ObjectiveTo explore the possible mechanisms of Wenyang Huazhuo Formula （温阳化浊方， WHF） in improving reproductive aging from the perspective of the ovarian mechanical microenvironment. MethodsThe experiment included five groups， 3-month group （20 female mice at 3 months of age）， 6-month group （20 female mice at 6 months of age）， 6-month + WHF group （20 female mice at 5 months of age treated with WHF）， 9-month group （20 female mice at 9 months of age）， and 9-month + WHF group （20 female mice at 8 months of age treated with WHF）. The 6-month + WHF group and 9-month + WHF group were orally administered WHF 41.2 g/（kg·d） once daily for 4 consecutive weeks. The other three groups received no intervention. Reproductive hormone levels were measured by ELISA. HE staining was used to count the numbers of various stages of follicles. Ovarian hyaluronic acid （HA） content and collagen fiber content were measured to evaluate the ovarian mechanical microenvironment. Superovulation was performed to observe the number of eggs obtained， as well as the number of offspring and birth weight to assess fertility. The in vitro fertilization and blastocyst culture of oocytes from female offspring in each group were observed to evaluate the effect of WHF on offspring reproductive potential. ResultsCompared with the 3-month group， the 6-month group and 9-month group showed significantly decreased serum levels of gonadotropin-releasing hormone （GnRH）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH）， decreased ovarian collagen content， and reduced numbers of primordial and secondary follicles. In contrast， the numbers of primary follicles， antral follicles， and atretic follicles increased. The levels of anti-Müllerian hormone （AMH）， ovarian HA content， and the fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring were significantly lower （P＜0.05）. Compared with the 6-month group， the 6-month + WHF group showed significantly reduced serum levels of GnRH， FSH， and LH， with a significant decrease in primary follicles， antral follicles， and atretic follicles as well as increase of AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， and offspring birth weight （P＜0.05）. Compared with the 9-month group， the 9-month + WHF group exhibited reduced GnRH， FSH， and collagen fiber content， as well as reduced number of primary follicles， antral follicles， and atretic follicles. However， AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， offspring numbers， birth weight， fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring all significantly increased （P＜0.05）. ConclusionWHF can significantly improve the ovarian reserve， fertility， and reproductive potential in offspring during reproductive mid-life and late-life stages. Its effect may be related to the remodeling of the mechanical microenvironment of aging ovaries. Moreover， the effect on the mechanical microenvironment remodeling of late-stage ovaries and the improvement of the offspring reproductive potential is more significant.

ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics， with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method， basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules， but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors， but only 4.9% of them reported such violations. In terms of forensic ethics education， 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile， the respondents showed a high degree of recognition for receiving forensic ethics education， with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies， new employee training， and regular post-employment training. ConclusionCurrently， there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge， enhance ethical awareness， and improve the quality of practice.

Background Job burnout and depressive symptoms are prevalent among occupational populations, with a close relationship between them. Sleep quality, as a potential mediating factor, significantly affects the mental health of workers. Objective To explore the relationship between job burnout, sleep quality, and depressive symptoms, and determine whether sleep quality mediates the relationship between job burnout and depressive symptoms. Methods From April 25 to May 1, 2024, this study employed cluster sampling to conduct a questionnaire survey among individuals engaged in various occupations across five cities in the Ningxia Hui Autonomous Region. The questionnaires included socio-demographic information, as well as the Chinese Maslach Burnout Inventory (CMBI), the Pittsburgh Sleep Quality Index (PSQI), and the Patient Health Questionnaire-9 (PHQ-9) for assessing burnout, sleep quality, and depressive symptoms, respectively. Out of the 4106 questionnaires distributed, a total of 3837 questionnaires were valid, and the valid recovery rate was 93.45%. The distribution among demographic variables in burnout, sleep quality and depressive symptoms were statistically analyzed. A binary logistic regression model was used for multifactor correlation analysis; Pearson correlation was used to test the correlation between burnout, sleep quality, and depressed mood. Modelling and mediated effect path mapping were performed using Amos 24.0 software. Results The postive rate of occupational burnout in the workers was 97.49% (3741/3837), the positive rate of poor sleep quality was 66.77% (2526/3837), and the positive rate of depressive symptoms was 75.68% (2904/3837). There were statistically significant differences in depressive symptoms by ages, shift types, working years, marital status, smoking habits, drinking habits, and exercising frequency (P < 0.05). The logistic model indicated that working years, drinking habits, job burnout, and overall sleep quality were significant factors influencing the occurrence of depressive symptoms (P < 0.05). The correlation analysis revealed positive correlations between depressive symptom scores and job burnout scores (r=0.045, P < 0.01), between depressive symptom scores and sleep quality scores (r=0.480, P < 0.01), and between job burnout scores and sleep quality scores (r=0.054, P < 0.01). Furthermore, the indirect effect of job burnout on depressive symptoms through sleep quality was 0.100 (95%CI: 0.204, 0.252; P < 0.01). Conclusion Job burnout and sleep quality are significant factors associated with the occurrence of depressive symptoms among occupational populations, and sleep quality plays a partial mediating role in depressive symptoms associated with job burnout. This finding may provide a scientific basis for developing intervention strategies to control depressive symptoms among workers.

