Objective:To analyze expression and models of CD39,CTLA-4,and PD-1 on T cells,to investigate effect of cyclic adenosine monophosphate(cAMP)on their expressions,and to analyze key pathways regulating their expressions.Methods:Small molecules such as adenylate cyclase(ACs)activators,phosphodiesterase(PDE)inhibitors,protein kinase A(PKA)inhibitors and PKA-CREB inhibitors were used to stimulate rhesus macaque peripheral blood mononuclear cells in vitro,and changes in ratios of CD39,CTLA-4,and PD-1 positive(CD39+,CTLA-4+,and PD-1+)T cells were detected by flow cytometry,and to analyze their expression patterns,and effects of small molecules on ratio of positively expressing/co-expressing cells were compared to clarify expres-sion patterns and molecules and pathways that regulated expression.Results:Normal macaque CD4+T and CD8+T cells had low ratios of CD39+,CTLA-4+,and PD-1+cells,and positive cells predominantly expressed only one of these molecules.Increasing intracellular cAMP levels did not affect CD39+T cell ratio,significantly increased CTLA-4+T cell ratio,and decreased PD-1+CD8+T cell ratio,involving cell populations with mono expression of CTLA-4 and PD-1.Inhibition of PKA activity reduced potentiation of CTLA-4 expression by broad-spectrum PDE inhibitor,3-isobutyl-1-methylxanthine(IBMX),but did not affect PD-1 expression.Exchange protein activated by cAMP did not affect CTLA-4 expression but downregulate PD-1+CD4+/CD8+T cells ratio.Upregulation of CTLA-4 by PDE4B selective inhibitors was similar to IBMX,while regulation of PDE3 and PDE5A selective inhibitors on PD-1 expression was similar to IBMX.Conclusion:CD39,CTLA-4 and PD-1 have different expression models on T cells but are differentially regulated by cAMP levels and have different cAMP downstream signal pathways involved in expression regulation.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

Objective:To explore the impact of intradialytic hypotension (IDH) on brain component volume, as well as its relationship with depression and cognitive function changes in maintenance hemodialysis patients.Method:It was a cross-sectional observational study. Clinical data of 119 patients under maintenance hemodialysis in Peking Union Medical College Hospital from July 2013 to July 2014 were collected, retrospectively. Patients were divided into IDH group and non-IDH group. 3.0T Magnetic resonance imaging examination of the head for all patients was completed and the results of volume analysis of each component of the brain were extracted. Cognitive function was assessed by the Chinese version of the simplified mental state examination scale (C-MMSE) and the Chinese version of the Montreal cognitive assessment scale (C-MoCA). Depressive status was assessed by the Hamilton depression scale 17 (HAMD_17) and living ability was assessed by the Alzheimer's disease collaborative study-daily living ability assessment questionnaire. In addition, the Philadelphia word learning test was used to measure memory, the Boston naming test to measure language, the connection test A and B to measure executive ability, and the Stroup test C to measure attention. The differences in brain component volume, cognitive function, emotion, and life ability between two groups of patients were compared, and the correlation between IDH and brain component volume was explored by regression analysis.Result:A total of 119 patients were included in this study, of whom 22 (18.5%) had hypotension during dialysis. The volumes of amygdala, cuneiform lobe, and posterior cingulate gyrus in IDH group were significantly smaller than those in the non-hypotension group [ (1.6±0.2) mm 3vs. (1.7±0.2) mm 3, t=2.674, P=0.009; (6.9±0.8) mm 3vs. (7.4±1.0) mm 3, t=2.187, P=0.031; (6.9±0.8) mm 3vs. (7.4±0.9) mm 3, t=2.252, P=0.024]. The differences of gray matter, white matter volume between the two groups showed a similar trend but did not reach statistical significance. And lacunar infarction and cerebral microbleeds were more common in IDH group. The daily living ability scores of the two groups were similar (65.51±11.52 vs. 65.71±11.53, Z=-0.456, P=0.648). The proportion of patients with cognitive abnormalities was higher in the IDH group, without statistical significance. The proportion of depression was similar. Univariate linear regression analysis showed that IDH was significantly negatively correlated with the volume of amygdala, cuneiform cortex, and posterior cingulate gyrus, which control emotions in the brain ( B=-0.117, 95% CI -0.203--0.030, P=0.009; B=-0.484, 95% CI -0.923--0.046, P=0.031; B=-0.485, 95% CI -0.911--0.058, P=0.026). After multivariate adjustment, decreased amygdala volume was still correlated with IDH ( B=-0.111, 95% CI -0.198--0.025, P=0.026). Conclusion:Recurrent IDH may lead to atrophy of various brain components, which may be one of the reasons for cognitive and emotional changes in maintenance hemodialysis patients.

