AIM:To investigate the therapeutic effect of mitochondrial fission inhibitor-1(Mdivi-1)on experi-mental autoimmune encephalomyelitis(EAE)in mice,and to explore its mechanism.METHODS:The mice immunized with myelin oligodendrocyte glycoprotein peptide fragment 35-55(MOG35-55)were randomly divided into DMSO model group and Mdivi-1 intervention group.All mice were sacrificed on the 28th day after the first immunization.The demyelination was analyzed by Luxol fast blue staining.The protective mechanism of Mdivi-1 in the spinal cord tissue was investigated by immunofluorescence staining,TUNEL staining and the in vitro experiment with MO3.13 oligodendrocytes treated with staurosporine.The mitochondrial depolarization was detected by JC-1 staining,the cell injury was checked by LDH leakage,and the viability of MO3.13 oligodendrocytes was determined by MTT assay.RESULTS:Compared with DMSO model group,the demyelinating injury was alleviated and the proportion of apoptotic CC1+ oligodendrocytes in Mdivi-1 group was decreased.The cleaved caspase-3,caspase-9,cytochrome C and Bax protein expression levels in the spinal cord of Mdivi-1-treated mice was also attenuated.The in vitro MO3.13 cell experiments suggested that Mdivi-1 inhibited MO3.13 cell mitochondrial depolarization,attenuated the cell damage and increased the cell viability.CONCLUSION:Mdivi-1 pro-tects against the myelin injury in EAE mice,which may be related to the suppression of oligodendrocyte apoptosis.

Coronary artery calcifications (CAC) is an independent risk factor for cardiovascular disease (CVD). It has been revealed that this condition can be automatically quantified through computerize tomographic (CT) scan contained in radiotherapy plan for patients with breast cancer, with which, physicians can identify the patients with increased risk of CVD after radiotherapy prematurely and take intervention measures in advance. In this article, the current literature and research progress on the correlation between CAC and cardiotoxicity in patients with breast cancer after radiotherapy were reviewed, expecting to provide a strategy to reduce the CVD risk in patients with breast cancer after radiotherapy.

Objective:To compare the results of invasive prenatal diagnosis and preimplantation genetic testing (PGT) and explore the underlying mechanism.Methods:Clinical data of pregnant women undergoing PGT and invasive prenatal diagnosis at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022 were collected. The results of PGT and invasive prenatal diagnosis were compared, and the outcomes of pregnancies were followed up. This study has been approved by the Medical Ethics Committee of the the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022SLYEC-491).Results:A total of 172 couples were included in this study, and 26 non-targeted variants were discovered upon prenatal diagnosis, including 10 cases (38.5%) by chromosomal karyotyping, 15 (57.7%) by chromosomal microarray analysis (CMA), and 1 (3.8%) by whole exome sequencing. The 10 karyotypic anomalies had included 6 chromosomal polymorphisms, 2 chromosomal mosaicisms, 1 paternally derived translocation, and 1 missed maternal chromosomal inversion. CMA has identified 15 copy number variations (CNVs), which included 11 microdeletions and microduplications, 3 loss of heterozygosity, and 1 low-level mosaicism of paternal uniparental disomy. One CNV was classified as pathogenic, and another one was likely pathogenic, whilst the remaining 13 were classified as variants of uncertain significance. Therefore, 8.7% of CNVs was detected by invasive prenatal diagnosis after PGT. 92.3% (24/26) of the non-targeted variants have been due to technological limitations of next-generation sequencing (NGS).Conclusion:Invasive prenatal diagnosis after PGT can detect non-targeted variants, which may further reduce the incidence of birth defects.

