1.Effect of Buzhong Yiqitang on Th17/Treg Immune Imbalance and Notch1 Signaling Pathway in AIT Mice
Zhuo ZHAO ; Nan SONG ; Ziyu LIU ; Pin LI ; Yue LUO ; Pengkun ZHANG ; Zhimin WANG ; Yuanping YIN ; Tianshu GAO ; Zhe JIN ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):19-27
ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 (Th17)/regulatory T cell (Treg) and Notch1 signaling pathway in mice with autoimmune thyroiditis (AIT). MethodA total of 60 8-week-old NOD.H-2h4 mice were randomly divided into the normal group, model group, western medicine group (selenium yeast tablet, 32.5 mg·kg-1), and low-dose (4.78 g·kg-1·d-1), middle-dose (9.56 g·kg-1·d-1), and high-dose (19 g·kg-1·d-1) Buzhong Yiqitang groups, with 10 mice in each group. The normal group was fed with distilled water, and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously, the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies (TGAb), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroid hormone (FT4) were detected by enzyme-linked immunosorbent assay (ELISA), and thyroid tissue changes were observed by hematoxylin-eosin (HE) staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt (RORγt), interleukin (IL)-17, forkhead box P3 (FoxP3), IL-10, Notch1, and hair division-related enhancer 1 (Hes1) in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultCompared with the normal group, the thyroid structure of the model group was severely damaged, and lymphocytes were infiltrated obviously. The levels of serum TGAb, FT3, and FT4 contents were significantly increased, and TSH content was significantly decreased (P<0.01). The mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were significantly increased, while those of FoxP3 and IL10 were significantly decreased in the model group (P<0.01). Compared with the model group, thyroid structural damage and lymphocyte infiltration were improved in the treatment groups, and serum TGAb, FT3, and FT4 contents were significantly decreased. TSH content was increased, and mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees (P<0.05, P<0.01), and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice, and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.
2.Discovery of a normal-tension glaucoma-suspect rhesus macaque with craniocerebral injury: Hints of elevated translaminar cribrosa pressure difference.
Jian WU ; Qi ZHANG ; Xu JIA ; Yingting ZHU ; Zhidong LI ; Shu TU ; Ling ZHAO ; Yifan DU ; Wei LIU ; Jiaoyan REN ; Liangzhi XU ; Hanxiang YU ; Fagao LUO ; Wenru SU ; Ningli WANG ; Yehong ZHUO
Chinese Medical Journal 2024;137(4):484-486
3.Preparation and performance evaluation of S100B time-resolved fluorescence immunoassay kit
Dong-Qing FENG ; Bu-Zhuo XU ; Shu-Hong LUO ; Yu-Nan WU ; Zhuo ZHANG ; Hao TANG ; Yi-Ming WENG ; Ruo-Pan HUANG ; Xu-Dong SONG
Chinese Medical Equipment Journal 2024;45(1):47-55
Objective To develop a time-resolved fluorescent immunoassay kit for the rapid,accurate and quantitative detection of S100B protein in serum and to evaluate its performance.Methods The test strip was prepared using time-resolved fluorescent microsphere-labeled anti-S100B polyclonal antibody and rabbit IgG antibody,labeling pads,sample pads,S100B nitrocellulose films and absorbent paper,and an S100B time-resolved fluorescence immunoassay kit was obtained by assembling the cartridge.The performance of the kit developed was evaluated by standard curve,accuracy,minimum detection limit,linear interval,specificity,reproducibility and stability.The reference intervals of 199 pieces of healthy human serum and plasma samples from a certain region were detected with the kit,and the clinical performance of the kit and Roche Elecsys S100 kit was tested by synchronous blind method to assess the consistency of the results of the two kits for 142 samples.Results The S100B time-resolved fluorescence immunoassay kit had the standard curve beingy=(1.133 02+1.752 24)/[1+(x/1.082 20)×(-0.603 52)]-1.752 24,R2=0.999 08 and the linear range being[0.05,30]ng/mL,which met the requirements of the relative deviation of the accuracy within±15%,the minimum detection limit not hgier than 0.05 ng/mL,the relative deviation of specificity within±15%and the coefficient of variation of intra-and inter-batch difference less than 15%.The stability test results indicated that the kit was valid for 12 months at 2-30 ℃ conditions.The reference intervals of serum and plasma samples measured by the kit were both lower than 0.3 ng/mL.Clinical trials showed that the results by the kit and Roche Elecsys S100 Assay Kit were in high agreement(Kappa=0.906 1>0.80)and met the requirements.Conclusion The kit developed detects the concentration of S100B protein in serum quickly,accurately and quantitatively,and provides references for the diagnosis and treatment of neurological diseases,autoimmune diseases,cerebrovascular diseases and etc.[Chinese Medical Equipment Journal,2024,45(1):47-55]
4.Executive function and clinical characteristics in children with attention-deficit hyperactivity disorder and emotional dysregulation
Yanping YANG ; Sixun LI ; Meiwen WANG ; Zhuo WANG ; Pei LIU ; Tingting LUO ; Yujie TAO ; Yi HUANG
Sichuan Mental Health 2024;37(4):307-311
