[Effects of high-fat and low-carbohydrate diet combined with radiotherapy on tumor microenvironment of Lewis lung cancer bearing mice].

Objective: To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts. Methods: C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry. Results: On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant (P＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant (P＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8+ T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞0.05]. The proportion, of CD4+ T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞0.05). Conclusion: High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[Analysis of contents of different kinds of fatty acids in carotid atherosclerotic plaques].

Objective: To analyze the contents of different kinds of fatty acids in carotid atherosclerotic plaques. Methods: A total of 24 patients who underwent carotid endarterectomy at the Second Affiliated Hospital of Naval Medical University from October 2021 to September 2022 due to moderate and severe carotid artery stenosis were retrospectively enrolled, including 20 males and 4 females, with a median age[M(Q1, Q3)] of 68.5 (63.5, 72.3) years. According to the symptoms of cerebral ischemia, the patients were divided into a symptomatic group (12 cases) and an asymptomatic group (12 cases). Regarding the pathological characteristics, the patients were divided into a stable group (14 cases) and a vulnerable group (10 cases) according to carotid plaque pathology scores. The expression differences of different types of fatty acids in carotid plaques were analyzed by targeted fatty acid metabolomics technology based on ultra-performance liquid chromatography-mass spectrometry (UPLC-ESI-MS/MS) analysis. Results: In the 24 samples, the median amount of fatty acids [M (Q1, Q3)] was 1 113 (330, 5 897) ng/g. A total of 13 medium and long-chain fatty acids were detected, including saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids. The content of saturated fatty acids was 584 (290, 9 888) ng/g, accounting for the highest proportion of 51.8%. The content of polyunsaturated fatty acids was 1 444 (393, 4 264) ng/g, accounting for 44.4%. The content of monounsaturated fatty acids was 2 793 (1 558, 3 247) ng/g, accounting for 3.8%. The contents of linoleic acid, α-linolenic acid and oleic acid in carotid plaques in the symptomatic group were 1 760 (581, 3 006), 682 (527, 886) and 2 081 (1 358, 2 907) ng/g, respectively, which were lower than those in the asymptomatic group 3 149 (2 226, 4 683), 1 423 (964, 2 270) and 3 178 (2 352, 3 993) ng/g (all P<0.05). The contents of linoleic acid, α-linolenic acid and oleic acid in carotid plaques in the vulnerable group were 1 537 (588, 2 921), 649 (477, 850) and 2 081 (1 129, 2 831) ng/g, respectively, which were lower than those in the stable group 3 149 (2 047, 4 416), 1 423 (940, 2 184) and 3 091 (2 201, 3 973) ng/g (all P<0.05). There were no significant differences in the contents of 11, 14-eicosadienoic acid, γ-linolenic acid, eicosapentaenoic acid, arachidonic acid, erucic acid, margaric acid, pentadecanoic acid, stearic acid, dodecanoic acid and palmitic acid (all P>0.05). Conclusions: Saturated fatty acids are the main type in carotid plaques. The contents of oleic acid, α-linolenic acid and linoleic acid decrease in vulnerable plaques.

Association of interleukin-6 and CD4+ T cells and two-week prognosis of patients with COVID-19: a predictive role.

OBJECTIVE: The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.

[Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses].

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

[Prevalence and related factors of visual disability, hearing disability and comorbidity of visual and hearing disability among the elderly in China].

