1.Genetic drivers for inflammatory protein markers in colorectal cancer:a Mendelian randomization approach to clinical prognosis study
Heping LI ; Gaohua LI ; Xuehua ZHANG ; Yanan WANG
Journal of Southern Medical University 2024;44(7):1361-1369
Objective To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization(MR)approach.Methods We obtained data pertaining to colorectal cancer from Genome-Wide Association Study(GWAS)datasets and used 91 inflammatory protein markers as the exposure variables.A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk.The robustness of the results was evaluated through heterogeneity,pleiotropy,and sensitivity analyses using 5 MR models:Inverse Variance Weighted(IVW),Weighted Median,MR Egger,Simple Mode,and Weighted Mode.We examined the mRNA expressions of PD-L1,AXIN1,and β-NGF using RT-qPCR in 86 untreated patients with colorectal adenocarcinoma admitted in Nanfang Hospital between December,2021 and December 2023,and analyzed their correlation with the clinical characteristics of the patients.Results Using the IVW model,MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1(OR=0.866,95%CI:0.754-0.994,P=0.040),β-NGF(OR=0.914,95%CI:0.843-0.990,P=0.028;OR=0.884,95%CI:0.784-0.998,P=0.047 using Weighted Median model),and PD-L1(OR=0.903,95%CI:0.824-0.989,P=0.028).No significant heterogeneity or pleiotropy was observed,indicating good stability of the results.Sensitivity analysis confirmed the reliability of the findings.The clinical study demonstrated a significant correlation between PD-L1 expression and TNM staging,particularly in stage IV patients(P=0.007).AXIN1 and β-NGF expression levels were significantly correlated with the degree of tumor differentiation,and their expressions were higher in poorly differentiated samples(P<0.001).Conclusion Lowered expressions of inflammatory protein markers AXIN1,β-NGF,and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation.These markers may thus serve as potential targets for colorectal cancer treatment and prevention.
2.Genetic drivers for inflammatory protein markers in colorectal cancer:a Mendelian randomization approach to clinical prognosis study
Heping LI ; Gaohua LI ; Xuehua ZHANG ; Yanan WANG
Journal of Southern Medical University 2024;44(7):1361-1369
Objective To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization(MR)approach.Methods We obtained data pertaining to colorectal cancer from Genome-Wide Association Study(GWAS)datasets and used 91 inflammatory protein markers as the exposure variables.A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk.The robustness of the results was evaluated through heterogeneity,pleiotropy,and sensitivity analyses using 5 MR models:Inverse Variance Weighted(IVW),Weighted Median,MR Egger,Simple Mode,and Weighted Mode.We examined the mRNA expressions of PD-L1,AXIN1,and β-NGF using RT-qPCR in 86 untreated patients with colorectal adenocarcinoma admitted in Nanfang Hospital between December,2021 and December 2023,and analyzed their correlation with the clinical characteristics of the patients.Results Using the IVW model,MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1(OR=0.866,95%CI:0.754-0.994,P=0.040),β-NGF(OR=0.914,95%CI:0.843-0.990,P=0.028;OR=0.884,95%CI:0.784-0.998,P=0.047 using Weighted Median model),and PD-L1(OR=0.903,95%CI:0.824-0.989,P=0.028).No significant heterogeneity or pleiotropy was observed,indicating good stability of the results.Sensitivity analysis confirmed the reliability of the findings.The clinical study demonstrated a significant correlation between PD-L1 expression and TNM staging,particularly in stage IV patients(P=0.007).AXIN1 and β-NGF expression levels were significantly correlated with the degree of tumor differentiation,and their expressions were higher in poorly differentiated samples(P<0.001).Conclusion Lowered expressions of inflammatory protein markers AXIN1,β-NGF,and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation.These markers may thus serve as potential targets for colorectal cancer treatment and prevention.
