BackgroundArrhythmia and obsessive-compulsive disorder （OCD） frequently co-occur in clinical and epidemiological settings， yet their shared genetic basis and potential heart-brain axis mechanisms remain unclear. ObjectiveTo systematically evaluate the genetic correlation between arrhythmia and OCD， and to elucidate their underlying molecular genetic mechanisms， so as to provide molecular evidence for the "heart-brain axis" to support risk assessment and integrated clinical strategies for these comorbidities. MethodsThe aggregated data from the genome-wide association study （GWAS） of arrhythmia in the UK Biobank （7 207 cases and 477 391 controls） and the GWAS data of OCD released by the Psychiatric Genomics Consortium （2 688 cases and 7 037 controls） were integrated， all of which were limited to individuals of European ancestry. The genome-wide genetic correlations were estimated using the linkage disequilibrium score regression （LDSC） and the high-definition likelihood （HDL）. Local genetic correlation analysis was conducted using the local analysis of variance annotation （LAVA）. Multi-trait analysis of GWAS （MTAG） was employed to identify pleiotropic loci. Shared risk genes were identified by combining summary-data based Mendelian randomization （SMR） and transcriptome-wide association study （TWAS）. Functional enrichment analysis was performed based on the functional mapping and annotation （FUMA） platform. ResultsBoth LDSC （r_g=0.248， 95% CI： 0.159–0.336， P=4.82×10^-3） and HDL （r_g=0.294， 95% CI： 0.237–0.351， P=5.87×10^-4） revealed significant positive genetic correlation between arrhythmia and OCD. LAVA identified 23 significantly local correlated regions in the genome （P<2.0×10^-5）. MTAG discovered 11 genome-wide significant pleiotropic SNPs， among which rs12754189 （intron of KCNN3） had potential functional harmfulness （CADD>12.37）. SMR and TWAS jointly identified 20 shared genes， enriched in neural-cardiovascular tissues such as the cerebral cortex， amygdala， and left ventricle， and involved in DNA damage response， RNA metabolism， transcriptional regulation， and FAS signaling pathway （FDR<0.05）. ConclusionArrhythmia and OCD share a common genetic basis. The co-morbidity mechanism may involve the common vulnerability of neurons and cardiac muscle cells in terms of gene expression regulation and stress response， supporting the role of the brain-heart axis in the pathophysiology of both conditions.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective:To develop a camelid single-domain antibody (SdAb) recognizing linear B-cell epitopes in glutamate dehydrogenase of Clostridium difficile(CD-GDH), and to apply it in Western blot and ELISA. Methods:Purified recombinant CD-GDH was used as bait to screen phage-displayed camelid SdAb library and obtain positive clones. Then those clones were confirmed by Western blot, and their variable domain of heavy chain of heavy chain antibody(VHH) nucleotide sequence were determined. The VHH sequence was synthesized after codon optimization and cloned into the expression vector pET28a. The SdAb was then expressed and purified, and its ability to detect CD-GDH protein in multiple assays was further explored.Results:Six positive clones were obtained, among which clone GA4 was chosen for recombinant expression in Escherichia coli and further purification. The purified GA4 binded well with CD-GDH with a Kd value of 3 nmol/L. In Western blot and ELISA, GA4 was proven to be able to selectively detect both recombinant and endogenous CD-GDH. Conclusions:A camelid SdAb targeting a linear B-cell epitope in CD-GDH is successfully developed, which provides a very useful tool for detecting CD-GDH.

Objective To investigate the impact of scenario class teaching on language expression,communication skills,and final exam performance of non-clinical majors students in the course of Medical Parasitology.Method Undergraduate students of non-clinical medical programs from Kunming Medical University in 2022 were selected as the subjects and randomly divided into a scenario class group and a non-scenario class group.Questionnaires were administered to compare the two groups regarding their interest in the laboratory classes,enjoyment levels,and knowledge retention.Additionally,the final exam scores of the two groups were compared.Results Students in the scenario class group showed significantly higher interest(82.6%)and enjoyment levels(88.3%)for laboratory classes compared to the non-scenario class group(73.0%and 60.1%,respectively,P<0.05).Students in the scenario class group believed that situational teaching enhanced their self-learning ability(82.06%),interest in learning(83.2%),willingness to express themselves(83.2%),confidence in expression(81.8%),and communication skills(87.9%).Additionally,It effectively facilitated their understanding of the occurrence and development of parasitic diseases(85.9%)and familiarity with the diagnosis and treatment process(86.8%),thereby cultivating clinical thinking.In terms of final exam scores,the scenario class group had a higher average score(22.80±0.18)than the non-situational classroom group(21.47±0.17,P<0.05).Conclusion Sc-enario class teaching in Medical Parasitology can effectively improve students'self-learning ability,language expression,and communication skills,cultivate clinical thinking,and enhance academic performance,demonstrating significant teaching advantages.

