Objective To investigate the screening results and factors affecting abnormal detection rates among high-risk groups of esophageal cancer and to explore effective intervention measures. Methods We investigated and collected the information on gender, education level, age, marital status, symptoms of reflux esophagitis (heartburn, acid reflux, belching, hiccup, foreign body sensation in the pharynx, and difficulty swallowing), consumption of pickled vegetables, salt use, and esophageal cancer incidence of villagers in a natural village in Wenfeng District, Anyang City, Henan Province. Changes in reflux esophagitis symptoms in the high-incidence area of esophageal cancer before and after 16 years were observed, and the relationship of such changes with esophageal cancer was analyzed. Results In 2008, 711 cases were epidemiologically investigated, including 213 cases with one of the symptoms of reflux esophagitis such as heartburn, acid reflux, belching, hiccups, foreign body sensation in the pharynx, and difficulty swallowing (sorted in accordance with the abovementioned symptoms; if there are multiple symptoms, then the former is taken); 55 cases with at least two related symptoms, among which the most symptom was heartburn in 108 cases (15.1%); followed by acid reflux, belching, etc. In 2024, the same group of people was investigated, and eight people were missing because of relocation. A total of 703 people were successfully investigated, of which 189 cases (26.8%) had one of the symptoms of reflux esophagitis, such as heartburn (sorted in accordance with relevant symptoms, if there are multiple symptoms, then the former will be selected); 167 cases (23.7%) had at least two related symptoms, among which the most symptom was heartburn in 139 cases (19.7%); followed by acid reflux. Over 16 years, among the 703 people investigated, 45 cases had esophageal cancer and they had one or more of the abovementioned symptoms. No significant differences in the reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.26); no significant differences in the composition of reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.299). Conclusion The detection rate of reflux esophagitis-related symptoms in the population in a high-risk area of esophageal cancer has not decreased in the past 16 years, and the high-risk factors still exist. Esophageal cancer is closely related to reflux esophagitis, and clinical practice can provide early diagnosis and treatment for high-risk population.

Rheumatoid arthritis （RA） is a chronic autoimmune disease characterized by synovitis as its pathological basis. Although current therapeutic drugs can alleviate symptoms， they are often accompanied by a high risk of side effects. In recent years， the use of flavonoids from traditional Chinese medicine （TCM） in the treatment of RA has garnered significant attention. Studies have shown that the mechanisms by which flavonoids treat RA include inhibiting the release of pro-inflammatory factors， regulating multiple cellular signaling pathways， alleviating oxidative stress， modulating immune system functions， inhibiting bone destruction， and suppressing angiogenesis. Due to their notable anti-inflammatory， antioxidant， and immunomodulatory activities， flavonoids hold promise as potential therapeutic agents for RA. A substantial number of articles in this field have been published. By reviewing Chinese and international literature and applying bibliometric and visual analysis using CiteSpace， this paper explored research hotspots and frontiers in this field， systematically reviewed the structures and anti-RA mechanisms of TCM flavonoids， provided a theoretical basis for their use in RA treatment and clinical applications， and offered new perspectives and references for the discovery of novel TCM-based anti-RA drugs.

Rheumatoid arthritis （RA） is a chronic autoimmune disease characterized by synovitis as its pathological basis. Although current therapeutic drugs can alleviate symptoms， they are often accompanied by a high risk of side effects. In recent years， the use of flavonoids from traditional Chinese medicine （TCM） in the treatment of RA has garnered significant attention. Studies have shown that the mechanisms by which flavonoids treat RA include inhibiting the release of pro-inflammatory factors， regulating multiple cellular signaling pathways， alleviating oxidative stress， modulating immune system functions， inhibiting bone destruction， and suppressing angiogenesis. Due to their notable anti-inflammatory， antioxidant， and immunomodulatory activities， flavonoids hold promise as potential therapeutic agents for RA. A substantial number of articles in this field have been published. By reviewing Chinese and international literature and applying bibliometric and visual analysis using CiteSpace， this paper explored research hotspots and frontiers in this field， systematically reviewed the structures and anti-RA mechanisms of TCM flavonoids， provided a theoretical basis for their use in RA treatment and clinical applications， and offered new perspectives and references for the discovery of novel TCM-based anti-RA drugs.

