This article further reveals the significance of "tiangui （天癸）" in female reproductive genetic diseases by analyzing the core influence of the "kidney-tiangui-chong and ren mai （冲任）-uterus" reproductive axis on the processes of birth， growth， robustness， and aging in females. Approaching tiangui through its heredity， material basis， temporality， rhythmicity， functional diversity and genetic polymorphism， and integrating reproductive genetics with epigenetics， it explores the potential associations between the characteristics of tiangui and the pathogenesis， clinical features， and therapeutic targets of female reproductive genetic diseases. This study furnishes a novel genetic interpretation of the physiological and pathological features of tiangui， offering scientific basis for the integrated prevention and treatment of female reproductive genetic diseases with traditional Chinese and western medicine.

This article further reveals the significance of "tiangui （天癸）" in female reproductive genetic diseases by analyzing the core influence of the "kidney-tiangui-chong and ren mai （冲任）-uterus" reproductive axis on the processes of birth， growth， robustness， and aging in females. Approaching tiangui through its heredity， material basis， temporality， rhythmicity， functional diversity and genetic polymorphism， and integrating reproductive genetics with epigenetics， it explores the potential associations between the characteristics of tiangui and the pathogenesis， clinical features， and therapeutic targets of female reproductive genetic diseases. This study furnishes a novel genetic interpretation of the physiological and pathological features of tiangui， offering scientific basis for the integrated prevention and treatment of female reproductive genetic diseases with traditional Chinese and western medicine.

Mitochondrial biogenesis represents a promising therapeutic target in triple-negative breast cancer (TNBC) due to its essential role in cancer cell metabolism and survival. The natural compound γ-Elemene exhibits potent anti-tumor activity, but its effects on mitochondrial regulation in TNBC remain unclear. In this study, we demonstrate that γ-Elemene induces dose-dependent cytotoxicity in MDA-MB-468 and HCC1806 TNBC cells while significantly impairing mitochondrial function, as shown by reduced membrane potential, oxidative phosphorylation capacity, and ATP production. γ-Elemene treatment markedly suppressed mitochondrial biogenesis, decreasing mitochondrial DNA content and downregulating key mitochondrial genes and proteins. These effects were associated with reduced expression of the master regulators NRF1 and TFAM, but independent of PGC-1α expression levels.Mechanistically, γ-Elemene upregulated the acetyltransferase GCN5, leading to enhanced PGC-1α acetylation. This upregulation occurs primarily through increased GCN5 transcription. Genetic ablation of GCN5 completely reversed γ-Elemene-induced PGC-1α acetylation and restored mitochondrial biogenesis and cell viability, establishing a critical role for GCN5 in mediating these effects. Our findings reveal a novel mechanism whereby γ-Elemene disrupts mitochondrial function in TNBC through GCN5-mediated PGC-1α acetylation, providing new insights into its anti-cancer properties and potential therapeutic applications against TNBC.

Most adult cases of depression originate during adolescence.In recent years,the incidence and suicide rate of adolescent depression raised gradually,seriously endangering physical and mental health as well as the life safety of minors.Resting-state functional MRI(rs-fMRI)was a core tool for exploring neurocognitive and psychiatric-behavioral disorders.The progresses in rs-fMRI research of adolescent depression with suicidal thoughts or behaviors were reviewed in this article.

Glaesserella parasuis is the causative agent of Gl?sser's disease in pigs.However,the pathogenic mechanisms underlying its virulence is not yet fully understood.The RuvB protein,a member of the AAA+superfamily,is implicated in various cellular processes,yet its specific role in the virulence of Glaesserella parasuis has not been fully characterized.In this study,we con-structed a RuvB gene deletion mutant,designated ΔRuvB,using the serotype 13 Glaesserella pa-rasuis strain ZJ1208 and a suicide plasmid-mediated natural transformation approach.To elucidate the functional role of the RuvB gene,we comprehensively evaluated the biological characteristics of the ΔRuvB strain through a series of assays,including growth kinetics,colony morphology,bac-terial staining,transmission electron microscopy(TEM),osmotic stress tolerance,high-tempera-ture tolerance,heat shock resistance,UV resistance,capsular polysaccharide quantification,serum bactericidal assays,and murine virulence experiments.Our findings revealed that the growth rate of ΔRuvB showed no significant difference compared to the parental strain.TEM revealed a notable increase in bacterial cell length;however,the number of outer membrane vesicles(OMVs)on the surface of ΔRuvB did not significantly increase.Notably,the ΔRuvB strain displayed a significant reduction in capsular polysaccharide production and serum resistance,as well as diminished toler-ance to UV radiation and high temperatures.Significant alterations were observed in its resistance to osmotic stress or oxidative stress.In the mouse toxicity challenge experiment,in com-parison with the parental strain ZJ1208,the mortality rate dropped by 20 percentage points,suggesting that the virulence of ΔRuvB has been weakened to some extent.Collectively,these results underscore the critical role of the RuvB gene in enhancing the environmental adaptability of Glaesserella parasuis.

