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.

OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

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.

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 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

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: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.