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Objective: This study aimed to analyze research on anxiety disorders using VOSviewer and CiteSpace to identify research hotspots and future directions. Methods: We conduct ed a comprehensive search on the Web of Science Core Collection (WoSCC) for relevant studies about anxiety disorders published within the past two decades (from 2004 to 2024). VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas. Results: A total of 22,267 publications related to anxiety disorders were retrieved. The number of publications about anxiety disorders has generally increased over time, with some fluctuations. The United States emerged as the most productive country, with Harvard University identified as the most prolific institution and Brenda W. J. H. Penninx as the most prolific author in the field. Conclusion: This research identified the most influential publications, authors, journals, institutions, and countries in the field of anxiety research. Future research directions are involved advanced treatments based on pharmacotherapy, psychotherapy and digital interventions, mechanism exploration to anxiety disorders based on neurobiological and genetic basis, influence of social and environmental factors on the onset of anxiety disorders.

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Infantile hemangioma (IH) is the most common benign vascular tumor during infancy and childhood and is characterized by abnormal vascular development. It is the most common vascular tumor and its related mechanisms and treatments remain a problem. IH-related biomarkers have been identified using transcriptome analysis and can be used to predict clinical outcomes. This study aimed to identify the key target genes for IH treatment and explore their possible roles in the IH pathophysiology. Gene records were acquired from the Gene Expression Omnibus database. Utilizing integrated weighted gene co-expression network examination, gene clusters were determined. Single-sample gene set enrichment analysis was performed to gauge immune infiltration. Essential genes were identified via Random Forest and Least Absolute Selection and Shrinkage Operator analyses. Ultimately, a set of five pivotal genes associated with the ailment was identified (NETO2, IDO1, KDR, MEG3, and TMSB15A). A nomogram for predicting IH diagnosis was constructed based on hub genes. The calibration curve showed valid agreement between the prediction and conclusion that the key genes in the model were clinically significant. Neuropilin and Tolloid-like 2 (NETO2) are closely associated with tumor development. The role value of NETO2 expression levels increased in hemangioma-derived endothelial cells (HemECs). After silencing NETO2, the growth and migration of cancer cells were significantly restrained. This study revealed the critical role of NETO2 in IH development, suggesting that targeting NETO2 may be effective in improving the therapeutic outcome of IH.

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Background: Epilepsy ranks among the most common neurological disorders worldwide, frequently accompanied by depression as a prominent comorbidity. This study employs bibliometric analysis to reveal the research of comorbid epilepsy and depression over the past two decades, aiming to explore trends and contribute insights to ongoing investigations. Methods: We conducted a comprehensive search on the Web of Science Core Collection database and downloaded relevant publications on comorbid epilepsy and depression published from 2003 to 2023. VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas. Results: A total of 5,586 publications related to comorbid epilepsy and depression were retrieved, with a general upward trend despite slight fluctuations in annual publications. Publications originated from 121 countries and 636 institutions, with a predominant focus on clinical research. The United States led in productivity (1,529 articles), while Melbourne University emerged as the most productive institution (135 articles). EPILEPSY & BEHAVIOR was the journal with the highest publication output (1,189 articles) and citation count. Keyword analysis highlighted emerging trends, including "recognitive impairment" and "mental health," indicating potential future research hotspots and trends. Conclusion: This study is one of the first to perform a bibliometric analysis of the 20-year scientific output of comorbid epilepsy and depression. While research has trended upwards, ambiguity in pathogenesis and the absence of standardized diagnostic guidelines remain concerning. Our analysis offers valuable guidance for researchers, informing that this might be a strong area for future collaborations.