3.Summary of best evidence for sexual health management in colorectal cancer patients
Jinghui FAN ; Lili ZHANG ; Siqin YAN ; Chengyuan FANG ; Gaohua WANG
Chinese Journal of Modern Nursing 2024;30(21):2837-2843
Objective:To integrate the best evidence of sexual health management for colorectal cancer patients both domestically and internationally, so as to provide guidance for clinical practice.Methods:Evidence on sexual health management of colorectal cancer patients in domestic and foreign databases and websites was systematically searched, and evidence from literature that met quality evaluation standards was extracted and summarized. The search period was from July 2003 to July 2023.Results:A total of 16 articles were included, including five clinical decisions, six clinical practice guidelines, three expert consensus/group standards, and two systematic reviews. Thirty-four recommended opinions were formed, including eight aspects of evaluation and screening, assessment tools, manifestations of sexual dysfunction, coping strategies for sexual problems, psychological intervention, measures for fertility protection, health education, and follow-up management.Conclusions:This study summarizes the best evidence for sexual health management in colorectal cancer patients. It is necessary to selectively apply evidence based on the evaluation of patient conditions by medical and nursing staff and clinical situations to ensure effective and scientific sexual health management strategies for patients, and promote the translation of best evidence into clinical practice.
4.Chinese expert consensus on neurosurgical treatment of psychiatric disorders
Chinese Medical Doctor Association Branch of Psychitrists League of Psychosurgery ; Chinese Medical Doctor Association Branch of Neuromodulation ; Yinjie LAN ; Bomin SUN ; Lin LU ; Gaohua WANG ; Wei WANG ; Jianguo ZHANG
Chinese Journal of Nervous and Mental Diseases 2024;50(7):385-402
Chinese expert consensus on neurosurgical treatment of psychiatric disorders is compiled by national experts in neurosurgery,psychiatry,and other related fields.Based on clinical research published up to December 2023 and evidence-based medicine standards,the consensus provides recommendations for neurosurgical treatment of psychiatric disorders.The covered diseases include obsessive-compulsive disorder,depressive disorder,tic disorder,bipolar disorder,anorexia nervosa,substance use-related disorders,and schizophrenia.This expert consensus outlines the safety and efficacy of neurosurgical treatments for psychiatric disorders in clinical practice,and preliminarily standardizes treatment procedures and surgical techniques.The aim is to establish professional standards for the application of surgical treatment techniques for clinical practitioners in the field of psychiatric disorder surgery,thereby maximizing treatment outcomes and promoting the future development of this treatment technology.
5.Safety and efficacy of stereotactic surgery in refractory mental disorders
Chenhui LI ; Weibin HE ; Huiling WANG ; Lingmin SHAO ; Huan HUANG ; Ying LIU ; Shudi ZHANG ; Renzhong LIU ; Gaohua WANG ; Wei YI
Chinese Journal of Neuromedicine 2024;23(4):340-347
Objective:To evaluate the clinical efficacy and safety of stereotactic surgery in patients with refractory mental disorders.Methods:A retrospective analysis was performed; clinical data, postoperative complications and medication intake of 149 patients with refractory mental disorders accepted stereotactic surgery in Department of Neurosurgery, People's Hospital, Wuhan University from August 2019 to December 2023 were collected. Outcomes were assessed at 1, 6, 12, and 24 months after surgery by Clinical Global Impression-Global Improvement (CGI-GI). Before and 1, 6, and 12 months after surgery, severities were assessed by Clinical Global Impression-Severity of Illness (CGI-SI); cognition was assessed by Montreal Cognitive Assessment (MoCA); positive and negative symptoms were evaluated by Positive and Negative Symptom Scale (PANSS); psychotic symptoms were evaluated by Brief Psychiatric Rating Scale (BPRS) and Symptom Checklist 90 (SCL-90); obsessive-compulsive symptoms, depressive symptoms, anxiety symptoms and manic symptoms were assessed by Yale-Brown Obsessive-Compulsive Symptoms Scale (Y-BOCS), Beck Depression Inventory (BDI)-II, Beck Anxiety Inventory (BAI), and Young Mania Rating Scale (YMRS), respectively; social functioning and quality of survival were evaluated by Social Disability Screening Schedule (SDSS) and World Health Organization Quality of Life-Bref Form (WHOQOL-BREF).Results:(1) Increased sleep was noted in 47 patients and fatigue in 38 patients within 1 week after surgery. Behavioral laziness and emotional apathy were still presented at 1 month after surgery in 6 patients, and complications disappeared in the rest patients. Mildly reduced initiative was presented at 12 months after surgery in 5 patients. (2) CGI-GI indicated that 149 patients were followed up 1 month after surgery with an overall efficiency of 85.90%; 135 patients were followed up at 6 months after surgery with an overall efficiency of 83.21%, 106 patients were followed up at 12 months after surgery with an overall efficiency of 79.24%, and 63 patients were followed up at 24 months after surgery with an overall efficiency of 80.95%. (3) Compared with those before surgery, significantly lower BPRS scores, significantly lower PANSS positive, negative, and overall scores, statistically lower BAI, BDI-II, YMRS, and MOAS scores, significantly lower Y-BOCS obsessional thinking, compulsive behavior and total scores, significantly higher WHOQOL-BREF (physical and psychological domains) scores, and significantly lower SDSS and SCL-90 scores were noted in patients at 1, 6, and 12 months after surgery ( P<0.05). (4) At 12 months after surgery, withdrawal drug was noted in 13 patients, reduced drug in 38, same dose in 52, and increased drug in 2 patients. Conclusion:Stereotactic surgery can obviously improve obsession, anxiety, depression, mania and aggression, and modify social functioning and quality of survival in patients with refractory mental disorders, enjoying good safety.