Background Comorbid attention-deficit/hyperactivity disorder(ADHD)and emotional dysregulation may represent a distinct subtype of ADHD,which is characterized by an increased risk of anxiety or depressive disorder and a poor clinical prognosis,so research is urgently required to explore its unique executive functioning profile and clinical characteristics.However,there is limited research comparing the clinical symptoms and executive function in children with ADHD in terms of the presence or absence of emotional dysregulation.Objective To explore the executive function and clinical characteristics of ADHD children with emotional dysregulation.Methods From June 2020 to December 2023,118 children aged 7 to 12 with ADHD attending the Mental Health Center of West China Hospital,Sichuan University and fulfilling the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)diagnostic criteria were enrolled.Children were classified into emotional dysregulation group(n=68)and non-emotional dysregulation group(n=50)based on the standard T-scores of Achenbach's Child Behavior Checklist(CBCL)-anxious/depressed,aggressive behavior and attention problems subscales.All children were then subjected to complete the Chinese version of Swanson Nolan and Pelham,Version IV Scale-parent form(SNAP-IV),Chinese Wechsler Intelligence Scale for Children(C-WISC),Weiss Functional Impairment Scale-Parent form(WFIRS-P)and 4 tests of the Cambridge Neuropsychological Test Automated Battery(CANTAB):①Stockings of Cambridge(SOC)testing spatial planning.②Intradimensional-extradimensional Set Shifting(IED)testing cognitive/attentional flexibility,adjusting the total errors across the task.③Spatial Working Memory(SWM)testing spatial working memory.④Rapid Visual Information Processing(RVP)testing sustained attention.Results The SNAP-IV Inattention,Hyperactivity/Impulsivity and Oppositional Defiant Disorder domain scores and total score were all higher in emotional dysregulation group compared with non-emotional dysregulation group(t=3.206,5.088,6.316,6.553,P<0.01).The WFIRS-P family,school learning,life skills,self-concept,social activities and risky activities domain scores and total score were all higher in emotional dysregulation group compared with non-emotional dysregulation group(t=6.074,4.406,4.143,3.984,6.575,6.662,8.254,P<0.01).In CANTAB,emotional dysregulation group made more total adjusted errors across the IED task compared with non-emotional dysregulation group(t=2.168,P<0.05).Conclusion Children with ADHD who exhibit emotional dysregulation have been observed to experience more severe core symptoms,impaired social functioning and poorer performance on tests assessing executive function,particularly in the area of cognitive flexibility.
5.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
6.Clinical application of split liver transplantation: a single center report of 203 cases
Qing YANG ; Shuhong YI ; Binsheng FU ; Tong ZHANG ; Kaining ZENG ; Xiao FENG ; Jia YAO ; Hui TANG ; Hua LI ; Jian ZHANG ; Yingcai ZHANG ; Huimin YI ; Haijin LYU ; Jianrong LIU ; Gangjian LUO ; Mian GE ; Weifeng YAO ; Fangfei REN ; Jinfeng ZHUO ; Hui LUO ; Liping ZHU ; Jie REN ; Yan LYU ; Kexin WANG ; Wei LIU ; Guihua CHEN ; Yang YANG
Chinese Journal of Surgery 2024;62(4):324-330
Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.
7.Advancements in Single-cell RNA Sequencing Technology in the Study of the Tumor Microenvironment in Lung Cancer
WANG YANHONG ; LUO BIN ; WANG ZHUO ; QUE ZUJUN ; JIANG LEI ; TIAN JIANHUI
Chinese Journal of Lung Cancer 2024;27(6):441-450
The immune microenvironment plays a key role in the development and progression of tumors.In recent years,with the rapid advancement of high-throughput sequencing technologies,researchers have gained a deeper under-standing of the composition and function of immune cells in the tumor microenvironment.However,traditional bulk sequenc-ing technologies are limited in resolving heterogeneity at the single-cell level,constraining a comprehensive understanding of the complexity of the tumor microenvironment.The advent of single-cell RNA sequencing technology has brought new opportunities to uncover the heterogeneity of the immune microenvironment in lung cancer.Currently,T-cell-centered im-munotherapy in clinical settings is prone to side effects affecting prognosis,such as immunogenic drug resistance or immune-related pneumonia,with the key factor being changes in the interactions between immune cells and tumor cells in the tumor microenvironment.Single-cell RNA sequencing technology can reveal the origins and functions of different subgroups within the tumor microenvironment from perspectives such as intercellular interactions and pseudotime analysis,thereby discovering new cell subgroups or novel biomarkers,providing new avenues for uncovering resistance to immunotherapy and monitoring therapeutic efficacy.This review comprehensively discusses the newest research techniques and advancements in single-cell RNA sequencing technology for unveiling the heterogeneity of the tumor micro environment after lung cancer immunotherapy,offering insights for enhancing the precision and personalization of immunotherapy.
