Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

This study aimed to investigate the effects of the peptide secreted protein isthmin-1 (ISM1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells. ISM1 expression in NSCLC was detected by immunohistochemistry (IHC). ISM1 was overexpressed in lung cancer cell lines by transient transfection of ISM1 plasmids, or establishing ISM1 overexpression stable cell lines, or by treating cells with recombined ISM1 (rISM1). CCK-8 was used to examine cell growth. The intracellular signal transduction pathways regulated by rISM1 were analyzed by transcriptome sequencing, and verified by qRT-PCR and Western blot. The levels of intracellular ROS and apoptosis were further detected using the kit. The results showed that the expression of ISM1 was decreased in human NSCLC tissue samples compared to normal lung tissue samples. Overexpression of ISM1 or rISM1 treatment significantly suppressed the growth of lung cancer cells. RNA sequencing revealed that rISM1 mainly regulated the FoxO signaling pathway. rISM1 treatment decreased the expression of FoxO3 and FoxO1, increased reactive oxygen species (ROS) production, and induced cell apoptosis. These results suggest that ISM1 can inhibit the growth of NSCLC by regulating the FoxO signaling pathway. These findings provide new strategies for cancer therapy.

To summarize the clinical characteristics and genetic mutation spectrum of patients with SELENON-related myopathy(SELENON-RM), in order to improve awareness among physicians.

AIM:The aim of this study was to explore the effects of Yiqi-Yangyin-Quyu prescription(YP)on skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome(SS),and to clarify the role of hy-droxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta(Hadhb)in mediating the effect of YP on skeletal muscle in SS.METHODS:The SS mice underwent YP treatment for 8 weeks.The morphological changes of the submandibular gland and muscle tissue were examined using hematoxylin-eosin staining.The mitochondrial status in mus-cle tissue was assessed through transmission electron microscopy.Additionally,combined transcriptome and proteome se-quencing was conducted on skeletal muscle samples.The omics sequencing results were validated by RT-qPCR.Immuno-fluorescence was used to confirm the levels of key proteins involved in the P53/peroxisome proliferator-activated receptor gamma(PPARG)signaling pathway.Immunohistochemistry and Western blot were employed to determine the levels of Hadhb key targets.RESULTS:Combined transcriptome and proteome analysis identified 1 523 differentially expressed genes(DEGs)and 182 differentially expressed proteins(DEPs)between the muscle tissue of SS mice(model group)and that of control animals(ICR group),12 of which showed co-differential expression at both transcriptomic and proteomic levels.Compared with model group,1 232 genes and 432 proteins were found to be differentially expressed in the muscle tissue of the mice in YP group.Among these,23 exhibited co-differential expression at both mRNA and protein levels.Gene Ontology(GO)analysis showed that the DEGs and DEPs between ICR and model groups were mainly involved in ener-gy metabolism and fatty acid oxidation,while the DEGs and DEPs between YP and model groups were primarily associated with sarcomere tissue and actin structure.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indi-cated that the DEGs and DEPs between ICR and model groups and between model and YP groups were enriched in the com-plement and coagulation cascade and lipid and pyruvate metabolism.The RT-qPCR validation results were consistent with those of the transcriptome analysis.Furthermore,the protein expression of the tumor suppressor P53 was significantly de-creased in YP group compared with model group,whereas that of PPARG was significantly increased.Western blot analy-sis showed that compared with ICR group,Hadhb protein expression was significantly decreased in model group,whereas the opposite trend was detected in YP group.CONCLUSION:The SS-related skeletal muscle damage is closely related to amino acid metabolism disorder and fatty acid degradation.Treatment with YP modulates innate immune defenses,lipid metabolism and energy metabolism in SS,and Hadhb is the key target of YP in SS-related skeletal muscle.

