OBJECTIVES: Investigating the protective effect of naringenin (NAR) on the osteogenic potential of human periodontal ligament stem cells (hPDLSCs) under oxidative stress and its related mechanisms. METHODS: The oxidative damage model of hPDLSCs was established using hydrogen peroxide (H₂O₂) andthe hPDLSCs were treated with different concentrations of NAR and 0.5 μmol/L forkhead box protein O-1 (FOXO1) inhibitor AS1842856. After that, the cell counting kit-8 (CCK8) was used to determine the optimal concentrations of H₂O₂ and NAR. The alkaline phosphatase (ALP) staining and real time fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR) were employed to assess the expression of ALP, runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) in hPDLSCs of each group. The enzyme-linked immunosorbent assay (ELISA) and 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining were utilized to evaluate the expression of reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) in hPDLSCs. Meanwhile, qRT-PCR and western blot were used to detect the expression levels of FOXO1 and β-catenin, both are pathway related genes and proteins. RESULTS: H₂O₂ exposure led to an increase in oxidative damage in hPDLSCs, characterized by a rise in intracellular ROS levels and increased expression of MDA and LDH (P<0.05). At the same time, the osteogenic differentiation ability of hPDLSCs decreased, as evidenced by lighter ALP staining and reduced expression levels of osteogenic differentiation-related genes ALP, RUNX2 and OCN (P<0.05). Co-treatment with NAR alleviated the oxidative damage in hPDLSCs, enhanced their antioxidant capacity, and restored their osteogenic ability. The FOXO1 inhibitor AS1842856 downregulated the expression of β-catenin (P<0.05) and significantly diminished both the antioxidant effect of NAR and its ability to restore osteogenesis (P<0.05). CONCLUSIONS NAR can enhance the antioxidant capacity of hPDLSCs by activating the FOXO1/β-catenin signaling pathway within hPDLSCs, thereby mitigating oxidative stress damage and alleviating the loss of osteogenic capacity.
Humans ; Oxidative Stress/drug effects* ; Periodontal Ligament/cytology* ; Hydrogen Peroxide ; Forkhead Box Protein O1/metabolism* ; Stem Cells/cytology* ; Flavanones/pharmacology* ; beta Catenin/metabolism* ; Osteogenesis/drug effects* ; Signal Transduction ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Alkaline Phosphatase/metabolism* ; Osteocalcin/metabolism* ; Cells, Cultured ; Cell Differentiation/drug effects*

Alzheimer's disease(AD)is the most common neurodegenerative disorder worldwide,characterized primarily by cognitive impairment and memory dysfunction.Its pathological mechanisms involve the toxic accumulation of amyloid β-protein(Aβ),hyperphosphorylation of Tau protein leading to neurofibrillary tangles,mitochondrial dysfunction,synaptic impairment,cholinergic system dysfunction,neuroinflammation,and oxidative stress.Current clinical treatments for AD include acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists,which can improve cognitive function but fail to slow disease progression and often have side effects.Research indicates that traditional Chinese medicine(TCM)may regulate the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway,promoting neuronal survival,inhibiting neuroinflammation,reducing oxidative stress,preventing apoptosis,and decreasing Aβ deposition,thus improving the symptoms of AD.This review summarizes the mechanisms by which individual TCM components,extracts,and formulas may regulate the PI3K/AKT pathway in the treatment of AD,with the aim of providing a theoretical foundation for the application of TCM in AD therapy.

Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.
Humans ; Male ; Embolization, Therapeutic/methods* ; Microsurgery/methods* ; Randomized Controlled Trials as Topic ; Sclerotherapy/methods* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; Varicocele/surgery*

OBJECTIVES: To investigate the role and mechanism of copper overload-mediated endoplasmic reticulum stress (ERS) in vascular endothelial injury in Kawasaki disease (KD). METHODS: Four-week-old male C57BL/6 mice were randomly divided into four groups: control, KD, KD plus copper chelator tetrathiomolybdate (TTM), and KD plus ERS inhibitor AMG PERK 44 (AMG) (n=20 per group). A KD mouse model was established using Candida albicans extract. Human umbilical vein endothelial cells (HUVECs) were divided into control (intervention with healthy children's serum), KD (intervention with KD patients' serum), and KD+TTM (intervention with KD patients' serum plus 20 µmol/L TTM). Copper deposition in mouse heart tissue was assessed using rubeanic acid staining. Vascular pathological changes were observed using hematoxylin-eosin staining and measurement of abdominal aortic diameter and area. ERS activation was detected by transmission electron microscopy and immunofluorescence. HUVEC viability, apoptosis, and functional changes were evaluated using CCK8, flow cytometry, cell scratch assay, and angiogenesis experiments. ERS marker protein expression levels were measured by Western blot. RESULTS: Compared to the KD group, the KD+TTM and KD+AMG groups showed reduced copper deposition in the vascular wall, decreased swelling of coronary endothelial cells and endoplasmic reticulum, reduced inflammatory cell infiltration, and less abdominal aortic lesion expansion. The abdominal aortic diameter and area, and the fluorescence intensity of ERS marker proteins (GRP78 and CHOP) were significantly lower (P<0.05). Compared to the KD group, the KD+TTM group exhibited increased cell viability, tube number, and scratch healing rate, along with decreased apoptosis rate and expression of ERS marker proteins (GRP78, CHOP, ATF6, and p-PERK) (P<0.05). CONCLUSIONS Copper overload aggravates vascular endothelial injury in KD by activating the ERS pathway. TTM can exert protective effects on the endothelium by regulating copper metabolism and inhibiting the ERS pathway.
Endoplasmic Reticulum Stress ; Copper/toxicity* ; Male ; Mucocutaneous Lymph Node Syndrome/metabolism* ; Animals ; Humans ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Mice ; Human Umbilical Vein Endothelial Cells ; Apoptosis ; Endothelium, Vascular/injuries*

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

Alzheimer's disease(AD)is the most common neurodegenerative disorder worldwide,characterized primarily by cognitive impairment and memory dysfunction.Its pathological mechanisms involve the toxic accumulation of amyloid β-protein(Aβ),hyperphosphorylation of Tau protein leading to neurofibrillary tangles,mitochondrial dysfunction,synaptic impairment,cholinergic system dysfunction,neuroinflammation,and oxidative stress.Current clinical treatments for AD include acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists,which can improve cognitive function but fail to slow disease progression and often have side effects.Research indicates that traditional Chinese medicine(TCM)may regulate the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway,promoting neuronal survival,inhibiting neuroinflammation,reducing oxidative stress,preventing apoptosis,and decreasing Aβ deposition,thus improving the symptoms of AD.This review summarizes the mechanisms by which individual TCM components,extracts,and formulas may regulate the PI3K/AKT pathway in the treatment of AD,with the aim of providing a theoretical foundation for the application of TCM in AD therapy.