8.Effects of Electroacupuncture on Urodynamics and Expression of ERK/CREB/Bcl-2 Pathway in Spinal Cord of Rats with Neurogenic Bladder after Suprasacral Spinal Cord Injury
Ming XU ; Kun AI ; Yue ZHUO ; Qiong LIU ; Xiaomeng LIU ; Ya LI ; Xiaoyuan LUO ; Hong ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):100-105
Objective To observe the effects of electroacupuncture at"Ciliao","Zhongji","Sanyinjiao"and"Dazhui"on urodynamics and expression of ERK/CREB/Bcl-2 pathway in spinal cord tissue of neurogenic bladder rats after suprasacral spinal cord injury.Methods Sixty female SD rats randomly selected 24 and divided into blank group and sham-operation group(12 rats in each group),the remaining 36 rats were subjected to surgical modeling.After modeling,rats were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.The electroacupuncture group received unilateral electroacupuncture stimulation at acupoints"Ciliao","Zhongji","Sanyinjiao",and"Dazhui"for 30 minutes each time,once a day,for 7 consecutive days.After administration,urodynamic testing was performed,HE staining was used to observe the morphology of bladder detrusor tissue,TUNEL method was used to detected apoptosis in spinal cord tissue,Western blot was used to detected expressions of p-ERK1/2,p-CREB,p-p90Rsk,CRE,Bcl-2,and Bax proteins in spinal cord tissue.Results Compared with the sham-operation group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the model group increased significantly(P<0.01),while the maximum capacity and compliance of the bladder decreased significantly(P<0.01);the structure of bladder smooth muscle cells was severely damaged and disorderly arranged,accompanied by a large amount of inflammatory cell infiltration;the apoptosis rate of spinal cord tissue cells significantly increased(P<0.01),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue were significantly decreased,while the expression of Bax protein significantly increased(P<0.01).Compared with the model group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the electroacupuncture group decreased significantly(P<0.05),while the maximum capacity and compliance of the bladder increased significantly(P<0.05,P<0.01);the integrity of bladder smooth muscle cells was enhanced,the degree of cell edema was reduced,and inflammatory cell infiltration was reduced;the apoptosis rate of spinal cord tissue cells was significantly reduced(P<0.05),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue significantly increased,while the expression of Bax protein was significantly decreased(P<0.05,P<0.01).Conclusion Electroacupuncture can promote the repair of bladder detrusor tissue in rats with neurogenic bladder model after suprasacral spinal cord injury,increase the maximum capacity and compliance of the bladder,alleviate the high pressure state in the bladder,and its mechanism is related to activating the ERK/CREB/Bcl-2 pathway,reducing secondary apoptosis of damaged neurons,effectively improving bladder innervation,and protecting bladder function.
9.Establishment and validation of depressive symptom predictive model in middle school students
TAN Zhenkun, ZHANG Zhuo, ZHANG Ying, PING Junjiao, LUO Jiali, ZHANG Jie, LIU Xinxia
Chinese Journal of School Health 2024;45(7):998-1002
Objective:
To investigate the influencing factors of depressive symptoms and to construct and verify the prediction model of depressive symptoms in middle school students, so as to provide risk assessment tools for effectively screening depressive symptom.
Methods:
Physical examination and questionnaire survey were conducted among middle school students in one city in Guangdong Province from September to October in 2021 ( n =2 376) and from September to October in 2022 ( n =4 344) by a multistage cluster sampling method, and a nomographic prediction model of depressive symptoms in middle school student was constructed. The questionnaire survey was conducted using the student health status and influencing factors questionnaire (secondary school version) and the Center for Epidemiological Studies Depression Scale (CES-D) to measure the lifestyle and depressive symptom of middle school students.
Results:
The detection rate of depressive symptoms in 2021 was 23.3%. Multivariate Logistic regression analysis showed that irregular breakfast ( OR =2.64), school bullying ( OR =4.28), being beaten by parents ( OR =2.86), using mobile devices for a long time ( OR =1.08) and sitting for a long time ( OR =1.05) were positively related to depressive symptoms in middle school students ( P <0.05). Long sleep duration ( OR =0.78) and outdoor activity durations of 1-<2, 2-<3 and ≥3 h/d (compared with <1 h/d, OR =0.63, 0.61, 0.49) were negatively related to depressive symptoms in middle school students ( P < 0.05 ). Multivariate Logistic regression analysis showed that 7 statistically signifucant predictive factors constructed a nomogram, and the AUC of the nomogram was 0.77, which had been verified internally and externally with good differentiation and reliability.
Conclusions
The nomogram prediction model of depressive symptoms provides a convenient and effective risk assessment tool for depressive symptoms among middle school students. The life behavior, diet behavior and injury behavior of middle school students play an important role in the formation of depressive symptoms. It should pay attention to the impact of the behavioral factors on the mental health of middle school students.
10.Artificial intelligence system for outcome evaluations of human in vitro fertilization-derived embryos
Ling SUN ; Jiahui LI ; Simiao ZENG ; Qiangxiang LUO ; Hanpei MIAO ; Yunhao LIANG ; Linling CHENG ; Zhuo SUN ; Hou Wa TAI ; Yibing HAN ; Yun YIN ; Keliang WU ; Kang ZHANG
Chinese Medical Journal 2024;137(16):1939-1949
Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.


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