Table of Content

  

10 November 2021
Volume 59 Issue 11

Mechanism of miR-146a accelerating macrophage migration induced arteriosclerosis via TLR4/MyD88 pathway

YANG Jia, ZHANG Man, CHEN Kaiming, CAO Xi

Journal of Shandong University (Health Sciences). 2021, 59(11):  1-7.  doi:10.6040/j.issn.1671-7554.0.2021.0162

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Objective To explore the specific mechanism of microRNA-146a(miR-146a)regulating macrophage migration induced arteriosclerosis via toll-like receptor 4(TLR4)and myeloid differentiation factor88(MyD88)pathway(TLR4/MyD88). Methods RAW264.7 macrophages were divided into blank group, ox-LDL group, miR-146a mimic group, miR-146a inhibitor group, siRNA-MyD88 group, siRNA-NC group, siRNA-MyD88+miR-146a mimic group, and siRNA-MyD88+miR-146a inhibitor group. Except the blank group, the other groups were treated with 50mg/L ox-LDL. The protein expressions of TLR4, MyD88, nuclear factor kappa-B(NF-κB), and interleukin-6(IL-6)were detected with Western blotting. The mRNA expressions of miR-146a, TLR4, MyD88, NF-κB and IL-6 were detected with qPCR. The migration ability of macrophages was detected with Transwell assay. Results (1) The ox-LDL group had higher protein expressions of TLR4 and IL-6, but lower migration ability of macrophages and lower mRNA expression of TLR4 than the blank group(P<0.01). (2) The miR-146a mimic group had lower mRNA and protein expressions of TLR4, lower migration ability of macrophages, but higher mRNA expression of miR-146a than the ox-LDL group(P<0.01). The miR-146a inhibitor group had higher mRNA and protein expressions of TLR4, higher migration ability of macrophages, but lower mRNA expression of miR-146a than the ox-LDL group(all P<0.01). (3) The shRNA-MyD88 group had lower protein expressions of MyD88, NF-κB and IL-6, and lower migration ability of macrophages than the ox-LDL group(P<0.01); there was no difference in the expressions of miR-146a and TLR4(P>0.05). The shRNA-MyD88+miR-146a mimic group had higher expression of miR-146a but lower expression of TLR4 than the shRNA-MyD88 group(P<0.01). There were no significant differences in the protein expressions of MyD88, NF-κB, IL-6 and migration rate of macrophages between shRNA-MyD88 group and shRNA-MyD88 group(P>0.05). The shRNA-MyD88+miR-146a inhibitor group had lower expression of miR-146a but higher expression of TLR4 than the shRNA-MyD88 group(P<0.01). There were no significant differences in the expressions of MyD88, NF-κB, IL-6 and migration rate of macrophages(P>0.05). Conclusion miR-146a is a protective factor of atherosclerosis, which can inhibit the process of macrophage migration by regulating the secretion of inflammatory factors by antagonizing TLR4/MyD88 pathway. This can provide a new therapeutic target for the prevention and treatment of arteriosclerosis.

Prognostic value of POU4F3 in 118 patients with lung adenocarcinoma and its effect on migration of lung adenocarcinoma cells

CHAI Xiaoxue, YE Hui, LYU Xinran, DING Xuchao, ZHEN Qiulai, DU Juan, CAO Lili

Journal of Shandong University (Health Sciences). 2021, 59(11):  8-18.  doi:10.6040/j.issn.1671-7554.0.2021.0193

