Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P＜0.01);decreased retinal thickness(P＜0.01);decreased retinal blood perfusion(P＜0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P＜0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P＜0.01);increased retinal blood flow(P＜0.01);increased amplitudes of ERG a wave and b wave(P＜0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P＜0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.

Objective To investigate the association of whole blood nucleophosmin 1(NPM1),monocyte chemotac-tic protein-1(MCP-1),and intestinal flora with gastric cancer progression and prognosis.Methods A total of 120 patients with gastric cancer who were admitted to the Nanyang Second People's Hospital from May 2018 to May 2020 were selected as the gastric cancer group,120 patients with benign gastric lesions underwent gastroscopy in the same period were selected as the benign gastric lesions group,and 120 patients with healthy physical examinations in the same period were selected as the control group.RT-qPCR was used to detect mRNA expression of NPM1 and MCP-1.The intestinal microbiota was examined by MicroScan microbial identification analysis system;The correla-tion between NPM1,MCP-1 and intestinal microbiota was analyzed by Pearson method.Multivariate COX regression was used to analyze the influencing factors of prognosis in gastric cancer patients.Results The level of NPM1 mRNA,exuberance of Bifidobacterium and Lactobacillus in the control group,gastric benign lesion group,and gastric cancer group decreased sequentially(P＜0.05),whereas MCP-1 mRNA,Enterococcus,and Escherichia coli increased sequentially(P＜0.05).Serum NPM1 mRNA,Bifidobacterium and Lactobacillus in stage Ⅲ-Ⅳ of gastric cancer were obviously lower than those found in stage Ⅰ-Ⅱ(P＜0.05),while MCP-1 mRNA,Enterococcus and Escherichia coli were obviously more than those found in stage Ⅰ-Ⅱ(P＜0.05).Pearson correlation analysis showed that,there was a negative correlation between serum NPM1 mRNA and MCP-1 mRNA levels in gastric cancer patients(P＜0.05),NPM1 mRNA was positively correlated with Bifidobacterium and Lactobacillus(P＜0.05)and negatively correlated with Enterococcus and Escherichia coli(P＜0.05).MCP-1 mRNA was negative-ly correlated with the quantity of Bifidobacterium and Lactobacillus(P＜0.05)but positively correlated with Entero-coccus and Escherichia coli(P＜0.05).The level of NPM1 mRNA,quantity of Bifidobacterium and Lactobacillus in the poor prognosis group were obviously lower than those found in the good prognosis group(P＜0.05),while the level of MCP-1 mRNA,quantity of Enterococcus and Escherichia coli were obviously higher than those in the good prognosis group(P＜0.05).COX regression analyses showed that MCP-1 mRNA,Enterococcus and Escherichia coli were risk factors affecting the prognosis of gastric cancer patients(P＜0.05),while NPM1 mRNA,Bifidobacterium,and Lactobacillus were protective factors(P＜0.05).Conclusions Decreased level of NPM1,decreased counting of Bifidobacterium intestinalis and Lactobacillus,increased level of MCP-1,increased counting of Enterococcus and Escherichia coli are strongly associated with gastric cancer progression and poor prognosis.

Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional LJF decoction piece as a reference. The flowability experiments showed that the flowability of medium-sized granules (10-24 mesh) was significantly better than that of traditional drinking tablets (P < 0.01); the results of the paste rate showed that there was no significant difference between the different particle sizes and the original decoction pieces (P > 0.05), but the small particle sizes (24-65 mesh) had poor decoction clarity and gelatinization; the transfer rate was calculated as chlorogenic acid and luteoloside, and there was no significant difference in the transfer rate between traditional slices and different particle sizes (P > 0.05); the pharmacological results showed that the contents of rat tumor necrosis factor-α (TNF-α), rat interleukin-1β (IL-1β) and rat prostaglandin E₂ (PGE₂), xylene ear swelling inhibition rate and granuloma inhibition rate showed that there was no significant difference between the traditional and new granule decoction pieces (P > 0.05). In this study, by examining the fluidity, paste rate, paste degree, and antipyretic and anti-inflammatory effects of the new granular decoction piece of LJF, it was initially revealed that the new granular drinking tablets of LJF were consistent with the basic properties and pharmacological effects of the commercially available traditional drinking tablets. Still, the new granular tablets were characterized by high utilization rate, homogeneous quality, and ease of clinical transfer, which had a good prospect for application. The animal experiment was approved by the Ethics Committee of the China Academy of Chinese Medical Sciences (approval number. 2022B214).

Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing α,β-unsaturated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.
Cell Movement ; Cell Proliferation ; Human Umbilical Vein Endothelial Cells ; Humans ; Oleanolic Acid/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism*

BACKGROUND: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. METHODS: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. RESULTS: In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (β = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P   <  0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). CONCLUSION Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Child ; Creatinine ; Cross-Sectional Studies ; Fluorides/urine* ; Formate-Tetrahydrofolate Ligase ; Humans ; Intelligence/genetics* ; Methylenetetrahydrofolate Dehydrogenase (NADP) ; Methylenetetrahydrofolate Reductase (NADPH2)

Objective: To analyze the influencing factors of healthy life expectancy (HLE). Methods: Seven Chinese and English databases were used for the retrieval of related literatures published by May 7, 2022 to identify influencing factors of HLE, including diseases and injuries and their risk factors. Based on the ecological model of health determinants, this study classifies the risk factors of diseases and injuries into five levels: personal characteristics, individual behavior and lifestyle, social network, living and working conditions, and macroscopic socio-economic, cultural and environmental conditions. Contents of research area, HLE indicators, research population, influencing factors, data sources and results were extracted. The frequencies of reported documents of different HLE indicators and influencing factors of different dimensions were visualized by using evidence map, and the empirical studies of four authoritative English medical journals and Chinese core medical journals were further compared and described. Results: A total of 90 studies were selected, in which 26 were conducted in China (28.9%). Fifty-three studies are about diseases and injuries in the first dimension, and all of them have studied non-communicable diseases, accounting for the highest proportion (58.9%). There were 77 studies about the analysis on the determinants of health at five levels by an ecological model, all the studies reported multi-level results. Among them, 53 studies reported personal characteristics (58.9%), 47 studies reported individual behavior and lifestyle (52.2%), 10 studies reported social networks (11.1%), 35 studies reported living and working environment (38.9%), 8 studies reported social economy, culture status and environment condition (8.9%). The literatures about HLE published by 4 authoritative English medical journals and 21 Chinese core medical journals in recent three years were selected. Non-communicable diseases and personal characteristics were the top two most commonly studied factors of HLE, and 11 (52.3%) and 12 (57.1%) studies reported these two kinds of factors respectively. The most important factor contributing to the global disability-adjusted life years of non-communicable diseases was individual behavior and lifestyle, which was the most changeable factor. Conclusions: In recent three years, studies involving influencing factors of HLE were mainly non-communicable diseases and personal characteristics. In the future, individual behavior, lifestyle and working environment should be strengthened.
Humans ; Noncommunicable Diseases ; Healthy Life Expectancy ; Life Style ; Asian People ; Risk Factors

Objective: To investigate the clinicopathological characteristics of reactive epithelial hyperplasia and dysplasia in the stomach, as well as the clinical value of mucin special staining and proliferating cell nuclear antigen (Ki-67) in distinguishing the two gastric lesions. Methods: The clinical pathological data of 63 patients with gastric reactive epithelial hyperplasia, 54 patients with low-grade dysplasia, and 63 patients with high-grade dysplasia diagnosed from May 2018 to May 2021 in Beijing Chaoyang Hospital, Capital Medical University, Beijing, China were analyzed. Alcian blue periodic acid Schiff (AB-PAS) and Ki-67 staining were performed to examine the mucin staining pattern, number of Ki-67 positive cells, Ki-67 staining patterns in the three groups of lesions, and histopathologic characteristics. Results: The positive rates of AB-PAS in the reactive epithelial hyperplasia and gastric dysplasia groups were 87.3%(55/63) and 10.3%(12/117), respectively. The expression of AB-PAS in the reactive epithelial hyperplasia was gradually increased from the base to the surface of the epithelium. In low-grade dysplasia and high-grade dysplasia, there was no mucin present in the dysplasia epithelium. The difference between the two groups was statistically significant (P<0.01). The positive rate of Ki-67 in the epithelial reactive hyperplasia (>10%) was 81.0% (51/63), and the positive cells were mainly located in the neck and middle parts of the mucosal glands (58/63, 92.1%). In the low-grade dysplasia group, the positive rate of Ki-67 (>10%) was 90.7%(49/54); the positive cells were mainly located in the upper mucosa (33/54, 61.1%), showing a banded distribution pattern; in the high-grade dysplasia group, the positive rate (>10%) was 95.2%(60/63), and the positive cells were mainly located in the whole mucosa (49/63, 77.8%), showing a diffuse/diffuse scattered distribution pattern. The three groups had statistically different rates and distribution patterns of Ki-67 expression (P<0.01). Conclusion: The gastric epithelial reactive hyperplasia and dysplasia can be differentiated using clinicopathological features, AB-PAS staining and Ki-67 expression pattern.
Alcian Blue ; Humans ; Hyperplasia ; Ki-67 Antigen/metabolism* ; Periodic Acid ; Staining and Labeling ; Stomach Neoplasms/diagnosis*