Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

ObjectiveTo establish a quantitative analysis multi-components by single marker method （QAMS） for five main components （aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin） in Eucommiae Folium， to verify its feasibility and applicability in the determination of Eucommiae Folium， so as to provide a scientific basis for the development of quality standard of this herb. MethodHigh performance liquid chromatography was performed on a Welch Boltmatetm™ C₁₈ column （4.6 mm×100 mm， 2.7 μm） with methanol （A）-0.2% phosphoric acid aqueous solution （B） as the mobile phase for gradient elution （0-8 min， 3%A； 8-10 min， 3%-11%A； 10-26 min， 11%A； 26-27 min， 11%-25%A； 27-60 min， 25%-32%A）， the column temperature was set at 30 ℃， the flow rate was 0.6 mL·min^-1， the detection wavelengths were at 210 nm and 254 nm. Chlorogenic acid was used as an internal reference to establish the relative correction factors （f） between it and the other four components， and the contents of the five components in 14 batches of Eucommiae Folium were determined by QAMS and external standard method （ESM）， respectively. ResultThe f values of chlorogenic acid to aucubin， geniposidic acid， asperuloside and rutin were 3.13， 1.45， 2.64 and 0.56， respectively. Repeatability was good under different experimental conditions， relative standard deviation （RSD） was <5.0%. The contents of aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin in 14 batches of Eucommiae Folium were 1.340-28.975， 0.252-36.086， 10.016-27.443， 1.396-8.646， 0.533-1.766 mg·g^-1， respectively. There were no significant difference between content results of QAMS and that of ESM （RSD<5.0%）. ConclusionQAMS established with chlorogenic acid as the internal reference can be used to determine the contents of five components in Eucommiae Folium， and this method is simple and accurate. After comprehensive evaluation， the quality standard of Eucommiae Folium in subsequent editions of Chinese Pharmacopoeia is suggested that three main active components， chlorogenic acid， aucubin and geniposidic acid， are selected as quality markers， and their content limits are recommended not less than 1.5%， 1.0% and 1.0%， respectively. This quality standard draft can avoid the potential quality risk due to poor specificity and low content limit of the index component （chlorogenic acid） in the previous editions of Chinese Pharmacopoeia.

Objective:To explore the changes of T follicular regulatory (T FR) cells/T follicular helper (T FH) cells and their related cytokines in peripheral blood of children with dust mite allergic asthma, and their clinical significance. Methods:A total of 25 children with acute dust mite allergic asthma (the asthma group) in Affiliated Hospital of Jiangnan University from January to December 2021 and 16 age- and sex-matched healthy volunteers (the healthy control group) at the same time were enrolled in the retrospective study.The percentages of peripheral T FR cells and T FH cells of the 2 groups were measured by flow cytometry.The plasma levels of cytokines[interleukin (IL)-10, IL-21] of the 2 groups were assessed by the flow cytometric microsphere-based array technology.The specific IgE (sIgE) levels of dust mites in 2 groups were detected by fluorescence enzyme immunoassay.The percentage of eosinophils in peripheral blood detected by blood cell analyzer.Data between groups were compared by t-test, and the correlation among indicators was analyzed by Spearman rank correlation analysis. Results:The asthma group had evident T FR cells/T FH cells immune imbalance.Compared with the healthy control group, the asthma group had a significantly lower T FR cells level[(0.11±0.03)% vs.(0.13±0.03)%], a significantly higher T FH cells level[(5.07±1.75)% vs.(3.80 ± 1.60)%], and a significantly lower ratio of T FR cells /T FH cells(0.02±0.01 vs.0.05±0.03) ( t=2.29, 2.30, 3.71; all P<0.05). Compared with the healthy control group, the asthma group had a significantly higher IL-21 level[(547.85±195.13) ng/L vs.(404.94±110.41) ng/L], and a significantly lower IL-10 level[(10.18±3.49) ng/L vs.(14.79±5.65) ng/L] ( t=2.60, 3.15; all P<0.05). The ratio of T FR cells/T FH cells in asthma group was negatively correlated with sIgE ( r=-0.444 2, P=0.026 1), but not related to the eosinophil percentage ( r=-0.135 2, P=0.519 3). Conclusions:Children with dust mite allergic asthma suffer from T FR cells/T FH cells subset imbalance.The imbalanced T FR cells, T FH cells and their related cytokines IL-10 and IL-21 may play a role in regulating the production of asthma sIgE.

