Transbronchoscopic freezing technology has made remarkable achievements in the treatment of respiratory diseases. Transbronchoscopic freezing technology uses the principle of low temperature freezing to treat pathological tissue. This technique has been widely used in the diagnosis and treatment of various respiratory pathological，including freeze-thaw and freeze-cutting techniques. With the development of bronchoscopic intervention technology，the application range of refrigeration technology has gradually expanded，and its safety and effectiveness have also been improved. This review systematically introduced the technique of transbronchoscopic freezing and its application in pediatric interventionarespiratory medicine，aiming to maket more pediatric peers aware of this technology,and apply it more effectively in respiratory intervention treatment.

ObjectiveTo investigate the effect of Ziziphi Spinosae Semen-Albiziae Flos on the nucleotide-binding oligomerization domain，NOD-like receptor thermal protein domain associated protein 1 （NLRP1）/chemokine ligand 1 （CXCL1）/chemokine receptor 2 （CXCR2） pathway in the hippocampus of the rat model of chronic unpredictable mild stress （CUMS）-induced depression. MethodA total of 120 male SD rats were randomized into blank，CUMS，CUMS + low-，medium-，and high-dose （4，8，16 g·kg^-1） Ziziphi Spinosae Semen-Albiziae Flos，and CUMS + venlafaxine hydrochloride （0.008 g·kg^-1） groups，with 20 rats in each group.The rat model of depression was established by solitary feeding combined with CUMS.The behaviors and spatial learning and memory abilities of rats were examined by sugar water consumption test，tail suspension test，forced swimming test，and Morris water maze test.Quantitative real-time PCR （Real-time PCR） and Western blot were employed to determine the expression of factors associated with the NLRP1/CXCL1/CXCR2 pathway in the hippocampus.Enzyme-linked immunosorbent assay was employed to determine the levels of tumor necrosis factor-α （TNF-α），interleukin （IL）-18，IL-1β，and IL-6 in the hippocampus.The immunofluorescence assay was used to measure the levels of reactive oxygen species （ROS） in the hippocampus. ResultCompared with the blank group，the CUMS group showed decreased preference to sugar water and times of crossing the platform （P<0.01），and increased immobility time of tail suspension，forced swimming floating time，and escape latency （P<0.01）.Compared with the CUMS group，the administration of Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride alleviated the effects of CUMS on the above-mentioned behaviors and spatial learning and memory abilities of the rats （P<0.05，P<0.01）.Compared with the blank group，the CUMS group showed up-regulated protein levels of NLRP1，CXCL1，and CXCR2 （P<0.01） and elevated levels of IL-18，IL-1β，TNF-α，and IL-6 （P<0.01） in the hippocampus.The treatment with Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride attenuated the activation of NLRP1/CXCL1/CXCR2 signaling pathway and lowered the levels of inflammatory cytokines in the hippocampus of CUMS rats （P<0.05，P<0.01）.In addition，Ziziphi Spinosae Semen-Albiziae Flos lowered the level of ROS in the hippocampus （P<0.05，P<0.01）. ConclusionZiziphi Spinosae Semen-Albiziae Flos can mitigate the depressive behaviors of the rat model of CUMS-induced depression by inhibiting the activation of NLRP1/CXCL1/CXCR2 signaling pathway.

OBJECTIVE To analyze the current status and research hot spots of traditional Chinese medicine （TCM）in the prevention and treatment of myocardial ischemia -reperfusion injury （MIRI），and to provide reference for developing relevant studies. METHODS A bibliometric analysis was performed with the literature on TCM treatments for MIRI included in the Web of Science as the data source . RESULTS A total of 972 literatures were included in this study . The research on TCM for prevention and treatment of MIRI in recent 10 years showed an increasing trend year by year ，and the literature published in 2021 were cited most frequently ；most research scholars focused in China ；Peking Union Medical College ，Chinese Academy of Medical Sciences had the most papers in this field ，and a lot of collaboration with other institutions ，which had a large influence in the field ；Sun Guibo and Sun Xiaobo were high -yielding authors in the field ，but the global authorship was not very close and had not formed cooperative teams of some scale ；Molecular Medicine Reports was perhaps the most popular journal in the field . Co-citation analysis found that the research direction in this field was mostly focused on exploring the pathogenesis of MIRI and finding intervention targets . Key words analysis revealed that TCM regulated apoptosis ， pyroptosis， mitochondrial dysfunction ， miRNA and other pathways to improve MIRI research was a hot spot in the field ，and more studies had focused on the Nrf 2 pathway，NF-κB pathway ，NLRP3 inflammasomepathway， TNF pathway ， SIRT3 pathway， JNK pathway ，PI3K/Akt pathway and AMPK pathway . CONCLUSIONS Much attention has been paid to the prevention and treatment of MIRI by TCM in the past 10 years，and the current hot spots in this field are mostly focused on the studies about the intervention mechanism of TCM ’s active ingredients and Chinese patent medicines on MIRI . Moreover，the research about TCM in the treatment of MIRI is mostly focused on the field of basic experiments at present ，and it is recommended that many large -scale，high-quality， multicenter，randomized controlled clinical studies should be carried out in the future ，to provide high -grade evidence -based evidence for the application of TCM in clinic .

