Objective: To explore the association between mediterranean diet (MD) patterns and dental caries among children and adolescents with neurodevelopmental disorders (NDD), so as to provide a basis for developing scientific anti caries strategies related to diet. Methods: From December 2021 to June 2024, a questionnaire survey, a three day 24 hour dietary review survey, oral health examination, physical development measurement and Childhood Autism Rating Scale (CARS) evaluation were conducted involving 147 children and adolescents aged 2-22 years with NDD from nine special education schools and rehabilitation institutions in Tianjin. Group comparisons were carried out using the Mann-Whitney U test, Chi-square test, or Fisher s exact probability method. The correlation between dietary quality and dental caries was analyzed by adopting multiple linear regression analysis and restricted cubic spline. Results: There were 46 children and adolescents (31.3%) in the non dental caries group and 101 children and adolescents (68.7%) in the dental caries group. The number of decayed missing and filled teeth (dmft) was 2.0 (4.0), and the MD score was 4.0 (2.0) points. There were 62 children and adolescents (42.2%) in the low MD scores group and 85 children and adolescents (57.8%) in the high MD scores group. There was no significant difference in MD scores between NDD children in the non dental caries group and those in the dental caries group [nondental caries group:4.0(2.0), dental caries group:4.0(2.0), Z= -0.14, P >0.05]. The MD scores and dmft exhibited increasing and then decreasing trend ( P total =0.02, P non lineary = 0.04 ). Children and adolescents with NDD in the MD high scores group had a lower number of dmft than those in the MD low scores group ( β= -2.00 , 95%CI =-3.39 to -0.62, P <0.05). However, in children and adolescents with NDD and CARS scores ≥30, the above association was insignificant ( β=-0.63, 95%CI=-0.29-0.15, P >0.05). Conclusion Children and adolescents with NDD who have dietary patterns similar to the Mediterranean diet, are found to have fewer dental caries, and this is observed among those with no or mild symptoms of autism spectrum disorder.

Objective To investigate the impact of Qizhi Jiangtang Capsule (QZJT) on renal damage in diabetic nephropathy (DN) mice via NOD like receptors family pyrin domain containing 3/caspase-1/ Gasdermin D (NLRP3/caspase-1/GSDMD) signaling pathway. Methods Mice were randomly allocated into six experimental groups: a normal control group (NC), a diabetic nephropathy model group (DN), a low-dose QZJT treatment group (L-QZJT), a high-dose QZJT treatment group (H-QZJT), a positive control group administered Shenqi Jiangtang Granules (SQJT), and an ML385 group (treated with an inhibitor of nuclear factor erythroid 2-related factor 2, Nrf2). Upon successful model induction, therapeutic interventions were commenced. Renal function impairment in the mice was evaluated through quantification of fasting blood glucose (FBG), 24-hour urinary albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and the kidney-to-body mass ratio (K/B). Renal tissue pathology was evaluated using HE and PAS staining. Serum levels of inflammatory cytokines IL-1β and IL-18 were quantified by ELISA. Levels of podocyte markers and proteins involved in relevant pathways were assessed using Western blot analysis. Results Compared with the NC group, FBG, 24 h UAlb, SCr, and BUN were increased in the DN group, and the K/B mass ratio was also increased. In contrast, compared with the DN group, FBG, 24 h UAlb, SCr, and BUN in both the low-dose (L-QZJT) and high-dose Quanzhou Jintang (H-QZJT) groups were decreased, and the K/B mass ratio was decreased as well. The therapeutic efficacy of H-QZJT was comparable to that of Shenqi Jiangtang Granules. QZJT ameliorated renal histopathological injury in DN mouse, increased the protein levels of Nephrin (a podocyte marker), and decreased the protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, and GSDMD-N. After ML385 treatment, renal cells exhibited swelling and morphological changes, the inflammatory infiltrate area was enlarged, the protein levels of NLRP3, ASC, pro-caspase-1, and GSDMD-N were up-regulated, and the levels of IL-1β and IL-18 were increased. Conclusion QZJT may inhibit podocyte pyroptosis by acting on the Nrf2 to regulate the NLRP3/caspase-1/GSDMD pathway, thus improving renal damage in DN mouse.
Animals ; Diabetic Nephropathies/pathology* ; Podocytes/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Pyroptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Signal Transduction/drug effects* ; Mice ; Phosphate-Binding Proteins/genetics* ; Male ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Kidney/pathology* ; Gasdermins

Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

AIM: To determine the patient-related risk factors for pain during phacoemulsification.METHODS: Retrospective case-control study. A total of 62 patients(62 eyes)diagnosed as cataract in the First Affiliated Hospital of Zhengzhou University from December 2023 to January 2024 were included. The numeric rating scale was used to assess the pain level within 5 min postoperatively. The highest pain value was used as the primary outcome during the procedure. Based on pain values, patients were divided into pain group(n=25)and pain-free group(n=37). Subsequently, patients in the pain group were further divided into mild(n=16), moderate(n=7), and severe groups(n=2). Spearman correlation and Logistic regression analysis were conducted to determine risk factors for pain during the phacoemulsification.RESULTS: Binary Logistic regression showed preoperative sleep durations and times of operations were important risk factors for intraoperative pain(all P<0.05). Spearman analysis showed that intraoperative pain was negatively correlated with sleep duration(rs=-0.386, P=0.002), and positively correlated with times of operations(rs=0.421, P<0.001). The results of the ordinal Logistic regression analysis showed that for every additional hour of sleep, the likelihood of experiencing one higher level of intraoperative pain decreased by 37.60%(OR=0.376, P=0.014). In contrast, the times of operations did not show a statistically significant difference(P=0.083). Receiver operating characteristic curve showed a joint prediction model of sleep duration and operative times with an area under the curve of 0.809, 84% sensitivity, and 73% specificity.CONCLUSION: The intraoperative pain during phacoemulsification is negatively correlated with sleep duration and positively correlated with times of operations.

The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.

ObjectiveTo evaluate the efficacy of three screening questionnaires for COPD in the community residents of Songjiang District， Shanghai， and to provide a basis for selecting COPD screening questionnaire and process that are more suitable. MethodsCommunity residents aged 40 years or over were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for the study with screening questionnaires and spirometry. Questionnaires included the COPD screening questionnaire （COPD-SQ）， the COPD population screener （COPD-PS） and the revised COPD diagnostic questionnaire （revised-CDQ）. Evaluation of the efficacy of these questionnaires was based on the area under the receiver operating characteristic curve （AUC） of the subjects. DeLong test was used to compare the accuracy of different questionnaires； Z test was used to compare the accuracy of different cut-off values for the same questionnaire. ResultsAmong 3 184 community residents， a total of 259 （8.1%） COPD patients were screened by spirometry. AUC values of these 3 screening questionnaires were >0.7 indicating that they were reliable COPD screening tools. The sensitivity and specificity of the questionnaires at the recommended cut-off values were COPD-SQ （63.7% and 72.2%）， COPD-PS （12.0% and 96.1%）， and revised CDQ （78.8% and 52.7%）， with the COPD-SQ having the highest screening accuracy （AUC=0.754）. The optimal and recommended cut-off values for the three questionnaires differed in this population， but the difference in accuracy was statistically significant only for COPD-PS. The optimal cut-off values for the three questionnaires differed between male and female， and the sensitivity and accuracy of COPD-SQ and COPD-PS improved when lower cut-off values were used for women. The AUC was greater when two questionnaires were utilized simultaneously for screening， but the differences were not statistically significant. ConclusionThe COPD-SQ is recommended for primary COPD screening； a lower cut-off value for women should be considered. The COPD screening questionnaire needs to be further improved for the early diagnosis and treatment of COPD patients.

BACKGROUND:Circular RNAs(circRNAs)play important roles in a variety of diseases or tumors,and recent findings have revealed that circRNAs are abnormally expressed in knee osteoarthritis and are involved in disease progression through microRNA/mRNA regulation. OBJECTIVE:To investigate the effect of circRNA WD repeat containing protein 1(circ-BRWD1)/miR-488-3p/DNA methyltransferase 3A(DNMT3A)on the proliferation and apoptosis of chondrocytes in knee osteoarthritis. METHODS:Real-time fluorescence quantitative PCR was performed to detect the expression of circ-BRWD1,miR-488-3p,DNMT3A in knee osteoarthritis chondrocytes.Cells were divided into si-NC group,si-circ-BRWD1 group,vector group,circ-BRWD1 group,si-circ-BRWD1+anti-miR-NC group,si-circ-BRWD1+anti-miR-488-3p group,miR-NC group,miR-488-3p group,anti-miR-NC group,anti-miR-488-3p group,miR-488-3p+vector group,miR 488-3p+DNMT3A group.Real-time fluorescence quantitative PCR was used to detect circ-BRWD1,miR-488-3p,DNMT3A expression,MTT and flow cytometry assay were used to detect cell proliferation and apoptosis.Western blot assay was used to detect DNMT3A and proliferation/apoptosis-related protein expression.Dual luciferase reporter assay was used to Dual luciferase reporter assay to detect the targeting relationship of circ-BRWD1 with miR-488-3p and miR-488-3p with DNMT3A. RESULTS AND CONCLUSION:circ-BRWD1 and DNMT3A were highly expressed and miR-488-3p was lowly expressed in knee osteoarthritis chondrocytes compared with normal chondrocytes.Knockdown of circ-BRWD1 or overexpression of miR-488-3p inhibited proliferation and induced apoptosis in knee osteoarthritis chondrocytes.circ-BRWD1 targeted negative regulation of miR-488-3p and inhibition of miR-488-3p reversed the effect of circ-BRWD1 knockdown on chondrocyte proliferation and apoptosis in knee osteoarthritis.miR-488-3p targeted negative regulation of DNMT3A and upregulation of DNMT3A reversed the effect of miR-488-3p overexpression on chondrocyte proliferation and apoptosis in knee osteoarthritis.circ-BRWD1 could regulate the expression of DNMT3A by regulating miR-488-3p.To conclude,knockdown of circ-BRWD1 inhibits chondrocyte proliferation and induces apoptosis in knee osteoarthritis,and the mechanism of action may be related to the regulation of miR-488-3p/DNMT3A axis.