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.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.
3.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.
4.The role of heat shock protein 70 in depression and its mechanisms
Chen LI ; Ling XIAO ; Yinping XIE ; Lujia SI ; Limin SUN ; Guohao YUAN ; Hailong GE ; Gaohua WANG
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(9):853-858
As a common psychiatric disorder, the etiology and pathogenesis of depression are complex and not yet fully elucidated.The diagnosis of depression mainly depends on the patients’ medical history, clinical symptoms and related examinations.Identification of biomarkers will provide important clues for the specific diagnosis and targeted treatment of depression.In addition to the widely recognized neurotransmitter dysregulation, hypothalamus-pituitary-adrenal axis hyperactivity, neuroplasticity, and neuro-inflammation theory, oxidative stress is also involved in the pathogenesis of depression in multiple ways.Many studies showed that the heat shock protein 70(HSP70)levels will increase in early stage to cope with the stress in patients with depression.However, lower HSP70 levels are often correlated with more severe depressive symptoms.HSP70 may be involved in depression through multiple pathways of oxidative stress, glucocorticoid receptors, neuroinflammation and neuroplasticity.Furthermore, increasing HSP70 expression results in significant improvement in depression-like behavior in animals.Thus, HSP70 possesses potential value as an early warning marker for depression as well as a therapeutic target.
5.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.
6.The influence of social support and family function in elderly preoperative patients psychological situation
Gaohua ZHANG ; Zhanhui ZHANG ; Jiahui LI ; Dacui CHEN ; Yuping DENG ; Zhiwei WANG ; Liren HU
Chongqing Medicine 2016;45(27):3830-3832
Objective To understand family function ,social support ,preoperative anxiety and depression status among elder‐ly operative patients ,and to explore their relationship .Methods 295 elderly preoperative patients were investigated by family AP‐GAR index (APGAR) ,social support rating scale (SSRS) ,self‐rating anxiety scale (SAS) and self‐rating depression scale(SDS) , descriptive and inferential analysis .Results Among 295 elderly preoperative patients ,there were 208 people with good family func‐tion ,accounting for 70 .51% ,67 people with moderate disability family function ,accounting for 22 .71% ,and 20 people with severe disability family function ,accounting for 6 .78% ;The total score of social support was 40 .42 ± 9 .03 and the scores of subjective support was 23 .32 ± 5 .42 ,objective support with 9 .45 ± 3 .73 and support availability with 7 .65 ± 1 .86 ;152 people were preoper‐ative anxiety ,accounting for 51 .53% ,98 people were preoperative depression ,accounting for 33 .22% .The rate of anxiety and de‐pression good family function group was lower than a family dysfunction group(P<0 .05) .The incidence of depression high social support group is higher than low group (P<0 .05);Among the scores of social support ,subjective support ,objective support and support availability ,we find that patients with family well‐functioning group was higher than patients with family dysfunction group (P<0 .05) .Multiple logistic regression analysis showed that influence factors of preoperative psychological abnormality had educa‐tion level ,whether the tumor diseases ,the total score of social support and family functioning condition .Conclusion Elderly preop‐erative patients have anxiety and depression to a certain extent .The anxiety and depression of patients were related to the family function and social support .We Should pay attention to the effect of farmily function and social support on mental health of elderly patients with operation ,and effective use .
7.Side effects of pemetrexed in the maintenance therapy of nonsmall-cell lung cancer at advanced stage and the nursing measures
Ruqiong WEI ; Gaohua LI ; Xiao LU ; Guozhen LING
Modern Clinical Nursing 2015;(5):48-50
Objective To explore the side effects of pemetrexed in the maintenane therapy of nonsmall-cell lung cancer (NSCLC) at advanced stage and summarize the nursing measures. Methods Fifty-one NSCLC patients were treated maintenance therapy by pemetrexed. The side effects were observed and corresponding nursing measures were taken. Results The side effects included bone marrow depression of 33 cases, adverse reactions in gastrointestinal tract of 14 cases, and skin rashes of 4 cases, all at the degree of I-II. All of them were alleviated after active treatments. Conclusion Such nursing measures as close of side effects and careful nursing to the NSCLC patients treated with maintenance therapy with temetrexed are main measures for the success of treatment.