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Objective To reveal the expression of POU domain class 4 transcription factor 3(POU4F3)in lung adenocarcinoma(LUAD)tissues and its association with the prognosis of lung adenocarcinoma(LUAD)patients, and to explore the effect of POU4F3 on the migration of LUAD cells. Methods Immunohistochemical staining(IHC)was used to detect the expression of POU4F3 in human LUAD and its adjacent tissues, both of the sample sizes being 118. Log-rank(Mantel-Cox)was used to examine the correlation between POU4F3 expression and the overall survival of LUAD patients. Taking the LUAD cells as the experimental subject, stable overexpression(Lv-POU4F3)and its control(Lv-control)or knockdown of POU4F3(shPOU4F3)and its control(control shRNA)lentivirus were constructed and transfected into SPCA1 and A549 cells, respectively. Western blotting was conducted to verify the efficiency of POU4F3 overexpression or knockdown transfection. Cell migration was detected by wound healing, Transwell migration assay, and phalloidine fluorescence experiment. Results IHC analysis showed that the expression of POU4F3 in LUAD tissues was significantly lower than that in adjacent tissues(1.5 vs 4.0), and the difference was statistically significant(P<0.001). Compared with LUAD patients with low POU4F3 expression, patients with high POU4F3 expression had significantly longer overall survival(HR=2.04, 95%CI: 1.158-3.607, P=0.028). Cell experiment results showed that stably transfected LUAD cell lines overexpressing or knocking down POU4F3 were constructed effectively. After overexpression of POU4F3, the wound healing expreriment showed that the wound healing rate of cells in the Lv-POU4F3 group was lower than that in the Lv-control group, the difference was statistically significant(F_{SPCA1 treatment}=69.86, P_SPCA1=0.001; F_{A549 treatment}=492.10, P_A549<0.001). Transwell migration assay showed that the number of transmembrane cells in the SPCA1-Lv-POU4F3 group was less than that in the SPCA1-Lv-control group(599.0±11.36 vs 806.3±18.72, t=16.40, P<0.001), and the number of transmembrane cells in the A549-Lv-POU4F3 group was less than that in the A549-Lv-control group(181.0±18.68 vs 314.7±23.46, t=7.72, P=0.002). The phalloidine fluorescence experiment showed that SPCA1 cells with overexpression of POU4F3 had thinner microfillets and fewer pseudopodia. The mean fluorescence intensity of Lv-POU4F3 group was lower than that of Lv-control group(23.30±1.34 vs 33.45±1.85), and the difference was statistically significant(t=7.67, P=0.002). After POU4F3 was knocked down, wound healing experiment showed that the cell wound healing rate of shPOU4F3 group was higher than that of control shRNA group, the difference was statistically significant(F_{SPCA1 treatment}=114.60, P_SPCA1<0.001; F_{A549 treatment}=1 710.00, P_A549<0.001). Transwell migration assay showed that the number of transmembrane cells in SPCA1-shPOU4F3 group was higher than that in the SPCA1-control shRNA group(970.00±14.53 vs 585.00±25.53, t=22.70, P<0.001), and the number of transmembrane cells in A549-shPOU4F3 group was higher than that in the A549-control shRNA group(528.00±29.14 vs 185.30±9.50, t=19.37, P<0.001). The phalloidine fluorescence experiment showed that after knockdown of POU4F3, SPCA1 cell microfilules became thicker and pseudopodia increased. The mean fluorescence intensity of shPOU4F3 group was higher than that of control shRNA group(48.53±3.30 vs 31.07±2.32), and the difference was statistically significant(t=7.50, P=0.002). Conclusion The expression of POU4F3 in human LUAD tissues is significantly lower than that in para-cancerous tissues. LUAD patients with high expression of POU4F3 have a better prognosis. POU4F3 can inhibit the migration of LUAD cells. POU4F3 may be a novel tumor suppressor gene of LUAD and a new target for the diagnosis and treatment of LUAD.

Construction of a stemness-based scoring model predicting the efficacy of immunotherapy in lung adenocarcinoma based on public databases

PANG Zhaofei, LIU Yong, ZHAO Xiaogang, YAN Tao, CHEN Xiaowei, DU Jiajun

Journal of Shandong University (Health Sciences). 2021, 59(11):  19-28.  doi:10.6040/j.issn.1671-7554.0.2021.0603

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Objective To predict immune checkpoint blockade(ICB)response in lung adenocarcinoma(LUAD)by identifying LUAD subtypes related to cancer stem cells and constructing a stemness-based scoring model. Methods LUAD RNA-seq data were obtained from TCGA database. By “limma” package, 329 differentially expressed genes(DEGs)related to cancer stem cells between LUAD(535 cases)and adjacent tissues(59 cases)were identified to classify LUAD into different subtypes(FDR<0.05, |log₂ Fold Change|>2). By univariate Cox regression analysis, the common prognostic DEGs among different subtypes were further screened out. Using principal component analysis(PCA)and the 123 common prognostic DEGs, a stemness-based scoring model was established for 630 LUAD patients from TCGA and GEO. The cutoff value, determined by Kaplan-Meier curves analysis, was used to stratify LUAD patients into high- and low-score groups(cutoff value=-1.91). Furthermore, difference of distinct subtypes and stemness-based scores on tumor microenvironment(TME)and ICB therapy were analyzed. Results Thirty-six differentially expressed genes and three LUAD subtypes related to cancer stem cells(CSC-A, CSC-B, and CSC-C)were identified, overall survival rates of which were statistically different(P=0.033). The three subtypes greatly affected immune infiltration levels and were associated with multiple immune pathways, such as antigen presentation and cytotoxicity. A total of 123 common prognostic genes(P<0.05)were screened out to construct stemness-based scoring model by univariate Cox regression. In the low-score group, the infiltration of various immune cells and mRNA expressions of PD1, PD-L1 and CTLA4 were up-regulated. No matter anti-CTLA4 or anti-PD1 treatment alone, or combination of them, efficacy of the low-score group was better than that of the high-score group, and there was no significant difference in the efficacy of the two groups without ICB(P=0.060). In the anti-PD-L1 and anti-PD1 immunotherapy cohorts, the response rates of the low-score group were higher than that of the high-score group(the response rate of the anti-PD-L1 treatment cohorts: 50% vs 20%; the response rate of anti-PD1 treatment cohorts: 23% vs 0%). Conclusion Stemness-based scoring model has a potential to predict the efficacy of ICB therapy in LUAD patients, which is expected to provide a theoretical basis for ICB therapy in LUAD patients.

