Radiation could induce DNA damage,cell death,and changes of tumor phenotype and tumor microenvironment leading to the regulation of immune response.Immune checkpoint signaling pathways are involved in the immune tolerance of anti-microorganism responses and thus limit tissue damage.In the anti-tumor immune response,these pathways are associated with anti-functional activation of specific cytotoxic T cells and also enhance the inhibition effect of immune response,which always result in immune escape.Blockade of the immune checkpoint signaling pathways benefits to the anti-tumor inmune responses and could delay tumor progress.As a result,the combination treatment of radiotherapy and immune checkpoint biockade has attracted more attentions in clinical application.This paper reviews the recent research progresses in the radiation effect of immune system,the regulation of immune checkpoints and the combination treatment of radiotherapy and immune checkpoint blockade in tumor therapy,trying to arouse some new clues in cancer therapy.

Aim To explore the mechanisms of action (MOA) of synergistic anticancer function in the combination of berberine and evodiamine.Methods We first analyzed the action of suppression in the drug combination from the cell level and validated the dose scope as well as ratio of concentration in synergistic effects of drug combination.Then, the miRNA chip of liver cancer cell BEL-7402 under different treatment was analyzed.By building the miRNA-mRNA network, the MOA of the synergistic drug combination was illustrated.Results Berberine and evodiamine used in combination could significantly synergistically suppress the proliferative ability of liver cancer cells.The special differentially expressed miRNAs (DEmiRNAs) mainly participated in some cancer proliferation-related pathways and biological processes, such as MAPK signaling pathway, endocytosis pathway and insulin signaling pathway.The special target genes influenced by the drug combination not only covered three kinds of membrane receptors, but also took part in the regulation of downstream pathways.Conclusions From the regulation of miRNAs, it is clear that berberine may play a primary role in the synergistical suppression activity of the drug combination in cancer cells.The discovery of synergistic MOA in the combination of berberine and evodiamine from the miRNA level will provide a new guidance to explore more synergistic drug combinations in the future.

Objective To explore the effect of CD40 small interfering RNA(siRNA)on the expressions of pe-ripheral blood interleukin(IL)-21 and IL -35 in rats with experimental autoimmune myocarditis (EAM)and its sig-nificance.Methods Twenty 6 -8 week male Lewis rats were divided into normal group,EAMgroup,CD40 siRNA group and siRNA group by using random number table,with 5 rats in each group.The normal rats were induced with phos-phate buffer saline in double foot pads on day 0 and day 7,while the rest 3 groups were induced with cardiac myosin protein to establish EAMmodels.The rats in CD40 siRNA group and siRNA group were respectively injected with CD40 siRNA and siRNA slow virus expression vector through the tail vein of rats on day 7.The rats were executed on 21 day after echocardiogram examination was made.The histopathologic changes were observed by using light microscope and the myocardial histopathology scores were calculated.Enzyme -linked immunosorbent assay was used to determine the levels of IL -21 and IL -35 in peripheral blood.Results (1)Except the normal group,the total incidence rate of rats of each group was 100%,and there was no rat death.(2)Compared with EAM group,the heart mass/body ratio and myocardial histopathology scores were lower in CD40 siRNA group,and the differences were significant (3.13 ±0.21 vs 3.80 ±0.29,2.22 ±0.43 vs 3.32 ±0.51,F =0.332,0.456,all P <0.05).(3)The echocardiogram showed that there was only 1 rat in EAM group with massive pericardial effusion,and there was no pericardial effusion in CD40 siRNA group.EAMgroup,CD40 siRNA group and siRNA group displayed hypertrophy of the ventricular septum and left ventricular wall,narrow heart cavity and weakening of ventricular wall motion.The left ventricular shortening rate in CD40 siRNA group was significantly higher than that in the EAMgroup[(63.34 ±11.06)% vs (38.56 ±6.98)%,F =16.080,P <0.05].(4)The peripheral blood level of IL -21 in CD40 siRNA group was lower than that in EAM group [(141.19 ±17.46)ng/L vs (157.81 ±17.58)ng/L,F =57.008,P <0.05],while its level of IL -35 was signifi-cantly higher than that in the EAMgroup [(195.96 ±18.26)ng/L vs (174.78 ±13.91 )ng/L,F =31.727,P <0.05].(5)The level of IL -21 in peripheral blood was positively correlated with myocardial histopathology scores in EAM group (r = 0.69,P < 0.05 ),but IL -35 was negatively correlated with myocardial histopathology scores (r =-0.64,P <0.05).Conclusions CD40 siRNA might relieve the myocardial inflammation and reduce the myocar-dial injury of EAMrats.The levels of IL -21 and IL -35 can partly reflect the degree of myocardial injury.The mecha-nism may be related to down -regulating the expression IL -21 and up -regulating the expression of IL -35.