6.Oral panorama reconstruction method based on pre-segmentation and Bezier function.
Changpeng HOU ; Fudong ZHU ; Gaohua ZHANG ; Zhen LYU ; Yunfeng LIU ; Weidong ZHU
Journal of Biomedical Engineering 2023;40(5):894-902
For patients with partial jaw defects, cysts and dental implants, doctors need to take panoramic X-ray films or manually draw dental arch lines to generate Panorama images in order to observe their complete dentition information during oral diagnosis. In order to solve the problems of additional burden for patients to take panoramic X-ray films and time-consuming issue for doctors to manually segment dental arch lines, this paper proposes an automatic panorama reconstruction method based on cone beam computerized tomography (CBCT). The V-network (VNet) is used to pre-segment the teeth and the background to generate the corresponding binary image, and then the Bezier curve is used to define the best dental arch curve to generate the oral panorama. In addition, this research also addressed the issues of mistakenly recognizing the teeth and jaws as dental arches, incomplete coverage of the dental arch area by the generated dental arch lines, and low robustness, providing intelligent methods for dental diagnosis and improve the work efficiency of doctors.
Humans
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Radiography, Panoramic/methods*
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Cone-Beam Computed Tomography/methods*
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Head
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Image Processing, Computer-Assisted/methods*
7.Associations of white matter microstructural abnormalities with clinical symptoms, cognitive impairment and clinical outcomes in the early course of first-episode schizophrenia
Shenhong WENG ; Gaohua WANG ; Shunsheng XU ; Zhongchun LIU ; Qinran ZHANG ; Xiufen ZOU ; Changchun HE ; Xujun DUAN ; Maolin HU ; Xiaofen ZONG
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(11):997-1004
Objective:To investigate the associations of brain white matter integrity deficits, and to explore the association of fractional anisotropy (FA) abnormality with clinical symptoms and cognitive impairments, as well as the prediction effect of the FA alterations on symptoms and cognitive function outcomes in the acute stage of schizophrenia from the whole brain level based on magnetic resonance diffusion tensor imaging (DTI).Methods:From November 2019 to December 2020, thirty-eight patients with first-episode schizophrenia and 38 healthy controls were recruited in this study. Wisconsin card classification test (WCST), digit span test (DST forward/backward), verbal fluency test, Stroop (A/B/C), trail making test (TMT-A/B), as well as positive and negative syndrome scale (PANSS) were utilized to evaluate patients' cognitive function and clinical symptoms both before and after 8 weeks of risperidone monotherapy. T1-weighted images and DTI data of all the subjects were collected . FSL and SPM8 were used to preprocess MRI data and compare the between-group differences of FA. Support vector machine (SVM) analysis was used to evaluate the accuracy of abnormal FA values in differentiating schizophrenic patients from healthy controls. Finally, stepwise multiple regression analysis or generalized linear models were used to explore the associations between white matter integrity and symptoms or cognition.Results:Before treatment, patients' FA values of right medial temporal lobe (mTL), cuneus, anterior cingulate gyrus (ACG) and inferior parietal lobe (IPL) were significantly lower than those in healthy controls ( P<0.01, GRF corrected), and patients' FA values of bilateral middle cingulate gyrus (mCG) were significantly higher than those in the control group ( P<0.01, GRF corrected). SVM analysis showed that four combinations could distinguish the patients from the control with the most accurate rate of 89.47%. Patients' baseline decreased FA values in the right IPL were positively associated with their increased total response time in WCST ( β=0.489, P=0.003, FDR corrected), correct response time in WCST ( β=0.450, P=0.008, FDR corrected), error response time in WCST ( β=0.435, P=0.008, FDR corrected), TMT-B ( β=0.296, P=0.042, FDR corrected), Stroop-C ( β=0.345, P=0.035, FDR corrected), and PANSS-P ( β=0.321, P=0.042, FDR corrected). Reduced FA values in the right mTL in patient group were significantly negatively related to the total time spent on the TMT-A ( β=-0.425, P=0.009, FDR corrected) and TMT-B ( β=-0.325, P=0.026 with FDR correction). Increased FA values in right mCG in patient group demonstrated positive associations with total response time in the WCST ( β=0.585, P=0.002, FDR corrected), correct response time in WCST ( β=0.524, P=0.003, FDR corrected), error response time in WCST ( β=0.536, P=0.003, FDR corrected) and total time consuming in TMT-B ( β=0.484, P=0.004, FDR corrected), as well as negative associations with DST-forward ( β=-0.319, P=0.042, FDR corrected). After treatment, patients' percentage changes in total response time of WCST ( β=0.715, P<0.001, FDR corrected), correct response time of WCST ( β=0.752, P<0.001, FDR corrected), as well as total time-consuming of TMT-A ( β=1.333, P=0.001, FDR corrected) showed positive correlations with baseline increased FA values in the left mCG. Percentage alteration of Stroop-B was negatively correlated with baseline FA values in the right cuneus ( β=-0.745, P=0.015, FDR corrected). Conclusions:The combination of abnormal FA values in multiple brain regions may be potential biomarkers to distinguish schizophrenic patients from healthy volunteers. There was regional dependence in the associations of the impairment of white matter integrity with the cognitive impairment, the severity of psychopathological symptoms as well as the prognosis of patients in the acute stage.
8.Effects of hippocampal AKT/GSK3β/CRMP2 signaling pathway on depression-like behavior and tubulin in rats
Yanyan WEI ; Jingxu CHEN ; Ling XIAO ; Zuotian WU ; Jing HE ; Nan ZHANG ; Gaohua WANG
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(8):713-718
Objective:To study the effects of LY294002, a phosphatidylinositol 3 kinase(PI3K) inhibitor, on the AKT/GSK3β/CRMP2 signaling pathway, and the effect of pathway alterations on the depression-like behavior and microtubulin proteins of SD rats.Methods:Sixteen adult male SD rats were randomly divided into LY294002 group and solvent DMSO group by blind method, 8 rats in each group.After anesthesia, the rats were subjected to stereotactic tube placement in the hippocampal CA1 area. After 1 week of the tube placement, stereoscopic injection of LY294002 or DMSO was given, and depression-like behaviors were detected. RT-qPCR technology was used to detect hippocampal AKT, GSK3β, CRMP2, and tubulin mRNA expression levels, and Western blot technology was used to detect the expression levels of hippocampal AKT, p-AKT, GSK3β, p-GSK3β, CRMP2, p-CRMP2, and microtubule dynamic-related proteins markers Acet-tubulin, Tyr-tubulin. Analysis and comparison of behavioral and molecular expression differences between the two groups were conducted.Results:The open field experiment showed that the central movement distance of the rats in the LY294002 group were significantly lower than those in the control group((3.64±2.17) cm, (31.51±12.68) cm; t=2.69, P=0.03), and the duration of the central area in the LY294002 group were also significantly lower than those in the control group((0.73±0.46)s, (4.85±2.10)s; t=2.33, P=0.04). The results of the forced swimming test showed that the immobility time of rats in the LY294002 group had upward trend, but the difference was not statistically significant. The sucrose preference results showed no significant difference in sugar water consumption between the two groups ( P>0.05). The RT-qPCR results showed that the expression level of CRMP2 mRNA in the LY294002 group decreased significantly ( P<0.05). Western blot results showed that compared with solvent DMSO group, the expression levels of p-AKT and p-GSK3β in the LY294002 group decreased ( P<0.05), the expression level of CRMP2 was decreased and the expression level of p-CRMP2 was significantly increased. At the same time, the expression level of Tyr-tubulin decreased, while Acet-tubulin level increased significantly, and the differences were statistically significant ( P<0.05). Conclusion:LY294002 affects AKT/GSK3β/CRMP2 signaling pathway, induces impairment of microtubular dynamic, and results in depression-like behavior in rats.