Analysis of dietary protein intake of 459 elderly women during in vitro fertilization

GENG Ling, ZHANG Huanhuan, ZHANG Tiantian

Journal of Shandong University (Health Sciences). 2021, 59(11):  29-34.  doi:10.6040/j.issn.1671-7554.0.2021.0451

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Objective To investigate the status of dietary protein intake of elderly women during in vitro fertilization(IVF). Methods A total of 459 elderly women who planned to receive IVF in the Center for Reproductive Medicine, Shandong University during Sep. 2018 and Sep. 2019 were selected. Their diets were surveyed using the food frequency method to calculate the daily dietary protein, amino acid intake and protein dietary sources. Results The median dietary protein intake was 61.73 g/d, and 65.14% of the subjects reached the recommended intake. The median dietary protein intake of urban and rural subjects was 62.76 g/d and 60.35 g/d, respectively, with no significant difference(P=0.019). The proportion of urban subjects who reached the recommended dietary protein intake was 70.56%, which was higher than that of rural subjects(59.65%, P=0.015). The main source of protein food was plant, accounting for 63.08%, and high-quality protein accounted for 33.66% of the protein supply. Protein from grain and potato was higher among rural subjects(P=0.070), while protein from livestock, poultry, fish, shrimp and milk was higher among urban subjects(P<0.05). The scores of essential amino acids ranged from 0.97 to 1.83. Conclusion The dietary protein intake of elderly women during IVF is appropriate. The source of protein is mainly plant food, and the essential amino acid model is close to the WHO/FAO recommended model, but some subjects have unreasonable protein intake. Rural subjects need to intake more animal protein.

Fluorescence in situ hybridization in the diagnosis of 197 cases of chronic lymphocytic leukemia

ZENG Rui, HU Xinting, YUN Xiaoya, TIAN Zheng, LI Qing, LIU Jie, ZHANG Ya, WANG Xin

Journal of Shandong University (Health Sciences). 2021, 59(11):  35-40.  doi:10.6040/j.issn.1671-7554.0.2021.0791

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Objective To explore the application of fluorescence in situ hybridization(FISH)in the diagnosis and prognosis assessment of chronic lymphocytic leukemia(CLL). Methods The 197 CLL patients treated during Jan. 2014 and Jan. 2021 received molecular genetic tests with RB1(13q14.1), D13S25(13q14.3), P53(17p13.1), ATM(11q22.3)and CSP12(+12), 62 of whom underwent karyotype analysis and 75 immunoglobulin heavy chain variable region(IGHV)mutation status detection. Results The total detection rate of abnormal molecular genetic markers was 56.4%(111/197). D13S25(13q14.3)accounted for 63.1%(70/111), followed by RB1(13q14.1)43.2%(48/111), p53(17p13.1)29.7%(33/111), ATM(11q22.3)22.5%(25/111), and CSP12(+12)13.5%(15/111). Patients with 2 chromosomal abnormalities accounted for 34.2%(38/111), among whom RB1 and D13S25 double-positive patients accounted for 25.2%(28/111). Patients with 3 or more chromosomal abnormalities accounted for 16.2%(18/111). The positive rate of FISH was significantly higher than that of conventional cytogenetics(P<0.001). The results of FISH test were correlated with the International Prognostic Index for Chronic Lymphocytic Leukemia(CLL-IPI). The proportion of high-risk and very high-risk patients with positive FISH test results was larger than that with negative FISH test results(P=0.009). The CLL-IPI scores of FISH-P53 positive patients were high or very high(P<0.001). Among FISH positive patients, 78% were IGHV mutated and 22% were IGHV unmated. Conclusion FISH is a critical molecular genetic detection method with higher sensitivity than chromosome karyotype analysis, which can provide rational guidance for the prognosis evaluation and treatment of CLL patients.

