Aim To investigate the effect of quercetin(Que)on podocyte inflammatory injury and the under-lying mechanism.Methods MPC5 cells were divided into normal glucose group(NG),mannitol group(MA),high glucose group(HG)and high glucose+quercetin group(HG+Que).Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry.The expression of SIRT1,STAT3,apoptosis-related proteins(Bax,Bcl-2,caspase-3)and pyroptosis pro-tein GSDME was detected by Western blot.The ex-pression levels of inflammatory factors(IL-6,TNF-α,IL-18,IL-1β)in cell supernatants were detected by ELISA.Then small interfering RNA technology was used to knockdown SIRT1 expression.To further eval-uate the biological significance of SIRT1 in response to high glucose and Que treatment,negative control group(HG+si-NC+Que)and SIRT1 interference group(HG+si-SIRT1+Que)were added in the presence of high glucose and Que.Results Compared with the high glucose group,40 μmol·L-1 Que could alleviate the apoptosis of MPC5 cells induced by high glucose,decrease the expression of apoptosis related protein Bax and caspase-3,as well as increase the expression of anti-apoptotic protein Bcl-2;ELISA results showed that Que could decrease the expression of TNF-α,IL-6,IL-1 β and IL-18 induced by high glucose.Mechanical-ly,Que could alleviate the inhibitory effect of high glu-cose on the expression of SIRT1,and further decrease the activation of STAT3 and N-GSDME,and inhibit pyroptosis.Compared with the si-NC group,si-SIRT1 group could reverse the protective effect of Que on the high glucose induced inflammatory damage of podo-cytes,the expression of apoptotic proteins Bax and caspase-3 increased,while the expression of anti-apop-totic protein Bcl-2 decreased.At the same time,the levels of inflammatory cytokines TNF-α,IL-6,IL-1 βand IL-18 in supernatants increased,and the expres-sion of STAT3 and N-GSDME increased.Conclusion Que could inhibit pyroptosis and relieve the inflam-matory damage of podocytes through SIRT1/STAT3/GSDME pathway.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. Renal ischemia-reperfusion injury (RIRI) is one of the main causes of AKI with the underlying mechanism incompletely clarified. The liver X receptors (LXRs), including LXRα and LXRβ, are members of the nuclear receptor superfamily. It has been shown that LXRs play an important role in regulating glucose and lipid metabolism, cholesterol efflux, and inflammation. The purpose of this study was to explore the role and mechanism of LXRs in RIRI. We determined the effects of LXR activation on renal function and histological changes in a mouse RIRI model and a cellular model of hypoxia/reoxygenation (H/R). In vivo results showed that LXRs agonist GW3965 significantly inhibited the increase of serum creatinine and urea nitrogen levels induced by RIRI. Both HE and PAS staining of kidney tissues revealed that GW3965 alleviated the morphological damages caused by RIRI. Immunohistochemical staining showed that GW3965 mitigated 4-HNE and GRP78 levels induced by RIRI. Furthermore, TUNEL assay indicated that GW3965 reduced RIRI-induced renal cell apoptosis. Quantitative real-time PCR (qPCR) analysis revealed that GW3965 attenuated RIRI-induced IL-6 and IL-1β mRNA expression. Compared with wild-type group, LXRα gene deficiency had little effect on RIRI-associated renal functional decline and morphological damages. Additionally, in vitro study demonstrated that GW3965 alleviated H/R-induced decrease of HK-2 human renal proximal tubule cell viability and restored the activity of superoxide dismutase (SOD) after H/R. Western blot results showed that GW3965 mitigated the increase of 4-HNE and GRP78 protein expression levels after H/R; However, knockdown of LXRβ using the small interfering RNA (siRNA) technique reduced cell viability compared to GW3965-treated group. Taken together, the LXRs agonist GW3965 significantly alleviates RIRI in mice possibly by reducing apoptosis, oxidative stress, endoplasmic reticulum stress and inflammation. These results also preliminarily confirm that the renal protective effects of LXRs agonists are dependent on LXRβ.
Animals ; Liver X Receptors/genetics* ; Reperfusion Injury/prevention & control* ; Mice ; Benzoates/pharmacology* ; Benzylamines/pharmacology* ; Male ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Apoptosis ; Acute Kidney Injury/prevention & control* ; Kidney/pathology* ; Humans

