Table of Content

  

10 May 2022
Volume 60 Issue 5

Protective effect and mechanism of growth differentiation factor-15 in LPS-induced models of Parkinsons disease

ZHANG Xiufang, LI Peizheng, ZHANG Bohan, SUN Congcong, LIU Yiming

Journal of Shandong University (Health Sciences). 2022, 60(5):  1-7.  doi:10.6040/j.issn.1671-7554.0.2022.0102

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Objective To investigate the protective effect and mechanism of growth differentiation factor 15(GDF15)in lipopolysaccharide(LPS)induced neuroinflammation associated with Parkinsons disease. Methods To explore the optimum time of LPS, BV2 cells were divided into blank, 3 h, 6 h, 12 h and 24 h groups; to explore the optimum concentration of LPS, BV2 cells were divided into blank, 0.5, 1 and 2mg/mL groups; to explore the effect of GDF15, BV2 cells were divided into blank, LPS and LPS+GDF15 groups. The mice were divided into WT, WT+LPS and KO-LPS group. The protein expressions of STAT3, NF-κB and ERK were detected with Western blotting. The mRNA expressions of TNF-α, IL-1β, iNOS and COX-2 were detected with qPCR. The effect of GDF15 on the morphology of LPS-induced BV2 cells was observed with a microscope. Results GDF-15 suppressed the expressions of TNF-α, IL-1β, iNOS and COX-2 by inhibiting the STAT3/NF-κB/ERK signaling pathway. In the substantia nigra and striatum of the GDF15 knockout mice, the expressions of TNF-α, IL-1β, iNOS and COX-2 increased. Conclusion GDF15 can attenuate the expressions of TNF-α, IL-1β, iNOS and COX-2 through STAT3/NF-κB/ERK signaling pathway, indicating it is a protective factor in the progression of Parkinsons disease. It can provide a new therapeutic target for the prevention and treatment of this disease.

GSK3β/eEF2K signaling involves in the induced differentiation of lung fibroblasts by regulating autophagy

QIN Chaoqun, HUANG Bin, YANG Fang, WANG Changming, XIAO Ying, HUANG Hancan, LI Liying, GAO Feng

Journal of Shandong University (Health Sciences). 2022, 60(5):  8-15.  doi:10.6040/j.issn.1671-7554.0.2021.0878

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Objective To explore the expression of glycogen syntheses kinases 3β(GSK3β)/eukaryotic elongation factor 2 kinases(eEF2K)during the conversion of lung fibroblasts into myofibroblasts, and to investigate its effects on cellular fibrosis and autophagy. Methods L-929 cells(control group)were cultured under appropriate conditions for 48 h, and transformed into myofibroblasts(TGF-β1 group)by 5ng/mL TGF-β1. Myofibroblasts were transfected with empty plasmid, si-eEF2K and si-GSK3β. The protein expressions of p-eEF2K and α-SMA were detected with immunofluorescence staining after 48 hours of culture, and the protein expressions of eEF2K, p-eEF2K, GSK3β, P62 and LC3-Ⅱ/Ⅰ were detected with Western blotting. Results Compared with the control group, the TGF-β1 group had increased expression of p-eEF2K, GSK3β and α-SMA(P<0.05). After transfection with si-eEF2K and si-GSK3β, the expressions of p-eEF2K and α-SMA decreased, while the expressions of P62 and LC3-Ⅱ/Ⅰ increased(P<0.05). Conclusion GSK3β/eEF2K signalling may promote the phenotypic transformation of lung fibroblasts to myofibroblasts by reducing autophagic activity and facilitating the process of cellular fibrosis.

Effects of orphan nuclear receptor NR4A1 on H₂O₂ induced injury of mouse renal podocytes

LIU Min, ZHANG Yuchao, MA Xiaoli, LIU Xinyu, SUN Lu, ZUO Dan, LIU Yuantao

Journal of Shandong University (Health Sciences). 2022, 60(5):  16-21.  doi:10.6040/j.issn.1671-7554.0.2021.1504

