Objective:To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories.Methods:The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory.Results:In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%).Conclusions:A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

[Objective] To evaluate the value of X-ray combined with MRI in the diagnosis of rotator cuff injury. [Methods] A retrospective study was conducted on the patients who underwent X-ray and MRI examinations at the First Affiliated Hospital of Air Force Medical University from January 2021 to March 2022. A total of 158 patients were recruited, among whom 146 had rotator cuff injury, 10 had rheumatoid arthritis, and 2 had shoulder joint space occupation. We compared the specificity, sensitivity, consistency, detection rate, missed diagnosis rate and misdiagnosis rate of various examinations, and compared the X-ray and MRI examination results. [Results] The sensitivity and specificity of X-ray for rotator cuff injury were 65.8% and 41.7%, those of MRI for rotator cuff injury were 78.1% and 66.7%, and those of the combined diagnosis were 93.8% and 83.3%, respectively. The Kappa value of the combined diagnosis of rotator cuff injury and surgical results was higher than that of X-ray and MRI diagnosis (P<0.05). The detection rate and missed diagnosis rate of the three groups differed significantly (χ²=6.095, 13.113, P<0.05). The detection rate of rotator cuff injury by the combined diagnosis was higher than that of X-ray and MRI diagnosis, and the missed diagnosis rate was lower than that of the latter (P>0.05). [Conclusion] The detection rate of rotator cuff injury of shoulder joint by the combined examination is higher than that of X-ray and MRI, and the rate of missed diagnosis and misdiagnosis is lower. The combined examination can provide detailed evaluation for preoperative diagnosis.

Objective:To explore whether cytoplasmic linker protein 170(CLIP170)affects papillary thyroid cancer(PTC)cell metastasis and invasion and clarify the underlying mechanisms.Methods:We analyzed CLIP170 expression levels in PTC using GEO and TCGA data and con-structed CLIP170 knockdown(CLIP170KD)cells using lentiviral transfection.Then,we evaluated their functions through Transwell transfer and invasion assays.We assessed how CLIP170 affected the cellular actin structure via immunofluorescence analysis.We detected transforming growth factor-β 1(TGF-β1)release in the cell culture medium using enzyme-linked immunosorbent assay(ELISA).We also assessed epithelial-mesenchymal transition(EMT)and TGF-β signaling pathway molecule expression using immunoblotting and reverse-transcription quantitat-ive fluorescence PCR and validated the results in a nude mouse lung metastasis model.Results:CLIP170 expression level in PTC was lower than that in normal thyroid tissue.Regarding the function,CLIP170KD significantly enhanced PTC cell metastasis both in vitro and in vivo.Re-garding the underlying mechanism,CLIP170KD triggered TGF-β pathway activation,subsequently promoted tumor cell migration and invasion.The inhibitor of TGF-β effectively inhibited TGF-β activation,and this inhibition significantly reversed the CLIP170KD-induced tumor metastasis.Conclusions:CLIP170 could be a promising therapeutic target to mitigate metastatic tendencies in PTC.

【Objective】 To construct a prediction model of severe obstructive sleep apnea (OSA) risk in the general population by using nomogram in order to explore the independent risk factors of severe OSA and guide the early diagnosis and treatment. 【Methods】 We retrospectively enrolled patients who had been diagnosed by polysomnography and divided them into training and validation sets at the ratio of 7∶3. Patients were divided into severe OSA group and non-severe OSA group according to apnea hypopnea index (AHI)>30. Variables entering the model were identified by least absolute shrinkage and selection operator regression model (Lasso), and logistic regression (LR) method. Then, multivariable logistic regression analysis was used to establish the nomogram, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative properties of the nomogram model. Finally, we conducted decision curve analysis (DCA) of nomogram model, STOP-Bang questionnaire and Berlin questionnaire to assess clinical utility. 【Results】 Through single factor and multiple factor logistic regression analyses, the independent risk factors for severe OSA were screened out, including moderate and severe sleepiness, family history of hypertension, history of smoking, drinking, snoring, history of suffocation, sedentary lifestyle, male, age, body mass index (BMI), waist and neck circumference. Lasso logistic regression identified smoke, suffocation time, snoring time, waistline, Epworth sleepiness scale (ESS) and BMI as predictive factors for inclusion in the nomogram. The AUC of the model was 0.795 [95% confidence interval (CI): 0.769-0.820] . Hosmer-Lemeshow test indicated that the model was well calibrated (χ²=3.942, P=0.862). The DCA results on the visual basis confirmed that the nomogram had superior overall net benefits within a wide, practical threshold probability range which displayed the nomogram was higher than that of STOP-Bang questionnaire and Berlin questionnaire, which is clinically useful. The Clinical Impact Curve (CIC) analysis showed the clinical effectiveness of the prediction model when the threshold probability was greater than 82% of the predicted score probability value. The prediction model determined that the high-risk population with severe OSA was highly matched with the actual population with severe OSA, which confirmed the high clinical effectiveness of the prediction model. 【Conclusion】 The model performed better than STOP-Bang questionnaire and Berlin questionnaire in predicting severe OSA and can be applied to screening. And it can be helpful to the early diagnosis and treatment of OSA in order to reduce social burden.