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVE: The mode of human immunodeficiency virus (HIV) transmission via injection drug use (IDU) still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi. METHODS: We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data. RESULTS: Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs. CONCLUSION HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces. Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.
Humans ; HIV-1/genetics* ; HIV Infections ; Drug Users ; Phylogeny ; Bayes Theorem ; China/epidemiology* ; Genotype

OBJECTIVES: To study the influence of family structure on depression and anxiety symptoms in adolescents and its mechanism. METHODS: The cluster sampling method was used to select the students from seven middle schools in Shanghai, China. An online questionnaire survey was conducted using a self-made general status questionnaire, Childhood Trauma Questionnaire, Children's Depression Inventory, and Screen for Child Anxiety Related Emotional Disorders. The methods including one-way analysis of variance, chi-square test, binary logistic regression analysis, and mediating effect analysis were used to evaluate depression and anxiety symptoms in adolescents and the difference in childhood trauma and its mediating effect. RESULTS: Compared with the adolescents from nuclear families, the adolescents from three-generation lineal families had a lower risk of depression symptoms (OR=0.794, 95%CI: 0.649-0.972, P<0.05), while those from host families had a higher risk of depression symptoms (OR=4.548, 95%CI: 1.113-18.580, P<0.05). The adolescents from inter-generational families and host families had a significantly higher score on the Childhood Trauma Questionnaire subscale of emotional neglect (P<0.05). Emotional neglect played a mediating role in the influence of inter-generational families and host families on depression symptoms in adolescents. CONCLUSIONS Parents and grandparents have a certain positive effect in family structures. Separation from parents may make adolescents perceive more emotional neglect, which may increase the occurrence of depression symptoms.
Child ; Humans ; Adolescent ; Depression/epidemiology* ; Family Structure ; Child Abuse/psychology* ; China ; Anxiety/epidemiology* ; Surveys and Questionnaires

OBJECTIVES: To investigate the association between maternal job burnout and adolescent depression and the mediating effect of maternal depression and parenting style. METHODS: A cross-sectional study was conducted. The cluster random sampling method was used to select 2 572 adolescents from 7 middle schools in Shanghai, China, from April to May, 2021. A survey was performed for these adolescents and their mothers. The research tools included a general information questionnaire, Maslach Burnout Inventory-General Survey, Center for Epidemiologic Studies Depression Scale, short-form of Egna Minnen av Barndoms Uppfostran, and Children's Depression Inventory. A structural equation model was established, and the Bootstrap method was used to investigate the mediating effect. RESULTS: The detection rate of depressive symptoms was 12.71% (327/2 572) among the adolescents. The scores of maternal job burnout, maternal depression, and negative parenting style were positively correlated with the score of adolescent depression (P<0.05), and the score of positive parenting style was negatively correlated with the score of adolescent depression (P<0.05). Maternal depression and parenting style played a mediating role between maternal job burnout and adolescent depression, including the individual mediating effect of maternal depression, the individual mediating effect of positive parenting style, and the chain mediating effect of maternal depression-negative/positive parenting style. CONCLUSIONS Maternal job burnout may affect adolescent depression through the mediating effect of depression, parenting style, and depression-parenting style, suggesting that the symptoms of adolescent depression can be reduced by alleviating maternal job burnout, improving maternal depression, increasing positive parenting behaviors, and reducing negative parenting behaviors.
Child ; Adolescent ; Humans ; Cross-Sectional Studies ; Depression/etiology* ; Parenting ; China ; Burnout, Psychological

OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. METHODS: The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. RESULTS: The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). CONCLUSION The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).
Humans ; Small Cell Lung Carcinoma/drug therapy* ; Lung Neoplasms/drug therapy* ; Retrospective Studies ; Prognosis ; Combined Modality Therapy