Objective:To explore the role of creative mind mapping combined with problem-based learning (PBL) in the teaching of standardized residency training of oncologists.Methods:A total of 37 doctors who were trained in the Department of Oncology of Linyi People's Hospital Affiliated to Shandong University from July 2018 to June 2019 were included in the control group, receiving traditional clinical teaching; 39 doctors who were trained from July 2019 to June 2020 were included in the observation group, having creative mind mapping combined with PBL teaching. The two groups were compared with each other in terms of the examination scores (theoretical and practical operation), each dimensional scores and the total score of the Chinese version of the Critical Thinking Disposition Inventory (CTDI-CV) before and after teaching, clinical quality and teaching satisfaction. SPSS 22.0 was used for t test, chi-square test and Z test. Results:There was no statistically significant difference in the scores of theoretical knowledge and operational skills between the two groups before the regular training. After the training, the scores of theoretical knowledge and operational skills of the observation group were both higher than those of the control group [(93.42±4.21) vs. (86.58±5.32), (92.81±4.39) vs. (87.96±5.89), ( P<0.05)]. There was no significant difference between the scores of all dimensions of the CTDI-CV and the total scores of the two groups before the training ( P>0.05). After the training, the scores of the two groups were both improved, and the improvement of the observation group was more significant ( P<0.05). After the training, the scores of the doctors in the observation group on expression and communication ability, humanistic care and literacy, inductive analysis ability, clinical work adaptability, contingency handling ability, hands-on ability, and autonomous learning ability were significantly higher than those of doctors in the control group ( P<0.05). After the training, the total satisfaction of the doctors in the observation group was higher than that in the control group [97.44% (38/39) vs. 81.08% (30/37)], and the difference was statistically significant ( P<0.05). Conclusion:The application of creative mind mapping combined with PBL in the teaching of standardized residency training of oncologists can significantly improve the learning effect of the training doctors, improve their critical thinking ability and clinical comprehensive ability, and can also improve their total satisfaction with teaching.

Objective To observe the clinical change of cytokines expression in peripheral blood in patients with allergic asthma and its significance .Methods Forty patients with allergic asthma and thirty healthy controls were enrolled .The concentrations of IL‐17 ,IL‐22 and IL‐10 in peripheral blood were measured by ELISA ;the serum IgE levels were measured by electrochemical lumi‐nescence method ;The eosinophil proportion was detected by blood cell analyzer ;the IL‐17 ,IL‐22 ,IL‐10 and the severity of asthma were conducted Pearson correlation analysis .Results The level of serum IgE and eosinophil proportion was significantly higher in patients with allergic asthma compared with the controls (P<0 .05);compared with the control group ,the concentration of IL‐17 and IL‐22 in peripheral blood of patients with allergic asthma were increased ,but the expression of IL‐10 were decreased (P<0 .05);the level of IL‐17 and IL‐22 were positively correlated with severity of allergic asthma (P<0 .01) ,but the level of IL‐10 was negatively correlated with severity of allergic asthma (P<0 .05) .Conclusion The expression of IL‐17 ,IL‐22 and IL‐10 play an im‐portant role in the pathogenetic mechanism of allergic asthma ,and a dynamic monitoring could be helpful for the diagnoses and treatment of allergic asthma .