Objective To preliminary formulated 2017 Chinese rare disease survey list by experts consensus.Methods By using checklist methods,we selected studied diseases from five available rare disease data sources in China.By summarizing,proofreading,removing of duplicate data,the primary survey list with 344 diseases was formulated.By organizing two rounds of consensus conferences,experts voted and revised the survey list,then ultimately formulated 2017 Chinese rare disease survey list.Results According to the poll,in selected 344 rare diseases which were discussed in consensus conferences,54 diseases were suggested to be deleted,9 pairs of diseases were suggested to be incorporated.For Chinese and English names of these rare diseases,306/344 diseases conform to nomenclature by discussion.According to the experts' tips and advice,we revised the primary survey list and ultimately formulated 2017 Chinese rare disease survey list including 281 diseases.Conclusions Experts consensus combines the scientificity of methodology and clinical experience of experts.In the background of medical big data and targeted poverty alleviation,the early stage of study is in accordance with the main stream of thought for the national survey of rate disease in China.

Objective:To investigate the clinical efficacy of vitamin D drops combined with insulin aspart in the treatment of gestational diabetes mellitus (GDM), and the effect of vitamin D drops on the serum levels of 1, 25 dihydroxyvitamin D 3 [1, 25(OH) 2D 3] and retinol binding protein 4 (RBP4). Methods:A total of 94 GDM patients admitted to the Baoding Second Central Hospital from March 2019 to March 2021 were selected and randomly divided into an observation group and a control group with 47 cases each using a random number table method. The control group received subcutaneous injection of insulin aspartate for treatment, while the observation group received oral vitamin D drops for treatment. After 4 weeks of continuous treatment, the blood glucose control effect and adverse reactions were observed in both groups. The glucose metabolism indicators of the two groups were compared before and after treatment, including fasting blood glucose (FPG), 2-hour postprandial blood glucose (2-hour PG), insulin resistance index (HOMA-IR), and pancreatic islets β Cell Function Index (HOMA-β) and serum levels of 1, 25(OH) 2D 3, RBP4, lipoprotein related phospholipase A2 (Lp-PLA2), and vascular cell adhesion molecule-1 (VCAM-1). All patients were followed up until the end of pregnancy, and Statistical analysis was conducted on the adverse outcomes of two groups of mothers and infants. Results:The time to reach the standard for FPG and 2-hour PG in the observation group, as well as the time for both to reach the standard were significantly shorter than those in the control group (all P<0.05). There was no statistically significant difference in the incidence of dawn phenomenon and hypoglycemia between the observation group and the control group (all P>0.05). After treatment, FPG and 2-hour PG in both groups were significantly reduced compared to those before treatment (all P<0.05); However, after treatment, there was no statistically significant difference between the groups (all P>0.05). Compared with before treatment, HOMA-IR in both groups significantly decreased (all P<0.05), All HOMA- β significantly increased (all P<0.05); And the improvement was more significant in the observation group (all P<0.05). After treatment, the serum levels of 1, 25(OH) 2D 3 in the observation group significantly increased compared to that before treatment ( P<0.05), but there was no significant change in the control group before and after treatment ( P>0.05). After treatment, the levels of serum RBP4, Lp-PLA2, and VCAM-1 in both groups significantly decreased compared to those before treatment (all P<0.05); After treatment, the serum levels of RBP4, Lp-PLA2, and VCAM-1 in the observation group were lower than those in the control group (all P<0.05). The incidence of adverse maternal and neonatal outcomes in the observation group was 14.9%(7/47) and 10.6%(5/47), respectively, which were lower than those in the control group [34.0%(16/47) and 27.7%(13/47)] (all P<0.05). There were 8 cases of hypoglycemia in 94 patients (3 in the observation group and 5 in the control group), and no other adverse events occurred. Conclusions:The combination of vitamin D drops and insulin aspartate in the treatment of GDM can safely, effectively, quickly, and steadily control patients′ blood sugar, improve IR and pancreatic islets β The effect of cell function on reducing the incidence of adverse maternal and fetal outcomes may be related to increasing serum 1, 25(OH) 2D 3 levels and down-regulating the expression levels of serum RBP4, Lp-PLA2, and VCAM-1.