In recent years, immune checkpoint inhibitors (ICIs) have greatly improved the survival rate of non-small cell lung cancer (NSCLC) patients without driver mutation. Compared with wild-type tumors, tumors with epidermal growth factor receptor (EGFR) mutations have greater heterogeneity in immune microenvironment characteristics such as programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB). Whether ICIs is suitable for NSCLC patients with EGFR mutation has been controversial. Clinical studies have shown that immunomonotherapy has no significant effect on patients with EGFR mutant NSCLC. ICIs combined with chemotherapy and antiangiogenic drugs show good survival benefits. This paper overviews the clinical research and related mechanism of ICIs single drug or combination therapy inadvanced NSCLC patients with EGFR mutation.
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B7-H1 Antigen/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology* ; ErbB Receptors/metabolism* ; Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Ligands ; Lung Neoplasms/pathology* ; Mutation ; Tumor Microenvironment

Objective: To discuss the effects of acupuncture plus Tuina (Chinese therapeutic massage) in intervening the mental development, motor function, cerebral hemodynamics, and muscle tone in kids with spastic cerebral palsy (CP). Methods: A retrospective analysis was conducted on 87 kids with spastic CP. They were divided into a control group and an observation group based on their original treatment plan. Kids in the control group received symptomatic treatment, motor development therapy, and Tuina treatment. The observation group was additionally given acupuncture treatment. One month was taken as a treatment course. After six courses, the efficacy, change in muscle tone, mental development, gross motor function, fine motor function, and the systolic velocity (Vs), mean velocity (Vm), and pulsatility index (PI) of the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) were compared between the two groups. Results: After treatment, the muscle tone score dropped in both groups (P<0.05) and was significantly lower in the observation group than in the control group (P<0.05). The observation group achieved more significant efficacy than the control group (P<0.05). After the intervention, the mental development index (MDI), psychomotor development index (PDI), gross motor function measure (GMFM) score, and fine motor function measure (FMFM) score all increased in both groups (P<0.05) and were notably higher in the observation group than in the control group (P<0.05). After treatment, the Vs and Vm of the ACA, MCA, and PCA were markedly higher in the observation group than in the control group (P<0.05), and the observation group was significantly lower than the control group comparing the PI of the ACA, MCA, and PCA (P<0.05). Conclusion: Based on the symptomatic treatment and motor development therapy, Tuina and acupuncture treatment can effectively treat spastic CP children, manifesting as reducing muscle tone, boosting mental development, and improving motor function and cerebral hemodynamics.

Objective:Objectives To introduce the preliminary experience of flexible vacuum-assisted ureteral access sheath(FV-UAS) in the treatment of upper urinary calculi in retrograde intrarenal lithotripsy(RIRS).Methods:The clinical data of 11 patients with upper urinary calculi who were treated in Jiangxi Provincial People's Hospital from August to September 2021 were analyzed retrospectively. There were 6 males and 5 females, with the mean age of 48 years (32-72 years), the mean size of stone of 15.5 mm (11-20mm), and the mean stone volume of 1 958 mm3 (1 108-4 036 mm3), including 1 case with upper ureteral calculi, 10 cases with renal calculi, and 2 cases with calculi in multiple renal calyces. Ureteral stents were placed in 2 cases preoperatively. There were 2 cases of grade Ⅱ hydronephrosis according to Grignon classification. All patients were treated by retrograde intrarenal lithotripsy, and the FV-UAS(F12/14) was used during the operation. FV-UAS can be passively bent(>90°) with the bending of the flexible ureteroscopy(f-URS), and connect vacuum suction devices. The method of placing the FV-UAS during the operation was the same as traditional ureteral access sheath. The FV-UAS should be as close to the target stone as possible by the f-URS during the operation. F6 ureteral stent was routinely indwelled for 2-4 weeks. The operation time, postoperative complications, and stone volume clearance rate were summarized and analyzed, and stone volume clearance rate was calculated as(1-residual stone volume/preoperative stone volume)×100%. The stone volume was obtained by CT 3-D reconstruction preoperatively and first day postoperatively.Results:All patients underwent RIRS successfully at the first stage, with the usage of FV-UAS(F12/14)during the operation. The mean operation time was 57.1 minutes(34-90 minutes), and the mean stone volume clearance rate was 98.9%(94.8%-100.0%)on the first day postoperatively. Seven cases reached 100.0% stone-free rate, and 4 cases presented residual calculi. The mean hemoglobin drop was 0.8 g/L, and 1 case presented vomiting without fever on the first day postoperatively. For the 4 cases with residual calculi, no residual stone was found by B-ultrasound when the ureteral stent was removed.Conclusions:Our preliminary study found that it is feasible and safe to use FV-UAS in RIRS, which can follow the f-URS to extend into the renal pelvis and renal calyces. Vacuum-assist can increase the probability of stone-free.