Objective: To estimate the prevalence of visual disability, hearing disability and comorbidity of visual and hearing disability among the elderly in China, and explore the related factors of comorbidity of visual and hearing disability in the elderly. Methods: This was a cross-sectional study. Based on the Second China National Sample Survey on Disability in 2006, the data of the elderly with visual and hearing disability were extracted and combined for descriptive analysis. Meanwhile, multivariate logistic regression model was used to analyze the related factors of comorbidity of visual and hearing disability among the elderly. Results: A total of 250 752 cases were in the final analysis (119 120 males and 131 632 females), and there were 164 003, 74 156 and 12 593 cases with the age of 65-<75, 75-<85 and ≥ 85 years, respectively. The prevalence of visual disability and hearing disability of the elderly in China was 8.10% (95%CI: 8.00%-8.21%), 13.41% (95%CI: 13.29%-13.54%), respectively, while the prevalence of comorbidity of visual and hearing disability was 1.97% (95%CI: 1.92%-2.02%). The severity of disability of the elderly with comorbidity of visual and hearing disability was higher, and the percentage of mild disabilities (18.31%, 966/5 277) was lower than those with visual (53.06%, 11 208/21 123) or hearing disabilities (32.96%, 11 536/34 995). Moreover, 19.40% (1 024/5 277) of visual or hearing disability occurred in the same year. Multivariate logistic regression analysis showed that education level below primary school (OR=0.65, 95%CI: 0.61-0.70, P<0.001), having a spouse (OR=0.68, 95%CI: 0.64-0.72, P<0.001), living in an urban area (OR=0.77, 95%CI: 0.71-0.82, P<0.001) and having a per capita household income higher than the national average (OR=0.73, 95%CI: 0.68-0.78, P<0.001) were protective factors for comorbidity of visual and hearing disability among the elderly. Conclusions: Visual disability is correlated with hearing disability in the elderly. Attention should be paid to the prevention and control of associated disabilities such as visual and hearing co-disabilities in the elderly population, with emphasis on strengthening publicity and education on prevention and control of visual and hearing disabilities for the elderly who are economically disadvantaged, have no spouse and live in remote areas.

[Analysis of 4 children with DYNC1H1 gene related spinal muscular atrophy with lower extremity predominant 1].

Objective: To investigate the clinical features and gene variation characteristics of children with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene associated spinal muscular atrophy with lower extremity predominant (SMALED) 1. Methods: The clinical data of 4 SMALED1 children admitted to Peking University First Hospital from December 2018 to May 2021, who were found to have pathogenic variation of DYNC1H1 gene through genetic testing, except for other genes known to be related to motor retardation, were retrospectively summarized to analyze the phenotype and genotype characteristics. Results: There were 3 males and 1 female. The age of onset was 1 year, 1 day, 1 day and 4 months, respectively. The age of diagnosis was 4 years and 10 months, 9 months, 5 years and 9 months, and 3 years and 1 month, respectively. The clinical manifestations were muscle weakness and muscular atrophy of lower limbs, 2 cases with foot deformity, 1 case with early non progressive joint contracture, 1 case with hip dislocation and 1 case with mental retardation. De novo heterozygous missense variations in DYNC1H1 gene were found in all 4 children. According to the rating of American College of medical genetics and genomics, they were all possible pathogenic and pathogenic variations, with p.R598C, p.P776L, p.Y1109D variations had been reported, and p.I1086R variation had not been reported. Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.

High species diversity in Diaporthe associated with citrus diseases in China.

Species in Diaporthe have broad host ranges and cosmopolitan geographic distributions, occurring as endophytes, saprobes and plant pathogens. Previous studies have indicated that many Diaporthe species are associated with Citrus. To further determine the diversity of Diaporthe species associated with citrus diseases in China, we conducted extensive surveys in major citrus-producing areas from 2017-2020. Diseased tissues were collected from leaves, fruits, twigs, branches and trunks showing a range of symptoms including melanose, dieback, gummosis, wood decay and canker. Based on phylogenetic comparisons of DNA sequences of the internal transcribed spacer regions (ITS), calmodulin (cal), histone H3 (his3), translation elongation factor 1-alpha (tef1) and beta-tubulin (tub2), 393 isolates from 10 provinces were identified as belonging to 36 species of Diaporthe, including 32 known species, namely D. apiculata, D. biconispora, D. biguttulata, D. caryae, D. citri, D. citriasiana, D. compacta, D. discoidispora, D. endophytica, D. eres, D. fusicola, D. fulvicolor, D. guangxiensis, D. hongkongensis, D. hubeiensis, D. limonicola, D. litchii, D. novem, D. passifloricola, D. penetriteum, D. pescicola, D. pometiae, D. sackstonii, D. sennicola, D. sojae, D. spinosa, D. subclavata, D. tectonae, D. tibetensis, D. unshiuensis, D. velutina and D. xishuangbanica, and four new species, namely D. gammata, D. jishouensis, D. ruiliensis and D. sexualispora. Among the 32 known species, 14 are reported for the first time on Citrus, and two are newly reported from China. Among the 36 species, D. citri was the dominant species as exemplified by its high frequency of isolation and virulence. Pathogenicity tests indicated that most Diaporthe species obtained in this study were weakly aggressive or non-pathogenic to the tested citrus varieties. Only D. citri produced the longest lesion lengths on citrus shoots and induced melanose on citrus leaves. These results further demonstrated that a rich diversity of Diaporthe species occupy Citrus, but only a few species are harmful and D. citri is the main pathogen for Citrus in China. The present study provides a basis from which targeted monitoring, prevention and control measures can be developed. Citation: Xiao XE, Liu YD, Zheng F, et al. 2023. High species diversity in Diaporthe associated with citrus diseases in China. Persoonia 51: 229-256. doi: 10.3767/persoonia.2023.51.06.