DNAzymes, screened through in vitro selection, were artificial nucleic acids with catalytic function . They could cleave specific substrates in the presence of cofactors with unique characteristics, such as high catalytic activity, high specificity for cofactors, excellent stability, and easy to synthesize and modify. The combination of DNAzymes with nanomaterials could retain the DNAzyme activity and realize the functional integration of recognition and signal transduction, promoting rapid development of biosensors. In the current paper, we mainly reviewed the recent progress in DNAzyme-nanomaterial based biosensors, and the nanomaterials included gold nanoparticles, graphene, quantum dots, magnetic nanomaterials, and so on.

Objective To observe the inhibited effect of gastrodin on chemotherapy-induced neuropathic pain and its mechanism.Methods Fifty SD rats,chosen according to the threshold of pain,were randomly divided into 5 groups(n=10):control group,model group,and gastrodin treatment groups (30 mg/kg,60 mg/kg and 120 mg/kg).Vincristine (125 μg/kg,i.p.) was administered on alternate days to establish chemotherapy-induced neuropathic pain models in the model group and gastrodin treatment groups,and then,on the 9th d of modeling rats in the gastrodin treatment groups were treated with different doses of gastrodin,while those in the control group and model group were given normal saline on the 16th d of modeling.Paw withdrawal mechanical threshold and thermal pain threshold were measured;protein expressions of CX3CR1 and p-p38MAPK were detected by Western blotting,and tumor necrosis factor α (TNF-α) protein expression was detected by ELISA.Results As compared with control group,model group had significantly decreased pain threshold and increased protein expressions of CX3CR1,p-p38MAPK and TNF-α (P＜0.05);as compared with those in the model group,the pain threshold increased and the expressions of CX3CR1,p-p38MAPK and TNF-α decreased in 60 mg/kg and 120 mg/kg gastrodin treatment groups,with significant differences (P＜0.05).Conclusion Gastrodin can relieve the chemotherapy-induced neuropathic pain,probably by inhibiting the expressions of CX3CR1 and p-p38MAPK in the activation passageway of microglial cells in the spinal cord,and then,reducing the expression of TNF-α.

Objective To study the levels of interleukin(IL)-2 ,interferon-γ(IFN-γ) and IL-10 in peripheral blood and the effec-tive concentration of lactate dehydrogenase(LDH) in serum of patients with acute leukemia .Methods 65 patients with acute leuke-mia were divided into non-remission group(n=35) and remission group(n=30) .50 healthy volunteers were used as control group . The levels of IL-2 ,IFN-γ ,IL-10 in peripheral blood were measured by enzyme linked immunosorbent assay(ELISA) .The effective concentration of LDH was measured by automatic biochemical analyzer .Results The levels of IL-2 ,IFN-γin non-remission group were significantly decreased compared with control group and remission group(P<0 .05) ,but the level of IL-10 in non-remission group was significantly increased compared with control group and remission group(P<0 .05) .The effective concentration of LDH in non-remission group was significantly higher than that in control group or remission group(P<0 .05) .Conclusion The levels of IL-2 ,IFN-γand IL-10 in peripheral blood and the effective concentration of LDH in serum of patients with acute leukemia have changed .Clinical detection of IL-2 ,IFN-γ,IL-10 and LDH may contribute to the early diagnosis of patients with acute leukemia .

Objective To investigate the percentage of Th17 cells and FOXP3 concentration in peripheral blood of children with bronchial asthma and their clinical significance .Methods Thirty children with bronchial asthma and thirty healthy children as con-trol group were enrolled in the study .The percentage of Th17 and CD4+CD25+ Treg cells in the peripheral blood were determined by flow cytometry(FCM) .The mRNA expression of FOXP3 in the peripheral blood was determined by quantitative real-time PCR . The concentrations of IL-17 and IL-10 in plasma were measured by using ELISA .Results In children with bronchial asthma ,the proportions of Th17 cells in the peripheral blood and concentration of IL-17 in plasma increased ,while the expression of FOXP3 in the peripheral blood and concentration of IL-10 in plasma decreased .Conclusion The imbalance of Th17/FOXP3 may contribute to the proceeding of bronchial asthma in children .