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.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.

Hydrogen sulfide(H2 S),an endogenous gas trans-mitter involved in the regulation of vascular tone,has a variety of physiological properties,such as antihypertensive,vascular re-laxation,anti-inflammatory and antioxidant potential,and plays an important role in cardiovascular regulation.Chinese scholars call essential hypertension combined with hyperhomocysteinemia(HCY≥10 μmol·L-1)as H-type hypertension.Studies have shown that H2S can antagonized hypertension and hyperhomocys-teinemia,suggesting that H2S may be a potential therapeutic tar-get for H-type hypertension.Therefore,this article briefly sum-marizes the mechanism of H2S on hypertension and homocys-teine.Homocysteine(HCY)is closely related to the occurrence and development of cardiovascular diseases.Hyperhomocysteine-mia(HCY ≥ 10 μmol·L-1)is a risk factor for coronary ath-erosclerotic heart disease,stroke,and other cardiovascular dis-eases,and Chinese scholars define primary hypertension accom-panied by hyperhomocysteinemia as H-type hypertension,which accounts for about 75％of the adult hypertensive patients in Chi-na.The treatment of H-type hypertension should simultaneously reduce blood pressure and plasma HCY levels.Studies have shown that hydrogen sulfide(H2 S)can antagonise hypertension and high HCY,suggesting that H2S may be a potential therapeu-tic target for H-type hypertension.Therefore,this paper summa-rizes the mechanism of action of H2S on hypertension and HCY.

Objective To observe the residual of lumbago and leg pain with contained type(CT)and non-contained type(NCT)lumbar disc herniation(LDH)after transforaminal endoscopic treatment,and to explore the role of hypoxia-inducible factor-1α(HIF-1α)and transient receptor potential vanillate 1(TRPV1)pathway.Methods A total of 68 single-segment LDH patients were selected from July 2021 to October 2022,including 44 males and 24 females;aged 26 to 67 years old with an av-erage of(43.63±11.94)years old;course of disease was 4 to 36(18.91±10.34)months;body mass index was(24.45±4.00)kg·m-2;there were 7 cases of L3.4 segments,32 cases of L4,5 segments,and 29 cases of L5S1 segments.All of them were per-formed with percutaneous intervertebral endoscopic extraction of nucleus pulposus and were divided into contained group(CT group)and non-contained group(NCT group)with 34 cases respectively according to the integrity of outer layer of fibrous an-nulus observed during operation.A total of 17 patients who underwent open surgery for scoliosis or vertebral fracture were se-lected as control group,including 12 males and 5 females;aged 21 to 65 years old with an average of(39.41±12.80)years old;body mass index was(24.86±4.11)kg·m-2.The relative mRNA expression quantity of HIF-1α,TRPV1 in nucleus pulposus were measured by quantitative real-time PCR.The contents of neurokinin 1 receptor(NK1R),nerve growth factor(NGF),vascular endothelial growth factor(VEGF)in nucleus pulposus and the serum substance P(SP)and calcitonin gene-related peptide(CGRP)were detected by enzyme linked immunosorbent assay(ELISA).The threshold of lumbar tenderness was de-tected by a pressure pain meter.The degree of lumbago and lumbar function were evaluated by visual analog scale(VAS)and Oswestry disability index(ODI)separately.The residual rate of postoperative lumbago and leg pain was assessed.Results The mRNA relative expression quantity of HIF-1α and TRPV1,and the contents of NK1R,NGF and VEGF in nucleus pulposus,and the levels of serum SP and CGRP before surgery in the NCT group were higher than those in the CT group(P＜0.05),and those in the CT group were higher than the control group(P＜0.05).At day 7 after surgery,the serum SP and CGRP levels,lum-bago and leg pain VAS scores and lumbar ODI index in two LDH groups were lower than before surgery(P＜0.05),and those in the NCT group were higher than the CT group(P＜0.05),and the threshold of lumbar tenderness in the NCT group was lower than the CT group(P＜0.05).The differences of lumbago and leg pain VAS scores,lumbar ODI index and lumbar tenderness threshold between preoperative and postoperative 7 days in the NCT group were lower than those in the CT group(P＜0.05).The residual rate of lumbago and leg pain at 7 days after surgery in the NCT group was higher than that in the CT group(P＜0.05).Conclusion HIF-1α and TRPV1 pathway promoted the excessive production of NGF,VEGF,NK1R in nucleus pulposus and serum neuropeptides SP and CGRP,which may lead to the higher residual rate of lumbago and leg pain with non-contained lumbar disc herniation postoperative.