Aging is a crucial factor influencing postural stability control and contributing to frequent falls, yet its underlying mechanisms remain incompletely understood. This study aims to explore the effects of aging on postural stability control by comparing differences in postural stability and node strength of electroencephalogram (EEG) brain network between elderly and young people under the conditions of congruent and incongruent visual-vestibular sensory inputs. Eighteen elderly volunteers without neuromuscular disorders and eighteen young individuals participated in the present study. Virtual reality (VR) technology was employed to manipulate visual rotation stimuli (clockwise and counterclockwise), and a horizontal rotating platform was used for vestibular rotation stimuli (clockwise). Based on the directional disparity of sensory input in the horizontal plane, visual-vestibular input consistency was categorized as congruent and incongruent. Postural stability was assessed by the center of pressure (COP) trajectory, and EEG signals were collected and analyzed using directed network analysis to observe EEG brain network node connectivity strength. The results revealed that, under conditions of incongruent visual-vestibular sensory inputs, the elderly exhibited significantly inferior postural stability performance in terms of COP anterior-posterior (Y-axial) sway speed, total path length, anterior-posterior and medial-lateral sample entropy, compared to the young adults. Moreover, the node connectivity strength of visual cortex in the elderly was notably higher, while node connectivity strength of superior temporal cortex was significantly lower than that in the young adults. These findings suggest that the elderly have a heightened reliance on visual information in postural control and an impaired ability to cope with sensory conflicts arising from incongruent visual-vestibular sensory inputs, leading to compromised postural stability. The outcomes of this study hold significant implications for future assessments of balance function in the elder and fall prevention trainings.
Young Adult ; Humans ; Aged ; Adolescent ; Posture ; Postural Balance ; Aging ; Brain

Objective:To investigate the genetic safety of allogeneic bone marrow mesenchymal stem cells (BMSCs) transplantation in traumatic brain injury (TBI).Methods:(1) In vivo experiment: BMSCs from male SD rats were isolated and cultured. Moderate TBI models were prepared by implanting and fixing micro-drug injection cannula into the left ventricle of 12 female SD rats, and 3 d after that, striking the right cerebral cortex of the rats with pneumatic precision percussion device was performed. Four h, and 3, 6, 9, and 12 d after modeling, TBI rats were given a single/multiple BMSCs infusion (2.5×10 5/time, total volume 10 μL) by cannula; 48 and 72 h, and 10 and 14 d after modeling, brain tissues of TBI rats (3 at each time point) were prepared into paraffin specimens. Immunofluorescent staining was used to detect the microglia activation, and RNAscope ? technology was used to detect the co-localization of astrocytes, neurons, microglia and transplanted BMSCs to observe whether the allogeneic BMSCs were integrated with the host brain cells after transplantation into TBI host. (2) In vitro experiment: the frozen and revived microglial cell line BV2 was transfected with green fluorescent protein (GFP)-positive lentiviral particles, and then, BMSCs prelabeled with pHrodo RED probe and BV2 cells pretreated with lipopolysaccharide were co-cultured in a certain ratio (BV2:BMSCs=1:1, 1:2, 2:1); after 36 and 72 h of co-culture, the phagocytosis between the 2 kinds of cells was observed under confocal fluorescence inverted microscope to observe the specific action forms of microglia on BMSCs. Results:(1) In vivo experiment: 48 and 72 h, and 10 and 14 d after modeling, no colocalization of transplanted BMSCs with astrocytes or neurons was found in paraffin sections of brain tissue in TBI rats; however, 10 and 14 d after modeling, microglia in TBI rats were obviously activated and migrated to the left lateral ventricle and choroid plexus, and co-localization of microglia with transplanted BMSCs was observed. (2) In vitro experiment: phagocytosis occurred after co-culture of BV2 cells at different proportions with BMSCs for 36 and 72 h. Conclusion:After transplantation, allogeneic BMSCs do not integrate with astrocytes or neurons of the TBI host, but they could be phagocytosed by microglia, indicating that allogeneic BMSCs transplantation for TBI is genetically safe.