Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for circular superficial esophageal cancer.Methods:A retrospective analysis was conducted on 74 consecutive cases of circular superficial esophageal squamous cell carcinoma treated with ESD at Nanjing Drum Tower Hospital from January 2015 to December 2019. The success rate of ESD, curative resection rate, incidence of complications, and additional treatment were mainly observed.Results:One case was transferred to surgery, and the remaining 73 cases successfully completed ESD treatment. The success rate of ESD was 98.6%. Postoperative pathology of ESD revealed that 39 cases achieved curative resection, with a curative resection rate of 53.4% (39/73). Intraoperative muscle layer injury occurred in 15 cases (20.5%), and intraoperative perforation occurred in 1 case (1.4%). Two cases (2.7%) experienced delayed bleeding, and one case (1.4%) experienced delayed perforation. Eleven cases were lost to follow-up, and the remaining 62 cases received follow-up for 36.4±19.0 months. Among the follow-up cases, 12 underwent additional surgery and 5 cases additional chemotherapy and radiotherapy. Among the 57 patients with follow-up data who did not underwent surgery, 49 developed esophageal stenosis after ESD, with an incidence rate of 86.0%.Conclusion:ESD for circular superficial esophageal cancer is generally safe, but it is prone to muscle layer injury during the operation, with a low curative resection rate, a high incidence of postoperative esophageal stenosis, and a high proportion of additional surgical procedures.

BACKGROUND: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether baseline serum lipid parameters influence the benefits of intensive SBP control is unclear. METHODS: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to <130 mmHg) and standard (SBP target of 130 to <150 mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. A total of 8283 participants from the STEP study were included in this post hoc analysis to examine whether the effects of the SBP intervention differed by baseline low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) concentrations. RESULTS: Regardless of the randomized SBP intervention, baseline LDL-C and non-HDL-C concentrations had a J-shaped association with the hazard of the primary outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline LDL-C level ( P for interaction = 0.80) and non-HDL-C level ( P for interaction = 0.95). Adjusted subgroup analysis using tertiles in LDL-C1 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.52-1.13; P = 0.18), LDL-C2 (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29), and LDL-C3 (HR, 0.68; 95% CI, 0.47-0.98; P = 0.04) was provided, with an interaction P value of 0.49. Similar results were showed in non-HDL-C1 (HR, 0.87; 95% CI, 0.59-1.29; P = 0.49), non-HDL-C2 (HR, 0.70; 95% CI, 0.48-1.04; P = 0.08), and non-HDL-C3 (HR, 0.67; 95% CI, 0.47-0.95; P = 0.03), with an interaction P -value of 0.47. CONCLUSION: High baseline serum LDL-C and non-HDL-C concentrations were associated with increased risk of primary cardiovascular disease outcome, but there was no evidence that the benefit of the intensive SBP control differed by baseline LDL-C and non-HDL-C concentrations. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03015311.
Aged ; Humans ; Cardiovascular Diseases ; Blood Pressure/physiology* ; Cholesterol, LDL ; Hypertension ; Cholesterol ; Risk Factors

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

Objective:To investigate the diagnostic value of DDIT3 immunohistochemical antibody in myxoid liposarcoma.Methods:A total of 53 patients diagnosed with myxoid liposarcoma and with DDIT3 gene rearrangement detected by fluorescence in situ hybridization (FISH) from 2010 to 2022 in Beijing Jishuitan Hospital were enrolled as the case group, and 50 patients with other tumors that needed to be differentiated from myxoid liposarcoma during the same period were enrolled as the control group. The immunochemical (IHC) expression of DDIT3 was evaluated in all cases and the specificity and sensitivity in the diagnosis of myxoid liposarcoma were calculated. The correlation between IHC DDIT3 expression and FISH detection of DDIT3 gene rearrangement was analyzed.Results:Among the 53 cases of myxoid liposarcoma, thirty-one patients were males and twenty-two were females. The patients ranged in age from 11 to 74 years, with a median age of 51 and an average age of 49.4 years. The expression rate of IHC DDIT3 expression in 53 cases of myxoid liposarcoma was 100%. No expression was found or only scattered individual cell (<10%) expression was seen in a very few cases in the. control group. There was no significant correlation between the proportion and intensity of IHC and FISH DDIT3 positive cells or the partner gene.Conclusions:The sensitivity and specificity of DDIT3 immunohistochemical antibody in the diagnosis of myxoid liposarcoma are both 100%, which are consistent with the results of FISH. It can be used as a convenient and economical diagnostic tool for myxoid liposarcoma.