Correlation between insulin resistance and expressions of local inflammatory factors and glucose transporter protein type-4 in the endometrium of patients with polycystic ovary syndrome

HA Lingxia, YIN Ting, WU Yangyang, LI Weixia, DU Yudong

Journal of Shandong University (Health Sciences). 2021, 59(11):  41-47.  doi:10.6040/j.issn.1671-7554.0.2021.0733

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Objective To explore the expressions of local inflammatory factors and glucose transporter protein type-4(GLUT-4)in the endometrium of patients with polycystic ovary syndrome(PCOS), and to analyze the correlation between insulin resistance(IR)and the expressions of inflammatory factors and GLUT-4. Methods A total of 60 PCOS patients treated during June 2018 and July 2020 were enrolled. Based on the homeostasis model assessment for insulin resistance index(HOMA-IR), the patients were divided into IR PCOS group(n=30)and non-IR PCOS group(n=30). Meanwhile, 60 non-PCOS patients were collected and divided into IR group(n=30)and normal control group(n=30). Follicle stimulating hormone(FSH), luteining hormone(LH), estradiol(E₂), testosterone(T), prolactin(PRL)and anti-Mullerian hormone(AMH)were detected. The expressions of tumor necrosis factor alpha(TNF-α), nuclear factor-kappa B(NF-κB)and GLUT-4 in the endometrium were detected with immunohistochemistry. Results (1) There were significant differences in body mass index(BMI), AMH, LH and T among the 4 groups(F=57.35, 29.54, 16.77, 21.20, P<0.001). Group A had higher BMI than group B; group C had higher BMI than group D. Groups A and B had higher levels of AMH and LH than groups C and D. Group A had higher T than group B. (2) There were significant differences in expressions of TNF-α, NF-κBp65 and GLUT-4 among the 4 groups(F=76.90, 45.13, 47.75, P<0.001). Group A had higher expressions of TNF-α and NF-κBp65 but lower GLUT-4 than group B. Group C had higher expressions of TNF-α and NF-κBp65 but lower expression of GLUT-4 than group D. (3)The results of multivariate Logistic regression analysis showed that HOMA-IR was positively correlated with the expression of NF-κBp65 but negatively correlated with the expression of GLUT-4 in PCOS and non-PCOS patients(P<0.05); HOMA-IR was positively correlated with BMI in non-PCOS patients(P<0.05). Conclusion Insulin resistance is associated with NF-κBp65 and GLUT-4 in PCOS patients. It may increase the expressions of local inflammatory factors and decrease the expression of GLUT-4 in the endometrium.

Correlation among PAX1 methylation, high-grade cervical intraepithelial lesions and HR-HPV classification

LIANG Tingting, YANG Yongxia, HOU Congzhe, HUANG Taisheng, WANG Huali, ZHU Lin

Journal of Shandong University (Health Sciences). 2021, 59(11):  48-52.  doi:10.6040/j.issn.1671-7554.0.2021.0795

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Objective To analyze the correlation among PAX1 methylation, cervical high-grade intraepithelial neoplasia and the type of high-risk HPV. Methods From Aug. 2019 to Oct. 2020, women who underwent thinprep cytologic test(TCT)and high-risk human papillomavirus(HR-HPV)DNA examinations in The Second Hospital of Shandong University were screened, and 397 patients with abnormal TCT results: ≥atypical squamous cells of undetermined significance(ASCUS), and/or HR-HPV positive were selected. According to the consensus of Chinese experts on the application of colposcopy in 2020, those with abnormal colposcopy results should also undergo biopsy and RT-qPCR to detect PAX1 methylation. Results Pathological grade of 397 patients were CIN3+(55 cases), normal/cervicitis(72 cases), CIN1(36 cases), and CIN2(72 cases); their PAX1 methylation levels were 18.64(4.01, 20.83), 20.22(19.24, 20.84), 20.33(19.65, 21.00), and 20.43(15.31, 21.08). The PAX1 methylation level of CIN3+ patients was higher than that of normal/CIN1/CIN2 patients(Z=3.03, 2.65, 3.06; P=0.002, 0.008, 0.002). The PAX1 methylation levels of HPV16-positive patients(89 cases)and type 12 high-risk HPV(12HR-HPV)-positive patients(174 cases)were 19.72(10.00, 20.91)and 21.00(18.97, 21.02)(Z=2.736, P=0.006). Among ASCUS patients, the methylation levels of CIN2+(23 cases)and normal/CIN1(19 cases)were 20.47(19.33, 21.18)and 18.03(11.2, 20.82)(Z=2.45, P=0.014). Conclusion The degree of PAX1 methylation is related to high-grade cervical intraepithelial lesions and HPV types. PAX1 methylation detection would benefit the early identification of CIN3+ and high-grade cervical lesions in ASCUS, help the diversion of ASCUS, and reduce the referral rate of colposcopy.