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Ferroptosis is a type of programmed cell death driven by iron-dependent lipid peroxidation. The TNF-mediated biosynthesis of glutathione has been shown to protect synovial fibroblasts from ferroptosis in the hyperplastic synovium. Ferroptosis induction provides a novel therapeutic approach for rheumatoid arthritis (RA) by reducing the population of synovial fibroblasts. The beginning and maintenance of synovitis in RA are significantly influenced by macrophages, as they generate cytokines that promote inflammation and contribute to the destruction of cartilage and bone. However, the vulnerability of macrophages to ferroptosis in RA remains unclear. In this study, we found that M2 macrophages are more vulnerable to ferroptosis than M1 macrophages in the environment of the arthritis synovium with a high level of iron, leading to an imbalance in the M1/M2 ratio. During ferroptosis, HMGB1 released by M2 macrophages interacts with TLR4 on M1 macrophages, which in turn triggers the activation of STAT3 signaling in M1 macrophages and contributes to the inflammatory response. Knockdown of TLR4 decreased the level of cytokines induced by HMGB1 in M1 macrophages. The ferroptosis inhibitor liproxstatin-1 (Lip-1) started at the presymptomatic stage in collagen-induced arthritis (CIA) model mice, and GPX4 overexpression in M2 macrophages at the onset of collagen antibody-induced arthritis (CAIA) protected M2 macrophages from ferroptotic cell death and significantly prevented the development of joint inflammation and destruction. Thus, our study demonstrated that M2 macrophages are vulnerable to ferroptosis in the microenvironment of the hyperplastic synovium and revealed that the HMGB1/TLR4/STAT3 axis is critical for the ability of ferroptotic M2 macrophages to contribute to the exacerbation of synovial inflammation in RA. Our findings provide novel insight into the progression and treatment of RA.

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The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/ß, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.

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In the process of searching for anti-breast cancer agents, five sesquiterpene lactones (1-5), including two previously undescribed ones, yjaponica B-C (1-2), were isolated from the herb of Youngia japonica. Their structures were elucidated by spectroscopic data analyses and Marfey's method. Cytotoxic activities of all compounds against A549, U87, and 4T1 cell lines were tested using the CCK8 assay. The result showed that compound 3 possessed the highest cytotoxic activity against 4T1 cells with an IC50 value of 10.60 µM. Furthermore, compound 3 distinctly induced apoptosis, inhibited immigration, and blocked the cell cycle of 4T1 cells. In addition, compound 3 induced the production of reactive oxygen species. Further anticancer mechanism studies showed that compound 3 significantly upregulated expression of the cleaved caspase 3 and PARP, whereas it downregulated the expression of Bcl-2, cyclin D1, cyclin A2, CDK4, and CDK2. Taken together, our results demonstrate that compound 3 has a high potential of being used as a leading compound for the discovery of new anti-breast cancer agent.

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Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. Systematic Review Registration: http://www.chinadrugtrials.org.cn, identifier CTR20210064.

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Replacing cement with industrial by-products is an important way to achieve carbon neutrality in the cement industry. The purpose of this study is to evaluate the effect of eggshell powder on cement hydration properties, and to evaluate its feasibility as a substitute for cement. The substitution rates of eggshell powder are 0%, 7.5%, and 15%. Studying the heat of hydration and macroscopic properties can yield the following results. First: The cumulative heat of hydration based on each gram of cementitious material falls as the eggshell powder content rises. This is a result of the eggshell powder's diluting action. However, the cumulative heat of hydration per gram of cement rises due to the nucleation effect of the eggshell powder. Second: The compressive strengths of ES0, ES7.5, and ES15 samples at 28 days of age are 54.8, 43.4, and 35.5 MPa, respectively. Eggshell powder has a greater negative impact on the compressive strength. The effect of eggshell powder on the speed and intensity of ultrasonic waves has a similar trend. Third: As the eggshell powder content increases, the resistivity gradually decreases. In addition, we also characterize the microscopic properties of the slurry with added eggshell powder. X-ray Diffraction (XRD) shows that, as the age increases from 1 day to 28 days, hemicaboaluminate transforms into monocaboaluminate. As the content of the eggshell powder increases, FTIR analysis finds a slight decrease in the content of CSH. Similarly, thermogravimetric (TG) results also show a decrease in the production of calcium hydroxide. Although the additional nucleation effect of eggshell powder promotes cement hydration and generates more portlandite, it cannot offset the loss of portlandite caused by the decrease in cement. Last: A numerical hydration model is presented for cement-eggshell powder binary blends. The parameters of the hydration model are determined based on hydration heat normalized by cement mass. Moreover, the hydration heat until 28 days is calculated using the proposed model. The strength development of all specimens and all test ages can be expressed as an exponential function of hydration heat.