Objective:Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer.Methods:Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage: 2 331 lung cancer cases and 3 077 healthy controls; validation stage: 626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer.Results:A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer ( P<0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model: OR=1.33, 95% CI:1.01-1.74, P=0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model: OR=0.71, 95% CI:0.52-0.96, P=0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model: OR=1.53, 95% CI: 1.01-2.32, P=0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model: OR=0.83, 95% CI: 0.69-0.98, P=0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele( OR=3.35,95% CI:2.10-5.34, P<0.001). Conclusion:There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.

Objective: To explore the relationship between childhood maltreatment and suicide ideation of college students,so as to provide basis for physical and mental health of college students. Methods: Students from 6 universities in Shanxi Province(3 854 college students provided eligible questionniare for childhood abuse and 3 882 for suicidal ideation) were selected by multi-stage random cluster sampling from May to July 2018, the Chinese Version of the Childhood Trauma Questionnaire and the Self-rating Idea of Suicide Scale were used in the survey. Results: Of all subjects,42.4% had at least one kind of abuse experience in childhood and 3.9% had suicidal ideation in the past week. By chi square test,the detection rate of suicidal ideation of college students who suffered physical abuse,emotional abuse,sexual abuse,physical neglect,emotional neglect in childhood was higher than that of college students without maltreatment (χ2=13.78，12.97，17.10，56.56，66.58，P<0.01)；Spearman correlation analysis showed that there was a positive correlation between each type of maltreatment in childhood and college students’ suicidal ideation(r=0.06，0.06，0.07，0.12，0.13，P<0.01)；Multivariate Logistic regression model found that after controlling other influencing factors,physical neglect and emotional neglect in childhood were independent risk factors for suicide ideation of college students (OR=2.18,2.07,P<0.05). Conclusion Physical neglect and emotional neglect in childhood can increase the risk of college students’ suicidal ideation. Paying enough attention and care to them in early childhood may help to prevent their suicidal ideation in adulthood.

To investigate the value of injecting a small amount of absolute ethanol into the benign solid nodules of the thyroid before radiofrequency ablation(RFA)to improve the efficiency of radiofrequency ablation. A total of 98 eligible patients(98 nodules)with pathologically confirmed benign solid nodules who were treated in our center from December 2016 to February 2018 were included and randomized into ethanol ablation(EA)combined with radiofrequency ablation(RFA)group(EA+RFA group)and RFA group,with 49 patients in each group.Routine ultrasound,contrast-enhanced ultrasound(CEUS),and thyroid function test were performed before treatment and 1,3,6,and 12 months after treatment.The general information,treatment time,ablation energy,ablation power,postoperative nodule volume reduction ratio(VRR),symptom score(SS)and cosmetic score(CS),thyroid function level,and incidence of complications were compared between these two groups. The mean treatment time [(441.30±243.31)s (790.70±349.82)s;= 4.403, =0.000],mean ablation energy [(3.92±2.01)kJ (5.15±2.12)kJ;=2.709, =0.009],and mean ablation power [(6.07±1.44)W (7.30±1.29)W;=3.612, =0.006] were significantly lower in the EA+RFA group than in the RFA group.At 3,6 and 12 months after surgery,the VRR in the EA+RFA group was(57.73±11.07)%(=-3.16, <0.001),(64.40±10.56)%(=-5.45, <0.001),and(77.29±8.48)%(=-10.46, <0.001),respectively;the VRR in the RFA group was(55.44±13.01)%(=-1.76, <0.001),(65.28±11.33)%(=-5.09, <0.001),and(75.17±9.84)%(=-8.93, <0.001),which were significantly smaller than those before surgery.There was no significant difference in VRR between the EA+RFA group and the RFA group at 1(=3.41, =0.33),3(=2.05, =0.21),6(=2.77, =0.49),and 12 months(=5.05, =0.10)after treatment.During the follow-up,no recurrence of nodules was observed on CEUS.In the EA+RFA group,the SS [(1.77±0.86).(5.54±2.15);=9.63, <0.001] and the CS[(1.39±0.77).(3.32±0.61);=10.09, =0.004]at 12 months after surgery were significantly lower than those before surgery.In the RFA group,SS [(1.63±1.04).(5.90±1.79);=12.72, <0.001] and CS [(1.64±0.83).(3.15±0.72);=8.13, =0.012] at 12 months after surgery were also significantly lower than those before surgery.The CSS in the EA+RFA group was significantly lower than that in the RFA group [(0.93±0.55).(2.44±0.53);=-11.70, =0.007].Both groups had no significant change in thyroid function during the follow-up period,and no serious complications were observed. Anhydrous alcohol injection can effectively improve the efficiency of radiofrequency ablation in treating benign solid thyroid nodules and is effective in reducing nodule volume,alleviating compressive symptoms,and decreasing cosmetic discomfort.
Catheter Ablation ; Ethanol ; Humans ; Neoplasm Recurrence, Local ; Prospective Studies ; Thyroid Nodule ; Treatment Outcome