Objective: To understand the relationships of social exclusion, personality trait and emotion regulation with willingness to seek help after being bullied, and to provide reference for rationalized intervention of campus bullying among middle school students. Methods: A tatal of 2 040 middle school students from a middle school in Jiangxi Province were selected as the research objects, and surveyed by general situation questionnaire, Olweus Bullying Questionnaire, Willingness to Seek Help Scale, social exclusion scale, personality scale and Emotion Regulation Scale. Among them, a further survey of 381 bullies was conducted and SPSS 26.0 was used for statistical processing of data. Results: About 55.88% (133/238) and 58.74% (84/143) reported willingness to seek help after being bullied among middle and high school students, respectively( χ 2=0.30, P >0.05). There were no significant differences in gender and residency( P >0.05). In junior middle school students, compared with the non help willingness group( 3.83± 0.78，3.35±1.03，3.33±1.03，29.81±7.77), the rejected scores of the help willingness group were lower(3.57±0.75), scores of affinity and openness in personality traits were higher(3.69±0.88，3.72±0.79), the cognitive reappraisal scores were higher( 32.42 ±8.25). Among senior middle school students, the rejected and expression suppression scores of the help willingness group were lower(3.51±0.67，26.96±7.47), while extroversion personality traits were higher(3.61±0.95). Multivariate unconditional Log binomial regression analysis showed that high score of expression suppression was associated with less willingness to seek help( OR=0.94, P =0.02). Conclusion Social exclusion, personality trait and emotional regulation may have certain influences on willingness to seek help after being bullied among junior and senior middle school students, effects varies by grade level.

Objective:To explore the immune infiltration cells in rheumatoid arthritis (RA) synovial lesions, and to provide new research directions and therapeutic targets for the pathogenesis and treatment of RA.Methods:The three gene expression data sets GSE77298, GSE55457 and GSE1919 were downloaded from gene expression omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo), and the data were merged with Perl. The "limma" package was used to adjust batch differences. In R, "CIBERSORT" software was used to obtain the expression matrix of 22 kinds of immune cells corresponding to RA synovial tissue samples and normal synovial tissue samples were analyzed with the three packages of "e1071", "parallel" and "preprocessCore". Perl was used to screen samples with P<0.05 in the immune cell matrix. R's "barplot" function was analyzed by the percentage of 22 immune cells in samples with P<0.05. The "pheatmap" package of R was used to visualize heatmaps, and "corrplot" package was used to draw correlation heatmaps. The "vioplot" package of R was used to draw violin plots of differences via the wilcox test. Results:The results of immune cell infiltration analysis showed that in RA synovial tissue samples and normal synovial tissue samples at P<0.05, B cells naive and natural killer cells resting were under-expressed in RA synovial tissue, and plasma cells, mast cells resting, macrophages M1, B cells memory and T cells regulatory were highly expressed in RA synovial tissue. This study also found that in the same sample, the correlation coefficient between natural killer cells resting and neutrophils ( r=0.91) was the highest, indicating synergistic effect between the two. In the same sample, the correlation coefficient between macrophages M0 and plasma cells ( r=-0.88) was the lowest, indicating antagonistic effect between the two. Conclusion:The immune infiltrating cells in RA synovial lesions discovered in this study provide a certain theoretical basis and research direction for the research on the disease mechanism and treatment of RA.

Objective:To analyze the genetic landscape of multiple fusion genes in patients with de novo acute myeloid leukemia (AML) and investigate the characteristics of immunophenotypes and mutations.Methods:The results of multiple fusion genes from 4192 patients with de novo AML were retrospectively analyzed from 2016 to 2020. In addition, the immunophenotypical data and the mutational results from high-through put method were statistically investigated and correlated as well.Results:①Among the 52 targets, 29 different types of fusion genes were detected in 1948 patients (46.47%) with AML, which demonstrated an "exponential distribution" . ② As the age increased, the number of patients with fusion gene increased first and then decreased gradually. The total incidence rate of fusion genes and MLL rearrangment in children were significantly higher than those in adults (69.18% vs 44.76%, 15.35% vs 8.36%) . ③The mutations involving FLT3 and RAS signaling pathway contributed most in patients with MLL rearrangment. ④No specific immunophenotypic characteristics were found in AML patients with MLL or NUP98 rearrangements. Conclusion:Nearly half of AML patients were accompanied by specific fusion gene expression, the proportions of different fusion genes in pediatric and adults patients were different by multiple PCR. The gene mutations and immunophenotype of these AML patients have certain rules.