Objective To observe the clinical efficacy of adjuvant PD-1 inhibitor in the treatment of patients with hepatocellular carcinoma after microwave ablation and the changes of lymphocyte subsets before and after treatment.Methods A total of 56 patients with hepatocellular carcinoma who underwent microwave ablation in our hospital were randomly divided into two groups according to different treatments,with 28 cases in each group.Patients in the group A received adjuvant treatment with PD-1 inhibitors after microwave ablation,while patients in the group B received microwave ablation alone.The local efficacy of microwave ablation,the survival of patients after adjuvant treatment of PD-1 inhibitor and the occurrence of related adverse reactions were observed.Peripheral venous blood was collected to detect the number of T lymphocyte subsets before microwave ablation in the two groups,after microwave ablation in the group B,and after six cycles of immunotherapy in the group A.Results There was no significant difference in the complete ablation rate of cases between group A and group B(89.3% vs.85.7%,P=0.69),and there was no significant difference in the complete ablation rate of lesions between group A and group B(91.7% vs.85.3%,P=0.40).The median progression-free survival(mPFS)of the group A was not yet reached,the mPFS of group B was 12.6 months,and there was a statistically significant difference in the mPFS between the two groups(P=0.03).The median overall survival(mOS)of the two group were not yet reached.The proportion of CD4+T lymphocytes after treatment in the group A significantly increased compared with that in the group B[(37.05±2.22)% vs.(29.23±2.88)%,P=0.03],while the proportion of CD8+T lymphocytes[(21.08±2.23)% vs.(27.18±1.75)%,P=0.04)]and the proportion of Treg cells[(4.26±0.31)% vs.(5.22±0.34)%,P=0.04]significantly decreased.There was no serious adverse reactions in all patients after microwave ablation,and 28 patients in the group A had no adverse reactions above grade 3 after PD-1 inhibitor treatment.Conclusion Adjuvant PD-1 inhibitor therapy after microwave ablation can prolong the progression-free survival of patients,enhance the function of T lymphocytes,and weaken the role of immunosuppressive cells,which may be an effective strategy to delay the recurrence of liver cancer after microwave ablation.

AP2 transcription factors belong to the AP2/ERF superfamily and are involved in the regula-tion of various biological processes in plant growth and development,as well as in response to biotic and abiotic stresses.However,studies on the AP2 transcription factor family of Perilla frutescens have not been reported.In this study,totally 18 AP2 family members were identified from the Perilla frutescens ge-nome and analyzed for gene structure,conserved motifs,and cis-acting elements using bioinformatics.WRINKLED1(WRI1)is a key regulator of lipid biosynthesis in many plant species and plays an impor-tant role in the regulation of lipid synthesis.Sequence comparison revealed that one member of WRI1 is highly homologous to AtWRI1 and contains two conserved AP2 domains,named PfWRI1.The expression levels of PfAP2 family genes were analyzed in different tissues of Perilla frutescens and at different stages of seed development in conjunction with the transcriptome data,and the results showed that PfWRI1 is highly expressed only in the seeds of Perilla frutescens,suggesting that PfWRI1 may be related to the de-velopmental process of the seeds.The overexpression vector of plant pCAMBIA1303-PfWRI1 was con-structed,and wild-type(Col)and mutant(wri1-1)Arabidopsis thaliana were transformed by Agrobacte-rium tumefaciens to obtain overexpression and complementation lines,respectively.The results showed that the expression of P fWRI1 led to an increase in oil content of Arabidopsis seeds by 8.90％-13.57％compared with Col,and promoted the accumulation of oleic acid(C18:1)and linoleic acid(18:2)and reduced the accumulation of palmitic acid(C16:0),arachidonic acid(C20:0),and cis-11-Eicosenoic acid(C20:1)in transgenic Arabidopsis seeds.In addition,PfWRI1 gene expression increased the ex-pression of glycolysis and fatty acid biosynthesis-related genes AtPKP-α,AtPKP-β1,AtBCCP2,AtSUS2,and AtLIP1.Taken together,PfWRI1 may promote lipid accumulation by increasing unsaturated fatty acid content through interaction with the above genes.