Value of MRI radiomics of glioma and peritumoral edema in evaluating tumor recurrence

SONG Zhenzhen, SUN Xiaoling, LI Haiou, WANG Fang, ZHANG Ran, YU Dexin

Journal of Shandong University (Health Sciences). 2021, 59(11):  53-60.  doi:10.6040/j.issn.1671-7554.0.2021.0997

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Objective To explore the value of MRI radiomics of glioma and peritumoral edema(PTE)in evaluating the postoperative recurrence. Methods A total of 120 patients with glioma confirmed by postoperative pathology during Jan. 2013 and Dec. 2020 were retrospectively selected, including 55 cases with recurrence and 65 cases without recurrence. The tumor and PTE were delineated by three-dimensional volumetric regions of interest based on the preoperative T₂WI and contrast enhanced T1WI images, which were divided into training group and validation group according to the ratio 8∶2. The relationship between tumor recurrence and the radiomic characteristics was analyzed. The receiver operating characteristic(ROC)curve was drawn, and the area under curve(AUC)and accuracy matrix were used to compare and evaluate the results of different radiomic models. Results For PTE, KNN classifier had the best prediction performance(AUC=0.910, sensitivity=0.84, specificity=0.88), while in the validation group, the AUC, sensitivity, and specificity were 0.916, 0.82 and 0.93, respectively. For tumor, LR classifier had the best prediction performance: the AUC, sensitivity and specificity of the training group were 0.777, 0.69 and 0.67, respectively, while in the validation group, they were 0.758, 0.82 and 0.92, respectively. In the model of tumor connected with PTE, LR classifier had the best prediction performance: the AUC, sensitivity and specificity of the training group were 0.977, 0.88 and 0.89, respectively, while in the validation group, they were 0.841, 0.73 and 0.83, respectively. Conclusion The MRI radiomic features of PTE and glioma are valuable to predict postoperative recurrence, and the KNN model of PTE has the best diagnostic efficacy.

Correlation between the copy number of plasma free mitochondrial DNA and severity of burn patients

XU Xiaofeng, WANG Jianzhen, YANG Zehua

Journal of Shandong University (Health Sciences). 2021, 59(11):  61-66.  doi:10.6040/j.issn.1671-7554.0.2021.0222

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Objective To investigate the changes of plasma free mitochondrial DNA(mtDNA)copy number in patients with different degrees of burns and its role in the severity of burns. Methods In accordance with the burn degree and total body surface area(TBSA), 30 patients with severe burns and 30 patients with moderate burns were selected. Another 30 healthy subjects were enrolled as controls. Plasma samples were collected on day 1, days 8-11, and days 18-21. DNA was extracted, and the copy numbers of plasma free mtDNA were detected with real-time fluorescent quantitative PCR. The correlation among mtDNA copy number, acute physiology and chronic health evaluation Ⅱ score(APACHE Ⅱ), multiple organ dysfunction syndrome score(MODS), TBSA, Ⅲ° burn area, burn index and biochemical indicators were analyzed, and Logistic regression was conducted. Results On day 1 of admission, the severe burn group had higher copy number of plasma free mtDNA than the other two groups, and the free mtDNA copy number reached the peak on days 8-11 and then decreased. The copy number of mtDNA was positively correlated with total burn size, Ⅲ° burn area, burn index, APACHE Ⅱ score and MODS(P<0.05), positively correlated with biochemical indicators such as aspartate aminotransferase, alanine aminotransferase, total bilirubin, procalcitonin, and white blood cells(P<0.01), but negatively correlated with total protein, albumin and prealbumin(P<0.01). Logistic regression analysis showed that APACHE Ⅱ score and mtDNA copy number on day 1 of admission were independent risk factors for burn severity(P<0.05). The area under the ROC curve for the diagnosis of burn degree of mtDNA copy number was 0.904, with a sensitivity of 0.833 and a specificity of 0.867. Conclusion The copy number of plasma free mtDNA in burn patients is correlated with the degree of burn and a number of biochemical indexes, which can provide references for the clinical classification of degree of burn.