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Objective To explore the expression of orphan nuclear receptor(NR4A1)in mouse renal podocytes(MPC-5)under H₂O₂ induced oxidative stress and to investigate the effects of NR4A1 on the viability and apoptosis of MPC-5. Methods MPC-5 were divided into blank control group(H₂O₂ concentration was 0 μmol/L or treatment time was 0 h), and treatment groups(related to different H₂O₂ concentrations or treatment time). After MPC-5 were treated with H₂O₂ to establish the oxidative stress model, the mRNA and protein expressions of NR4A1 and Caspase 3(17 kDa)were detected with Q-PCR and Western blotting, respectively. After MPC-5 were infected with lentivirus with cDNA encoding NR4A1, the stable cell lines with NR4A1 over-expression(Ad-NR4A1 group)and the empty vector(Ad-Ctrl group)were selected with puromycin. After H₂O₂ treatment, the protein expression of Caspase 3(17 kDa), viability and apoptosis were detected with Western blotting, CCK8 assay and TUNEL staining, respectively. Results After H₂O₂ treatment, both protein and mRNA expressions of NR4A1 were significantly higher in the treatment groups than in the blank control group(P<0.05), and the protein expression of Caspase 3(17 kDa)also significantly increased(P<0.05). The protein expression of NR4A1 was much higher in Ad-NR4A1 group than in Ad-Ctrl group(P<0.001). After H₂O₂ treatment, the protein expression of caspase 3(17 kDa)was significantly higher in Ad-NR4A1 group than in Ad-Ctrl group, the apoptotic rate was significantly higher(P<0.05), and the cell viability was significantly lower(P<0.05). Conclusion H₂O₂ induced oxidative stress contributes to the decreased cell viability and increased cell apoptosis in MPC-5. The possible mechanism is related to the activation of Caspase 3 by NR4A1.

Evening primrose oil resists oxidative stress in the ovaries of rats with polycystic ovary syndrome

HU Na, SUN Miao, XING Shasha, XU Danxia, HAI Xiaoming, MA Ling, YANG Li, MIAN Yuchen, HE Rui, CHEN Dongmei, MA Huiming

Journal of Shandong University (Health Sciences). 2022, 60(5):  22-30.  doi:10.6040/j.issn.1671-7554.0.2022.0016

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Objective To investigate the effects of evening primrose oil(EPO)on the hormonal, metabolic and oxidation levels in rats with polycystic ovary syndrome(PCOS)induced by high-fat diet combined with letrozole, and to explore the expression of NAD-dependent deacetylase sirtuin-1(SIRT1)/Forkhead box O1(FoxO1)signaling pathway in the ovarian tissue. Methods A total of 72 rats were divided into 6 groups, with 12 as the normal control group, and the other 60 rats were fed high-fat diet(40%)for 8 weeks. In the last 3 weeks of the feeding program, letrozole at a concentration of 1 mg/kg/d was added to prepare PCOS models. After the models were established, the serum hormonal levels in the tail of rats were analyzed, and 2 rats with large deviation were removed from each group. Plus the normal control group, the PCOS models were divided into 5 groups, with 10 rats in each group: PCOS model group, metformin group, EPO low-dose group, EPO medium-dose group, and EPO high-dose group. The serum fasting plasma glucose(FPG), serum insulin(FINS), testosterone(T), luteinizing hormone(LH), follicle stimulating hormone(FSH), superoxide Dismutase(SOD), total antioxidant capacity(T-AOC)and malondialdehyde(MDA)of each group were detected with ELISA and biochemical method. The ovarian morphology was observed with hematoxylin and eosin(HE)staining. The locations and expressions of SIRT1/FoxO1 pathway, SOD1 and glutathione S-transferase(GST), SIRT1 and FoxO1 were detected with immunohistochemistry and Western blotting. Results Compared with the blank control group, the PCOS model group had significantly increased weight, FPG, FINS, T, LH, FSH(P<0.05), significantly decreased SOD and T-AOC(P<0.05), and significantly increased MDA(P<0.01). ELISA results showed that after EPO and metformin treatment, the weight, FPG, FINS and MDA decreased(P<0.05), but SOD increased(P<0.05)compared with the PCOS model group. Compared with PCOS model group, the metformin group, medium-dose and high-dose groups had significantly increased T-AOC(P<0.05), but significantly decreased T and LH(P<0.05). Compared with the PCOS model group, the metformin group and high-dose group had significantly decreased FSH level(P<0.05). Immunohistochemical results showed that SOD1, GST and SIRT1 were positively expressed in granulosa cells, mesenchymal cells, primordial follicles and corpus luteum. Western blotting results showed that compared with the blank control group, the PCOS model group had significantly increased expressions of SIRT1, FoxO1, P -FoxO1, P-FoxO1/FoxO1, SOD1 and GST(P<0.05). Compared with the PCOS model group, the high-dose group had significantly decreased levels of SOD1, GST and P-FoxO1(P<0.05); the medium-dose group had significantly decreased levels of SIRT1 and FoxO1(P<0.05). Conclusion EPO affects the levels of oxidative factors and hormones in the serum of PCOS model rats, inhibits the expression of SIRT1/FoxO1 signaling pathway, enhances the antioxidant capacity of ovarian tissue and improve the oxidative stress.