AIM:To investigate the alleviating effect of ethyl acetate extract from Platycladus orientalis leaves(EAEPOL)on diabetic cardiomyopathy(DCM)and its mechanisms.METHODS:Healthy adult C57BL/6 mice were ran-domly divided into normal control group,DCM group,and EAEPOL group.Cardiac structure and function of the mice were assessed by echocardiography.Myocardial fibrosis was evaluated though myocardial hydroxyproline content determi-nation,myocardial Masson and Sirius red staining,and collagen type I(Col I)and collagen type Ⅲ(Col Ⅲ)immunohis-tochemistry.The degree of myocardial oxidative stress was assessed by measuring malondialdehyde(MDA),superoxide dismutase(SOD)and total antioxidative capacity(T-AOC)levels using kits,as well as detection of nuclear factor E2-re-lated factor-2(Nrf-2)and heme oxygenase-1(HO-1)expression by qRT-PCR and Western blot.Endothelial-mesenchy-mal transition(EndMT)was evaluated by detecting CD31 and α-smooth muscle actin(α-SMA)protein expression by Western blot,and cadherin 5(CDH5)and fibroblast specific protein 1(FSP1)mRNA expression by qRT-PCR,as well as α-SMA immunofluorescence staining.RESULTS:(1)Mouse echocardiography revealed that compared with normal control group,heart rate(HR)and ejection fraction(EF)were significantly reduced in DCM group(P<0.05 or P<0.01),while left ventricular anterior wall thickness at systole and diastole(LVAWs and LVAWd)and left ventricular pos-terior wall thickness at systole and diastole(LVPWs and LVPWd)were significantly increased(P<0.05).Compared with DCM group,the mice in EAEPOL group showed significant increases in HR and EF(P<0.01),and marked decreases in LVAWs,LVAWd,LVPWs and LVPWd(P<0.05).(2)Compared with normal control group,the content of hydroxypro-line in mouse myocardium,the collagen area ratio shown by Sirius red and Masson staining,and the immunohistochemical positive area ratio of Col I and Col Ⅲ in DCM group were significantly increased(P<0.01).Compared with DCM group,the above myocardial fibrosis indicators in EAEPOL group were significantly reduced(P<0.05 or P<0.01).(3)Com-pared with normal control group,the myocardial MDA content and the expression of Nrf-2 in DCM group were significantly increased,while the SOD activity,the T-AOC and the expression of HO-1 was significantly decreased(P<0.01).Com-pared with DCM group,the myocardial MDA content in EAEPOL group was significantly reduced,while the SOD activity,the T-AOC,and the HO-1 and Nrf-2 expression were significantly enhanced(P<0.05 or P<0.01).(4)Compared with normal control group,the myocardial expression of CD31 and CDH5 in DCM group was significantly reduced,the expres-sion of α-SMA and FSP1 was significantly enhanced(P<0.05 or P<0.01),and the α-SMA positive area ratio by immuno-fluorescence staining was also increased(P<0.01).Compared with DCM group,EAEPOL significantly up-regulated the expression of CD31 and CDH5 and down-regulated the expression of α-SMA and FSP1,and the α-SMA positive area ratio by immunofluorescence staining was evidently decreased(P<0.05 or P<0.01).CONCLUSION:EAEPOL may attenuate myocardial fibrosis and improve cardiac function in DCM mice by suppressing oxidative stress and alleviating EndMT.

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a₂b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.
Humans ; Quality of Life ; Cross-Sectional Studies ; Cardiovascular Diseases/complications* ; Stress, Psychological