9.Expert advice on practical use of amisulpride in treatment of schizophrenia
Ying LIANG ; Dengtang LIU ; Tianmei SI ; Yi LI ; Congpei ZHANG ; Tao LI ; Xiufeng XU ; Chengge GAO ; Zhimin WANG ; Li KUANG ; Qingrong TAN ; Zhiyu CHEN ; Shenxun SHI ; Tiebang LIU ; Fude YANG ; Gaohua WANG ; Jingping ZHAO ; Kaida JIANG ; Xin YU
Chinese Mental Health Journal 2017;31(6):425-431
Amisulpride,a kind of the second generation antipsychotics,was marketed in China in 2010.A series of clinical research and experience before and after listed,especially the data based on Chinese population,provided evidence for the generalization and application of amisulpride.In order to optimize the clinical application of amisulpride,and improve the prognosis of patients,Expert Advice on the Practical Use of Amisulpride in the Treatment of Schizophrenia is presented here.This advice is based on the recent evidence and clinical experience,for guiding the clinical medication of amisulpride.
10.Relationship between APE1 single nucleotide polymorphism and prognosis of primary small cell carcinoma of esophagus
Yunyao YE ; Gaohua HAN ; Kaijin LU ; Shengbin DAI ; Lixin ZHANG
Clinical Medicine of China 2016;32(1):64-68
Objective To examine the single nucleotide polymorphism(SNP) of apurinic/apyrimidinic endonuclease1 (APE1) in primary small cell carcinoma of esophagus(PSEC) ,then investigate the relationship between these SNPs and the prognosis.Methods Sixty cases first-treated patients with PSEC were recruited, patients with esophageal squamous cell carcinoma (ESCC) and healthy blood donors were recruited as positive and negative controls.APE1 (Asp148Glu) of the patients with PSEC and controls were genotyped by the TaqMan method.Every patient was treated with platinum-based chemotherapy(EP regimen for PSEC and TP regimen for ESCC)and radiotherapy(3D-CRT) ,then every case was followed-up for 2 years.The relationship between these SNPs and the follow-up outcome was analyzed.Results Compared with the ESCC group and control group, APE1 148 pure mutant(Glu/Glu) of PSEC group increased significantly(PSEC group was 40% (12/30), ESCC group was 13.3% (4/30) , control group was 10% (2/20)), the difference was statistically significant (x2 =7.248,P =0.027).According to data of following-up, there was a significant increase in rate of progress (1year:40.0% (12/30) vs 16.7% (5/30), x2 =4.022, P =0.045;2 years: 86.7% (26/30) vs 40.0% (12/30) ,P =0.004) and a significant decrease in survival (33.3% (10/30) vs 76.7% (23/30)) of PSEC compared with ESCC.The SNPs of APE1 Asp148Glu was significantly correlated with frequency of progress, a significant increase was found in rate of progress of the patients with mutant type(Asp/Glu±Glu/Glu) compared with wild genotype(1 year: 50.0%(11/22) ,x2 =3.854,P=0.05;2 years: 81.8% (19/22) ,x2 =10.519,P =0.001) ,the survival of the patients with mutant genotype was significantly lower than wild type (22.7% (5/22) ,x2=10.77,P=0.001).Conclusion The most of polymorphisms of APE1(Asp148Glu) are mutation type in PSEC.Pure mutant genotype (APE1 148Glu/Glu) carry significant enhancement of progression.The polymorphisms of APE1 (Asp148Glu) maybe one of those molecular mechanisms of high frequency of progress and poor prognosis in PSEC.

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