Perilla frutescens,a short-day plant,is rich in biologically active substances and nutrients.Current research on Perilla frutescens focuses on agronomic traits such as yield and fatty acid accumula-tion,with limited exploration of the flowering process and floral organ development.The molecular regu-latory mechanisms underlying these aspects remain unclear.FLOWERING LOUC T(FT)is a florigen in Arabidopsis,plays critical roles in floral transition.PfFT3 is unannotated by genome but annotated by transcriptomics data to the FT-like subfamily.Its function in controlling flowering is yet to be explored.Here subcellular localization analysis showed that PfFT3 is localized in the nucleus and cytoplasm.The plant over-expression vector pCAMBIAI1303-PfFT3 was constructed and transformed into wild-type(Col-0)and mutant fd-2,fd-3,and ft-10 plants by agrobacterium-mediated inflorescence infiltration as a means of obtaining genetically stable and pure overexpression and backfill transgenic lines in Arabidopsis,respectively.Analysis of the results showed that overexpression of PfFT3 significantly promoted early flowering in Arabidopsis and rescued the late-flowering phenotype of the mutants fd-2,fd-3,and ft-10,and that expression of the exogenous PfFT3 promoted the expression of the downstream endogenous flow-ering genes AtSOC1,AtAP1,AtFUL,and AtLFY.This study demonstrates the positive role of PfFT3 in promoting flowering,providing a foundation for further investigation of PfPEBP function and advancing the breeding of early-flowering Perilla frrutescens cultivars.

Objective:To explore the genotypes and frequency distribution of thalassemia in Lingui District,Guilin City,and provide reference for the prevention and control of thalassemia in this area. Methods:The results of genetic testing for thalassemia in 1501 suspected cases at the Second Affiliated Hospital of Guilin Medical University were analyzed retrospectively. The deletional mutations of α-thalassemia were detected by gap-PCR,the non-deletional mutations of α-thalassemia and β-thalassemia mutations were detected by PCR-reverse dot blot (PCR-RDB). Results:In 1501 samples,a total of 678 cases of thalassemia carriers were detected,with a detection rate of 45.17％. Among them,379 cases were α-thalassemia (including deletional α-thalassemia and non-deletional α-thalassemia),with a detection rate of 25.25％,the most common genotype was--SEA/αα (227 cases,15.12％),followed by-α3.7/αα (53 cases,3.53％). 270 cases of β-thalassemia were detected,with a detction rate of 17.99％,and βCD41-42/βN (144 cases,9.59％) was the main genotypes,followed by βCD17/βN (66 cases,4.40％) . In addition,there were 29 cases of αβ compound thalassemia,accounting for 1.93％,and the most common genotype was--SEA/αα complex βCD41-42/βN (5 cases,0.33％). Conclusion:Lingui District in Guilin City is a high-incidence area of thalassemia,and the genotypes of carriers are complex and diverse,with genetic heterogeneity. The results of this study provide a scientific basis for genetic counseling and prenatal diagnosis in this area.