Objective:To observe the effects of acupuncture and moxibustion on phosphatase and PTEN-induced putative kinase 1(PINK1)/Parkin signaling pathway in the midbrain substantia nigra of Thy1-α synuclein(αSyn)transgenic model mice with Parkinson disease(PD). Methods:Twenty-four Thy1-αSyn transgenic mice were randomly divided into a model group,an acupuncture group,an acupuncture + moxibustion group,and a Western medicine group.Six wild-type mice in the same litter were used as the wild-type group.In the acupuncture group,Baihui(GV20)and Yanglingquan(GB34)were selected for acupuncture.In the acupuncture + moxibustion group,Guanyuan(CV4)was added on the basis of the acupuncture group.The Western medicine group was given rapamycin intraperitoneal injection at a dose of 10 mg/(kg·bw).The wild-type group and the model group were fixed without intervention.The overall rod performance(ORP)score of mice was observed in each group.The immunohistochemical method was used to detect the tyrosine hydroxylase(TH)positive neurons in the substantia nigra of mice in each group.The αSyn was detected by the immunofluorescence chemical method.The expression levels of αSyn,microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,autophagy protein sequestosome-1/protein 62(SQSTM-1/p62),PINK1,Parkin,and ubiquitin-specific protease 30(USP30)proteins were detected by Western blotting assay.The expression levels of LC3B,p62,PINK1,Parkin,and USP30 mRNAs were detected by fluorescence quantitative polymerase chain reaction. Results:Compared with the wild-type group,the ORP score,the p62,PINK1,and Parkin protein expression levels decreased significantly(P<0.01),the PINK1 mRNA expression level decreased(P<0.05),while the protein and mRNA expression levels of USP30 increased(P<0.05)in the model group.Compared with the model group,the ORP score in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the expression level of LC3-Ⅱ/LC3-Ⅰ protein in the acupuncture + moxibustion group and the Western medicine group increased(P<0.05);the protein expression levels of p62,PINK1,and Parkin increased(P<0.05),while the USP30 protein expression level decreased significantly(P<0.01)in the acupuncture group,the acupuncture + moxibustion group,and the Western medicine group;the Parkin mRNA expression level in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the USP30 mRNA expression level in the acupuncture + moxibustion group decreased(P<0.05). Conclusion:Acupuncture and moxibustion regulate the related molecule expression levels of PINK1/Parkin signaling pathway in the Thy1-αSyn transgenic PD model mice and promote the autophagy degradation of αSyn to exert the protective effect of dopaminergic neurons.

Objective Explore the feasibility and accuracy of using deep learning techniques for gender inference in panoramic dental radiography images of Chinese Han population.Methods A total of 10,600 OPG images from Han individuals aged 18 to 70(5,300 males and 5,300 females)were collected and randomly divided into training set,validation set,and test set in an 8:1:1 ratio.MobileNetV2,Swin Transformer Small,and Swin Transformer Tiny models were trained,and the classification performance of the models was evaluated and visually displayed using accuracy,F1 score,and Grad-CAM algorithm.Results The accuracy of MobileNetV2,Swin Transformer Small,and Swin Transformer Tiny models was 97.57%,95.13%,and 96.28%respectively,with MobileNetV2 model showing the best overall performance.The Grad-CAM algorithm revealed that male OPG images mainly focused on the left and right mandibular branches and alveolar bone,while female OPG images mainly focused on the maxillary sinus,left mandibular branch,and posterior alveolar bone.Conclusion This study demonstrates that the gender inference model based on deep learning techniques for OPG images of Chinese Han population has high accuracy and generalization ability,providing a new approach for forensic gender determination in forensic medicine.

Involuntary hospitalization system is a controversial issue in international mental health legislation. During the legislation and implementation process of Mental Health Law of the People’s Republic of China, the substantive and procedural elements of the involuntary hospitalization system have always been under dispute and discussion. These disputes have profound ethical implications, highlighting the phenomenon of the coexistence of "insufficient" and "excessive" regarding China’s involuntary hospitalization system in protecting individual autonomy. From the perspective of public health ethics, the values of respect, justice, and care can provide ethical guidance for improving the involuntary hospitalization system and promoting the construction of mental health law.