Distal tubular acidosis caused by homozygous deletion of ATP6V0A4 gene: a case report and 12 years follow-up analysis

WU Xia, WANG Wenhong

Journal of Shandong University (Health Sciences). 2021, 59(11):  67-71.  doi:10.6040/j.issn.1671-7554.0.2021.0902

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Objective To analyze the clinical features, genotypes and prognosis of distal tubular acidosis(dRTA)(MIM602722). Methods The clinical data of a child with dRTA were retrospectively analyzed and a literature review was performed. Results The full-term cesarean section boy did not gain weight on the 34th day after birth. The blood gas analysis showed the hyperchlorinated acidosis with normal anion gap, hypokalemia, alkaline urine, renal pyramidal calcification, and renal osteopathy. The child was followed up for 12 years. After treatment with citric acid mixture, the childs physical development caught up to normal, and renal osteopathy disappeared. The child developed hearing impairment, proteinuria and renal impairment at the age of 11. Gene sequencing showed that there was a homozygous deletion in exon 3-5 of APT6V0A4 gene. Both parents had a loss of heterozygosity in this gene. This mutation was pathogenic and consistent with the diagnosis of autosomal recessive dRTA. Conclusion Early intervention should be given to younger patients with dRTA to achieve satisfactory physical development outcome. Gene sequencing is an important means to determine the genetic pathogenic factors, which can predict the long-term prognosis. It is of great significance for genetic counseling and should be followed up for a long time.

Cerebrotendinous xanthomatosis: a case report and literature review

KONG Wencheng, XU Guangrun, JIA Junli, CUI Xinyu

Journal of Shandong University (Health Sciences). 2021, 59(11):  72-75.  doi:10.6040/j.issn.1671-7554.0.2021.0849

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Objective To investigate the clinical manifestations, imaging features and gene mutations of 1 patient with cerebrotendinous xanthomatosis(CTX), in order to raise clinicians awareness of this disease. Methods The clinical data of 1 patient with CTX treated in our hospital were analyzed, and relevant literature was reviewed. Results The male patient was 30 years old, with poor vision since childhood, admitted to our hospital due to unstable walking for 2 years. Physical examination showed bilateral Achilles tendon masses and cavus, high muscle tone in the extremities, and positive bilateral pyramidal tract sign. Brain MRI showed slightly high intensity in bilateral cerebellar dentate nuclei on T2WI. Ankle MRI showed bilateral Achilles tendon xanthoma. The scores of Mini Mental State Examination and Montreal Cognitive Assessment were 15/30 and 10/30, respectively. Genetic testing of the patient and his parents showed the patient had compound heterozygous for c.1214G > A and c.1004C > T in CYP27A1. Conclusion Early symptoms of CTX are occult and non-specific. Patients may have a history of neonatal chronic diarrhea, juvenile cataract, juvenile osteoporosis and tendon xanthoma. When patients develop neurological symptoms such as cognitive impairment, progressive ataxia and pyramidal tract sign, CTX should be considered and genetic testing should be performed as early as possible. Early treatment can delay disease progression.

Mediating effect of meaning in life on the association between psychological strain and suicidal behavior risk among college students

QIN Yiwen, YANG Xiaofan, WEI Yanxin, LIU Baopeng, Bob Lew, JIA Cunxian

Journal of Shandong University (Health Sciences). 2021, 59(11):  76-83.  doi:10.6040/j.issn.1671-7554.0.2021.0357

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Objective To explore the mediating effect of meaning in life between psychological strain and suicidal behavior risk in college students. Methods A total of 1,574 college students from a university in Jinan were investigated by Psychological Strain Scale, Purpose in Life Test-Short Form and Suicidal Behaviors Questionnaire-Revised. Results A total of 244 college students were classified with suicidal behavior risk. The score of meaning in life was negatively correlated with the score of psychological strain and the score of suicidal behavior risk(r=-0.482, -0.297, both P<0.001), and the score of psychological strain was positively correlated with the score of suicidal behavior risk(r=0.335, P<0.001). Mediating effect test showed that meaning in life played a partial mediating role between college students psychological strain and suicidal behavior risk, and the mediating effect accounted for 25.12% of the total variance. Conclusion Reducing college students psychological strain and cultivating their meaning in life could reduce the risk of suicidal behavior.