Effects of diabetes mellitus on the subsets and function of NK cells in myasthenia gravis

LI Tao, YANG Chunlin, DU Tong, LI Heng, WANG Congcong, LI Xiaoli, DUAN Ruisheng,ZHANG Peng

Journal of Shandong University (Health Sciences). 2022, 60(5):  31-36.  doi:10.6040/j.issn.1671-7554.0.2022.0051

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Objective To explore the changes and functional characteristics of NK cells subtypes in myasthenia gravis(MG)patients with diabetes mellitus. Methods The clinical data of 26 MG patients treated during Jan. 2021 and Dec. 2021 were collected, including 13 MG patients with diabetes mellitus(MG+DM group)and 13 MG patients without diabetes mellitus(MG group). The frequency of NK cells and their subtypes, expressions of IFN-γ and IL-17 in NK cells, and ratio of Th1 and Th17 cells were detected with flow cytometry. In in vitro experiment, the expressions of IFN-γ in NK cells cultured with high glucose were detected with flow cytometry. Finally, the correlation of IFN-γ secreted by NK cells with the frequency of Th1 and Th17 cells was analyzed. Results The frequency of CD56^bright NK was higher in MG+DM group than in MG group(P=0.022), and frequency of CD56^bright was positively correlated to the quantitative MG(QMG)score(r_s=0.47, P=0.015). The frequency of IFN-γ⁺ NK cells(P=0.043)and mean fluorescence intensity(MFI)of IFN-γ in IFN-γ⁺ NK cells(P= 0.029)were increased in the MG+DM group. The frequency of IFN-γ⁺ NK cells(P=0.046)and MFI of IFN-γ(P=0.011)were increased in high-glucose environment than in the control. The frequency of IFN-γ⁺ NK cells and MFI of IFN-γ in IFN-γ⁺ NK cells were positively correlated with the frequency of Th1 cells(r=0.52, P=0.009; r=0.41, P=0.045)and Th17 cells(r=0.66, P<0.001; r=0.60, P=0.002). Conclusion Diabetes mellitus may induce abnormal differentiation of Th1 and Th17 cells by promoting NK cells’ secretion of IFN-γ in MG patients.

Clinical and imaging characteristics of 4 cases of secondary hypertrophic olivary degeneration

GONG Yu, GAO Zhen, WANG Huqing, YANG Jingwen, ZHANG Guilian, ZHAN Shuqin, ZHANG Ru, WU Haiqin

Journal of Shandong University (Health Sciences). 2022, 60(5):  37-42.  doi:10.6040/j.issn.1671-7554.0.2021.0969

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Objective To explore the clinical and imaging characteristics of secondary hypertrophic olivary degeneration(HOD)so as to improve the clinical recognition and diagnosis. Methods The clinical and imaging data of 4 patients treated during Apr. 2019 and Jan. 2020 were retrospectively analyzed, and the mechanism was discussed. Results All cases were secondary HOD. Symptoms of extra-vertebral system appeared, while symptoms of pyramidal system in different lesions of the brainstem and cerebellum were stable. Limited high signal was observed in the enlarged inferior olivary nucleus on T₂WI imaging. Conclusion Variant lesions in brain stem or cerebellum may lead to the occurrence of secondary HOD. When extra-vertebral system symptoms appear in addition to stable vertebral system symptoms, HOD should be considered. A clear diagnosis requires appropriate imaging examinations.

Characterization of regulatory T cells in gastric cancer based on single-cell RNA sequencing data

GAO Huiru, DU Tiantian, WANG Yunshan, DU Lutao, WANG Chuanxin

Journal of Shandong University (Health Sciences). 2022, 60(5):  43-49.  doi:10.6040/j.issn.1671-7554.0.2022.0121

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Objective To explore the cell composition of gastric cancer and normal gastric tissues and to analyze the difference in regulatory T cells between gastric cancer and normal gastric tissues. Methods The downloaded single-cell RNA sequencing data were subjected to quality control, dimensional-reduction clustering and cell annotation. Regulatory T cells were extracted for differential gene, developmental trajectories, GSVA and cell interaction analysis to observe the differences between regulatory T cells from normal tissues and cancer tissues. Results In terms of cell composition, there was great heterogeneity in different patients and different sample types. Compared with normal tissues, cancer tissues had higher proportion of regulatory T cells which were related to cell death, cell cycle and other pathways. Cell interaction analysis showed that regulatory T cells in cancer tissues interacted with other cells with lower frequency and greater intensity, and the interaction patterns changed significantly. Conclusion Regulatory T cells mainly exist in the microenvironment of gastric cancer. There are significant differences in the number and function of regulatory T cells between gastric cancer and normal tissues.

