BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

ObjectiveTo investigate the therapeutic effects of the Anemarrhenae Rhizoma water extract （AR） on Alzheimer's disease （AD） model rats and to explore its potential underlying mechanisms. MethodsMale rats were intraperitoneally injected with D-galactose （100 mg·kg^-1） for 42 days， and on day 14， 1 μL of β-amyloid （Aβ_25-35， 2 g·L^-1） solution was injected into the hippocampus. Rats were randomly divided into a model group， low-dose AR （0.6 g·kg^-1）， medium-dose AR （1.2 g·kg^-1）， high-dose AR （2.4 g·kg^-1）， and a positive control group （donepezil， 5 mg·kg^-1）. Healthy rats receiving only a hippocampal injection of 1 μL of sterile saline served as the sham-operated group. From day 21， rats in the treatment groups were administered the corresponding drugs by gavage once daily for 21 consecutive days， while the blank control and model groups received an equal volume of saline. Learning and memory abilities were assessed using the Morris water maze. Brain tissue damage was observed by hematoxylin and eosin （HE） staining， and neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining. Levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） in brain tissues were measured by enzyme-linked immunosorbent assay （ELISA）. BV2 microglial cells were co-cultured with Aβ_25-35 （40 μmol·L^-1） for 2 h， and cell viability was determined by the CCK-8 assay to screen the optimal concentration of AR-containing serum （S-AR）. Cells were divided into blank control， Aβ_25-35， S-AR， EX527 ［silent information regulator 1 （SIRT1） inhibitor］， and S-AR+EX527 groups. Immunofluorescence staining was used to detect the expression of CD16， CD206， and high-mobility group box 1 （HMGB1）. Western blot analysis was performed to measure the protein expression of CD16， inducible nitric oxide synthase （iNOS）， CD206， arginase （Arg）， and proteins related to the SIRT1/HMGB1/nuclear factor-κB （NF-κB） signaling pathway. ResultsIn vivo experiments showed that， compared with the sham-operated group， the model group exhibited reduced platform crossings and time spent in the target quadrant （P<0.01）， prolonged escape latency， increased hippocampal neuronal apoptosis （P<0.01）， and obvious hippocampal damage. The expression levels of IL-6， TNF-α， IL-10， CD16， and iNOS in brain tissues were significantly elevated （P<0.01）， while CD206 and Arg protein expression showed an increasing trend without statistical significance. Compared with the model group， all AR-treated groups significantly increased platform crossings and target quadrant time （P<0.05， P<0.01）， alleviated hippocampal damage， reduced escape latency and neuronal apoptosis， downregulated the expression of TNF-α， IL-6， CD16， and iNOS （P<0.05， P<0.01）， and upregulated the expression of IL-10， CD206 and Arg （P<0.05， P<0.01）. In vitro experiments demonstrated that， compared with the blank control group， the Aβ_25-35 group showed increased fluorescence intensity of CD206， CD16， and HMGB1， as well as elevated protein expression of iNOS and CD16 （P<0.01）， while CD206 and Arg protein expression exhibited an increasing trend without statistical significance. After S-AR intervention， CD206 fluorescence intensity and the protein expression of Arg and CD206 were significantly increased （P<0.01）， whereas the fluorescence intensity of CD16 and HMGB1 and the protein expression of iNOS and CD16 were significantly decreased （P<0.01）. These effects were reversed by EX527 （P<0.05， P<0.01）. Furthermore， compared with the blank control group， the Aβ_25-35 group showed significantly increased cytoplasmic HMGB1 expression and p-p65/p65 ratio （P<0.01）， along with significantly decreased SIRT1 and nuclear HMGB1 expression （P<0.01）. In contrast， the S-AR group exhibited opposite trends compared with the Aβ_25-35 group， and the regulatory effects of S-AR on these proteins were reversed by EX527 （P<0.01）. ConclusionAR exerts neuroprotective effects in AD model rats by regulating microglial polarization and alleviating neuroinflammation， potentially through modulation of the SIRT1/HMGB1/NF-κB signaling pathway.