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Fourteen sesquiterpenes, including one undescribed sesquiterpene lactone, were isolated from Youngia japonica, and their structures were identified by NMR, HRESIMS, ECD and calculated ECD. Cytotoxic activities of all isolates against A549, HeLa, and 4 T1 cell lines were detected by CCK8 assay. Among them, 2 showed obvious cytotoxic activity against A549 cells. Subsequently, the production of ROS, and apoptosis of A549 cells treated with 2 were evaluated. The result showed that 2 distinctly increased the ROS level, and induced the apoptosis of A549 cells. Further anticancer mechanism studies showed that 2 increased the expression of cleaved caspase 3. Taken together, our results demonstrated that 2 might become potential leading compounds for the treatment of lung cancer.

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BACKGROUND: Although there is increasing interest in minimally invasive prosthesis breast reconstruction (PBR), whether meshes application in minimally invasive PBR can improve complications and cosmetic effects remains controversial. The author retrospectively analyzed postoperative complications and evaluated patient-reported quality-of-life outcomes in minimally invasive PBR with and without mesh. METHODS: This study enrolled patients who underwent minimally invasive nipple-sparing mastectomy (NSM) followed by PBR. We used the TiLOOP bra for the mesh-assisted procedure. Patient demographics and postoperative complications data were compared between the procedures. Patient-reported outcomes were evaluated with the Breast-Q. RESULTS: A total of 158 patients underwent 160 minimally invasive NSM-PBR (with mesh, n = 64; without, n = 94). Postoperative complications were comparable in the mesh-assisted (5 [7.7%]) and non-mesh-assisted (5 [5.3%]) groups (p = 0.533). The most common complication in non-mesh-assisted group was infection, with four (4.2%) cases. In mesh-assisted group, implant exposure occurred in two (3.1%) patients. Removal of prosthesis was uncommon, with two (3.1%) and three (3.2%) cases in the mesh-assisted and non-mesh groups, respectively (p = 0.977). The BREAST-Q questionnaire was completed by 52 (81.3%) patients in the mesh-assisted group and 68 (72.3%) in the non-mesh-assisted group. Comparing the non-mesh group, patients in mesh-assisted group had improved scores on the BREAST-Q Satisfaction with breast (66.0) (p < 0.05), Physical Well-being (80.0), and Sexual Well-being (56.0). CONCLUSIONS: Mesh-assisted minimally invasive NSM-PBR has good aesthetic outcomes and high patient satisfaction. There were no significant differences in complication rates between the mesh-assisted and non-mesh-assisted groups.