Constraints on Sub-GeV Dark Matter-Electron Scattering from the CDEX-10 Experiment.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

Observations of the Outer Heliosphere, Heliosheath, and Interstellar Medium.

The Voyager spacecraft have left the heliosphere and entered the interstellar medium, making the first observations of the termination shock, heliosheath, and heliopause. New Horizons is observing the solar wind in the outer heliosphere and making the first direct observations of solar wind pickup ions. This paper reviews the observations of the solar wind plasma and magnetic fields throughout the heliosphere and in the interstellar medium.

[Comparative study of three scores in predicting the death risk of severe burn patients].

Objective: To explore the predictive values of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score on the death risk of severe burn patients. Methods: A retrospective case series study was conducted. From February 2018 to November 2019, 260 severe burn patients who met the inclusion criteria were admitted to the Department of Burns of the First Affiliated Hospital of Nanchang University, including 158 males and 102 females, aged 36 (3, 53) years. According to the final outcome, the patients were divided into survival group (n=229) and death group (n=31). Data of patients were compared and statistically analyzed with chi-square test or Mann-Whitney U test between the two groups, including the gender, age, cause of burn, site of burn, total burn area, depth of burn, combined inhalation injury, and combined underlying diseases on admission, and the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score calculated based on part of the aforementioned data. The Kendall tau-b coefficient method was used to analyze the consistency of the above-mentioned three scores in 260 severe burn patients. The receiver operating characteristic (ROC) curves of the above-mentioned three scores predicting the death risk of 260 severe burn patients were drawn, and the area under the curve (AUC), the optimal threshold, and the sensitivity and specificity under the optimal threshold were calculated. The quality of AUC of the above-mentioned three scores was compared by Delong test. Results: The gender, site of burn, and depth of burn of patients between the two groups were all similar (P>0.05). The age, total burn area, proportion of flame burn, proportion of combined inhalation injury, and proportion of combined underlying diseases of patients in death group were significantly higher than those in survival group (with Z values of 5.53 and 17.78, respectively, χ2 values of 16.23, 15.89, and 17.78, respectively, P<0.01); the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score of patients in death group were 142 (115, 155), 7 (5, 7), 2 (2, 3), all significantly higher than 64 (27, 87), 1 (0, 3), 0 (0, 1) in survival group (with Z values of 7.91, 7.64, and 7.61, respectively, P<0.01). In 260 severe burn patients, the results between the modified Baux score and Ryan score, modified Baux score and Belgian Outcome in Burn Injury score, Ryan score and Belgian Outcome in Burn Injury score were significantly consistent (with Kendall tau-b coefficients of 0.75, 0.71, and 0.86, respectively, P<0.01). The AUCs of ROC curves of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score for predicting the death risk of 260 severe burn patients were 0.92, 0.89, and 0.85, respectively (with 95% confidence intervals of 0.86-0.98, 0.83-0.95, and 0.78-0.93, respectively, P<0.01); the optimal thresholds were 106.5, 4.5, and 1.5 points, respectively; the sensitivity under the optimal threshold were 88.5%, 76.9%, and 73.1%, respectively, and the specificity under the optimal threshold were 88.5%, 87.2%, and 86.3%, respectively. The modified Baux score was similar to Belgian Outcome in Burn Injury score in the AUC quality (z=1.25, P>0.05), which were both significantly better than the AUC quality of Ryan score (with z values of 2.35 and 2.11, respectively, P<0.05). Conclusions: The modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score have good ability in predicting the death risk of severe burn patients. From the perspective of clinical practice, the modified Baux score is more suitable as a predictive tool for the prognosis of severe burn patients.

[Serum exosomal miRNAs profiling and functional study in patients with non-alcoholic fatty liver disease].

