Objective: To explore the mechanism of miR-141-5p and its effect on Imatinib(IM) resistance in CML. Methods: qRT-PCR was used to detect miR-141-5p mRNA levels in IM resistant and sensitive patients.Western blot was used to detect the expression of proteins such as MMP-3,MMP-9,and Bcl-2 before and after transfection in K562 and K562/G01 cells.CCK-8 was used to detect of K562 and K562/G01 cell activity;Flow cytometry assay was used to detect the binding of miR-141-5p with ABCG1;Nude mice were used to validate the effect of miR-141-5p on tumors in vivo. Results: The results showed that miR-141-5p was downregulated in IMresistant CML patients and IM-resistant CML cells and overexpression of miR-141-5p could inhibit the growth of IMresistant CML cells and promote their apoptosis.Research on tumor bearing mice had shown that miR-141-5p inhibits tumor growth in vivo.Finally,it was found that miR-141-5p could directly target ABCG1 in IM-resistant CML cells to regulate CML occurrence. Conclusion miR-141-5p and ABCG1 form a competing endogenous RNA(ceRNA) network to function in IM resistance,thus facilitating CML progression.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective:To explore whether multi-parametric MRI (mpMRI) combined with 68Ga-prostate specific membrane antigen (PSMA) PET/CT can improve the detection efficiency of clinically significant prostate cancer (csPCa). Methods:Clinical and imaging data of 152 patients (age (68.5±8.5) years) who underwent mpMRI and 68Ga-PSMA PET/CT examination for suspected prostate cancer in the First Affiliated Hospital of the Air Force Medical University from January 2021 to November 2022 were retrospectively analyzed, with the histopathological results from transrectal ultrasound guided biopsy as reference. Lesions with Gleason scores (GS) ≥3+ 4 from the biopsy were diagnosed with csPCa, and lesions with negative biopsy or GS 6 were diagnosed with non-csPCa. MpMRI was evaluated independently by two radiologists according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. The radioactive uptake of 68Ga-PSMA PET/CT in prostate lesions was evaluated by SUV max. The independent-sample t test, Mann-Whitney U test and χ2 test were used to compare differences between the two groups, and then multivariate logistic regression analysis was performed. ROC curves analysis was used to analyze the diagnostic efficacies of individual and combined factors and Delong test was used. Results:There were 85 csPCa and 67 non-csPCa confirmed. Prostate specific antigen (PSA), PI-RADS score and SUV max were significantly different between the csPCa group and the non-csPCa group ( χ2=68.06, U values: -7.66, -8.98, all P<0.001). Multivariate logistic regression analysis indicated that PI-RADS score (odds ratio ( OR)=3.424, 95% CI: 1.651-7.100) and SUV max ( OR=1.931, 95% CI: 1.403-2.658) were independent predictors of csPCa (both P<0.001). ROC curves analysis revealed that the cut-off value for diagnosing csPCa was 4 for PI-RADS score and 5.6 for SUV max. The accuracy of mpMRI and PET/CT alone in csPCa diagnosis was 80%(122/152) (AUC of 0.789(95% CI: 0.711-0.866) with the sensitivity and specificity of 91%(77/85) and 67%(45/67)), and 87%(132/152) (AUC of 0.876(95% CI: 0.817-0.936) with the sensitivity and specificity of 81%(69/85) and 94%(63/67)), respectively. Several joint models incorporating 68Ga-PSMA PET/CT with mpMRI data were investigated, the model of PI-RADS 5 or PI-RADS 3-4 and SUV max>5.6 showed better performance than mpMRI and PET/CT alone and other joint models ( z values: 2.01-3.64, all P<0.05), with the accuracy of 91%(138/152) (AUC of 0.910(95% CI: 0.857-0.962) with the sensitivity and specificity of 89%(76/85) and 93%(62/67)). Conclusion:MpMRI combined with 68Ga-PSMA PET/CT can significantly improve the detection efficiency of csPCa, with the principal effect being improved in risk stratification of PI-RADS 3-4 lesions in mpMRI.

This paper discussed the current education status on medical ethics and styles and the assessment condition in the examination of doctors' qualification， as well as the existing problems and potential solutions by reviewing domestic and foreign literature and summarizing the practice experience. Traditionally， medical ethics and styles have always been integrated into clinical medical practice in China. However， under the modern medical education system， it is challenged to integrate traditional education on medical ethics and styles with the rules of modern medical knowledge. By summarizing the education and assessment status of medical ethics and styles in the examination of doctors' qualification， it is found that the current examination is relatively poor in the evaluation content， and the way of evaluation is not diverse， with lack of curriculum of medical humanities. The solutions suggested are enriching relevant examination content， introducing more and comprehensive evaluation method， and establishing more medical humanities-related courses.