Objective : To investigate the effects of sinapine on lung tissue inflammation and mucus hypersecretion in asthmatic mice. Methods: Eight-week-old female C57BL/6J mice were randomly divided into Control group, ovalbumin(OVA) group, Sinapine group, and Sinapine+OVA group. The asthmatic mice model were established by intraperitoneal injection of OVA combined with aluminum hydroxide [Al(OH)3] suspension and OVA nasal stimulation. One hour before OVA nasal stimulation, the mice in Sinapine+OVA group and Sinapine group were intraperitoneally injected with sinapine solution, and the mice in OVA group and Control group were treated with the same dose of 0.9% sodium chloride solution. 24 hours after the last OVA stimulation, the inflammation of lung tissue of mice were observed by HE staining; the mucus secretion were evaluated by PAS staining; the mRNA expression levels of Interleukin-4(IL-4), Interleukin-5(IL-5), Interleukin-13(IL-13), tumor necrosis factor-alpha(TNF-α), Mucin 5ac(Muc5ac), and the mRNA of the key genes of Notch pathway such as Notch receptor 1(Notch1), Notch receptor 2(Notch2), Notch receptor 3(Notch3), and hes family bHLH transcription factor 1(Hes1) in lung tissues were detected by real-time fluorescent quantitative PCR(RT-qPCR); the expression levels of Notch1, Notch2, Notch3 and Hes1 proteins were determined by Western blot. Results : Compared with Control group, the inflammation score and PAS score of lung tissues of mice in OVA group increased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in OVA group were enhanced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in OVA group significantly increased(P<0.001), while there was no significant difference in the mRNA and protein expression levels of Notch1. Compared with OVA group, the inflammation score and PAS score of lung tissues of mice in Sinapine+OVA group decreased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in Sinapine+OVA group were reduced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in Sinapine+OVA group were downregulated(P<0.05), while there was no significant difference in the mRNA and protein expression levels of Notch1. Conclusion Sinapine can alleviate the lung tissue inflammation and mucus hypersecretion in asthmatic mice, and its mechanism may be related to the inhibition of Notch2/Notch3-Hes1 signal pathway.

Objective To investigate the relationship between serum microRNA-30a-5p(miR-30a-5p),Runt-associated transcription factor 2(RUNX2)and the severity and prognosis of patients with sepsis-induced acute lung injury(ALI).Methods A total of 193 patients with sepsis-induced ALI(ALI group)and 54 pa-tients with simple sepsis(non-ALI group)admitted to the Fifth Affiliated Hospital of Xinjiang Medical Uni-versity from January 2021 to February 2024 were selected,and the patients with sepsis-induced ALI were di-vided into a mild ALI group(57 cases),a moderate ALI group(64 cases),and a severe ALI group(72 cases)according to the oxygenation index,and were divided into a death group(71 cases)and a survival group(122 cases)according to the 28 day prognosis situation.Serum miR-30a-5p level was detected by real time fluores-cent quantitative PCR,serum RUNX2 level was detected by enzyme-linked immunosorbent assay,and the binding sites of miR-30a-5p and RUNX2 were predicted by online database.Pearson's correlation coefficient was used to analyze the correlation between miR-30a-5p and RUNX2 in patients with sepsis-induced ALI,and Spearman's correlation coefficient was used to analyze the correlation between serum miR-30a-5p,RUNX2 levels and oxygenation index in patients with sepsis-induced ALI.With the prognosis of patients with sepsis-induced ALI as the dependent variable,multivariate unconditional Logistic regression was used to determine their influencing factors,and receiver operating characteristic curve was plotted to evaluate the prognostic val-ue of serum miR-30a-5p and RUNX2 levels in patients with sepsis-induced ALI.Results Compared with the non-ALI group,serum miR-30a-5p level was lower and RUNX2 level was higher in the ALI group(t=-11.749,11.691,P＜0.001).There was a binding site between miR-30a-5p and RUNX2 at the 3'-untranslat-ed region 3 348-3 354.miR-30a-5p was negatively correlated with RUNX2 in patients with sepsis-induced ALI(r=-0.759,P＜0.001).The level of serum miR-30a-5p increased in the severe ALI group,the moderate ALI group and the mild ALI group in turn(P＜0.001),and the level of RUNX2 decreased in the severe ALI group,the moderate ALI group and the mild ALI group in turn(P＜0.001).Oxygenation index was negative-ly correlated with serum miR-30a-5p level(r=-0.749,P＜0.001),and positively correlated with RUNX2 level in patients with sepsis-induced ALI(r=0.723,P＜0.001).Independent protective factors for death in patients with sepsis-induced ALI were increased oxygenation index(OR=0.988,95％CI:0.981-0.996,P＜0.05),elevated miR-30a-5p(OR=0.814,95％CI:0.744-0.892,P＜0.05),and independent risk factors were increased Sequential Organ Failure Assessment(SOFA)score(OR=1.391,95％CI:1.116-1.734,P＜0.05),elevated blood lactate(OR=1.824,95％CI:1.211-2.748,P＜0.05),and elevated RUNX2(OR=1.366,95％CI:1.170-1.595,P＜0.05).The area under the curve of serum miR-30a-5p and RUNX2 levels combined to predict the death in patients with sepsis-induced ALI was 0.895(95％CI:0.842-0.934),which was greater than 0.788(95％CI:0.724-0.844)of serum miR-30a-5p and 0.786(95％CI:0.721-0.842)of RUNX2 levels alone(Z=4.015,3.746,P＜0.001).Conclusion Increased miR-30a-5p level and decreased RUNX2 level are associated with the aggravation of the disease and the increased risk of death in patients with sepsis-induced ALI.The combination of serum miR-30a-5p and RUNX2 levels has relatively high value in pre-dicting the prognosis of patients with sepsis-induced ALI.