AIM: To compare the agreement between the ARK Biometer Combo and OA 2000 in patients wearing orthokeratology lenses.METHODS: A prospective study. A total of 148 patients(148 eyes)who were wearing orthokeratology lenses and returned for follow-up at the Shanghai Eye Disease Prevention and Treatment Center from August to September 2024 were included. Biometric measurements were performed using both the ARK Biometer Combo and OA 2000. Parameters including axial length(AL), corneal central thickness(CCT), anterior chamber depth(ACD), lens thickness(LT), corneal curvature(Kf and Ks), astigmatism(AST), white-to-white corneal diameter(WTW)and pupil diameter(PD)were obtained. Differences in measurement parameters between the two biometers were compared, and agreement was assessed.RESULTS: There were no statistically significant differences in the measurements of Kf, Ks and AST between the two biometers(P>0.05). Statistically significant differences were found in the measurements of AL, CCT, ACD, LT, WTW and PD(t=2.559, P=0.012; t=16.771, P<0.0001; t=4.749, P<0.0001; t=-15.212, P<0.0001; t=-14.915, P<0.0001; t=-2.402, P=0.018). ICC ranged from 0.615 to 0.999. Bland-Altman analysis showed that the maximum absolute values of the 95% limits of agreement(LoA)of AL, CCT, ACD, LT, Kf, Ks, AST, WTW and PD were 0.07 mm, 35.07 μm, 0.07 mm, 0.12 mm, 0.66 D, 1.14 D, 1.00 D, 0.76 mm, and 0.98 mm, respectively.CONCLUSION: In orthokeratology patients, the ARK Biometer Combo and OA 2000 showed good agreement in measuring AL, CCT, ACD, Kf and LT, and can be used interchangeably.