Prediction of hepatocellular carcinoma prognostic genes based on bioinformatics

LI Linlin, WANG Kai

Journal of Shandong University (Health Sciences). 2022, 60(5):  50-58.  doi:10.6040/j.issn.1671-7554.0.2022.0128

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Objective To screen hepatocellular carcinoma(HCC)prognostic genes based on bioinformatics methods and explore the action mechanism of related genes. Methods The expression of NUF2 in liver cancer tissues and normal liver tissues was studied based on the TCGA-LIHC dataset, the Gene Expression Omnibus(GEO)database, and the Ualcan database. The relationship of NUF2 expression and clinicopathological features of HCC was analyzed using the Wilcoxon rank-sum test. Survival analysis, univariate analysis of prognosis, and multivariate analysis were carried out using Kaplan-Meier method and Cox proportional risk regression model, respectively. The functional mechanisms was explored based on the GO and KEGG pathway enrichment analysis. NUF2 protein interaction network was constructed using the STRING database. The NUF2 interaction genes were analyzed using the LinkedOmics database to explore the regulatory mechanism of NUF2 in hepatocarcinogenesis. In addition, the relationship between NUF2 expression and tumor-infiltrating immune cell status was investigated using the TIMER database and CIBERSORT. Results Compared to normal liver tissues, NUF2 was significantly highly expressed in HCC tissues. Multivariable Cox regression analysis identified NUF2 as an independent risk factor in HCC, and patients with high NUF2 expression had significantly shorter overall survival than those with low NUF2 expression. In addition, the NUF2 protein interaction network was constructed by the STRING database and LinkedOmics database, and the functional analysis showed that NUF2 and its associated genes were mainly involved in nuclear division, chromosome segregation, mitosis, chemical-induced carcinogenesis, cell cycle and other processes. Finally, a high proportion of resting memory CD4T cells, activated memory CD4T cells, follicular helper T cells, regulatory T cells(Treg)and M0 macrophages was observed in patients with high NUF2 expression. Conclusion Upregulation of NUF2 in HCC tissues plays a key role in HCC development. High expression of NUF2 can serve as a potential diagnostic and prognostic marker to identify early and late HCC, improve timeliness and diagnostic and prognostic accuracy. NUF2 plays a key role in the immune mechanism during HCC tumorigenesis.

Comparison among ERCP combined with ursodeoxycholic acid and other therapies in the treatment of choledocholithiasis complicated with cholecystolithiasis

DONG Xiaoqian, LI Guanjiang, XU Qianqian, XU Hongwei

Journal of Shandong University (Health Sciences). 2022, 60(5):  59-66.  doi:10.6040/j.issn.1671-7554.0.2021.1065

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Objective To investigated the curative effects of endoscopic retrograde cholangiopancreatography(ERCP)combined with ursodeoxycholic acid(UDCA)and other two mainstream therapies in the treatment of patients over 75 with choledocholithiasis complicated with cholecystolithiasis, and to analyze factors affecting quality of life after surgery. Methods Clinical data of 184 elderly patients(≥75 years old)with choledocholithiasis and cholecystolithiasis treated in Shandong Provincial Hospital Affiliated to Shandong First Medical University during June 2017 and June 2019 were retrospectively analyzed. According to the treatment options, the patients were divided into ERCP+UDCA group with 66 patients, laparoscopic cholecystectomy(LC)+laparoscopic common bile duct exploration(LCBDE)group with 64 patients, and ERCP+LC group with 54 patients. The general data, short-term and long-term complications, and surgical condition were compared, and the quality of life was assessed with Gastrointestinal Quality of Life Index(GIQLI)scale two years after surgery. One-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data, and chi-square test or Fishers exact test was used for comparison of categorical data between groups. Bonferroni correction was used for multiple comparisons. Multinomial Logistic regression model was used to explore the independent factors of GIQLI scale two years after surgery. Results The three groups were comparable in age, sex, stone number and previous history(P>0.05). There were statistically significant differences among the ERCP+UDCA group, LC+LCBDE group and ERCP+LC group in operation time ［43.0(37.0, 61.8)min vs 200.0(170.0, 243.8)min vs 189.0(172.0, 215.5)min］, hospitalization costs ［31.9(27.1, 38.0)thousand yuan vs 45.8(38.1, 52.5)thousand yuan vs 54.4(48.6, 65.2)thousand yuan］, hospital stay ［6.0(5.0, 8.8)d vs 10.5(8.0, 12.0)d vs 13.0(9.0, 15.5)d］ and time to extraction of drainage tube ［3(2,4)d vs 30(28,30)d vs 4(4,7)d, all P<0.001］. Compared with the other two groups, the ERCP+UDCA group had shorter operation time, hospital stay and extraction of drainage tube, and lower hospital costs(all P<0.05). There were no significant differences in the rate of surgical success, postoperative catheterization, incidence of short-term and long-term complications, and GIQLI score among the three groups(all P>0.05). Age increase and postoperative complications were independent risk factors affecting GIQLI scale 2 years after surgery. Conclusion ERCP+UDCA could effectively control the disease without reducing elderly patients quality of life. Comprehensive therapy and individualized treatment based on the characteristics of the disease should be carried out in clinical treatment instead of performing the LC blindly. Early detection, early treatment and reduction of postoperative complications are effective ways to improve postoperative quality of life.