Objective To establish animal models by implanting Gynemesh polypropylene mesh and Mersilene tape into the abdominal walls of rats,followed by conducting mechanical experiments and performing HE staining on abdominal wall tissues at 30 and 90 days post-implantation,respectively,in order to evaluate the biomechanical properties and histocompatibility of the two types of meshes.Methods The Gynemesh mesh and Mersilene tape were implanted into the abdominal wall of adult female rats(n=10)using W6977M polyester non-absorbable sutures and V-Loc absorbable sutures.The rats were randomly assigned to either a 30-day group or a 90-day group(n=5 per group)based on different experimental time points.Mechanical tests were conducted at these time points to evaluate the ultimate load required for avulsion of the meshes from the abdominal wall.Following the mechanical experiments,the tissues surrounding the meshes were harvested for hematoxylin and eosin(HE)staining.The inflammatory response,neovascularization,and fibroblast proliferation in the tissues were scored to compare the histocompatibility of the two types of meshes.Results(1)In the 30-day group,the ultimate load values were as follows:Gynemesh+6977(14.96±2.22)N,Gynemesh+V-Loc(12.73±1.11)N,Mersilene+6977(10.65±0.91)N,and Mersilene+V-Loc(8.70±1.18)N.No statistically significant difference was observed in the ultimate load between the Gynemesh+6977 and Gynemesh+V-Loc groups(P=0.12),whereas statistically significant differences were noted among the other groups(P<0.05).(2)In the 90-day group,the ultimate load values were as follows:Gynemesh+6977(18.97±0.59)N,Gynemesh+V-Loc(18.18±0.54)N,Mersilene+6977(13.87±0.67)N,and Mersilene+V-Loc(10.41±0.73)N.No statistically significant difference was observed in the ultimate load between the Gynemesh+6977 and Gynemesh+V-Loc groups(P=0.06),while statistically significant differences were noted among the other groups(P<0.05).(3)The ultimate load at 90 days for each group was significantly greater than that at 30 days,with statistically significant differences observed across all groups(P<0.05).(4)In the 30-day group,Gynemesh exhibited a lower inflammatory response compared to Mersilene tape(2.0±0.69 vs.3.10±0.71,P<0.05),with no statistically significant differences in neovascular-ization or fibroblast proliferation(2.37±0.61 vs.2.40±0.62,P=0.84;2.43±0.73 vs.2.63±0.67,P=0.27).In the 90-day group,Gynemesh demonstrated a lower inflammatory response score(1.10±0.66 vs.2.00±0.74,P<0.05),reduced fibroblast proliferation(2.87±0.68 vs.3.27±0.67,P<0.05),and no significant difference in neovascular proliferation(2.20±0.55 vs.2.13±0.68,P=0.68)compared to Mersilene tape.(5)The inflam-matory response for both mesh types was higher in the 30-day group compared to the 90-day group(Gynemesh group:2.0±0.69 vs.1.10±0.66,P<0.05;Mersilene group:3.13±0.73 vs.2.0±0.74,P<0.05).Additionally,the degree of fibroblast proliferation was lower in the 30-day group than in the 90-day group(Gynemesh group:2.43±0.73 vs.2.87±0.68,P<0.05;Mersilene group:2.63±0.67 vs.3.27±0.69,P<0.05).However,there was no statistically significant difference in neovascularization proliferation between the two groups(Gynemesh group:2.53±0.74 vs.2.47±0.74,P=0.81;Mersilene group:2.40±0.62 vs.2.13±0.68,P=0.12).Conclusion Compared with Mersilene tape,Gynemesh polypropylene mesh exhibits superior tensile strength and enhanced biocompatibility.

Drug-induced liver injury is a critical adverse drug reaction, and its pathogenic spectrum encompass diverse classes of drug such as herbal medicines, antibiotics, and antineoplastics.Its nonspecific clinical manifestations and lack of definitive diagnostic markers hinder timely diagnosis, posing challenges in clinical management.Older individuals are particularly vulnerable owing to their unique physiology, medication preferences, frequent multimorbidity and polypharmacy.This article focuses on research achievements and progress in the field of the diagnosis and management of drug-induced liver injury in older individuals, aiming to improve the understanding of drug-induced liver injury in healthcare providers for older adults, as well as the ability of early identification and timely intervention, to reduce the occurrence of drug-induced liver injury and related adverse events.