Objective To investigate the factors influencing pathologic complete response(pCR)after neoadjuvant chemotherapy(NAC)and its correlation with prognosis in patients with human epidermal growth factor receptor 2(HER2)-low breast cancer.Methods A retrospective analysis was conducted on patients with HER2-low breast cancer who underwent NAC at the Second Affiliated Hospital of Jiujiang College from February 28,2018 to February 28,2021.Patients were divided into pCR group(achieved pCR,n=143)and non-pCR group(did not achieve pCR,n=300)based on pCR status.General clinicopathological data were collected and compared between the two groups,including age,surgical method,NAC regimen,postoperative radiotherapy,clinical tumor stage,tumor cT stage,tumor cN stage,pathological type,tumor Nottingham grade,hormone receptor(HR)status,Ki-67 status,menopausal status,and endocrine therapy.Binary logistic regression analysis was used to identify factors influencing pCR after NAC.Propensity score matching(1:1)was employed to balance baseline characteristics between the two groups.The matched groups'baseline data were compared.Kaplan-Meier method was used for survival analysis of the matched cohorts.Multivariate Cox proportional hazards regression models were used to analyze the independent influence of pCR on disease-free survival(DFS)and overall survival(OS)in HER2-low breast cancer after matching.Results A total of 443 patients with HER2-low breast cancer receiving NAC were included,with a mean age of(49.5±8.0)years.Binary logistic regression analysis identified clinical tumor stage(OR=0.498,95%CI 0.267-0.930),HR status(OR=0.513,95%CI 0.328-0.801),Ki-67 status(OR=2.580,95%CI 1.366-4.874),tumor Nottingham grade Ⅲ(OR=3.197,95%CI 1.147-8.910),and endocrine therapy(OR=0.513,95%CI 0.328-0.801)as independent factors influencing pCR after NAC(P<0.05).After propensity score matching,80 patients remained in each group(PCR and non-PCR).No significant differences were found in clinicopathological characteristics between the matched groups(P>0.05).The median follow-up time was 45.0 months(95%CI 43.1-46.9)for pCR group and 43.0 months(95%CI 41.0-45.0)for non-pCR group.The DFS rate was significantly higher in pCR group than that in non-pCR group(87.5%vs.70.0%,P=0.004),but there was no significant difference in OS rate(88.8%vs.85.0%,P=0.438).Multivariate Cox regression analysis showed that pCR was an independent factor influencing on DFS(HR=0.312,95%CI 0.142-0.688,P=0.004),but not OS in HER2-low breast cancer patients.Conclusions Patients with HER2-low breast cancer who have a lower clinical tumor stage,HR-negative status,high Ki-67 expression,high tumor Nottingham grade,and absence of endocrine therapy are more likely to achieve pCR.Achieving pCR prolongs DFS significantly but does not significantly improve OS in these patients.