Associations between self-harm behavior and psychosocial-polymorphism in female freshmen

XU Xiaoming, ZENG Qi, CAO Jun, CHEN Xiaorong, LYU Zhen, WANG Wo, AI Ming, KONG Yiting, KUANG Li

Journal of Shandong University (Health Sciences). 2021, 59(11):  84-92.  doi:10.6040/j.issn.1671-7554.0.2021.0470

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Objective To explore the factors associated with self-harm behavior in female freshmen by using multi-modal data such as single nucleotide polymorphisms(SNPs)of serotonin receptor gene, social demographic characteristics, and psychological characteristics. Methods iMLDR^TM multiplex SNP typing was used to detect 4 SNPs, i. e., rs878567, rs10042486, rs1364043, and rs1423691, in HTR1A gene and 9 SNPs, i. e., rs3125, rs1745837, rs1928042, rs2770296, rs731779, rs6313, rs2070037, rs6311, and rs2070040, in HTR2A gene from 68 female freshmen with self-harm behavior(self-harm group)and 46 healthy controls(control group). The genotypes, alleles, and haplotype frequencies were compared. Additionally, the gene-psychosocial-self-harm interaction was analyzed. Results There were significant differences in the family history of mental illness, structured clinical interview for SCID diagnosis, impulsive personality, aggressive personality, and internet addiction behavior between the self-harm and control group(P<0.05). There was no significant difference in the frequencies of genotypes and alleles of the 13 candidate SNPs between the self-harm and control groups. In the dominant model, the G/T-T/T genotype in rs1364043 locus in self-harm group was 2.19(95%CI=1.01-4.74)times of that in the control group. rs10042486-rs1364043-rs1423691-rs878567 in HTR1A gene and rs2770296-rs731779-rs2070037-rs2070040-rs6313-rs6311 in HTR2A gene showed strong linkage disequilibrium, respectively. There was no significant difference in haplotypes between the self-harm and control groups(P>0.05, adjusted for age, economic level, BMI, chronic somatic disease, family history of mental illness, SCID diagnosis, aggressive personality, impulsive personality, and internet addiction). The interaction between rs6313 and rs6311 loci and impulsive personality showed a significant difference between the control and self-harm groups. Similarly, after the interaction of rs10042486, rs1423691, and rs878567 loci with internet addiction behavior and SCID diagnosis, respectively, significant differences have been shown between the self-harm and control groups(P<0.05). Conclusion The SNPs of the HTR1A and HTR2A gene are related to the self-harm behavior in the female freshmen or play an indirect role through interaction with impulsive personality, internet addiction, or diagnosis of mental disorders.

Relationship between sense of meaning in life and suicidal ideation in medical students

ZHANG Yilin, WANG Chao, ZOU Guangshun, LYU Juncheng

Journal of Shandong University (Health Sciences). 2021, 59(11):  93-99.  doi:10.6040/j.issn.1671-7554.0.2020.0073

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Objective To investigate the sense of meaning in life and suicidal ideation in medical students, so as to explore their relationship and influencing factors. Methods From May to October 2020, 2 000 medical students from Weifang Medical College and Binzhou Medical College were selected by random stratified cluster sampling method, and surveyed with a self-compiled general questionnaire, Purpose in Life Test(PIL)and Beck Suicidal Ideation Scale Chinese Version(BSI-CV). A total of 1 847 valid questionnaires were collected. Results The average age of medical students was(19.39±1.26)years, and the detection rate of suicidal ideation in the past week was 21.33%. The average score of the sense of meaning in life was 53.73±17.18. Medical students with low sense of meaning in life were more likely to develop suicidal ideation than those with high scores (t=-16.041, P<0.001). There was a negative correlation between sense of meaning in life and suicidal ideation(r_s=-0.390, P<0.001). Multiple Logistic regression showed that the factors related to suicidal ideation were high sense of meaning in life(OR=0.521, 95%CI: 0.472-0.575), democratic child discipline(the reference group was other)(OR=0.583, 95%CI: 0.360-0.944), no friends or relatives committing suicide(OR=0.555, 95%CI: 0.382-0.806), unavailability of help under stress and difficulties(OR=1.527, 95%CI: 1.003-2.323), number of close friends(3 or more in the reference group)being 0(OR=2.494, 95%CI: 1.650-3.769)and 1(OR=1.955, 95%CI: 1.432-2.669), gap between ideal and reality(no gap in the reference group)being large(OR=2.084, 95%CI: 1.220-3.559)and very large(OR=2.235, 95%CI: 1.171-4.264). Conclusion The rate of suicidal ideation among medical students is high. Those with low sense of meaning in life are more likely to develop suicidal ideation. The sense of meaning in life is associated with suicidal ideation. Medical colleges and universities should take targeted measures such as strengthening the sense of meaning in life education so as to reduce suicidal ideation.