Objective:To investigate the molecular testing of liquid-based cytology (LBC) specimens from advanced non-small cell lung cancer (NSCLC) patients and the reliability of guiding targeted therapy.Methods:The LBC specimens and clinical data of 412 advanced NSCLC patients from March 2015 to April 2017 in the Cancer Hospital, Chinese Academy of Medical Sciences were collected, of which 32 patients had postoperative or biopsy specimens. The real-time quantitative polymerase chain reaction was used to detect mutations of EGFR, KRAS and BRAF, and analyze the correlation between gene mutations and clinicopathological characteristics. The results of genetic testing of LBC specimens and histology specimens were examined for concordance. Clinical efficacy was evaluated in 142 patients treated with EGFR-tyrosine kinase inhibitor (TKI) drugs, and survival analysis was performed using the Kaplan-Meier method.Results:Of the 412 LBC specimens, 216 (52.4%) had EGFR mutations, 36 (8.7%) had KRAS gene mutations, and 3 (0.7%) had BRAF gene mutations. EGFR mutation was associated with gender, pathology type, and specimen source, with a higher EGFR mutation rate in female patients (63.0%) than in male patients (40.8%, P<0.001) and a higher EGFR mutation rate in adenocarcinoma (54.3%) than in non-adenocarcinoma (0.0%, P<0.001). KRAS mutation was related to gender, with a higher EGFR mutation rate in male patients (12.2%) than in female patients (5.6%, P=0.016). The three cases with multiple co-mutations were all stage Ⅳ male adenocarcinoma patients. Thirty-two patients with both LBC specimens and histology specimens had concordant genetic results between LBC specimens and histology specimens in 30 patients ( Kappa=0.91). Twelve patients with both histology and LBC specimens from metastases had identical genetic results ( Kappa=1.00). Nineteen patients with histology specimens from primary foci in lungs and LBC specimens from metastases had concordant genetic results between two specimens in 18 patients ( Kappa=0.92). The disease control rate (DCR) for EGFR mutation-positive patients treated with EGFR-TKI was 89.0% (89/100) and the progression-free survival time (PFS) was 13.8 months, both higher than those of EGFR mutation-negative patients [DCR of 30.8% (4/13) and median PFS of 1.4 months, P<0.01]. Conclusions:The results of molecular testing of LBC specimens and histological specimens are highly consistent, which demonstrates LBC specimens can be a crucial source of gene testing for advanced NSCLC. Molecular typing of advanced NSCLC based on the results of genetic testing of LBC specimens and guiding EGFR-TKI drug-targeted therapy can achieve high DCR and PFS, which has important clinical value.

Objective:To investigate the molecular testing of liquid-based cytology (LBC) specimens from advanced non-small cell lung cancer (NSCLC) patients and the reliability of guiding targeted therapy.Methods:The LBC specimens and clinical data of 412 advanced NSCLC patients from March 2015 to April 2017 in the Cancer Hospital, Chinese Academy of Medical Sciences were collected, of which 32 patients had postoperative or biopsy specimens. The real-time quantitative polymerase chain reaction was used to detect mutations of EGFR, KRAS and BRAF, and analyze the correlation between gene mutations and clinicopathological characteristics. The results of genetic testing of LBC specimens and histology specimens were examined for concordance. Clinical efficacy was evaluated in 142 patients treated with EGFR-tyrosine kinase inhibitor (TKI) drugs, and survival analysis was performed using the Kaplan-Meier method.Results:Of the 412 LBC specimens, 216 (52.4%) had EGFR mutations, 36 (8.7%) had KRAS gene mutations, and 3 (0.7%) had BRAF gene mutations. EGFR mutation was associated with gender, pathology type, and specimen source, with a higher EGFR mutation rate in female patients (63.0%) than in male patients (40.8%, P<0.001) and a higher EGFR mutation rate in adenocarcinoma (54.3%) than in non-adenocarcinoma (0.0%, P<0.001). KRAS mutation was related to gender, with a higher EGFR mutation rate in male patients (12.2%) than in female patients (5.6%, P=0.016). The three cases with multiple co-mutations were all stage Ⅳ male adenocarcinoma patients. Thirty-two patients with both LBC specimens and histology specimens had concordant genetic results between LBC specimens and histology specimens in 30 patients ( Kappa=0.91). Twelve patients with both histology and LBC specimens from metastases had identical genetic results ( Kappa=1.00). Nineteen patients with histology specimens from primary foci in lungs and LBC specimens from metastases had concordant genetic results between two specimens in 18 patients ( Kappa=0.92). The disease control rate (DCR) for EGFR mutation-positive patients treated with EGFR-TKI was 89.0% (89/100) and the progression-free survival time (PFS) was 13.8 months, both higher than those of EGFR mutation-negative patients [DCR of 30.8% (4/13) and median PFS of 1.4 months, P<0.01]. Conclusions:The results of molecular testing of LBC specimens and histological specimens are highly consistent, which demonstrates LBC specimens can be a crucial source of gene testing for advanced NSCLC. Molecular typing of advanced NSCLC based on the results of genetic testing of LBC specimens and guiding EGFR-TKI drug-targeted therapy can achieve high DCR and PFS, which has important clinical value.