Pre-testing preparation is the basis and starting point of genetic testing.The process includes collection of clinical information,formulation of testing scheme,genetic counseling before testing,and completion of informed consent and testing authorization.To effectively identify genetic diseases in clinics can greatly improve the diagnostic rate of next generation sequencing (NGS),thereby reducing medical cost and improving clinical efficacy.The analysis of NGS results relies,to a large extent,on the understanding of genotype-phenotype correlations,therefore it is particularly important to collect and evaluate clinical phenotypes and describe them in uniform standard terms.Different types of genetic diseases or mutations may require specific testing techniques,which can yield twice the result with half the effort.Pre-testing genetic counseling can help patients and their families to understand the significance of relevant genetic testing,formulate individualized testing strategies,and lay a foundation for follow-up.

With high accuracy and precision,next generation sequencing (NGS) has provided a powerful tool for clinical testing of genetic diseases.To follow a standardized experimental procedure is the prerequisite to obtain stable,reliable,and effective NGS data for the assistance of diagnosis and/or screening of genetic diseases.At a conference of genetic testing industry held in Shanghai,May 2019,physicians engaged in the diagnosis and treatment of genetic diseases,experts engaged in clinical laboratory testing of genetic diseases and experts from third-party genetic testing companies have fully discussed the standardization of NGS procedures for the testing of genetic diseases.Experts from different backgrounds have provided opinions for the operation and implementation of NGS testing procedures including sample collection,reception,preservation,library construction,sequencing and data quality control.Based on the discussion,a consensus on the standardization of the testing procedures in NGS laboratories is developed with the aim to standardize NGS testing and accelerate implementation of NGS in clinical settings across China.

Clinical genetic testing results are compiled into a standardized report by genetic specialists and provided to clinicians and patients (Should the patient be intellectually disabled or under 18,the report will be provided to his/her parents or legal guardians).The content of genetic testing report should conform to relevant guidelines,industry standards and consensus.The decisions of clinicians will be made based on the report and clinical indications.Genetic counselors should provide post-test counseling to clinicians and patients or their authorized family members.A mechanism of follow-up visit after the genetic testing should be established with informed consent.Data should be shared by clinical institutions and genome sequencing institutions.As findings upon follow-up visit can help with further evaluation of the results,genome sequencing institutions should regularly re-analyze historical and follow-up data,and the updated results should be shared with clinical institutions.All activities involving reporting,genetic counselling,follow-up visiting,and re-analyzing should follow the relevant guidelines and regulations.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Objective Aspirin is a non steroidal anti-inflammatory drugs, whether or not which does harm to renal function in the course of using, there is a big debate at home and abroad.In this paper, The aim of this study was to observe the effects of different doses of aspirin on renal function in elderly patients with cardiovascular disease at different ages.MethodsWe Selected a total of 288 patients with cardiovascular disease from January 2014 to March 2016 in Zhejiang Rongjun hospital.There were 288 cases of cardiovascular disease, including 144 cases of normal uric acid, 144 cases with hyperuricemia (including gout).The two groups according to the age of 60 to 70 years, 71 to 80 years old, over 80 years old respectively into three subgroups, each subgroup of 48 cases;Each subgroup was randomly selected without the use of aspirin (0mg/d) and the use of different doses of aspirin (50mg/d, 100mg/d, 150mg/d) for a total of four groups, each which is 12 patients.We detect patients routine blood tests, liver and kidney function, blood urea nitrogen (BUN), blood creatinine (SCR) levels and glomerular filtration rate (GFR) (MDRD) and blood and urine beta 2-microglobulin used aspirin before and used after 6 months and 12 months.ResultsBefore treatment, there were no significant differences in body mass index (BMI), blood pressure, hemoglobin, serum albumin and platelet count between various groups of the same age group.After treatment for 6 and 12 months,Uric acid normal patients and high uric acid patients with 0mg/d, 50mg/d, 100mg/d or 150mg/d dose of aspirin has no statistical difference in BUN, Scr and eGFR, 2-microglobulin Ccr, blood, urine beta 2-microglobulin.ConclusionRegardless of uric acid, different doses of aspirin had no significant effect on renal function in elderly patients with cardiovascular disease, and can be safely used.