Causes of misdiagnosis and mistreatment of lumbar degenerative diseases complicated with hip joint diseases(hip-spine syndrome)

ZHANG Jingliang, LIU Xinyu, YUAN Suomao, WANG Lianlei

Journal of Shandong University (Health Sciences). 2022, 60(5):  67-73.  doi:10.6040/j.issn.1671-7554.0.2022.0045

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Objective To summarize the clinical characteristics of hip joint diseases complicated with lumbar degenerative diseases, and to analyze the causes and countermeasures of misdiagnosing them as lumbar degenerative diseases. Methods Cases diagnosed as lumbar degenerative diseases who had poor therapeutic outcomes were collected during Apr. 2013 and Aug. 2020. During the follow-up, 33 patients with hip disease requiring surgical treatment were involved, including 18 males and 15 females, aged from 41 to 79 years, with an average of(51±12)years. Preoperative diagnosis was lumbar spinal stenosis in 24 cases and lumbar disc herniation in 9 cases. Preoperative symptoms included low back pain in 9 cases(27.3%), hip pain in 11 cases(33.3%), greater trochanter pain in 5 cases(15.2%), groin pain in 2 cases(6.1%), anterior/posterior thigh pain in 4 cases(12.1%), knee pain in 5 cases(15.2%), lower leg pain in 3 cases(9.1%), and intermittent claudication in 21 cases(63.6%). Preoperative physical examination included straight-leg raising test(+)in 7 cases, Patrick sign(-)in 19 cases, Patrick sign(+)in 5 cases and no original medical records in 9 cases. Primary lumbar spine operation methods were lumbar lamina fenestration and discectomy in 6 cases, PETD in 2 cases, lumbar laminectomy and decompression in 5 cases, Open-PLIF in 19 cases and MIS-TLIF in 1 case. Results During the average follow-up of(3.4±1.3)years, 21 cases had poor symptom relief and were confirmed 3 months after operation, 10 cases were confirmed 3 months to 1 year after operation, and 2 cases were confirmed more than 1 year after operation. The re-diagnosis results included aseptic necrosis of femoral head in 16 cases(unilateral in 14 cases, bilateral in 2 cases), and acetabular dysplasia complicated with osteoarthritis in 17 cases(unilateral in 16 cases, bilateral in 1 case). Secondary preoperative clinical symptoms were low back pain in 1 case(3.0%), hip pain in 11 cases(33.3%), greater trochanter pain in 5 cases(15.2%), groin pain in 2 cases(6.1%), anterior/posterior thigh pain in 4 cases(12.1%), knee pain in 5 cases(15.2%), lower leg pain in 3 cases(9.1%), and limb in 14 cases(42.4%). Physical examination included straight leg lifting test(+)in 1 case, Patrick sign(-)in 4 cases,(+)in 23 cases and(±)in 6 cases. Conclusion When the imaging examination of lumbar degenerative diseases is inconsistent with the symptoms and signs, we should be alert to the possibility of hip joint diseases. The clinical manifestations of osteoarthritis of hip joint and idiopathic femoral head necrosis are sometimes atypical, which may simply manifests as pain and discomfort in waist and buttocks, and pain can radiate to the front of thigh or similar to sciatica. In patients with hip-spine syndrome, the diagnostic specificity of straight leg lifting test and Patrick sign is not high. Careful preoperative physical examination and necessary imaging screening can effectively reduce misdiagnosis and mistreatment.