Objective To introduce a practical high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)method for the detection of seven growth hormone-releasing peptides (GHRPs)including GHRP-1,GHRP-2,GHRP-4,GHRP-5,GHRP-6,Hexarelin and Alexamorelin and two growth hormone secretagogues(GHS)including anamorelin and ipamorelin,and study the stability of these nine substances in the human urine.Method The urine samples were purified and extracted by a solid phase extraction procedure using Oasis(R) WCX column.The urine was first centrifuged and taken out 1 mL into a small column,cleaned by 5％ NH4OH and 20％ CH3CN respectively,eluated using the mixture of water and acetomitrile(1/3)with 2％ formic acid,blow-dried in the nitrogen at 35℃ and finally redissolved to be injected into the LC-MS/MS.Result The limits of detection were between 0.01～0.5 ng/mL accordingly.The spiked recoveries at the low concentration(1 ng/mL),medium concentration(2 ng/mL)and high concentration(10 ng/mL)ranged between 40％ and 76％.The intra-and interday precisions of the target substances at these three concentrations were all less than 15％.The indoor temperature,refrigeration condition and multigelation were observed to have significant impact on the anamorelin,GHRP-2,GHRP-4 and GHRP-5.Conclusion The method established in this study is simple,and its specificity and sensitivity meets the international standard and technical documents for laboratories set up by the Wworld Anti-Doping Agency.It has been applied in our routine work.Multigelation should be avoided in the transport,detection and long-term laboratory storage of urine samples.

Background::Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Methods::Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. Results::The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) ( χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exact P = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) ( χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2 = 6.95, P = 0.008), BDG ( χ2 = 10.43, P = 0.001), and fungal culture ( χ2 = 12.70, P < 0.001). Conclusions::Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

Objective:To investigate the characteristics of consonant among children with speech sound disorder (SSD) and to provide an empirical basis for the subsequent clinical evaluation and evidence-based intervention.Methods:In this retrospective research a total of 1 395 children diagnosed with SSD from the Language-Speech Clinic of the Department of Children Health Care, Children′s Hospital, Capital Institute of Pediatrics from January 2007 to December 2018 were enrolled and underwent the phonological examination on the lexical level with picture naming, according to phoneme development in Chinese mandarin. The Chi-square trend test was applied to analyze the differences and trends of the proportion of consonant error subtypes in children of different age groups. The Chi-square test was conducted to compare the proportion of consonant error subtypes in different gender.Results:The 1 395 children diagnosed with SSD included 1 044 boys and 351 girls, with an age of (5.1±0.8) years. The occurrence of consonant errors in different locations of articulation was the highest for blade-alveolar /l/ (71.8%, 1 002/1 395) and the lowest for labial/b/(9.3%, 130/1 395). The occurrence of consonant errors of labial/p/f/, supra-dental/z/c/s/, blade-alveolar/t/l/, blade-palatal/ch/r/, velar/k/h/, and lingua-palatal/q/decreased with age (all P<0.05). The occurrence of consonant errors of labial/b/m/, supra-dental/z/c/, blade-alveolar/n/l/, blade-palatal/sh/, velar/h/, and lingua-palatal/x/were higher in boys than those in girls (10.3% (108/1 044) vs. 6.3% (22/351), 11.4% (119/1 044) vs. 6.0% (21/351), 64.8% (676/1 044) vs. 51.9% (182/351), 67.8% (708/1 044) vs. 59.8% (210/351), 16.7% (174/1 044) vs. 8.8% (31/351), 73.7% (769/1 044) vs. 66.1% (232/351), 58.0% (606/1 044) vs. 47.6% (167/351), 24.0% (251/1 044) vs. 14.2% (50/351), and 39.9% (417/1 044) vs. 27.6% (97/351); χ2 =5.167, 8.533, 16.889, 7.447, 12.863, 7.412, 11.650, 14.900, and 17.099, all P<0.05). The error types of consonant were substitution, omission, and distortion. Omission was the main error type of blade-alveolar/l/(53.3%, 743/1 395), distortion was the main error type of velar/h/(11.8%, 165/1 395), and substitution was the main error type of all other consonants. Substitution with blade-palatal/ch/having the highest occurrence of error (60.2%, 840/1 395). Conclusions:The occurrence of the blade-alveolar/l/error is the highest in children with SSD, with boys demonstrating more serious articulation problems. The main error type of consonant is substitution, with blade-palatal/ch/having the highest occurrence of error. These results suggest the necessity of attending to preschoolers′ articulation development. Phonological training targeting blade-alveolar/l/and blade-palatal/ch/should be carried out as early as possible.

Adaptation, Psychological ; Adolescent ; COVID-19 ; Child ; China ; Cross-Sectional Studies ; Female ; Humans ; Male ; SARS-CoV-2