This study aims to investigate whether the dietary supplement coenzyme Q10(CoQ10)alleviates bisphenol A(BPA)-induced mouse Leydig cell line(TM3)damage through autophagy pathway.Cell activity was measured by CCK-8 assay when treated with different concentrations of BPA for 24 h.TM3 cells were then divided into 5 groups:CON group,BPA group,Torin2 group,CQ group and BPA+CoQ10 group,with three repeats in each group.The morphology of TM3 cells were observed under inverted light microscope.Western blot was used to determine the protein ex-pression of p62 and LC3-Ⅰ/Ⅱ.The autophagy level of TM3 cells was detected by MDC cell auto-phagy staining,the mRNA expression levels of Atg7,Beclin 1,p62 and Atg5 genes were deter-mined by RT-qPCR,and the apoptosis rate of TM3 cells was detected by flow cytometry.The results showed that compared with 0 μmol/L BPA treatment group,the viability of TM3 cells de-creased significantly after 24 h treatment with 60 μmol/L BPA(P＜0.01).Compared with CON group,the number of TM3 cells markedly reduced in the BPA-treated group,the expression of au-tophagy-related proteins(p62,LC3-Ⅱ)significantly increased(P＜0.01),comparable to the CQ group.The MDC fluorescence intensity dramatically enhanced(P＜0.01),the mRNA expression levels of autophagy-related genes(Atg7,Beclin1,p62,Atg5)significantly elevated(P＜0.01),and the apoptosis rate significantly increased(P＜0.01).Compared with BPA group,the expression levels of autophagy-related genes Atg7 and Beclin1 mRNA(P＜0.05),p 62 and Atg5 mRNA(P＜0.01)in TM3 cells treated with BPA+CoQ10 significantly decreased.Moreover,the expres-sion levels of autophagy-related protein p62(P＜0.01)and LC3-Ⅱ(P＜0.05),MDC fluorescence intensity(P＜0.05)and apoptosis rate(P＜0.01)also markedly reduced.In conclusion,CoQ10 could subsequently reduce the apoptosis of TM3 cells by improving the abnormal autophagy flux induced by BPA.

Objective:To analyze the epidemiological characteristics of tick-borne encephalitis (TBE) in Heilongjiang province, to provide a scientific basis for the prevention and control of TBE.Methods:The epidemiological characteristics of TBE were systematically analyzed by the data of TBE cases reported in Disease Surveillance Information Reporting System.Results:A total of 1 127 TBE cases were reported from 2006 to 2020. The average age was 45.8 year, and the case fatality rate was 1.2%. Most TBE cases occurred from April to August, with a peak in June.Conclusions:This research elucidated the epidemiological characteristics of TBE in Heilongjiang province, and provides important basic data for the disease prevention and control.

This study aims to investigate whether the dietary supplement coenzyme Q10(CoQ10)alleviates bisphenol A(BPA)-induced mouse Leydig cell line(TM3)damage through autophagy pathway.Cell activity was measured by CCK-8 assay when treated with different concentrations of BPA for 24 h.TM3 cells were then divided into 5 groups:CON group,BPA group,Torin2 group,CQ group and BPA+CoQ10 group,with three repeats in each group.The morphology of TM3 cells were observed under inverted light microscope.Western blot was used to determine the protein ex-pression of p62 and LC3-Ⅰ/Ⅱ.The autophagy level of TM3 cells was detected by MDC cell auto-phagy staining,the mRNA expression levels of Atg7,Beclin 1,p62 and Atg5 genes were deter-mined by RT-qPCR,and the apoptosis rate of TM3 cells was detected by flow cytometry.The results showed that compared with 0 μmol/L BPA treatment group,the viability of TM3 cells de-creased significantly after 24 h treatment with 60 μmol/L BPA(P＜0.01).Compared with CON group,the number of TM3 cells markedly reduced in the BPA-treated group,the expression of au-tophagy-related proteins(p62,LC3-Ⅱ)significantly increased(P＜0.01),comparable to the CQ group.The MDC fluorescence intensity dramatically enhanced(P＜0.01),the mRNA expression levels of autophagy-related genes(Atg7,Beclin1,p62,Atg5)significantly elevated(P＜0.01),and the apoptosis rate significantly increased(P＜0.01).Compared with BPA group,the expression levels of autophagy-related genes Atg7 and Beclin1 mRNA(P＜0.05),p 62 and Atg5 mRNA(P＜0.01)in TM3 cells treated with BPA+CoQ10 significantly decreased.Moreover,the expres-sion levels of autophagy-related protein p62(P＜0.01)and LC3-Ⅱ(P＜0.05),MDC fluorescence intensity(P＜0.05)and apoptosis rate(P＜0.01)also markedly reduced.In conclusion,CoQ10 could subsequently reduce the apoptosis of TM3 cells by improving the abnormal autophagy flux induced by BPA.