Objective To study changes of serum IL-17 and IL-35 levels in patients with heart failure. Methods 60 patients with heart failure (observation group)were selected as research subjects.60 patients accord-ing to different severity were divided into acute period heart failure (34 cases)and stable stage heart failure (26 ca-ses);60 patients graded according to the NYHA standards were divided into 24 cases of heart failure with grade Ⅱ, 20 cases of grade Ⅲ ,16 cases of grade Ⅳ.According to the different primary diseases :expansion cardiomyopathy group (20 cases in group A),the coronary heart disease group (group B,24 cases),hypertensive heart disease group (group C,16 cases).During the same period,42 healthy elderly people in our hospital were selected as control group. The serum IL-17,IL-35 levels were tested,and the serum IL-17,IL-35 levels in patients with heart failure were ana-lyzed.Results Serum level of IL-17 in the observation group was higher than the control group,and the difference was significant [(15.61 ±4.02)pg/mL vs (9.49 ±3.96)pg/mL,t =9.018,P <0.01].Serum level of IL-35 in the observation group was significantly lower than that of the control group,and the difference was significant[(52.78 ± 4.29)pg/mL vs (61.49 ±4.81)pg/mL,t =11.963,P <0.01].The level of serum IL-17 in acute stage of patients with heart failure was higher than that of stable heart failure,and the difference was significant (t =6.278,P <0.01);IL-35 level in serum of patients with heart failure in acute phase was lower than that of stable heart failure,the difference was significant (t =9.529,P <0.01).With the increase in heart failure grade,serum IL-17 level showed a rising trend,and the differences among three groups had statistical differences (F =6.098,P <0.01);serum IL-35 level decreased,and the differences among three groups had statistical differences(F =8.978,P <0.01).The serum IL-17 level of A group was higher than that in B group and C group,there were significant differences (F =6.096, P <0.01),the serum IL-17 level between B group and C group had no statistical difference (t =0.172,P >0.05). The serum IL-35 level of A group was lower than that of B group and C group,there were significant differences (F =8.978,P <0.01),the serum IL-35 level between B group and C group had no statistical difference (t =0.208,P >0.05).Serum IL-17 and serum IL-35 level was negatively correlated (r =-0.429,P =0.009).Conclusion High expression of IL-17 in elderly patients with heart failure,while IL-35 decreased in elderly patients with heart failure, IL-17,IL-35 are closely related to the senile congestive heart failure and the severity of illness.Serum IL-17 is nega-tively correlated with the level of serum IL-35.

Objective:To explore the association and gene-environment interaction between single nu-cleotide polymorphisms (SNPs)involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate (NSCL/P)among Chinese population.Methods:A total of 806 NSCL/P trios were drawn by an international consortium,which conducted a genome-wide association study (GWAS)using a case-parent trio design to investigate genes affecting risks to NSCL/P.The transmission disequilibrium test (TDT)was used to explore the association between cell-cell adhesion genes,including CDH1,CT-NNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P.Conditional Logistic regression models were used to estimate effects on risk of exposed and unexposed children.Four common maternal exposures including maternal smoking,environmental tobacco smoke,alcohol consumption and multivita-min supplementation during pregnancy were included in this study.Results:A total of 226 SNP markers were tested after quality control in this study.Although 23 SNPs in three genes (CTNNB1,CDH1, ACTN1)showed nominal significant association with NSCL/P in the TDT (P <0.05).There were no sig-nificant evidence of linkage and association that remained in the transmission disequilibrium test after Bonferroni correction(P >0.000 2).Tests for gene-environment interaction yielded significant results be-tween rs7431 27 in ACTN1 and environmental tobacco smoke (P =0.000 1 )with an estimated OR (case |G and E)=2.00(95%CI:1 .23 -3.26)and OR (case |G no E)=0.59 (95%CI:0.38 -0.90).Among the lower P value results in gene-environment tests,there were no significant results be-tween rs1 475034,rs370535,rs227341 9 in ACTN1,rs1 06871 in CTNNB1 and environmental tobacco smoke interaction.There were also no significant results between rs7634000,rs2971 366,rs2634553, rs1 489032,rs762481 2 in PVRL3 and multivitamin supplementation during pregnancy in gene-environ-ment tests(P >0.000 2).Conclusion:There is no association between cell-cell adhesion genes,inclu-ding CDH1,CTNNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P when the genes are considered alone.But our results suggest that SNPs in ACTN1 may influence the risk to NSCL/P through gene-environment interaction.