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Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos. Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital. The primary outcomes were safety and immunogenicity, with efficacy as an exploratory endpoint. Participants who were fully immunized with a two-dose inactivated vaccine for more than 6 months were assigned equally to either the SW-BIC-213 group (25 µg) or BBIBP group. The primary safety endpoint was to describe the safety profile of all participants in each group up to 6 months post-booster immunization. The primary immunogenic outcome was to demonstrate the superiority of the neutralizing antibody response, in terms of geometric mean titers (GMTs) of SW-BIC-213, compared with BBIBP 28 days after the booster dose. The exploratory efficacy endpoint aimed to assess the relative efficacy of SW-BIC-213 compared to BBIBP against virologically confirmed symptomatic COVID-19 over a 6-month period. The trial was registered with ClinicalTrials.gov (NCT05580159). Findings: Between October 10, 2022, and January 13, 2023, 1200 participants were assigned to SW-BIC-213 group and 1203 participants in the BBIBP group. All adverse reactions observed during the study were tolerable, transient, and resolved spontaneously. Solicited local reactions were the main adverse reactions in both the SW-BIC-213 group (43.8%) and BBIBP group (14.8%) (p < 0.001). Heterologous boosting with SW-BIC-213 induced higher live virus neutralizing antibodies to SARS-CoV-2 wildtype and BA.5 strains with GMTs reaching 750.1 and 192.9 than homologous boosting with BBIBP with GMTs of 131.5 (p < 0.001) and 47.5 (p < 0.001) on day 29. The statistical findings revealed that, following a period of 14-day to 6-month after booster vaccination, the SW-BIC-213 group exhibited a relative vaccine efficacy (VE) of 70.1% (95% CI: 34.2-86.4) against symptomatic COVID-19 when compared to the BBIBP group. Interpretation: A heterologous booster with the COVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and proves highly immunogenic and efficacious in preventing symptomatic COVID-19 in individuals who have previously received two doses of inactivated vaccine. Funding: Shanghai Strategic Emerging Industries Development Special Fund, Biomedical Technology Support Special Project of Shanghai "Science and Technology Innovation Action Plan", Shanghai Municipal Science and Technology Commission.

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This study aimed to explore and develop data mining models for adult age estimation based on CT reconstruction images from the sternum. Maximum intensity projection (MIP) images of chest CT were retrospectively collected from a modern Chinese population, and data from 2700 patients (1349 males and 1351 females) aged 20 to 70 years were obtained. A staging technique within four indicators was applied. Several data mining models were established, and mean absolute error (MAE) was the primary comparison parameter. The intraobserver and interobserver agreement levels were good. Within internal validation, the optimal data mining model obtained the lowest MAE of 9.08 in males and 10.41 in females. For the external validation (N = 200), MAEs were 7.09 in males and 7.15 in females. In conclusion, the accuracy of our model for adult age estimation was among similar studies. MIP images of the sternum could be a potential age indicator. However, it should be combined with other indicators since the accuracy level is still unsatisfactory.

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BACKGROUND: Maternal oxygen supplementation is usually used as an intrauterine resuscitation technique to prevent fetal hypoxia and acidemia during delivery. However, there has been a great deal of controversy regarding the effects of prophylactic maternal oxygen during cesarean section, during which the incidence of fetal acidemia seems to be higher compared with that during labor. High-flow nasal oxygen (HFNO) can improve oxygenation better in patients with high-flow oxygen airflow. The purpose of this study is to determine whether maternal oxygen supplementation with HFNO has a positive effect on fetal acidemia during cesarean section through umbilical arterial blood gas analysis. METHOD: This prospective, single-center, randomized, double-blinded trial will enroll 120 patients undergoing cesarean section. Participants will be randomly assigned to the HFNO group or air group at a 1:1 ratio. For parturients in the HFNO group, the flow rate is 40L/min, and the oxygen is heated to 37℃ with humidity 100% oxygen concentration through the Optiflow high-flow nasal oxygen system. And for the air group, the flow rate is 2 L/min with an air pattern through the same device. The primary outcome was umbilical artery (UA) lactate. Secondary outcomes include UA pH, PO2, PCO2, BE, the incidence of pH < 7.20 and pH < 7.10, Apgar scores at 1 and 5 min, and neonatal adverse outcomes. DISCUSSION: Our study is the first trial investigating whether maternal oxygen supplementation with HFNO can reduce the umbilical artery lactate levels and the incidence of fetal acidemia in cesarean section under combined spinal-epidural anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05921955. Registered on 27 June 2023.