OBJECTIVE To analyze the situation of urinary tract infections(UTIs)in children of different age groups in a health care hospital of Guangxi,and to analyze the detected pathogens and drug resistance rate.METHOD Data on urinary tract infections in children between 2017 and 2023 in Guangxi provincial maternal and child healthcare hospitals were retrospectively analyzed,and children were classified according to age:neonates(≤28 days),infants(＞28 days and ≤1 year),preschoolers(＞1 year and＜6 year)and 6-14 years old.The urina-ry tract infections,pathogen identification and drug resistance rates of major pathogens in children of different age groups were analyzed.RESULTS The pathogens of pediatric UTIs in each group were dominated by gram-negative bacilli(44.16％-67.36％),with the highest percentage of Escherichia coli(21.81％—38.60％),gram-posi-tive infections were dominated by Enterococcus faecium(5.96％—21.40％)and Enterococcus faecalis(4.66％—13.68％),and fungi were dominated by Candida albicans(8.03％-12.75％).Admission to intensive care unit was higher in the neonates group(37.38％,P＜0.001).Urine culture positivity rate was elevated in the 6-14 years age group(31.93％,P＜0.001),with girls being more common(59.47％,P＜0.001).The rate of E.coli resistance to cephalosporins was relative high in urine culture isolates from the infant group(28％—54％).In ad-dition,the resistance rate of Enterococcus faecium from urine to ampicillin was higher in the infant group than that in the preschool children and 6-14 years old groups(P=0.002).CONCLUSIONS The gram-negative bacteri-a were dominant among the pathogens isolated from the children with urinary tract infections and showed certain drug resistance to the commonly used antibiotics.Urinary tract infections are more difficult to diagnose and treat in younger children,and pediatricians should pay more attention to them.

BACKGROUND:The blood-brain barrier is an important structure that protects the central nervous system,and the study of the effects of high glucose on the blood-brain barrier is important for the prevention of high glucose-induced damage to the central nervous system.OBJECTIVE:To investigate the potential effect of high glucose on the blood-brain barrier function of hCMEC/D3 human brain microvascular endothelial cells.METHODS:hCMEC/D3 cells were cultured in regular sugar medium(glucose concentration of 25 mmol/L)and high-sugar medium(glucose concentration of 55 mmol/L).The morphology of cells in each group was observed by light microscopy.CCK-8 assay was used to detect changes in cell viability.A monolayer blood-brain barrier model was established using hCMEC/D3 cell line with Transwell chamber device.Changes in cell transmembrane resistance were monitored daily.The permeability of cell monolayers was detected by phenol red permeability.Flow cytometry was used to detect the apoptosis rate of the cells.Western blot assay was used to detect the expression of Bcl-2,Bax,Caspase-3,ZO-1,Occludin,Claudin-1,and histone deacetylase 4.The levels of histone deacetylase in cell supernatant were detected by ELISA.The expression of histone deacetylase 4 in cells was detected by immunofluorescence.RESULTS AND CONCLUSION:(1)The cell viability of high sugar group was significantly lower than that of control group(P＜0.000 1).(2)The cells of the control group were in a good growth state,interwoven into a dense mesh,with interconnections between synapses.The cell growth of high glucose group was suppressed,and the connection of inter-cellular synapses was reduced.(3)Compared with the control group,the transmembrane resistance value of the high glucose group was reduced(P＜0.05);phenol-red permeability of the monolayer cell membrane was increased(P＜0.05);cell apoptosis rate was increased(P＜0.01);the expression of Bax protein was increased(P＜0.000 1);the expression of Caspase-3 protein had no significant change(P＞0.05);the expression of Bcl-2,ZO-1,Occludin,Claudin-1,and histone deacetylase 4 proteins was decreased(P＜0.01,P＜0.001,P＜0.01,P＜0.000 1,P＜0.01);the fluorescence expression of histone deacetylase 4 was decreased(P＜0.001)in the high glucose group.(4)The level of histone deacetylase 4 in the cell supernatant of the high glucose group was lower than that of the control group(P＜0.05).The results show that high glucose induces the increased apoptosis and enhances permeability of hCEMCE/D3 cells,and its mechanism may be related to the decreased expression level of histone deacetylase 4.