Expression of aryl hydrocarbon receptor nuclear translocator-like 2 in endometrial cancer

SHEN Xiaochang, SUN Yiqing, YAN Lei, ZHAO Xingbo

Journal of Shandong University (Health Sciences). 2022, 60(5):  74-80.  doi:10.6040/j.issn.1671-7554.0.2021.1475

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Objective To explore the expression and function of aryl hydrocarbon receptor nuclear translocator-like 2(ARNTL2)in endometrial cancer(EC)and its possible signal pathway. Methods The expression of ARNTL2 in EC and normal tissues was detected with immunohistochemistry, RT-PCR and Western blotting. After ARNTL2 knock down with Si-RNA(Si-ARNTL2), cell proliferation, invasion and migration were detected with CCK-8 assay, scratch healing test and Transwell assay, respectively. The epithelial-mesenchymal transition(EMT)indicators, including E-cad, N-cad, Vimentin, Snail and Slug, and Wnt/β-catenin signal pathway related proteins, including Wnt and β-catenin, were detected with Western blotting. Results Immunohistochemistry, RT-PCR and Western blotting showed that the expression of ARNTL2 was up-regulated in EC tissue(t_{Immunohistochemistry}=2.213, P=0.033; t_RT-PCR=4.766, P<0.001; t_{Western blotting}=2.659, P=0.012). Si-ARNTL2 transfection successfully reduced ARNTL2 expression in EC cell lines(KLE and Ishikawa). After knockdown of ARNTL2, CCK8 assay showed reduction in the absorbance of both cell lines(P<0.05); Scratch healing test showed a suppression on wound healing rate(P<0.001); Transwell invasion and migration assay showed that the number of transmembrane cells decreased(P<0.01). Western blotting showed that the expression of E-cad in the two cell lines increased, while the expressions of N-cad, Vimentin, Snail and Slug decreased(P<0.05), and the expressions of Wnt and β-catenin decreased(P<0.05). Conclusion The expression of ARNTL2 is higher in EC tissue than in normal tissue. Knockdown of ARNTL2 can inhibit cell proliferation and metastasis in EC. ARNTL2 may promote tumor proliferation and metastasis through Wnt/β-catenin pathway.

Optimal anesthesia depth with propofol closed-loop administration to effectively inhibit surgical stress response in patients undergoing robot-assisted radical thyroidectomy via bilateral axillo-breast approach

KUANG Fengxia, ZHAO Xiaohong, HAN Baojia, GAO Chengjie

Journal of Shandong University (Health Sciences). 2022, 60(5):  81-86.  doi:10.6040/j.issn.1671-7554.0.2021.1315

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Objective To investigate the optimal anesthesia depth with closed-loop administration of propofol guided by bispectral index(BIS)monitor to effectively inhibit surgical stress response in patients undergoing robot-assisted radical thyroidectomy(RAT)via bilateral axillo-breast approach(BABA). Methods A total of 60 patients undergoing BABA-RAT were enrolled and randomly assigned to the high target BIS group(55±5, n=30)and low target BIS group(45±5, n=30). Heart rate(HR), mean arterial pressure(MAP)were measured at the time points of pre-induction of anesthesia(T₀), 1h after operation beginning(T₁), the end of operation(T₂)and 6 h after operation(T₃). Serum concentration of IL-6 and C-reaction protein(CRP)were measured at T₀, T₂, T₃ and T₄(24 h after operation). Propofol consumption and incidence of adverse events were recorded. Results Propofol consumption was higher in the low target BIS group than in high target BIS group. There were no significant differences in MAP and HR at all the time-points between the two groups(P>0.05). Ascensional range of IL-6 and CRP were significantly lower in low target BIS group at T₃ and T₄(P<0.05). VAS was lower in low target BIS group 24 h postoperatively(P<0.05). No adverse events such as hypotension, intraoperative awareness or postoperative cognitive dysfunction occurred. Conclusion Anesthesia depth maintained at BIS of 45±5 is more effective than 55±5 to restrain surgical stress response and postoperative pain.

Predictive value of CT-based radiomics nomogram for the invasiveness of lung pure ground-glass nodules

GAO Lin, YU Xinxin, KANG Bing, ZHANG Shuai, WANG Ximing

Journal of Shandong University (Health Sciences). 2022, 60(5):  87-97.  doi:10.6040/j.issn.1671-7554.0.2022.0500