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Postoperative cognitive dysfunction (POCD) is a common complication after surgery, characterized by deficits in memory, attention and cognitive flexibility. However, the underlying mechanisms of POCD remain unclear. Neuroinflammation and blood-brain barrier disruption have been implicated as potential pathological processes. This study explores the neuroprotective effects and mechanisms of the matrix metalloproteinase（MMP-9）inhibitor GM6001 against POCD. We hypothesize GM6001 may reduce neuroinflammation and preserve blood-brain barrier integrity through direct inhibition of MMP-9. Moreover, GM6001 may stabilize aquaporin-4 polarity and glymphatic clearance function by modulating MMP-9-mediated cleavage of dystroglycan, a key protein for aquaporin-4 anchoring. Our results demonstrate GM6001 alleviates postoperative cognitive deficits and neuroinflammation. GM6001 also preserves blood-brain barrier integrity and rescues aquaporin-4 mislocalization after surgery. This study reveals a novel dual role for MMP-9 inhibition in cognitive protection through direct anti-neuroinflammatory effects and regulating aquaporin-4 membrane distribution. Targeting MMP-9 may represent a promising strategy to prevent postoperative cognitive dysfunction by integrating multiple protective mechanisms.

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OBJECTIVE: Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression; however, the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive. It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets. METHODS: We employed high-throughput sequencing-based high-throughput screening (HTS2) to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators. Then, bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer. RESULTS: Utilizing these gene expression signatures, we classified the epigenetic regulators into five distinct clusters, each characterized by specific functions. We discovered functional similarities between BAZ2B and SETMAR, as well as CLOCK and CBX3. Moreover, we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation. Notably, we constructed an epigenetic regulatory network based on the gene expression signatures, which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer. CONCLUSIONS: Our work deciphered the extensive regulation among hundreds of epigenetic regulators. The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

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Exercise rehabilitation can improve the prognosis of patients with coronary heart disease. However, a bibliometric analysis of the global exercise rehabilitation for coronary heart disease (CHD) research topic is lacking. This study investigated the development trends and research hotspots in the field of coronary heart disease and exercise rehabilitation. CiteSpace software was used to analyze the literature on exercise therapy for CHD in the Web of Science Core Collection database. We analyzed the data of countries/institutions, journals, authors, keywords, and cited references. A total of 3485 peer-reviewed papers were found, and the number of publications on the topic has steadily increased. The most productive country is the USA (1125), followed by China (477) and England (399). The top 3 active academic institutions are Research Libraries UK (RLUK) (236), Harvard University (152), and the University of California System (118). The most commonly cited journals are Circulation (2596), The most commonly cited references are "Exercise-based cardiac rehabilitation for coronary heart disease" (75), Lavie CJ had published the most papers (48). World Health Organization was the most influential author (334 citations). The research frontier trends in this field are body composition, participation, and function. Research on the effects of physical activity or exercise on patients with CHD is a focus of continuous exploration in this field. This study provides a new scientific perspective for exercise rehabilitation and CHD research and gives researchers valuable information for detecting the current research status, hotspots, and emerging trends for further research.