Mediating effect of cognition on the relationship between social capital and functional health of elderly people

LIU Xinyu, WANG Quan, JU Haojie, SUN Xiaojie

Journal of Shandong University (Health Sciences). 2021, 59(11):  100-107.  doi:10.6040/j.issn.1671-7554.0.2021.0429

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Objective To estimate the mediating effect of cognition on the association between social capital and functional health. Methods The database of China Health and Retirement Longitudinal Study(CHARLS)was applied in the study and 4,451 seniors aged 60 years and above in Wave 4(2015)of the survey were retrieved. Social capital was measured by social trust, social support, social participation and reciprocity. The total effect was classified as direct effect and indirect effect through Logistic regression analysis based on the Karlson-Holm-Breen method. Results After the potential confounders were adjusted, including age, marital status, bank deposit, literacy, residence, smoking, drinking, sleep duration at night, self-rated health, chronic diseases and disability, older adults with high social trust(OR=1.249, 95%CI: 1.072-1.455), care(OR=1.351, 95%CI: 1.180-1.546)and social participation(OR=1.167, 95%CI: 1.021-1.334)had better functional health. Cognition played a mediating role in the total effect of social participation on functional health(OR=1.046, 95%CI: 1.008-1.085). The mediating effect of cognition accounted for 29.22% of the total effect. Conclusion Cognition has a mediating effect on the association between social capital and functional health. Improving the level of social capital of older adults can directly improve their functional health, and contribute to their physical function by enhancing cognition.

A cluster analysis of suicide attempters in rural Shandong Province according to their suicidal behaviors

WEI Yanxin, WANG Xinting, LIU Baopeng, LI Yuanyuan, ZHANG Jiyu, JIA Cunxian

Journal of Shandong University (Health Sciences). 2021, 59(11):  108-113.  doi:10.6040/j.issn.1671-7554.0.2021.0034

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Objective To classify and explore the characteristics of different types of suicide attempters in terms of the suicidal behaviors. Methods The demographic characteristics, psychosocial factors, and details of suicide attempts of 408 medically serious suicide attempters in rural areas of Shandong Province were collected by face-to-face interviews. Cluster analysis was performed using the two-step method. Results The suicide attempters fell into two types: 231(56.62%)in the impulsive cluster, characterized by low suicide intent, low lethality, and high impulsiveness; 177(43.38%)in the well-planned cluster, characterized by high suicide intent, high lethality, and more histories of attempted suicide. The well-planned group was associated with older age(P=0.003), mental illness(P<0.001), and higher depression and hopelessness(P<0.001). Conclusion Cluster analysis extracts two distinct groups of suicide attempters showing different patterns of suicidal behaviors. Targeted prevention strategies should be formulated for different groups.

Distribution of cerebrovascular stenosis and construction of a screening model

YANG Jiulong, YU Tao, XUE Fuzhong

Journal of Shandong University (Health Sciences). 2021, 59(11):  114-119.  doi:10.6040/j.issn.1671-7554.0.2021.0450

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Objective To establish a screening model of cerebrovascular stenosis based on Logistic regression. Methods This study selected 1,118 physical examiners without cerebrovascular stenosis by magnetic resonance angiography(MRA)as the control group, and 1,329 with cerebrovascular stenosis diagnosed by digital subtraction angiography(DSA)as the case group. Distribution of the sites of cerebrovascular stenosis was described. Routine and economic examination indicators were adopted to construct a Logistic screening model of cerebrovascular stenosis in both male and female. The model was evaluated with area under the receiver operator characteristic curve(AUC). Results Among the 1,329 cerebrovascular stenosis patients, 985 were male and 344 were female. In the Logistic screening model with age adjustment, 8 variables were screened out for male, including age, aspartate transaminase, albumin, high-density lipoprotein, neutrophil value, hypertension, smoking and drinking, while 5 variables were screened out for female, including albumin, high-density lipoprotein, fasting blood glucose and hypertension. The high-density lipoprotein, albumin, hypertension and neutrophil value were involved in both male and female. The AUC was 0.927 and 0.888 for male and female, respectively. After 10-fold cross validation, the AUC was 0.928 and 0.885, respectively. Conclusion The model has good screening ability and is useful for identifying high-risk individuals with cerebrovascular stenosis.