Objective To determine the improved effect of methylene blue(MB)on cognitive func-tion in brain-inflammatory-aging rats and investigate the underlying mechanism.Methods A total of 38 healthy 12-month-old SD rats were randomly divided into healthy control group,lipopo-lysaccharide(LPS)group,MB vehicle group and MB group,with 8 rats in the control and 10 rats in the other three groups.LPS was injected into the fourth ventricle with aid of a subcutaneous sustained release pump to establish a rat model of brain chronic inflammatory aging.MB of 0.5 mg/(kg·d)was added into the pump in the rats from the MB group.T-maze test and new object recognition test were employed to evaluate the learning and memory abilities of the rats.The acti-vation of microglia and astrocytes in the hippocampal CA1 region of the rats was detected by im-munofluorescence assay.The release of inflammatory factors IL-1β and IL-6 was measured by ELISA,and neuronal death in the CA1 region was assessed by neuronal nuclei(NeuN)fluores-cence staining.Results There was no significant difference in the exploration time for new and old objects between the LPS group and the MB solvent group(P＞0.05).The MB group spent significantly longer time in exploring the new objects than the old object(22.50±4.32 s vs 11.60± 3.01 s,P=0.000).The alternating selection rate of new arm and expression level of NeuN antigen were significantly decreased,and the expression levels of ionized calcium binding adaptor mole-cule-1(Iba-1)and glial fibrillary acidic protein(GFAP)and the contents of IL-1β and IL-6 were obviously increased(P＜0.05)in the LPS group and the MB vehicle group than the healthy con-trol group.Compared with the MB vehicle group,the MB group had notably increased alternating selection rate of new arms and higher NeuN expression level,and decreased Iba-1 and GFAP ex-pression and IL-1β and IL-6 contents(P＜0.05).Conclusion Subcutaneous administration of MB could significantly inhibit the damages of spatial learning and memory abilities in the LPS-induced brain chronic inflammatory aging rats.The mechanism may be closely associated with MB inhibi-ting inflammatory glial cells and protecting hippocampal pyramidal neurons.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Objective To compare and analyze the differences in CD8+naive,effector,memory,exhausted and regulatory T cells in order to investigate the impact of gender on the differentiation fate of CD8+T cells in the context of type 1 diabetes (T1D)based on female and male non-obese diabetic (NOD)mice and healthy Institute for Cancer Research (ICR)mice.Methods The frequencies and phenotypes of CD8+T cell differentiation subsets including naive T cells (TN),central memory T cells (TCM),effector T cells(TEFF),effector precursor T cells (TEP),exhausted T cells (TEX),precursor exhausted T cells (TPEX)and regulatory T cells (Tregs)in the spleen,pancreatic draining lymph nodes (pLN)and pancreas infiltrating lymphocytes (PIL)of male and female NOD mice were detected by flow cytometry.Results The frequencies of IFN-γ+,CD107a+and CCL5+CD8+TEFF in pLN and PIL of female NOD mice were significantly higher than those of male NOD mice.However,the frequencies of CD8+TN,CD8+TCM,CD8+TEX,CD8+TPEX and CD122+CD8+Tregs subsets in the spleen were significantly decreased.While there were no significant differences in the above CD8+T cell subsets except CD8+Tregs between female and male ICR mice. Conclusion Androgen may inhibit the differentiation of memory T cells into effector T cells and promote the exhaustion of effector T cells,leading to the difference in morbidity between the male and female mice.

Objective:To explore the clinical characteristics and pathogenic variant in a child with Cantú syndrome (CS).Methods:A male who was admitted to the Children′s Hospital Affiliated to Zhengzhou University on February 23, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole-exome sequencing (WES). Candidate variant was verified by Sanger sequencing. This study was approved by Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-087).Results:The child, a 3-year-and-2-month-old male, was born with hirsutism, with heavy hair all over the body and peculiar facial features. Routine echocardiography 1 month before had discovered atrial septal defect. Sequencing revealed that the child has harbored a heterozygous c. 2438G>C (p.S813T) variant of the ABCC9 gene, which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 2438G>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP3). Conclusion:The heterozygous c. 2438G>C variant of the ABCC9 gene probably underlay the pathogenesis of CS in this child.

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

Objective    To study the effect of Tangeretin on non-small cell lung cancer (NSCLC) and the tumor stemness, and to find the molecular mechanism of its effect. Methods    We used cell counting and cell cloning experiments to study the effect of Tangeretin on the proliferation of NSCLC cells in vitro. The effect of Tangeretin on the invasion of NSCLC cells was detected by transwell assay. We detected the effect of Tangeretin on the proliferation of NSCLC cells in vivo by nude mouse tumor-bearing experiment. The effect of Tangeretin on tumor stemness of NSCLC cells was detected by self-renew assay, and CD133 and Nanog protein expressions. The expressions of PI3K/AKT/mTOR signaling pathway-related proteins were detected by Western blotting (WB). Results    Tangeretin had a good inhibitory effect on the proliferation of NSCLC cells in vivo and in vitro. Cell counting experiment, clonal formation experiment and nude mouse tumor-bearing experiment showed that Tangeretin could inhibit the proliferation activity, clonal formation ability, and tumor size of NSCLC cells in vivo. Self-renew experiments showed that Tangeretin could inhibit the self-renew ability of NSCLC cells. WB experiments showed that Tangeretin inhibited the expressions of tumor stemness markers CD133 and Nanog in NSCLC cells. Tangeretin could inhibit the activation of PI3K/AKT/mTOR signaling pathway-related proteins in NSCLC cells, and the activation of PI3K/AKT/mTOR signaling pathway could partially remit the inhibitory  effect of Tangeretin on tumor stemness of NSCLC cells. Conclusion    Tangeretin can inhibit the tumor stemness of NSCLC cells, which may be related to the regulation of PI3K/AKT/mTOR signaling pathway.