Objective: To explore the relationship between cyberbullying and depression in college students, and to provide a scientific basis for the prevention of cyberbullying. Methods: A total of 3 914 college students from 6 universities in Shanxi Province were selected as research objects. The students’ cyberbullying behavior scale and depression self-rating scale were used to investigate the students. Results: The overall reported rate of cyberbullying among college students was 17.4%. Boys who suffered from online verbal bullying and online fraud scored higher than girls. Students whose parents divorced scored higher than those whose parents did not divorce in all dimensions of cyber-bullying. There was a statistically significant difference in the overall scores of students with different degrees of education and time spent online( P <0.05). Depression was reported in 15.6% of participants. The depression scores of female students were higher than that of male students.College students whose parents were divorced had higher depression scores than those whose parents were not divorced.There were statistically significant differences in depression scores among college students with different fathers’ education levels and different time spent online every day( t / F =2.05, 6.64, 3.91 , 19.52, P <0.05). Pearson correlation analysis showed that online speech bullying, online fraud and identity concealment bullying were positively correlated with depression scores( r s =0.40, 0.36, 0.46, P <0.01). Multiple linear regression analysis showed that three forms of cyberbullying were risk factors for the increase of depression in college students( β =0.89, 0.38, 0.38, P <0.01). Conclusion Cyber-bullying is one of the risk factors for increasing the severity of depression among college students.Strengthening the management of Internet use, promotion college students’ interpersonal conununication and active cooperating between society, school and family are great significance to reduce the occurrence of cyberbullying.

Objective: To explore the relationship between childhood abuse and cyberbullying among college students and to provide theoretical support for early intervention of cyberbullying among college students. Methods: A total of 3 850 sophomores and juniors from 6 universities in Shanxi Province, randomly selected by stratified cluster sampling method, were investigated by using the Questionnaire on Cyberbullying and the Chinese Version of the Child Abuse Questionnaire. Results: Male students reported higher rates of sexual abuse, emotional neglect and physical neglect than female students(χ2=5.22, 4.39, 7.53 P<0.05). The child abuse report rate of college students whose parents divorced was higher than that of those whose parents were not divorced(χ2=86.80, 134.06, 130.18, 175.64, 118.46，P<0.05). In addition to physical neglect, childhood abuse rate of only children was higher than that of non-only children, with statistically significant differences(χ2=9.44, 12.44, 21.18, 21.26, all P<0.05). The scores of all factors and total scores of cyberbullying implemented by male students were higher than those by female students(t=9.35, 5.59, 5.83, 7.57，P<0.05); the scores of all factors and total scores of cyberbullying implemented by only-child students were higher than those by non-only-child students(t=2.79, 3.74, 4.78, 4.40，P<0.05); the scores of all factors and total scores of cyberbullying implemented by students whose parents were divorced were higher than those by students whose parents were not divorced, with statistically significant differences(t=6.99,6.78, 8.04，11.33, P<0.05). Multiple linear regression model showed that there was a positive correlation between the childhood abuse of college students and the implementation of cyberbullying, and regression coefficient differences of all factors were statistically significant(β=0.10, 0.11, 0.05, 10.08,0.06, P<0.05). Conclusion Childhood abuse experiences increase the risk of college students practicing cyberbullying.