Among gynecologic malignancies, ovarian cancer is the most lethal, primarily due to its insidious early symptoms, lack of effective screening methods, and high risk of recurrence. It poses substantial challenges to clinical diagnosis and treatment. In recent years, the clinical application of poly ADP-ribose polymerase inhibitors has promoted a comprehensive management model that integrates targeted therapy with conventional treatments. This review, aiming to provide new perspectives and approaches for future research, summarizes the high-risk factors and first-line treatment strategies for ovarian cancer. Further studies should focus on optimizing personalized treatment strategies and exploring novel targeted therapies to improve patient survival outcomes.

Objective To explore the potential relationship between ubiquitination of transforming growth factor kinase 1(TAK1)/nuclear factor-κB(NF-κB)signaling pathway mediated by ring finger protein 99(RNF99)and septic acute respiratory distress syndrome(ARDS).Methods Plasmid and siRNA transfection were conducted to overexpress or knock down RNF99 in MLE12,and expressions of p65 phosphate and p65 protein were analyzed.The protein interaction between RNF99 and TRAF6 or TAK1 was analyzed by immunoprecipitation assay.Forty mice were randomly divided into WT plus PBS,WT plus LPS,RNF99 specific expression(TG)plus PBS,and TG plus LPS groups,with 10 mice in each group.Sepsis was induced by intraperitoneal injection of 30 mg/kg LPS.Results As compared with vector group,protein expression levels of TRAF6 and TAK1 in MLE12 cells decreased significantly in RNF99 group(P<0.05).Ubiquitinated TRAF6 protein increased in MLE12 cells with RNF99 knockdown.As compared with LPS plus vector group,phosphorylation level of p65 in MLE12 cells was signifi-cantly lower in LPS plus RNF99 group(P<0.05).As compared with si-NC group,protein expression levels of RNF99 and IκBα in si-RNF99 group decreased significantly(P<0.05).As compared with LPS plus si-NC group,phosphorylation level of p65 in LPS plus si-RNF99 group increased significantly(P<0.05).The staining percentage of CD68 macrophages in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Phosphorylation level of p65 in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Conclusion RNF99 regulates NF-κB signaling pathway by interacting with the key regulator of NF-κB signaling pathway(TRAF6/TAK1),and improves lung injury after intraperitoneal injection of LPS in mice.

Social behavior is extremely important for the physical and mental health of individuals, their growth and development, and for social development. Social behavioral disorders have become a typical clinical representation of a variety of psychiatric disorders and have serious adverse effects on the development of individuals. The prefrontal cortex, as one of the key areas responsible for social behavior, involves in many advanced brain functions such as social behavior, emotion, and decision-making. The neural activity of prefrontal cortex has a major impact on the performance of social behavior. Numerous studies demonstrate that neurons and glial cells can regulate certain social behaviors by themselves or the interaction which we called neural microcircuits; and the collaboration with other brain regions also regulates different types of social behaviors. The prefrontal cortex (PFC)-thalamus projections mainly influence social dominance and social preference; the PFC-amygdala projections play a key role in fear behavior, emotional behavior, social exploration, and social identification; and the PFC-nucleus accumbens projections mainly involve social preference, social memory, social cognition, and spatial-social associative learning. Based on the above neural mechanism, many studies have focused on applying the non-invasive neurostimulation to social deficit-related symptoms, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES) and focused ultrasound stimulation (FUS). Our previous study also investigated that repetitive transcranial magnetic stimulation can improve the social behavior of mice and low-intensity focused ultrasound ameliorated the social avoidance behavior of mice by enhancing neuronal activity in the prefrontal cortex. In this review, we summarize the relationship between neurons, glial cells, brain projection and social behavior in the prefrontal cortex, and systematically show the role of the prefrontal cortex in the regulation of social behavior. We hope our summarization will provide a reference for the neural mechanism and effective treatment of social disorders.

Objective To analyze the prevalence and genetic characteristics of influenza A(H3N2) viruses in the city of Xiangyang in 2022-2023, and to provide a scientific basis for predicting the epidemic and mutation of influenza virus. Methods Throat swab specimens of the influenza like cases were collected from national influenza monitoring sentinel hospitals in Xiangyang every week. RNA was extracted from the specimens for influenza diagnosing using real-time RT-PCR．Viruses were isolated from H3N2 positive specimens, and HA and NA genes were amplified and sequenced．3D modeling analyses were conducted. Results The gene phylogenetic tree showed that the H3N2 isolates in 2022-2023 belonged to 3C.2a1b.2a1 and 3C.2a1b.2a2 branches, respectively. The A(H3N2) influenza virus strains all had amino acid point mutation sites on important antigenic determinants of HA protein. The epitope mutations of the 2022 A(H3N2) strain mainly occurred in regions B, C, and D. The epitope mutations of the A(H3N2) strain in 2023 mainly occurred in regions C and D. Different glycosylation sites of HA gene were found in 2022-2023 strains. No variation was found in key amino acid sites associated with neuraminidase inhibitor resistance. The difference of overall structure was not obvious in the three-dimensional simulation structure diagram. Conclusion The A(H3N2) influenza strains isolated in this study have shown antigenic drift, especially the mutation of HA, which may affect the protective effect of the vaccine on the local population and lead to influenza epidemic. The variations of HA and NA suggest that close attention should be paid to the epidemic and genetic variation of H3N2 subtype influenza virus, to provide a scientific basis for the selection of influenza virus vaccine strains and the prevention and control of influenza.