Objective:To evaluate the clinical value of high-risk human papillomavirus (HPV) viral load for the cervical cancer screening and triage of high-risk HPV positive populations without additional tests.Methods:(1) This study conducted a retrospective analysis of 29 720 women aged 35-64 years who received cervical cancer screening in Quanzhou, China, in 2021. Fourteen high-risk HPV types (including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) were detected for cervical cancer primary screening using hybrid capture-chemiluminescence method. High-risk HPV positive samples were further subjected to HPV 16/18 genotyping using hybrid capture-chemiluminescence method. Among them, HPV 16/18 positive women were directly referred to colposcopy, while the other 12 high-risk HPV positive samples were further subjected to liquid based cytology test. Those with abnormal or suspicious cytology were referred to colposcopy. Biopsies were taken for histopathological examination of suspicious or abnormal individuals under colposcopy. (2) Ten cases of colposcopy loss or refusal to undergo examination were excluded, and the data from the 29 710 cases were analyzed. The HPV viral loads of the other 12 high-risk HPV positive populations were focused and evaluated their HPV viral loads for further cervical intraepithelial neoplasia (CIN) Ⅱ and above lesions (CINⅡ +) triage in cervical cancer screening. Results:(1) Among 29 720 women, 2 487 women (8.37%, 2 487/29 720) were positive for high-risk HPV, including 807 women (2.72%, 807/29 720) were positive for HPV 16/18 and 1 680 patients (5.65%, 1 680/29 720) were positive for the other 12 high-risk HPV types. Among 1 680 women who tested positive for the other 12 high-risk HPV types, 573 patients were atypical squamous cell carcinoma of unclear significance or above, 346 patients were CIN Ⅰ, 122 patients were CIN Ⅱ-Ⅲ, 9 patients were squamous cell carcinoma patients, and 4 patients were adenocarcinoma in situ. The immediate risk of CIN Ⅱ + in HPV 16/18 positive women (11.13%) was approximately four times higher than that of other 12 high-risk HPV positive women (2.74%). (2) Through the viral load analysis of the other 12 high-risk HPV types, we found that the viral load of the other 12 high-risk HPV provide a good value for the pathological results, with a clinical cutoff (CO) value of 11.21 relative light unit/CO (RLU/CO) for the CINⅡ + detection. Except for HPV 16/18 positive patients, when the viral load values of the other 12 high-risk HPV types were greater than 10 RLU/CO, these patients had a higher risk of CINⅡ +, with a positive predictive value of 31.29%. CINⅡ + was not found in any of the other 12 high-risk HPV positive with viral load values less than or equal to 10 RLU/CO. Conclusions:Using hybrid capture-chemiluminescence HPV tests for HPV 16/18 genotyping, combined with the viral loads (>10 RLU/CO) of the other 12 high-risk HPV analysis, one could triage HPV positive population without additional tests. Such triage strategy could promote the coverage of cervical cancer screening, particularly where cytology pathologists or economic resources are limited.

Objective To explore the experiences of children with Crohn's disease and their parents regarding the exclusion diet,and to provide a basis for formulating personalized dietary guidance programs.Methods A total of 12 children with Crohn's disease and their parents,hospitalized in the Department of Gastroenterology at a tertiary children's hospital in Guangzhou from June to December 2023,were selected as research subjects using objective sampling.Semi-structured interviews were conducted,and the data were analyzed and refined using Colaizzi's seven-step analysis method.Results Totally 3 themes and 14 sub-themes were extracted.①Lack of cognition and trust in Crohn's disease exclusion diet(unfamiliarity with the contents of the diet,misunderstanding of the diet's preparation,inadequate response to daily exclusion diet practices,parents' distrust in the exclusion diet).②The practical challenges of the Crohn's disease exclusion diet(the challenge of personal dietary preferences,the challenge of family meal preparation,the challenge of school feeding,food intolerance,feelings of monotony and weariness following the exclusion diet).③Innovations in practicing the Crohn's disease exclusion diet(managing taste fatigue,managing visual fatigue,innovative cooking methods,prioritizing exclusive enteral nutrition followed by the exclusion diet,overcoming the desire for universal food).Conclusion Children with Crohn's disease and their parents exhibit insufficient cognition and trust in the exclusion diet and face various challenges in practice.Clinical medical staff should adopt personalized coping strategies tailored to the specific circumstances of each child.