Objective:This study aimed to analyze the genetic subtypes and drug resistance transmission characteristics of HIV-1 among the preoperative population in Ningxia from 2018 to 2023, to provide a scientific basis for the prevention and control of the AIDS epidemic.Methods:Plasma samples and demographic information of HIV/AIDS patients receiving antiviral treatment in Ningxia from 2018 to 2023 were collected. Blood samples with a viral loads >200 copies/ml from preoperative testing were amplified, sequenced, and subjected to genotypic resistance testing to analyze their genetic subtypes and drug resistance characteristics. The TN93 model in MEGA11 software was used to calculate the genetic distance between each pair of all sequences, and a molecular transmission network was constructed in Cytoscape 3.10.0 with 1.9% as the genetic threshold.Results:Among 101 preoperative HIV/AIDS patients, CRF07_BC and CRF01_AE were the predominant subtypes. The majority were male (85.15%, 86/101), aged 41-60 years (45.54%, 46/101), residing in Yinchuan city (61.39%, 62/101), and infected via heterosexual transmission (71.29%, 72/101), with most cases being late-detected. Of 39 drug-resistant sequences, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) alone (18.81%, 19/101) and dual resistance to nucleoside reverse transcriptase inhibitors (NRTIs)-NNRTIs (13.86%, 14/101) were most common. Among 44 sequences forming 13 transmission clusters, nine clusters harbored drug-resistant mutations. Four subtypes entered the molecular network, primarily involving heterosexual transmission, individuals with junior high school education or below, and men aged≥50 years.Conclusions:From 2018 to 2023, the preoperative HIV/AIDS patients had diversified genetic subtypes, with higher rates of overall drug resistance and late detection, stronger drug resistance and higher mortality rate. Strengthening molecular epidemiological research and developing targeted screening strategies are critical to improve early detection and reduce transmission risks.

Most adult cases of depression originate during adolescence.In recent years,the incidence and suicide rate of adolescent depression raised gradually,seriously endangering physical and mental health as well as the life safety of minors.Resting-state functional MRI(rs-fMRI)was a core tool for exploring neurocognitive and psychiatric-behavioral disorders.The progresses in rs-fMRI research of adolescent depression with suicidal thoughts or behaviors were reviewed in this article.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

OBJECTIVE: To explore the genetic basis for a girl with primary microcephaly and growth retardation. METHODS: A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278). RESULTS: DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c.2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. CONCLUSION Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.
Female ; Humans ; Cell Cycle Proteins ; Heterozygote ; Microcephaly/genetics* ; Mutation ; Nerve Tissue Proteins/genetics* ; Pedigree

Objective:To explore inhibitory effect of Tianzhi granule on neuroinflammation in vascular dementia(VD)rats.Methods:Sixty rats were randomly divided into Sham group,VD group,TZG-L group and TZG-H group,with 15 rats in each group.Bilateral common carotid artery occlusion was used to construct VD rats model,Sham group was not ligated.Rats in TZG-L group and TZG-H group were gavaged with Tianzhi granule 5 g/kg,20 g/kg every day,while rats in Sham group and VD group were gavaged with same amount of normal saline for 8 weeks.Y-maze test was used to detect cognitive ability of rats;Nissl staining and FJC staining were used to assess neuronal damage;TUNEL staining was used to detect neuronal apoptosis;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 protein levels in temporal cortex tissue.PC12 cells was divided into Control group,Glutamate group,TZG-L group and TZG-H group.Glutamate(20 μmol/L)was used to construct neuron injury model.TZG-L group and TZG-H group were added with Tianzhi granule 1 mg/ml,4 mg/ml.Neurons in each group were incubated for 48 h.CCK8 method and TUNEL staining were used to detect activity and apoptosis of neurons;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,Nrf2,HO-1 protein levels in cells.Results:Compared with Sham group,cognitive ability of rats in VD group were decreased,TUNEL positive neurons ratio was increased,Bcl-2 level was decreased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 levels were increased(all P<0.05).Compared with VD group,cognitive ability of rats in TZG-L group and TZG-H group were increased,TUNEL positive neurons ratio was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO levels were decreased(all P<0.05).Morphology of neurons in control group were normal;compared with control group,neurons in Glutamate group were swollen,activity of neurons was decreased,apoptosis rate was increased,Bcl-2 level was decreased,Bax,Caspase-3,Nrf2,HO-1 levels were increased(all P<0.05);compared with Glutamate group,cell damage in TZG-L group and TZG-H group were reduced,activity of neurons was increased and apoptosis rate was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3 levels were decreased(all P<0.05).Conclusion:Tianzhi granule can inhibit neuronal apoptosis and expression of NLRP3 inflammasome in VD rats,inhibit activa-tion of microglia/astrocytes and neutrophil infiltration,improve neuroinflammation of VD,which may play a role by activating Nrf2/HO-1 signaling pathway in neurons.