In the past 20 years, with the development of molecular biology, the treatment of non-small cell lung cancer (NSCLC) has been developing. Targeted therapy has improved the survival period of patients with positive mutation of tumor driver gene. More and more targets have been found gradually. Drugs targeting different driving genes have brought the treatment of NSCLC into a promising target era. Among the many driving genes of NSCLC, the fusion of transfection proto oncogene (RET) is the addition of the epidermal growth factor receptor (EGFR), analytic lymphama kinase (ALK) and c-ros oncogene 1-receptor tyrosine kinase (ROS1) are emerging targets. Targeted drugs for RET gene fusion have been constantly updated. Recently, new high selective RET inhibitors blu-667 and loxo-292 have made important breakthroughs. This paper will review the review of the fusion mutation of RET gene in NSCLC, the detection methods, clinicopathological characteristics, targeted treatment and the research progress after drug resistance.
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Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd

"Liquid biopsy" have been intensively studied in recent decades. The exosomes carry their maternal partial functional proteins and genes. As a form of intercellular vesicular transport, exosome-mediated intercellular communication participates in a variety of physiological and pathological processes. The information transmission mediated by exosomes is associated with pathophysiological status and plays an important role in the pathogenesis of cancer. Their detection may be beneficial for the diagnosis and treatment of tumor. This article reviews advances in knowledge on the exosome properties, the effect of exosomes on malignant tumorigenesis, and their clinical application. The data will provide a reference for clinical practitioners.

Objective:To observe the effects of Xiaoqinglong Decoction and Tingli-Dazao-Xiefei Decoction in treating chronic heart failure with syndrome of cold phlegm obstructing lung. Methods:Eighty-six chronic heart failure patients from January of 2017 to December of 2018 in our hospital who met the inclusion criteria were selected and divided into 2 groups according to the random number table method with 43 patients in each group. The control group was treated with conventional therapy, and the observation group was orally treated with Xiaoqinglong Decoction and Tingli-Dazao-Xiefei Decoction. Both groups were treated for 3 months. Then scored the symptoms of cold phlegm obstructing lung from four aspects: palpitations, cough and asthma, uria and edema, and sputum. The ultrasonic cardiogram was used to detect the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF). The ELISA method was used to measure levels of vascular pseudohemophilia factor (vWF),endothelin-1 (ET-1) and serum levels of total antioxidant capacity (TAC), lipid peroxide (LPO), SOD, MDA. The efficacy was evaluated. Results:The total effective rate of the observation group was 90.7% (39/43), significantly higher than that of the control group as 69.8% (30/43), and the difference between the two groups was statistically significant ( χ2=4.692, P=0.030). After the treatment, scores of palpitation, cough and asthma, urine and sputum in the observation group were obviously lower than those of the control group ( t value were 7.621, 7.033, 6.831, 6.635, respectively, all Ps<0.01); the LVEDD (51.41 ± 5.69 mm vs. 58.49 ± 6.77 mm, t=9.809), LVESD (40.04 ± 4.48 mm vs. 43.25 ± 5.21 mm, t=6.776) of the observation group were significantly lower than that of the control group, and while LVEF (50.16% ± 5.89% vs. 45.87% ± 5.16%, t=7.761) was significantly higher than that of the control group ( P<0.01). Plasma levels of vWF (103.55% ± 11.98% vs. 138.11% ±15.71%, t=41.453) and ET-1 (67.05 ± 7.18 pg/ml vs. 81.72 ± 10.03 pg/ml, t=18.990) in the observation group were significantly lower than that of the control group ( P<0.01). The serum levels of TAC and SOD levels in the observation group were significantly higher ( t value were 4.662, 13.331, respectively, all Ps<0.01), while LPO and MDA levels were significantly lower than the control group ( t value were 4.982, 4.031, all Ps<0.01). Conclusions:The Xiaoqinglong Decoction and Tingli-Dazao-Xiefei Decoction in treating chronic heart failure can improve the heart function and symptoms with syndrome of cold phlegm obstructing lung, and increaseclinical efficacy.