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Objective To assess whether radiomic characteristics extracted from non-contrast computed tomography(NCCT)and contrast enhanced computed tomography(CECT)images could improve the ability to distinguish the histological invasive lesions manifesting as pure ground-glass nodules(pGGNs), and to develop a nomogram to improve the prediction ability to differentiate atypical adenomatous hyperplasia(AAH)and adenocarcinoma in situ(AIS)from minimally invasive adenocarcinoma(MIA)and invasive adenocarcinoma(IAC). Methods Our study recruited 332 patients with 364 lung pGGNs during Dec. 2018 and Jun. 2021 in Shandong Provincial Hospital Affiliated to Shandong First Medical University. According to pathological types, the patients were divided into prodromal lesion group(n=157, including AAH and AIS)and invasive lesion group(n=207, including MIA and IAC). Image features were extracted from each nodular region of interests on NCCT and CECT images. Least absolute shrinkage and selection operator(LASSO)was employed for feature selection, and the chosen characteristics were used to build a radiomics signature according to their weights in LASSO. Clinical variables and CT morphological features were combined to develop a clinical factor model. A nomogram including independent clinical variables and Rad-score was developed. The nomogram performance was confirmed by receiver operating characteristic(ROC)curve, calibration and decision curve analysis(DCA). Results The tri-phase including non-contrast, arterial and venous phase Rad-score showed a good discrimination in an average area under ROC curve(AUC)of 0.915 and 0.841 in the training and validation sets, higher than those in normal scan(0.882, 0.796), arterial phase(0.884, 0.814), venous phase(0.897, 0.841), and clinical factor model(0.805, 0.747). Radiomics nomogram consisting of tri-phase Rad-score and clinical factors had a better performance(AUC=0.928, 0.854)than the performance of Rad-score and clinical factor models. Conclusion The radiomic features extracted from CECT images can improve the determination ability, and the radiomics nomogram can help in predicting the invasiveness of adenocarcinoma manifesting as pGGNs.

Comparison of ultrasound and enhanced CT percutaneous puncture of mixed density chest lesions

DONG Liang, CUI Wenchao, ZHOU Qing, ZHANG Longyun, ZHOU Wei, ZHANG Xin, ZHAO Chao

Journal of Shandong University (Health Sciences). 2022, 60(5):  98-103.  doi:10.6040/j.issn.1671-7554.0.2021.0871

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Objective To compare the differences in puncture success rate, pathological diagnosis compliance rate, and complication rate between ultrasound-guided and enhanced CT-guided means during percutaneous puncture of mixed-density chest lesions, and to analyze the causes. Methods From February 2015 to June 2020, a total of 328 cases with CT-displayed mixed-density lesions in the chest were enrolled. CT showed uneven density inside the lesions, which were adjacent to the chest wall. The cases received ultrasound-guided puncture(the ultrasound group, n=136)or control preoperative enhanced CT-guided puncture(the enhanced CT group, n=192). The differences in the rates of successful puncture, compliant pathological diagnosis and complications between the two groups were compared. Results There was no statistical difference between puncture success rates of the ultrasound group and enhanced CT group ［94.12%(128/136)vs 93.75%(180/192), P>0.05］. Also, there was no statistical differences between complication rates of the two groups ［8.82%(12/136)vs 9.38%(18/192), P>0.05］. While, the pathological diagnosis compliance rate of the ultrasound group ［81.25%(104/128)］ was lower than that of the enhanced CT group ［97.78%(176/180)］ with the statistical difference(χ2=24.73,P<0.001). Conclusion Enhanced CT-guided percutaneous puncture of mixed-density thoracic lesions is more accurate and effective than ultrasound-guided sampling by identifying the active zone of the lesion and avoiding large vessels and non-distended lungs.

A case report of early-onset diabetes mellitus carrying paired box 4 gene mutation and literature review

TANG Qinlian, ZHANG Yuchao, ZHAO Huichen, MA Xiaoli, YU Minmin, LIU Yuantao

Journal of Shandong University (Health Sciences). 2022, 60(5):  104-108.  doi:10.6040/j.issn.1671-7554.0.2021.1523

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Objective To explore the clinical features of early-onset diabetes caused by paired box 4(PAX4)gene mutation so as to improve the understanding of the disease. Methods The clinical data of a patient with early-onset diabetes mellitus with PAX4 gene mutation were retrospectively analyzed, and the literature was reviewed. Results A 25-year-old female patient was admitted due to fatigue, thirst, polydipsia and polyuria for more than 40 days, and nausea and anorexia for 4 days. The diagnosis was diabetic ketoacidosis. Insulin autoantibody test was negative. During hospitalization, the patient was treated with a variety of hypoglycemic drugs, but with poor curative effects and islet secretion failure. Genetic testing revealed a heterozygous variant of G > A at codon 192(CGT)in exon 5 of PAX4 gene, which was R192H. Conclusion For patients with suspected monogenic diabetes, gene sequencing is of great significance, especially in the diagnosis and typing. Accurate genetic diagnosis can assure professional treatment.