OBJECTIVE：To investigate the reversal effects and potential mechanism of levoshikonin （L-SHK）on cisplatin （DDP）resistance of human cervical carcinoma HeLa cells. METHODS ：Human cervical carcinoma HeLa cells were used as research objects ，and drug-resistant HeLa/DDP cells were induced by DDP. CCK- 8 assay was used to determine drug resistance index of HeLa/DDP cells ，the inhibition rate of different doses of L-SHK （0.125，0.25，0.5，1，2，4，8，16 μmol/L）on cell proliferation，IC50 and the reversion index of L-SHK on HeLa/DDP cells. Effects of low ，medium and high doses of L-SHK （0.3， 0.6，1.2 μmol/L）combined with DDP on cell cycle and apoptosis rate were determined by flow cytometry. Western blotting assay was used to detect the effects of low ，medium and high doses of L-SHK （0.3，0.6，1.2 μmol/L）combined with DDP on the expression of apoptosis-related protein （Cleaved caspase- 3，Bcl-2 and Bax ）. RESULTS ：The drug resistance index of HeLa/DDP cells was 11.8. The inhibition rate of L-SHK on HeLa/DDP cells increased with the increase of dose. Compared with DDP alone ， IC50 of DDP+low-dose ，medium-dose and high-dose L-SHK groups were decreased significantly ，with a dose-dependent manner （P＜0.05）. The reversion indexes were 1.38，2.80，6.71 in DDP+low-dose ，medium-dose and high-dose L-SHK groups. Compared with blank control group ，the proportion of cells at phase G 0/G1 and phase S in administration groups ，as well as early and late apoptosis rate and total apoptosis rate of cells ，the protein expression of Bax and Cleaved caspase- 3 in L-SHK combination groups were increased significantly ；the proportion of cells at phase G 2/M in administration group as well as the protein expression of Bcl-2 in L-SHK combination groups were decreased significantly （P＜0.05）. Compared with DDP group ，the proportion of cells at phase S and G 2/M and the protein expression of Bcl- 2 in L-SHK combination groups were significantly decreased ；the proportion of cells at phase G 0/G1，early and late apoptosis rate and total apoptosis rate ，the protein expression of Bax and Cleaved caspase- 3 in L-SHK combination groups were significantly increased （P＜0.05）. CONCLUSIONS ：HeLa/DDP cells are resistant to DDP ，and L-SHK can reverse the drug resistance. L-SHK combined with DDP can promote the apoptosis of HeLa/DDP cells ，which is better than DDP alone. Its mechanism may be related to the influence of cell cycle and the regulation of apoptosis-related protein expression.

The basic principles of medical ethics included respect and autonomy,beneficial and nonmaleficence,informed consent and confidentiality,impartiality and mutual assistance.During medical journal editing,medical ethics principles should be strictly applied.Focused on two types of medical thesis,medical scientific research and clinical trials,this paper concluded the ethics issues related to experimental animals,cells and gene researches,all these should be noticed in manuscripts.Meanwhile,this paper analyzed the ethics principles about contrast set and the use of placebo that should be abided in clinical trial,and the respects of patients'privacy during clinical observation,etc.Some review key points were put forward from the perspective of editors.

Objective: To investigate the incidence, molecular features and clinical significance of RNA splicing machinery genes mutation in myelodysplastic syndromes (MDS) and related diseases. Methods: Mutational analysis of splicing factor 3B subunit 1 (SF3B1) (K700E) , U2 small nuclear RNA auxiliary factor 1 (U2AF1) (S34, Q157P) and serine/arginine-rich splicing factor 2 (SRSF2) (P95) in 118, de novo MDS and related diseases were separately performed by using polymerase chain reaction (PCR) followed by sequence analysis. Results: Of 118 MDS patients, 76 males and 42 females, the median age was 53.5 (13-84) years old. 19.49% (23/118) had SF3B1 (K700E) mutation. As compared with those with wild type SF3B1, patients with SF3B1 K700E were of older[58 (32-78) years vs 51 (13-84) years, z=-1.981, P=0.048], lower HGB level[63 (40-95) g/L vs 77 (34-144) g/L, z=-3.192, P=0.001], higher platelet counts[121 (22-888) ×10⁹/L vs 59 (6-1 561) ×10⁹/L, z=-3.305, P=0.001], lower bone marrow blast cell counts[0.007 (0-0.122) vs 0.017 (0-0.268) , z=-2.885, P=0.004], higher ring sideroblasts percent [0 (0-64%) vs 0 (0-58%) , z=-4.664, P<0.001]. Of 105 MDS patients, 21.9% had U2AF1 (S34, Q157P) mutations. Of 107 MDS patients, 8 patients (7.48%) had SRSF2 (P95) mutations. Patients with SRSF2 mutations were older at diagnosis, the median age was 63 (50-84) years old, including 4 cases RAEB-1. The ratio of mutation was 14.29% (4/28) , and three patients transformed to AML. SF3B1 K700E and SRSF2 P95H mutations coexisted in 1 patient, and SF3B1 K700E and U2AF1 S34Y mutations were found concomitantly in 2 patients. Conclusion Only SF3B1 gene mutation was closely related to ring sideroblasts, it was the key to pathogenesis of MDS.