Objective To investigate the value of methyltransferase-like protein 16(METTL16)in the clinical di-agnosis and prognostic prediction of multiple myeloma(MM)patients.Methods The expression level and prog-nostic potential of each gene involved in N6-methyladenosine(m6A)modification in MM were respectively ana-lyzed in the databases of the Multiple Myeloma Research Foundation(MMRF)and the Genotype-Tissue Expression Project(GTEx).Bone marrow specimens from 26 patients with initial diagnosis of MM and 19 patients with MM af-ter treatment with standard regimens and peripheral blood specimens from 24 normal subjects were collected respec-tively,and the expression levels of m6A genes were determined by qRT-PCR.The correlation between METTL16 expression and various laboratory and clinical indexes was analyzed:hemoglobin(Hb),white blood cell count(WBC),platelet count(PLT),blood creatinine(Scr),serum calcium(Ca2+),β-microglobulin(β-MG),bone destruction,ISS stage,type,and overall survival(OS)in the patients with primary diagnosis.The expression lev-els of interleukin(IL)-4,IL-6,IL-10,IL-18 and chemokine ligand 2(CCL2),CCL3,CCL4 in the specimens were further examined and their correlation with the expression of METTL16 was investigated.Results Database a-nalysis suggested that METTL16 expression was significantly higher in MM patient samples compared with normal controls,which was associated with poor prognosis and had certain diagnostic value.qRT-PCR results showed that the expression level of METTL16 in the bone marrow of patients with initial diagnosis of MM was significantly higher than that of treated patients and normal controls.Its expression was positively correlated with hemoglobin,leuko-cytes and stage,and its expression was positively correlated with CCL4 expression.Conclusion METTL16 expres-sion was significantly elevated in patients with MM,and its expression level was correlated with anemia,more bone destruction and worse stage,which might indicate a poor prognosis.The significant correlation between the expres-sion of METTL16 and CCL4 suggests that METTL16 may play a corresponding pathogenic role through the relevant pathway.METTL16 will have significant clinical value in the management of MM.

Objective To explore the changes in cerebral blood flow caused by mandibular retrusion,as well as the impact and potential mechanisms on stroke recovery.Methods 6-week-old SD male rats were selected as experi-mental subjects.The metal cannula was bonded to the rat maxillary incisor for one week,forcing mandibular retru-sion(MR).Cerebral blood flow was detected by laser speckle imaging.Cognitive function was detected by the Morris water.Then,the stroke model was constructed in MR rats by using the middle cerebral artery occlusion(MCAO)method for one week.Meanwhile,metal cannulae were then removed in rats to restore the lower jaw's position(MCAO RO),serving as a positive control group.Consequently,rats were randomly divided into the fol-lowing groups:Sham groups,MCAO groups,MCAO MR groups,and MCAO RO groups.Neurological recovery was assessed through the modified neurological severity score(mNSS).The area of cerebral infarction was evalua-ted by using triphenyltetrazolium(TTC)staining.The changes in nerve cells were observed by using hematoxylin eosin(HE)staining.The protein expression level of vascular endothelial growth factor(VEGF)was detected by immunohistochemistry.The protein expression levels of platelet-endothelial cell adhesion molecule(CD31),sirtuin 6(SIRT6),and thioredoxin interaction protein(TXNIP)were detected by Western blot.The mRNA expression levels of SIRT6,TXNIP,and VEGF were determined by qRT-PCR.Microglia activation marker molecule 1(IBA-1)was detected by immunofluorescence.Resluts Because of mandibular retrusion,laser speckle showed de-creased cerebral blood flow,and the water maze showed decreased cognitive function.Compared to other groups,MCAO MR showed a larger ischemic area in TTC staining,while HE staining and neurological scoring showed poo-rer neurological function recovery.Western blot and qRT-PCR showed that the MCAO MR group inhibited the mR-NA and protein expression levels of SIRT6,upregulated the mRNA and protein expression levels of TXNIP,and in-creased the activation of microglia.Conclusion Mandibular retrusion reduces cerebral blood flow and alters cogni-tive function in rats.Mandibular retrusion inhibits recovery in stroke through the SIRT6/TXNIP axis.