Objective: Differential expression of serum exosomal miRNAs were detected for NAFLD patients and healthy controls, thereby determining the role of serum exosomal miRNAs in the pathogenesis, diagnosis, and treatment of NAFLD. Methods: Four patients with S2-3 NAFLD who shared similar demographic features and personal histories, and matched healthy controls were recruited for high-throughput sequencing of serum exosomal miRNAs. Four miRNAs with the most significant differential expression were verified by qRT-PCR in three groups (S1, S2-3, and control groups) with 20 cases in each group. Target gene prediction was performed for these differentially-expressed miRNAs, along with GO and KEGG enrichment analyses for the target genes. T-test or ANOVA were used for normally distributed data. Wilcoxon rank sum test was used for ranked data and non-normally distributed data. The count data used Pearson chi-square test or Fisher's exact test. Results: There were 19 serum exosomal miRNAs with significantly different levels of expression (P < 0.05) and a fold-change > 2. The expression of hsa-miR-122-5p, hsa-miR-146b-5p, and hsa-miR-197-3P was highest in the S2-3 group, followed by the S1 and control groups (in order); hsa-miR-483-3p expression was higher in the NAFLD group (S1 or S2-3) than the control group. There were 84 pathways significantly enriched in target genes. From 20 pathways closely related to NAFLD, at least 5 target genes which were simultaneously correlated to all 10 pathways were screened (PIK3R2, AKT2, AKT3, MAPK1, and NFKB1). Conclusion: Differential expression of serum exosomal miRNAs was detected in NAFLD patients and healthy controls. Four miRNAs with the greatest fold-changes were assessed to judge the severity of fatty degeneration of the liver. The research findings provide reference for non-invasive identification of new biomarkers and specific targets for NAFLD treatment.

[Application of next-generation sequencing technology in prenatal screening and diagnosis].

Developed rapidly for more than ten years, next-generation sequencing (NGS) has derived a series of new technologies which are widely used clinically, such as noninvasive prenatal testing(NIPT), noninvasive prenatal testing-plus(NIPT Plus), copy number variation sequencing(CNV-seq), and exome sequencing(ES), and plays an important role in birth defects prevention. Moreover, with in-deep development, the superiority of NGS is gradually recognized by clinicians, but there are still many challenges in practical application process. This study specifically elaborates on the development status, technological breakthroughs and future prospects of NGS in the field of prenatal screening and prenatal diagnosis at home and abroad.

[Study on the feature of cortical auditory evoked potential under different auditory tasks in cochlear implant children].

Objective: To investigate the variation regularity and influencing factors of cortical auditory evoked potential (CAEP) evoked by pure tone, syllable and tone stimuli in cochlear implant (CI) children. Methods: Cortical auditory evoked potential (CAEP) responses were collected from 46 CI children in the sound field. Pure tones with frequencies of 1 kHz and 2 kHz were used as the standard and the deviant respectively in the pure tone stimulation condition. The Chinese Mandarin tokens/ba/-/pa/and/ba1/-/ba4/pairs were used as the stimuli respectively in the syllable and tone stimulation condition. The latency, amplitude and presence rate of P1 and mismatch negative(MMN) were obtained and the correlation between the difficulty of auditory task, the age of hearing month, the duration of severe-profound hearing loss, the wearing history of hearing aid before CI, the hearing threshold of the better ear before CI and the latency and amplitude of P1 and MMN were analyzed. All statistical analyses and figures were conducted using SPSS 25.0. Results: The P1 presence rate of pure tone, syllable and tone group was 100% (17/17), 100% (13/13) and 75.0% (12/16), respectively, with significant difference (χ²=8.214, P=0.016). There was significant difference between pure tone group and tone group (χ²=4.836, P=0.028), but no significant difference between pure tone group and syllable group, syllable group and tone group. The MMN presence rate of pure tone, syllable and tone group was 94.1% (16/17), 84.6% (11/13) and 62.5% (10/16), respectively, but no significant difference among the three groups with different auditory tasks(χ²=0.066, P=0.066). No significant difference was observed among the three groups of different auditory tasks in the latency and amplitude of P1 and MMN. Multiple linear regression analysis showed that the latency of P1 was positively correlated with the difficulty of auditory task and the hearing threshold of the better ear before CI, and negatively correlated with hearing age and the history of hearing aid before CI. The latency of MMN was positively correlated with the difficulty of auditory task, and negatively correlated with hearing age. Conclusions: The P1 presence rate of pure tone auditory task is significantly higher than that of tone auditory task. The difficulty of auditory task, hearing age, the history of hearing aid before CI, and the hearing threshold of the better ear before CI has significant effects on the P1 latency. The difficulty of auditory task and hearing age has significant effects on the MMN latency.