A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

BACKGROUND:Pulsed electromagnetic fields,as an important physical therapy,are exactly effective in the treatment of osteoarthritis,but the mechanism has not been fully clarified. OBJECTIVE:To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS:Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment.Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group(n=8)and pulsed electromagnetic field group(n=8).The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention,once a day,5 days per week for continuous 8 weeks.The rats in the old group were given no treatment.All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION:Compared with the young group,serum type Ⅱ collagen C-terminal peptide level was increased in the old group(P<0.05);compared with the old group,serum type Ⅱ collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group(P<0.05).Micro-CT showed that the bone volume fraction,bone mineral density,and number of bone trabeculae decreased(P<0.05)and the trabecular separation increased(P<0.05)in the tibia of rats in the aged group compared with the young group;and the bone volume fraction,bone density,and number of trabeculae increased(P<0.05)and the trabecular separation decreased(P<0.05)in the tibia of rats in the pulsed electromagnetic field group compared with the aged group.The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized,and the number of chondrocytes was obviously reduced,and the tidal line could not be distinguished.The above results were improved in the pulsed electromagnetic field group.RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1,matrix metalloproteinase 13,P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group(P<0.05)and decreased in the pulsed electromagnetic field group compared with the old group(P<0.05).To conclude,pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence,alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.

Epilepsy is one of common diseases of nervous system,which is mainly manifested as repeat-ed abnormal neuronal discharges in the brain.If it cannot be effectively controlled,it can cause irreversible neuronal damage in the brain.Non-coding RNAs plays an important role in the development and progression process of epilepsy and are involved in regulating autophagy,apoptosis,neuroinflammation,synaptic remode-ling and other physiological and pathological processes,especially in the regulation of autophagy in epileptic neuronal cells.This article reviews the regulatory relationship between microRNA and long non-coding RNAs,circRNAs in non-coding RNAs with autophagy in the occurrence and development of epilepsy to pro-vide a direction for the precise treatment and prevention of epilepsy.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To explore the clinical characteristics and genetic basis for a child with global developmental delay and autism.Methods:A child who had presented at West China Second University Hospital of Sichuan University on April 13, 2021 was selected as the study subject. Clinical manifestations, laboratory examination and result of genetic testing were analyzed.Results:The main symptoms of the child had included cognitive, language and motor delay, autism and epilepsy. Electroencephalogram revealed multiple focal discharges in both waking and sleeping stages, with the remarkable one seen at the sleeping stage. Cranial MRI showed pachygyria and local cortical thickening, Whole exome sequencing (WES) revealed that the child has harbored a heterozygous c. 1589_1595dup (p.Gly533Leufs*143) frameshifting variant in the TBR1 gene (OMIM 604616). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PS2+ PVS1_Supporting+ PM2_Supporting). After treated with levetiracetam and rehabilitation training, the child did not have seizure in the past 5 months, and his motor development has also significantly improved. Conclusion:The c. 1589_1595dup variant of the TBR1 gene probably underlay the disease in this patient.

Objective To investigate the effect of cinobufacini on immune escape of acute myeloid leukemia(AML)by regulating myosin heavy chain 9(MYH9)/ubiquitin-specific protease 7(USP7)/cellular-myelocytomatosis viral oncogene(c-MYC)pathway.Methods(1)In vivo experiment:a nude mouse xenograft tumor model was established to evaluate the effect of cinobufotalin on the growth and immune escape of AML cells in vivo.(2)In vitro experiments:human AML cell line HL-60 was treated with different concentrations of cinobufacini,cell viability was detected by cell counting kit 8(CCK-8),and HL-60 cell invasion was detected by Transwell assay.HL-60 cells were co-cultured with activated CD8+ T cells,the expression of CD25,the surface marker of CD8+ T cells,was detected by flow cytometry,the levels of cytokines[interleukin-2(IL-2)and interferon(IFN-γ)]in the co-culture supernatant were detected by enzyme-linked immunosorbent assay(ELISA).CytoTox96 non-radioactive cytotoxicity assay was used to evaluate the cytotoxicity of CD8+ T cells to HL-60 cells.The protein expressions of MYH9,USP7 and c-MYC in HL-60 cells were detected by Western Blot.The interaction between MYH9,USP7 and ubiquitination was detected by co-immunoprecipitation(Co-IP)assay.The MYH9 overexpression plasmid was tranfected to verify the mechanism of cinobufacini in AML.Results Cinobufacini treatment inhibited xerograft tumor growth in nude mice and enhanced the anti-tumor ability of CD8+ T cells.Cinobufacini treatment inhibited HL-60 cell viability and invasion in a concentration-dependent manner.Cinobufacini treatment up-regulated the expression of CD25,a surface marker of CD8+ T cells,and also up-regulated the levels of IL-2 and IFN-γ.Cinobufotalin enhanced the toxicity of CD8+ T cells to HL-60 cells.Cinobufacini inhibits the protein expressions of MYH9,USP7 and c-MYC in HL-60 cells.MYH9 promotes c-MYC deubiquitination by recruiting USP7,but cinobufacini inhibits MYH9-mediated c-MYC deubiquitination.Conclusion Cinobufacini can reduce the recruitment of c-MYC by deubiquitinating enzyme USP7 by inhibiting the expression of MYH9,and promote the ubiquitination and degradation of c-MYC,thereby inhibiting the immune escape of AML cells.