To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine，the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13，2024，the 36^th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing，focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction （ED）. The conference brought together leading experts from traditional Chinese medicine，western medicine，and interdisciplinary fields，facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED，researching and developing new drugs of traditional Chinese medicine，and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs，it identified key directions for future scientific layout and scientific research tackling： （1） Standardization of syndrome differentiation system of traditional Chinese medicine for ED. （2） Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. （3） High-quality clinical research guided by evidence-based medicine. （4） In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. （5） Clinical translation and application promotion of new drugs of traditional Chinese medicine. （6） Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction，key focus areas，expected objectives，and clinical value were further refined，along with the establishment of a scientifically sound priority funding level evaluation system. Therefore，building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine，this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management，effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout， research and development decision-making in new drugs of traditional Chinese medicine，research topic planning，and clinical guideline formulation.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Purpose To investigate the predictive value of the methylation regulator heterogeneous nuclear ribonu-cleoprotein C(HNRNPC)in the extracellular vesicles(EVs)derived from cervical cancer cells for tumor invasion and metastasis.Methods In vitro experiments were conducted using a human normal cervical epithelial cell line(Hcer-Epic),three cervical cancer cell lines(HeLa,SiHa and CaSki)and human umbilical vein endothelial cells(HU-VECs).HNRNPC protein expression was assessed by Western blot.CaSki cells were transfected with either sh-NC or sh-HNRNPC,and EVs were subsequently isolated from culture supernatant.The effects of EVs on the proliferation,migration and invasion of SiHa cells,as well as on angiogenesis in HUVECs,were investigated respectively.For tissue microarray analysis,normal cervical tissues(n=8),low-grade squamous intraepithelial lesions(LSIL,n=32)and high-grade squamous intraepithelial lesions(HSIL,n=37),and cervical carcinoma specimens(n=153)were ob-tained from our institution.Based on HNRNPC immunoscores,cervical cancer patients were divided into two groups:high(n=99)and low(n=54)HNRNPC expression group,and their clinicopathological features and prognosis were compared.Results Compared with HcerEpic cells,the expression of HNRNPC increased in SiHa,HeLa and CaSki cells.In SiHa cells treated with EVs from CaSki cell,the group receiving EVs from sh-HNRNPC-transfected CaSki cells showed significantly reduced proliferation,colony formation,migration,and invasion compared with the sh-NC-EVs group(P＜0.05).Similarly,in HUVECs treated with CaSki-EVs,compared with sh-NC-EVs group,the sh-HNRNPC-EVs group demonsteated significantly lower protein expression of PCNA and VEGFA and reduced angiogene-sis length(P＜0.05).HNRNPC expression gradually increased during the transformation of cervical epithelial cells(F=106.9,P＜0.001),and was significantlyelevated in HSIL and cervical cancer tissues compared with normal tis-sues(P＜0.001).Moreover,in cervical cancer,high HNRNPC expression was significantly related to poorer cellular differentiation,larger tumor size,parametrial and vaginal infiltration,advanced FIGO stage,and pelvic lymph node metastasis(P＜0.05).Kaplan-Meier analysis showed that that patients with high HNRNPC expression had significant-ly shorter overall survival post-surgery compared with those with low expression(P＜0.05).Conclusion EVs contai-ning HNRNPC contribute to cervical cancer progression by promoting tumor growth,invasion,and angiogenesis,there-by accelerating metastasis.In addition,high HNRNPC expression in cervical cancer tissue is related to poor prognosis of patients,indicating that EV-associated HNRNPC may serve as a potential therapeutic target.

Objective To investigate the application effect of cold snare endoscopic mucosal resection(CS-EMR)in the treatment of 6 to 9 mm colorectal small polyps.Methods A total of 82 patients with small colonic polyps in our hospital from March 2022 to August 2023 were collected and divided into the observation group(45 cases received CS-EMR)and the control group[37 cases received hot snare endoscopic mucosal resection(HS-EMR)]according to different surgical methods.The clinical efficacy,polyp resection status,complete polyp resection rate,perioperative indicators and occurrence of complications were compared between the two groups.Results Follow-up for 1 month after operation,the effective rate of treatment in the observation group was higher than that in the control group(P<0.05).There was no statistically significant difference in the polyp resection status or perioperative indicators between the two groups(P>0.05).There was no statistically significant difference in the complete polyp resection rates of patients with different pathological types or total complete resection rate between the two groups(P>0.05).The incidence of delayed bleeding and endoscopic hemostasis rate in the observation group were lower than those in the control group(P<0.05).Conclusion The complete resection rate of 6～9 mm colorectal polyps through CS-EMR was comparable to that of HS-EMR,and CS-EMR has a better efficacy and lower risk of perioperative bleeding,along with higher safety.