[Genetics Analysis of patients with Dravet syndrome due to mosaicism variation of paternal SCN1A gene].

Genetic analysis was performed on a family of fraternal twins affected with Dravet syndrome by genetic tests whose parents were normal. To further analyze the cause of the disease, the fraternal twins were subjected to whole exome sequencing (WES), and the family was verified by Sanger sequencing, with the father semen and peripheral blood DNA were further analysed by target sequencing. The WES test identified a heterozygous c.5348C>T (p.Ala1783Val) variant of the SCN1A gene in the fraternal twins, which was predicted to be pathogenic and was detected in the father peripheral blood and semen, but not in the mother. So the mosaicism mutation of paternal SCN1A gene might be the genetic cause of Dravet syndrome in offspring.

Circ100284 promotes invasion and migration of osteosarcoma cells by down-regulating PTEN and EMP1.

OBJECTIVE: To investigate the role of circ100284 in osteosarcoma (OS) and the underlying mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the level of circ100284 in OS tissues and cells, and to examine the association between its level and clinicopathological features such as tumor size, tumor stage, and survival time. In addition, circ100284 was knocked out in MG63 and U2OS cells to observe the effect of circ100284 on cell viability, migration, cycle, and apoptosis by Cell Counting Kit-8 (CCK-8), transwell assay, and flow cytometry assay. Correlations of circ100284 with lysine-specific histone demethylase 1A (LSD1) and enhancer of zeste homolog 2 (EZH2) target proteins were analyzed by RNA co-precipitation experiments. Furthermore, the chromatin immunoprecipitation assay (ChIP)-qPCR assay was performed to analyze the relationship between circ100284 and its target protein and target gene. RESULTS: Circ100284 had a high level in OS tissues. The high expression of circ100284 was positively correlated with tumor size, pathological stage, and lung metastasis, and negatively correlated with patient survival time. Knocking down circ100284 in OS cells damaged the cell viability and invasiveness, blocked cell cycle, and promoted cell apoptosis. Further experiments showed that circ100284 could epigenetically inhibit cell proliferation by negatively regulating Phosphatase and tensin homolog (PTEN) and epithelial membrane protein 1 (EMP1) in OS. CONCLUSIONS: Circ100284 promotes the progression of OS cells by downregulating PTEN and EMP1.

Direct Detection Constraints on Dark Photons with the CDEX-10 Experiment at the China Jinping Underground Laboratory.

We report constraints on the dark photon effective kinetic mixing parameter (κ) with data taken from two p-type point-contact germanium detectors of the CDEX-10 experiment at the China Jinping Underground Laboratory. The 90% confidence level upper limits on κ of solar dark photon from 205.4 kg-day exposure are derived, probing new parameter space with masses (m_{V}) from 10 to 300 eV/c^{2} in direct detection experiments. Considering dark photon as the cosmological dark matter, limits at 90% confidence level with m_{V} from 0.1 to 4.0 keV/c^{2} are set from 449.6 kg-day data, with a minimum of κ=1.3×10^{-15} at m_{V}=200 eV/c^{2}.

Search for Light Weakly-Interacting-Massive-Particle Dark Matter by Annual Modulation Analysis with a Point-Contact Germanium Detector at the China Jinping Underground Laboratory.

We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m_{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m_{χ}<6 GeV/c^{2} among WIMP AM measurements to date.

Constraints on Spin-Independent Nucleus Scattering with sub-GeV Weakly Interacting Massive Particle Dark Matter from the CDEX-1B Experiment at the China Jinping Underground Laboratory.

We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m_{χ}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m_{χ} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ_{χN}^{SI} at 90% confidence level are derived as 2×10^{-32}∼7×10^{-35} cm^{2} for TI analysis at m_{χ}∼50-180 MeV/c^{2}, and 3×10^{-32}∼9×10^{-38} cm^{2} for AM analysis at m_{χ}∼75 MeV/c^{2}-3.0 GeV/c^{2}.