Prenatal diagnosis for a fetus of mosaic trisomy 6q

SONG Min, ZHOU Yuxia, GAO Lu, LIU Na, WANG Ju, GU Jin, ZHANG Yanping

Journal of Shandong University (Health Sciences). 2022, 60(5):  109-113.  doi:10.6040/j.issn.1671-7554.0.2021.1081

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Objective To explore the prenatal diagnosis of chromosome moasic. Methods The clinical data of a pregnant woman whose ultrasound scans suggested fetal ventricular septal defect and single umbilical artery were retrospectively analyzed. As peripheral venous blood for serological screening indicated high risk of trisomy 21, the woman received non-invasive prenatal testing(NIPT)in another hospital at 17⁺² weeks of gestation. For further prenatal diagnosis, she received amniocentesis, karyotype analysis, chromosome microarray analysis(CMA), 6pter/6qter probe fluorescence in situ hybridization(FISH), and CMA of fetus placenta and skin tissue at 25⁺⁵ weeks of gestation. A total of 82 cells were counted and 5 cells were analyzed in karyotype analysis of amniotic fluid cells. Results NIPT suggested a low risk of trisomy 21, 18 and 13 syndromes. The karyotype of amniotic fluid was 47,XN,+del(6)(p21.1)［24］/46,XN［58］. CMA indicated normal in the uncultured amniotic fluid cells, but 6q trisomy moasic in the cultured cells. FISH analyzed 100 uncultured cells, among which 89 were normal, and 6 were 6q trisomy. FISH test was normal. No abnormality was found in CMA of the placenta and skin tissue of the induced fetus. Conclusion Based on the results of fetal ultrasound, karyotype analysis and molecular genetic testing, the fetus was determined to be moasic with a very low proportion of trisomy 6q, and the risk of false negative was reduced.

MRKH syndrome-related abdominal scar endometriosis after inguinal uterine hernia repair: a case report and literature review

CHEN Zhongshao, CHU Ran, LI Mingbao, ZHANG Xiangning

Journal of Shandong University (Health Sciences). 2022, 60(5):  114-117.  doi:10.6040/j.issn.1671-7554.0.2021.1259

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Objective To provide reference for the clinical treatment of cases with MRKH syndrome-related abdominal scar endometriosis after inguinal uterine hernia repair. Methods The clinical data of a patient with MRKH syndrome-related abdominal scar endometriosis after inguinal uterine hernia repair and relevant literature were reviewed. Results After admission, the patient completed relevant auxiliary examinations, underwent laparoscopic bilateral primordial hysterectomy, right salpingotomy, pelvic adhesionolysis, transabdominal abdominal incision endometriosis lesion resection. After surgery, she received subcutaneous injection of leuprorelin acetate sustained-release microspheres of 3.75 mg for 6 cycles, and the effect was satisfactory. Conclusion For patients with MRKH syndrome, surgical treatment is feasible to improve the symptoms and quality of life. Pain associated with endometriosis may be relieved by surgical resection or destruction of the lesion, but lifelong management is required.

Latent class analysis of workplace psychological violence experienced by nurses and its association with job burnout

LU Yane, WANG Juan, ZHANG Xuan, MAO Fangxiang, SUN Meng, CAO Fenglin

Journal of Shandong University (Health Sciences). 2022, 60(5):  118-124.  doi:10.6040/j.issn.1671-7554.0.2021.1023

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Objective To identify different patterns of workplace psychological violence experienced by nurses from colleagues and to explore the association between different patterns of psychological violence and job burnout. Methods A total of 1,954 nurses in Shandong Province were surveyed with a self-compiled general information questionnaire, Workplace Psychologically Violent Behaviors Instrument, and Maslach Burnout Inventory. Results The workplace psychological violence could be classified into three patterns: isolation from work/attack on the professional status type(C1, 24.7%), suffering from high psychological violence type(C2, 23.1%), and suffering from low psychological violence type(C3, 52.2%). The risk of job burnout was highest among nurses suffering from high psychological violence(OR=1.91, P<0.001), followed by nurses suffering from isolation from work/attack on the professional status(OR=4.64, P<0.001). Conclusion Three patterns of workplace psychological violence could be identified among nurses, including isolation from work/attack on professional status type, suffering from high psychological violence type, and suffering from low psychological violence type. The risk of job burnout is high among those who suffer from isolation from work/attack on professional status and high psychological violence. These nurses are the high-risk group for early screening and intervention in clinical practice.