Objective To provide foundational data for exploring the association between KIR genes and diseases by an-alyzing the frequency and polymorphism of killer-cell immunoglobulin-like receptor(KIR)genes in Han,Manchu and Kore-an populations in Jilin Province.Methods KIR gene typing was performed on 129 Manchu,198 Korean and 201 Han indi-viduals from Jilin using the polymerase chain reaction-sequence specific primers(PCR-SSP)technique.Results KIR3DL2,KIR3DL3,KIR3DP1 and KIR2DL4 were detected in all subjects.KIR2DL1,KIR2DL3,KIR2DS4,KIR3DL1 and KIR2DP1 genes had high detection frequencies,ranging from 93％to 98％across the three ethnic groups.In contrast,the detection rates of KIR2DL2,KIR2DL5,KIR3DS1,KIR2DS1,KIR2DS2,KIR2DS3 and KIR2DS5 were lower,ranging from 13％to 45％.Notably,the detection frequencies of KIR2DL5(17.83％)and KIR2DS1(17.83％)in the Manchu population were significantly lower than those in the Korean(42.93％,47.47％)and Han(33.83％,33.33％)populations in Jilin.The detection frequencies of KIR2DL5(42.93％)and KIR2DS1(47.47％)were significantly higher in the Korean popula-tion compared to the Han(33.83％,33.33％)and Manchu(17.83％,17.83％)population.The frequency of the KIRAA hap-lotype in the Han population was the highest among the three ethnic groups in Jilin at 61.19％,significantly higher than that in the Korean population(42.93％).Differences between the three groups were statistically significant(P＜0.05),and remained significant after Bonferroni correction(Pc＜0.05).Conclusion The distribution of KIR genes in the Korean,Manchu and Han population in Jilin reflects the polymorphism of KIR genes in the Chinese population and also showcases unique ethnic genetic and regional characteristics.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To discuss the expression levels of Eps15 homology domain-containing protein 2(EHD2),microRNA let-7c(miR-let-7c),and long non-coding RNA(lncRNA)FOXD2-AS1 in laryngeal squamous cell carcinoma(LSCC)tissue,and to clarify the association between EHD2/miR-let-7c/FOXD2-AS1 signaling axis and occurrence of LSCC.Methods:Forty LSCC tissue samples were collected and classified into low grade group(moderately or high differentiated,32 cases)and high grade group(poorly differentiated,8 cases)according to the pathology results;according to the tumor node metastasis(TNM)clinical staging results,the samples were divided into TNM early stage group(stagesⅠ-Ⅱ,13 cases)and TNM late stage group(stages Ⅲ-Ⅳ,27 cases);based on the lymph node metastasis results,the samples were divided into metastasis group(21 cases)and non-metastasis group(19 cases).Additionally,40 corresponding normal adjacent tissue samples were collected as control group.Immunohistochemistry method was used to detect the expressions of EHD2 in various groups and its relationships with clinical pathoparameters of the LSCC patients were analyzed;bioinformatics method was used to confirm that the miR-let-7c was the candidate microRNA(miRNA)and FOXD2-AS1,which had binding sites in its promoter region,was a candidate lncRNA.Ten pairs of fresh LSCC tissue samples and adjacent normal tissue samples were collected.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of EHD2 mRNA,miR-let-7c,and FOXD2-AS1 in the samples in two groups,and their associations were verified.Results:Compared with adjacent normal tissue,the expression level of EHD2 in LSCC tissue was significantly decreased(P＜0.01).The positive expression rate of EHD2 in LSCC tissue of the patients in TNM early stage group was significantly higher than that in TNM late stage group(P＜0.05).There was no significant association between EHD2 expression and pathological type or lymph node metastasis(P＞0.05).Compared with control group,the expression level of miR-let-7c in LSCC tissue was significantly decreased(P＜0.05),while the expression level of FOXD2-AS1 was significantly increased(P＜0.05).In LSCC tissue,the expression level of FOXD2-AS1 was negatively correlated with the expression level of miR-let-7c(r=-0.67,P＜0.05),and the expression level of miR-let-7c was negatively correlated with the expression level of EHD2 mRNA(r=-0.83,P＜0.01).Conclusion:EHD2 and miR-let-7c both express at low levels in LSCC tissue and may be new tumor suppressor genes;FOXD2-AS1 is highly expressed in LSCC tissue and may be a new oncogene.FOXD2-AS1/miR-let-7c/EHD2 signaling axis may be involved in the occurrence and development of LSCC.