8.Effects of quetiapine on the memory and the expression of doublecortin in the hippocampus of schizophrenia model mice induced by cuprizone
Rui LI ; Shanshan HE ; Xia WANG ; Gaohua LIU ; Zhengwu PENG ; Huaning WANG ; Qingrong TAN
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(11):970-973
Objective To investigate the effect of quetiapine (QUE) on the memory and doublecortin (DCX) expression in the hippocampus of C57BL/6 mice with cuprizone (CPZ)-induced schizophrenia in C57BL/ 6 mice.Methods 1% dimethyl sulfoxide (DMSO) was used as a vehicle to dissolve QUE.Three group of mice,16 in each of three groups,were treated with vehicle (control group),0.2% CPZ alone (CPZ group) or 0.2% CPZ combined with 10 mg· kg-1 · d-1 QUE (QUE+CPZ group) for six weeks,respectively.Spatial working memory was evaluated by Y-type maze test 24 hours after the completion of the treatment period.The number of DCX positivenew neurons was calculated by immunofluorescence staining assay.The expression of Notch1 and Hes1 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.Results (1) Y-maze test:CPZ group achieved a much lower percentage of correct alternation than control group ((22.70±6.70) % vs (57.69 ±6.70)%) in Y-maze test (P<0.05).The percentage of correct alternation in CPZ + QUE group ((54.69± 10.06) %) was significantly increased compared with CPZ group (P<0.01).CPZ mice exhibited significant spatial working memory impairment.(2) Immunofluorescence staining:the number of DCX-positive cells in the hippocampus of the CPZ group (6342.85± 1801.72) was significantly decreased compared with that in control group (19428.57±2507.13) (P<0.01),and it was reversed by QUE intervention (15928.57±2049.97).(3) RT-PCR:the Notch1 and Hes1 mRNA expression in CPZ group were significant lower than that in sham and CPZ + QUE group,(Notch1 (0.97±0.29) vs (0.23±0.20),P<0.01);Hes1 (1.00±0.41) vs (0.38±0.30),P<0.01),and there was no significant difference between sham group and CPZ + QUE group.Conclusion QUE is helpful to relieve CPZ-induced cognitive impairment and decreases expression of DCX in hippocampal,which may be related with activation of Notch1 pathway.
9.Effect of Huperzine A on Spatial Memory in Rats with Repeated Electroconvulsive Stimulation
Jing CHENG ; Ling XIAO ; Gaohua WANG ; Chengyan LI
Chinese Journal of Rehabilitation Theory and Practice 2013;19(10):927-930
Objective To explore the effects of Huperzine A on memory in rats with repeated electroconvulsive stimulation. Methods 48 adult male Sprague-Dawley rats were randomly divided into true electroconvulsive stimulation group (E group) and sham electroconvulsive stimulation group (C group). Then both groups were randomized to receive Huperzine A (EH group and CH group) or normal saline (ES group and CS group). There were 12 rats in each subgroup. Huperzine A or normal saline was administered during 1~17 d. During 8~17 d,true or sham electroconvulsive stimulation were administered. On the 18th d, the rats were tested in Morris water maze. Then 6 rats of each group were randomized to be taken for probe tests after 48 h. Memory test indexes include swimming speed, latency, and search time. Results There was no significant difference in the latency between CS group and CH group (P>0.05). The latency was significantly longer in ES group than in CS group (P<0.01), and shorter in EH group than in ES group (P<0.05). There were significant difference in the search time between around the hidden platform and in the opposite area in CS group, CH group and EH group (P<0.05). But there was no difference in ES group (P>0.05). Conclusion Chronic repetitive electroconvulsive stimulation can lead to spatial memory impairment in rats. Huperzine A may attenuate electroconvulsive stimulation induced amnesia.
10.Intraoperative ultrasonography for repeated hepatic resections for hepatocellular carcinoma
Keming ZHANG ; Gaohua LI ; Zhixian HONG ; Ruizhao QI ; Zhaohai WANG ; Wei TANG ; Kokudo NORIHIRO ; Makuuchi MASATOSHI
Chinese Journal of Hepatobiliary Surgery 2012;18(4):273-277
Objective To evaluate the efficacy of intraopèrative ultrasonography (IOUS) on primary and repeated hepatectomies for hepatocellular carcinoma (HCC).Methods 430 patients underwent 555 operations for HCC.New tumors detected by IOUS at the primary and repeated hepatectomies were retrospectively analyzed.The long-term outcomes were also studied.Results IOUS had the highest sensitivity in the routinely used imaging examinations.The detection rate by each imaging modality decreased slightly but uniformly at the second hepatectomy.IOUS detected 56 new tumors in 30 patients (7.1%) at the primary hepatectomy and 13 new tumors in 8 (7.3%) at the second.The average size of tumor detected was 8.7±3.8 and 9.0±5.2 mm at the primary and second resections,respectively.The preoperative surgical plan was changed due to the IOUS findings alone in 24 patients (5.6%) at the primary hepatectomy,and in 7 (6.4%) at the second.Although recurrence was frequent in patients with new tumors detected at the primary hepatectomy,long-term survival after appropriate treatment for recurrence was similar to those patients without new tumors detected.Conlusions Despite recent progress in imaging modalities,IOUS is still the most sensitive examination.The same degree of precaution is necessary to detect new tumors using IOUS in repeated hepatectomy.Patients with new tumors detected by IOUS are at high risk for recurrence so that regular check-up is important to improve patient survival.


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