Objective:To analyze the epidemiological characteristics of tick-borne encephalitis (TBE) in Heilongjiang province, to provide a scientific basis for the prevention and control of TBE.Methods:The epidemiological characteristics of TBE were systematically analyzed by the data of TBE cases reported in Disease Surveillance Information Reporting System.Results:A total of 1 127 TBE cases were reported from 2006 to 2020. The average age was 45.8 year, and the case fatality rate was 1.2%. Most TBE cases occurred from April to August, with a peak in June.Conclusions:This research elucidated the epidemiological characteristics of TBE in Heilongjiang province, and provides important basic data for the disease prevention and control.

Objective To evaluate the value of SOX1 and PAX1 gene methylation detection in the sec-ondary triage of high-grade cervical lesions.Methods Exfoliated cervical cells were collected from 122 patients tested positive for human papilloma virus(HPV)and subjected to thin-prep cytologic test(TCT)and SOX1/PAX1 gene methylation tests.Results The HPV test combined with TCT showed the sensitivity of 95.24％and the specificity of 23.75％for detecting cervical intraepithelial neoplasia(CIN)grade 2 and above(CIN2+).After the addition of the SOX1/PAX1 gene methylation detection in secondary triage,the sensitivity for detecting CIN2+was 83.33％,which had no statistically significant difference from the sensitivity of TCT combined with HPV test(P=0.078).However,the specificity reached 77.50％,which was significantly higher than that of HPV test combined with TCT(P＜0.001).The SOX1/PAX1 gene methylation level in the CIN2+group was higher than those in the normal cervical tissue and the CIN1 group(P＜0.001).The cut-off values of SOX1 and PAX1 gene methylation for CIN2+detection were-11.81 and-11.98,respectively.Conclusion Adding the detection of SOX1/PAX1 gene methylation in secondary triage significantly improves the efficiency and accuracy of CIN2+detection.

Objective To evaluate the effects of the multiple factors especially image geometric accuracy of the imaging system on the segmentations of target areas and organs-at-risk.Methods The study used phantoms to test the imaging performance of the 1.5T magnetic resonance(MR)linear accelerator system,including the assessments of MR image geometric distortion and the segmentation errors caused by factors such as image geometric distortion.Model 604-GS large field MR image distortion phantom was used to explore the geometric distortion of the MR images for MR-guided radiotherapy;and CIRS Model 008z upper abdominal phantom was used to analyze the segmentation errors of target areas and organs-at-risk.Results The average geometric distortion and maximum distortion of 3D T1WI-FFE images vs 3D T2WI-TSE images were 0.54 mm vs 0.53 mm and 1.96 mm vs 1.68 mm,respectively;and the control points of the large distortions were distributed at the edges of the phantom,which was consistent with the MR imaging characteristics previously reported.Compared with CT-based segmentation contour,the MDA was 1.17 mm and DSC was 0.91 for 3D T1WI-FFE,while MDA was 0.86 mm and DSC was 0.94 for 3D T2WI-TSE.Conclusion The study quantitatively assesses the geometric accuracy of the imaging system for MR-guided radiotherapy.The phantom-based contour analysis reveals that with CT image as gold standard,the segmentation error in MRI images meets the clinical requirements,and that 3D T2WI-TSE image is advantageous over 3D T1WI-FFE image in segmentation accuracy.