Objective To explore the relationship between triglyceride-glucose index(TyG)and acute ischemic stroke with large vessel occlusion(AIS-LVO)of anterior circulation.Methods A retrospective study was conducted on patients with anterior circulation AIS-LVO who underwent emergency endovascular thrombectomy at Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2019.According to modified Rankin scale(mRS)score 90 d after operation,the patients were assigned to favorable outcome group(mRS score 0-2)or unfavorable outcome group(mRS score 3-6),and the TyG was compared.According to the median of TyG,the patients were assigned to low-TyG group(TyG＜8.57)or high-TyG group(TyG ≥8.57),and the clinical data,laboratory indexes,and imaging characteristics were compared.Receiver operating characteristic curve was used to evaluate the predictive value of TyG for poor prognosis.Results A total of 135 patients were enrolled,with 72 in the favorable outcome group and 63 in the unfavorable outcome group.The TyG of the unfavorable outcome group was significantly higher than that of the favorable outcome group(8.82+0.63 vs 8.43+0.60,P＜0.001).There were 67 patients in the low-TyG group and 68 in the high-TyG group.Compared with the low-TyG group,the proportion of patients with hyperlipidemia history(P=0.003),systolic blood pressure at admission(P=0.018),fasting blood glucose level(P＜0.001),and triglyceride level(P＜0.001)were significantly higher in the high-TyG group,the infarct core volume was significantly larger(P=0.025),the high density lipoprotein-cholesterol level was significantly lower(P=0.013),and the mRS score 90 d after operation was significantly higher(3[1,5]vs 1[0,5],P=0.049).The TyG had certain predictive value for poor prognosis in anterior circulation AIS-LVO patients(area under curve value=0.662,95％confidence interval 0.571-0.753).Conclusion TyG is elevated in anterior circulation AIS-LVO patients with poor prognosis,and may be a potential prognostic indicator for anterior circulation AIS-LVO patients.

Objective To investigate the clinical efficacy of Xinxuetong Oral Liquid in the treatment of patients with acute coronary syndrome(ACS).Methods A total of 80 patients with ACS of blood stasis syndrome who were hospitalized in Shunde Hospital of Guangzhou University of Chinese Medicine from January 2023 to September 2023 were randomly divided into the treatment group and control group according to random number table method,40 patients in each group.The patients in the two groups were given conventional western medicine treatment including lifestyle guidance,percutaneous coronary intervention(PCI),and conventional western medicine therapy.Additionally,the treatment group was treated with Xinxuetong Oral Liquid.The course of treatment for the two groups covered eight weeks.Before and after treatment the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome score,blood stasis syndrome score,angina pectoris score,blood lipid indicators,carotid ultrasonography indicators,echocardiography indicators,and serum levels of trimethylamine-N-oxide(TMAO),nitric oxide(NO),endothelin 1(ET-1),interleukin 8(IL-8),serine/threonine-protein kinase 1(AKT-1),and vascular endothelial growth factor A(VEGF-A).After treatment,the efficacy on TCM syndrome efficacy and the safety of the regimen in the two groups were evaluated.Results(1)During the trial,there were two cases of loss to follow-up and one case of withdrawal due to pneumonia,and eventually a total of 77 patients completed the full course of treatment,among which 39 patients were in the treatment group and 38 patients were in the control group.(2)After eight weeks of treatment,the total effective rate of the treatment group was 89.74％(35/39),and that of the control group was 63.16％(24/38).The intergroup comparison(tested by chi-square test)showed that the effective rate of TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the scores of TCM symptoms such as chest pain,chest distress,symptom aggravation at night,and palpitation in the two groups,as well as the score of gloomy complexion in the treatment group,were significantly decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease of scores of chest distress,symptom aggravation at night,and palpitation in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(4)After treatment,the blood stasis syndrome score and angina pectoris symptom score of the two groups of patients were significantly decreased compared with those before treatment(P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the serum TMAO,ET-1,IL-8,AKT-1,and VEGF-A levels in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the serum NO level was significantly increased compared with that before treatment(P＜0.01).The decrease of serum TMAO,ET-1,IL-8,and AKT-1,VEGF-A levels and the increase of serum NO level in the treatment group were significantly superior to those of the control group(P＜0.05 or P＜0.01).(6)After treatment,the total cholesterol(TCHO)and low-density lipoprotein cholesterol(LDL-C)levels of the two groups(P＜0.01)and the triglyceride(TG)level of the treatment group(P＜0.05)were decreased significantly compared with those before treatment,while the high-density lipoprotein cholesterol(HDL-C)level of the treatment group was increased significantly compared with that before treatment(P＜0.01).No obvious changes of TG and HDL-C levels before and after treatment were shown in the control group(P＞0.05).The comparison of blood lipid indicators after treatment between groups showed that there were no statistically significant differences(P＞0.05).(7)After treatment,the carotid ultrasonography indicators of carotid intima-media thickness(IMT)and Crouse score of the carotid plaque in the two groups were significantly improved compared with those before treatment(P＜0.01).However,there was no statistical significance in the comparison of the two indicators between the two groups after treatment(P＞0.05).(8)The observation of echocardiography indicators showed that only the post-treatment left ventricular diameter(LVd)of the treatment group was significantly larger than that before treatment(P＜0.05),while no obvious changes of the other echocardiography indicators before and after treatment were shown in the two groups(P＞0.05).The comparison between the groups after treatment also showed no statistically significant differences(P＞0.05).(9)During the treatment,no serious drug-induced adverse reactions or drug-related severe cardiovascular events and complications occurred in the two groups.Conclusion The combination of Xinxuetong Oral Liquid with conventional western medicine treatment exerts certain efficacy and safety on improving the clinical symptoms of patients with ACS of blood stasis syndrome,and its therapeutic mechanism may be related to the improvement of blood lipid levels,inflammatory response,and TMAO level.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

In recent years, the incidence of myopia has been increasing alongside the growing global population, emerging as a significant public health challenge worldwide. Individuals with myopia exhibit an elongated axial length, which leads to various structural and functional ocular changes, resulting in the risk of related eye diseases and, in severe cases, blindness. Unfortunately, once myopia develops, it is irreversible. The only way to prevent or slow its progression is through appropriate treatment. The current focal point in myopia prevention and control is the peripheral myopic defocus theory. This paper summarizes the relevant research on defocus incorporated multiple segments(DIMS)lenses, following a systematic analysis of the literature. It analyzes the advantages and disadvantages of DIMS compared to other myopia control methods, and discusses the application prospects and future directions of defocus lenses represented by DIMS, aiming to provide reference and guidance for the control of myopia progression in children and adolescents.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.