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MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a human paracaspase protein with proteolytic activity via its caspase-like domain. The pharmacological inhibition of MALT1 by MI-2, a specific chemical inhibitor, diminishes the response of endothelial cells to inflammatory stimuli. However, it is largely unknown how MALT1 regulates the functions of vascular smooth muscle cells (SMCs). This study aims to investigate the impact of MALT1 inhibition by MI-2 on the functions of vascular SMCs, both in vitro and in vivo. MI-2 treatment led to concentration- and time-dependent cell death of cultured aortic SMCs, which was rescued by the iron chelator deferoxamine (DFO) or ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, but not by inhibitors of apoptosis (Z-VAD-fmk), pyroptosis (Z-YVAD-fmk), or necrosis (Necrostatin-1, Nec-1). MI-2 treatment downregulated the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy polypeptide 1 (FTH1), which was prevented by pre-treatment with DFO or Fer-1. MI-2 treatment also activated autophagy, which was inhibited by Atg7 deficiency or bafilomycin A1 preventing MI-2-induced ferroptosis. MI-2 treatment reduced the cleavage of cylindromatosis (CYLD), a specific substrate of MALT1. Notably, MI-2 treatment led to a rapid loss of contractility in mouse aortas, which was prevented by co-incubation with Fer-1. Moreover, local application of MI-2 significantly reduced carotid neointima lesions and atherosclerosis in C57BL/6J mice and apolipoprotein-E knockout (ApoE-/-) mice, respectively, which were both ameliorated by co-treatment with Fer-1. In conclusion, the present study demonstrated that MALT1 inhibition induces ferroptosis of vascular SMCs, likely contributing to its amelioration of proliferative vascular diseases.

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BACKGROUND: Aging, a complex and profound journey, leads us through a labyrinth of physiological and pathological transformations, rendering us increasingly susceptible to aging-related diseases. Emerging investigations have unveiled the function of bromodomain containing protein 4 (BRD4) in manipulating the aging process and driving the emergence and progression of aging-related diseases. AIM OF REVIEW: This review aims to offer a comprehensive outline of BRD4's functions involved in the aging process, and potential mechanisms through which BRD4 governs the initiation and progression of various aging-related diseases. KEY SCIENTIFIC CONCEPTS OF REVIEW: BRD4 has a fundamental role in regulating the cell cycle, apoptosis, cellular senescence, the senescence-associated secretory phenotype (SASP), senolysis, autophagy, and mitochondrial function, which are involved in the aging process. Several studies have indicated that BRD4 governs the initiation and progression of various aging-related diseases, including Alzheimer's disease, ischemic cerebrovascular diseases, hypertension, atherosclerosis, heart failure, aging-related pulmonary fibrosis, and intervertebral disc degeneration (IVDD). Thus, the evidence from this review supports that BRD4 could be a promising target for managing various aging-related diseases, while further investigation is warranted to gain a thorough understanding of BRD4's role in these diseases.

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Gastric cancer (GC) is one of the severe malignancies with high incidence and mortality, especially in Eastern Asian countries. Significant advancements have been made in diagnosing and treating GC over the past few decades, resulting in tremendous improvements in patient survival. In recent years, traditional Chinese medicine (TCM) has garnered considerable attention as an alternative therapeutic approach for GC due to its multicomponent and multitarget characteristics. Consequently, natural products found in TCM have attracted researchers' attention, as growing evidence suggests that these natural products can impede GC progression by regulating various biological processes. Nevertheless, their molecular mechanisms are not systematically uncovered. Here, we review the major signaling pathways involved in GC development. Additionally, clinical GC samples were analyzed. Moreover, the anti-GC effects of natural products, their underlying mechanisms and potential targets were summarized. These summaries are intended to facilitate further relevant research, and accelerate the clinical applications of natural products in GC treatment.

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Background: Alpha-synuclein (SNCA) copy number variations (CNV) have been certified as a causative mutation in patients with familial and sporadic Parkinson's disease (PD). Case: We report three SNCA duplication cases diagnosed as PD. Through whole-exome sequencing, we identified a de novo 4.56 Mb repeated region in one patient and a 2.50 Mb repeated region in familial PD with two patients. Literature review: In review of previous cases, we suggest that aggressive behavior is more remarkable in CNV4 patients. Meanwhile, frequency of cognition decline and dementia were slightly increased in CNV4 patients. We also illustrate a younger onset age in offspring than parent in familial SNCA multiplication PD cases. No difference was observed in disease duration between parent and offspring generation. Conclusions: Our findings demonstrated the clinical and genetic characteristics in PD with SNCA multiplication and provided strong evidence for genetic anticipation. These results may be instructive for future disease diagnosis and genetic counseling.