In recent years, the field of genetics has witnessed a burgeoning interest in the non-coding region, an area previously dubbed the"dark matter"of the genome. This once enigmatic domain is now progressively revealing its secrets, emerging as a rich terrain for genetic diagnosis and treatment. This editorial centers on diverse diagnostic analyses and intervention techniques associated with the non-coding region, delving into its significance in the etiology, diagnosis, and treatment of both monogenic and polygenic disorders within the nervous system. In doing so, it offers a comprehensive perspective for the exploration of genetic disorders in the nervous system.

In response to the Opinions of the CPC Central Committee and the State Council on Promoting the Inheritance， Innovation， and Development of traditional Chinese medicine（TCM） and the spirit of the National Conference on TCM， Chinese Association of Chinese Medicine organized experts in Otorhinolaryngology Head and Neck Surgery of traditional Chinese and western medicine to discuss the clinical advantages of TCM and integrated traditional Chinese and western medicine in the treatment of allergic rhinitis （AR） and they reached a basic consensus. In recent years， the prevalence of AR has been on the rise， threatening the quality of life of patients and giving rise to a heavy burden to both the patients and the society. AR is resulted from immune imbalance rather than reduced immunity or hyperimmunity， and the imbalance is similar to the Yin-yang disharmony in TCM. In the treatment of this disease， western medicine features rapid onset. However， it is cost-intensive and causes severe surgical trauma， and the recurrence is common. TCM boasts diverse methods for AR， which can be used in all stages of this disease. It has advantages in controlling symptoms such as nasal congestion， runny nose， or dysosmia in the attack stage， preventing recurrence in the remission stage， and treating refractory AR or steroid-resistant AR. In particular， acupuncture enjoys a reputation in treatment of AR， which has been supported by evidence-based medicine and recommended by guidelines. While treating local symptoms of AR， TCM regulates the psychosomatic conditions， which facilitates chronic disease management and long-term follow-up. We should integrate the advantages of TCM and western medicine， give full play to the unique nonnegligible and irreplaceable advantages of TCM， formulate a comprehensive diagnosis and treatment scheme for learning and promotion， and summarize the research outcomes to promote the theoretical innovation of TCM on AR from the perspective of integrated traditional Chinese and western medicine.

Objectives:To analyze the potential biomarkers of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD) continuum.Methods:A prospective cohort study was consecutively conducted on 179 patients with AD continuum (135 presented with BPSD, 44 patients without BPSD as control) from Capital Medical University, Beijing Tiantan Hospital, the Chinese imaging biomarkers and lifestyle cohort between January 1, 2021 and December 31, 2022. Gender, age, body max index, education level, diagnosis, the apolipoprotein E epsilon4 allele (APOE ε4) carrier status, the scores of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), cerebrospinal fluid (CSF) AD-related pathological biomarkers (Aβ 42, Aβ 40, Aβ 42/40, tTau, pTau181), and blood biomarkers (white blood cell count, red blood cell count, hemoglobin, platelet, total bilirubin, albumin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting glucose, erythrocyte sedimentation rate, homocysteine, vitamin B 12, folate) were compared between the two groups by using hypothesis testing and univariate logistic regression analysis. Multivariate logistic regression analysis was used to analyze the potential biomarkers associated with BPSD in patients with AD. Results:Among the 179 patients with AD continuum in the final analysis, 77 patients were men, 102 cases were women; 35 patients were identified with mild cognitive impairment (MCI) due to AD and 144 patients with AD dementia stage, the mean age was (66.54±9.75) years. Compared with those in control group, patients with BPSD had lower cerebrospinal fluid (CSF) Aβ 40 and blood hemoglobin levels [7.08 (4.42, 15.42) vs 9.62 (6.45, 12.12) pg/L, (132.70±13.37) vs (138.80±14.38) g/L] ( U=-1.856, t=2.579, P<0.05). The levels of CSF Aβ 40 ( OR=0.030, 95% CI: 0.001-0.760) and blood hemoglobin ( OR=0.051, 95% CI: 0.004-0.670) were independently negatively associated with BPSD in patients with AD continuum (both P<0.05). Conclusion:The decreased levels of CSF Aβ 40 and blood hemoglobin could be considered as potential biomarkers in detecting BPSD in patients with AD continuum.

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.