OBJECTIVE: To explore the key target molecules and potential mechanisms of oridonin against non-small cell lung cancer (NSCLC). METHODS: The target molecules of oridonin were retrieved from SEA, STITCH, SuperPred and TargetPred databases; target genes associated with the treatment of NSCLC were retrieved from GeneCards, DisGeNET and TTD databases. Then, the overlapping target molecules between the drug and the disease were identified. The protein-protein interaction (PPI) was constructed using the STRING database according to overlapping targets, and Cytoscape was used to screen for key targets. Molecular docking verification were performed using AutoDockTools and PyMOL software. Using the DAVID database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. The impact of oridonin on the proliferation and apoptosis of NSCLC cells was assessed using cell counting kit-8, cell proliferation EdU image kit, and Annexin V-FITC/PI apoptosis kit respectively. Moreover, real-time quantitative PCR and Western blot were used to verify the potential mechanisms. RESULTS: Fifty-six target molecules and 12 key target molecules of oridonin involved in NSCLC treatment were identified, including tumor protein 53 (TP53), Caspase-3, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase kinase 8 (MAPK8), and mammalian target of rapamycin (mTOR). Molecular docking showed that oridonin and its key target molecules bind spontaneously. GO and KEGG enrichment analyses revealed cancer, apoptosis, phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), and other signaling pathways. In vitro experiments showed that oridonin inhibited the proliferation, induced apoptosis, downregulated the expression of Bcl-2 and Akt, and upregulated the expression of Caspase-3. CONCLUSION Oridonin can act on multiple targets and pathways to exert its inhibitory effects on NSCLC, and its mechanism may be related to upregulating the expression of Caspase-3 and downregulating the expressions of Akt and Bcl-2.
Diterpenes, Kaurane/chemistry* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Network Pharmacology ; Lung Neoplasms/pathology* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Gene Expression Regulation, Neoplastic/drug effects* ; Reproducibility of Results ; Gene Ontology

Objective:To evaluate the feasibility, safety, and short-term efficacy of robot-assisted unilateral axillary approach for partial or total thyroidectomy without inflation. Methods:A retrospective analysis was performed on the clinical data of 98 patients who underwent gasless unilateral axillary approach robot-assisted resection of bilateral thyroid lesions at Sun Yat-sen University Cancer Center between October 2022 and October 2024. Perioperative indicators were recorded and compared among patients undergoing different surgical approaches（total thyroidectomy vs. bilateral partial thyroidectomy） and with different body mass index（BMI） values, including operative time, intraoperative blood loss, number of lymph nodes dissected, incidence of postoperative hoarseness, incidence of postoperative hypocalcemia, and other postoperative complications. Results:A total of 98 patients were included, of whom 78.57% were female, with a median age of 39 years（interquartile range[IQR]: 35-49） and a median BMI of 24.08 kg/m²（IQR: 21.43-25.98）. The median intraoperative blood loss was 32.14 mL（IQR: 20.00-50.00）, the median operative time was 130.0 minutes（IQR: 104.80-150.30）, and the median hospital stay was 2.01 days（IQR: 1.00-2.00）. The most common postoperative complication was transient hypocalcemia, with an incidence of 16.32%. There were no cases of permanent recurrent laryngeal nerve palsy or conversion to open surgery. Compared with the non-total thyroidectomy group, the total thyroidectomy group had a significantly longer operative time（135.10±33.28 min vs 120.30±30.53 min, P=0.033）. Subgroup analysis based on BMI showed no statistically significant differences in operative time, hospital stay, drainage volume, or incidence of hypocalcemia between patients with BMI≥25 kg/m² and those with BMI<25 kg/m². Conclusion:The gasless unilateral axillary approach for robot-assisted partial or total thyroidectomy demonstrates favorable safety, cosmetic outcomes, and feasibility. Appropriate selection of surgical techniques and meticulous protection of critical structures during the procedure can further reduce the risk of complications and optimize therapeutic outcomes.
Humans ; Thyroidectomy/methods* ; Retrospective Studies ; Female ; Robotic Surgical Procedures/methods* ; Male ; Adult ; Middle Aged ; Axilla/surgery* ; Operative Time ; Postoperative Complications ; Thyroid Neoplasms/surgery* ; Thyroid Gland/surgery* ; Lymph Node Excision

In recent years, robot-assisted thyroid surgery has gained widespread adoption in major hospitals worldwide, offering advantages such as a shorter learning curve and superior cosmetic outcomes while overcoming the limitations of endoscopic surgery. Currently, the main surgical approaches include the transaxillary, bilateral axillo-breast（BABA）, retroauricular, and transoral vestibular routes. However, the widespread adoption of robotic thyroidectomy still faces several challenges, including technical complexity, prolonged operative time, a higher complication rate during the learning curve, and high costs. Nevertheless, when performed by experienced surgeons on carefully selected patients, robotic thyroidectomy can achieve outcomes comparable to those of conventional open transcervical thyroidectomy. This article provides a systematic review of the development and latest advances in robotic thyroid surgery.
Humans ; Robotic Surgical Procedures/methods* ; Thyroidectomy/methods* ; Thyroid Gland/surgery*