kidney transplantation.Furthermore, caspofungin is effective and safe for preventing fungal infection and has no effect on tacrolimus concentration; therefore, it can be used as a new anti-fungal agent after kidney transplantation.
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Wuzhuyu Tang is a classical formula for treating migraine, but its' pharmacological ingredients is unclear yet. Present study employed the everted intestinal sac model to collect the absorption samples of 10 kinds of Wuzhuyu decoction, and then analyzed the contents of 9 ingredients in Wuzhuyu Tang and absorption samples quantitatively or semi-quantitatively by HPLC-DAD method. Reserpine was used to establish the mice model of migraine, and then the contents and activities of 5-hydroxytryptamine, noradrenaline, dopamine, nitric oxide and nitricoxide synthase in brain tissues and serums were determined respectively after oral administration of Wuzhuyu Tang. Using the partial least squares regression method to correlate the total absorption quantity of 9 ingredients and pharmacodynamics. The result shows that limocitrin-3-O-beta-D-glucoside, ginsenoside Rg1 and Rb1, rutaevine, limonin, evodiamine and rutaecarpine are the main ingredients influenced the effects in absorption samples in everted intestinal sacs, especially ginsenoside Rg1, rutaevine, evodiamine and rutaecarpine among them have obvious improving effects to most pharmacodynamics index, might be the pharmacological ingredients influenced the therapeutical effects of Wuzhuyu Tang treating migraine.
Subject(s)
Animals , Female , Male , Mice , Rats , Drugs, Chinese Herbal , Pharmacology , Intestinal Absorption , Intestines , Mice, Inbred ICR , Migraine Disorders , Drug Therapy , Rats, WistarABSTRACT
<p><b>BACKGROUND</b>Partial nephrectomy is currently the standard treatment for clinical T1 renal neoplasms, as it can provide oncologic outcomes equivalent to radical nephrectomy. The aim was to evaluate the efficacy of self-retaining suture (SRS) in renorrhaphy technique in retroperitoneal laparoscopic partial nephrectomy (LPN) for a single renal mass of moderate or high complexity by assessing peri-operative outcomes.</p><p><b>METHODS</b>A retrospective analysis was done of 64 patients between 2010 and 2012 for complex renal mass (RENAL score ≥ 7) in whom retroperitoneal LPN was performed with two layers using continuous knotless barbed suture (Quill PDO SRS group; n = 34) and absorbable vicryl (non-SRS group; n = 30), respectively. Cases were matched for RENAL score. All the surgical procedures were performed by the same surgeon with experience of more than 500 cases of LPN. Comparisons were made in patients and preoperative outcomes and peri-operative complications between SRS group and non-SRS group.</p><p><b>RESULTS</b>Mean warm ischemia time (WIT) in SRS group was less than non-SRS group (18.0 vs. 24.8 minutes, P = 0.021). Renorrhaphy suture cost in SRS group was lower than non-SRS group ($269.6 vs. $335.8, P = 0.001). There were no significant differences between the two groups for postoperative changes in creatinine and estimated glomerular filtration rate and the rate of peri-operative complications.</p><p><b>CONCLUSION</b>SRS was safe for complex renal tumor with two layers, continuous and unknot suture, during LPN and would reduce the WIT and renorrhaphy suture cost significantly.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Kidney , Pathology , General Surgery , Kidney Neoplasms , General Surgery , Nephrectomy , Retrospective Studies , Suture Techniques , Warm IschemiaABSTRACT
<p><b>OBJECTIVE</b>To explore the associations between sugar-sweetened beverage (SSB) consumption and obesity as well as obesity-related cardiometabolic disorders among children in China.</p><p><b>METHODS</b>A total of 6974 (boys 3558, girls 3412) children aged 6-13 years participated in the study. Each participant's height, weight, waist circumference, fasting glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. The type of beverage consumption was determined using a self-administered questionnaire.</p><p><b>RESULTS</b>SSBs were consumed regularly by 46.1% of the children. The prevalence [adjusted odds ratio (95% confidence internal (CI)] of obesity was 7.6% [as the reference group (ref.)], 10.1% [1.36(1.07, 1.74)], and 11.6% [1.46(1.21, 1.75)], among children who regularly drank milk, other beverages and SSBs, respectively. Regularly drinking SSBs elevated the likelihood of abdominal obesity [adjusted odds ratio (95% CI): 1.36 (1.17, 1.59)]. The prevalence [adjusted odds ratio (95% CI)] of obesity among children who regularly drank sports/caloric beverages, carbonated beverages, sweet tea, and plant protein beverages was 16.8% [2.00(1.31, 3.07)], 12.7% [1.52(1.23, 1.88)], 11.5% [1.52(1.18, 1.95)], and 10.4% [1.41(1.03, 1.94)], respectively, which was higher than that of regular milk drinkers [7.6 % (ref.)]. The prevalence [adjusted odds ratio (95% CI)] of abdominal obesity among children who regularly drank sweet tea, fruit/vegetable juices, and carbonated beverages was 17.7% [1.55(1.26, 1.90)], 16.2% [1.36(1.09, 1.70)], and 15.3% [1.24(1.03, 1.50)], respectively, which was much higher than that of regular milk drinkers [12.8% (ref.)].</p><p><b>CONCLUSIONS</b>Regular SSB consumption was positively related to obesity and abdominal obesity. This relationship should be investigated further using a longitudinal study design.</p>