In recent years, the application of artificial intelligence (AI) in the field of biology has witnessed remarkable advancements. Among these, the most notable achievements have emerged in the domain of protein structure prediction and design, with AlphaFold and related innovations earning the 2024 Nobel Prize in Chemistry. These breakthroughs have transformed our ability to understand protein folding and molecular interactions, marking a pivotal milestone in computational biology. Looking ahead, it is foreseeable that the accurate prediction of various physicochemical properties of proteins—beyond static structure—will become the next critical frontier in this rapidly evolving field. One of the most important protein properties is thermodynamic stability, which refers to a protein’s ability to maintain its native conformation under physiological or stress conditions. Accurate prediction of protein stability, especially upon single-point mutations, plays a vital role in numerous scientific and industrial domains. These include understanding the molecular basis of disease, rational drug design, development of therapeutic proteins, design of more robust industrial enzymes, and engineering of biosensors. Consequently, the ability to reliably forecast the stability changes caused by mutations has broad and transformative implications across biomedical and biotechnological applications. Historically, protein stability was assessed via experimental methods such as differential scanning calorimetry (DSC) and circular dichroism (CD), which, while precise, are time-consuming and resource-intensive. This prompted the development of computational approaches, including empirical energy functions and physics-based simulations. However, these traditional models often fall short in capturing the complex, high-dimensional nature of protein conformational landscapes and mutational effects. Recent advances in machine learning (ML) have significantly improved predictive performance in this area. Early ML models used handcrafted features derived from sequence and structure, whereas modern deep learning models leverage massive datasets and learn representations directly from data. Deep neural networks (DNNs), graph neural networks (GNNs), and attention-based architectures such as transformers have shown particular promise. GNNs, in particular, excel at modeling spatial and topological relationships in molecular structures, making them well-suited for protein modeling tasks. Furthermore, attention mechanisms enable models to dynamically weigh the contribution of specific residues or regions, capturing long-range interactions and allosteric effects. Nevertheless, several key challenges remain. These include the imbalance and scarcity of high-quality experimental datasets, particularly for rare or functionally significant mutations, which can lead to biased or overfitted models. Additionally, the inherently dynamic nature of proteins—their conformational flexibility and context-dependent behavior—is difficult to encode in static structural representations. Current models often rely on a single structure or average conformation, which may overlook important aspects of stability modulation. Efforts are ongoing to incorporate multi-conformational ensembles, molecular dynamics simulations, and physics-informed learning frameworks into predictive models. This paper presents a comprehensive review of the evolution of protein thermodynamic stability prediction techniques, with emphasis on the recent progress enabled by machine learning. It highlights representative datasets, modeling strategies, evaluation benchmarks, and the integration of structural and biochemical features. The aim is to provide researchers with a structured and up-to-date reference, guiding the development of more robust, generalizable, and interpretable models for predicting protein stability changes upon mutation. As the field moves forward, the synergy between data-driven AI methods and domain-specific biological knowledge will be key to unlocking deeper understanding and broader applications of protein engineering.

Objective To understand the disease spectrum of a natural village in an area with high incidence of esophageal cancer to provide a reference for precise prevention and control. Methods From 2008 to 2024, 711 asymptomatic people over the age of 35 years in a natural village with high incidence of esophageal cancer in China were surveyed, and 171 of them were subjected to gastroscopy, biopsy, and pathological examination. All participants were followed up for a long time, and their disease history was recorded. Results A total of 16 years of follow-up were performed, and 703 people were effectively followed up. In 2008, 171 people underwent gastroscopy, and 160 people had biopsy and pathological results in endoscopic screening. By 2024, 76 people had been diagnosed with malignant tumors of 12 different types, and among these people, 45 had esophageal cancer. Conclusion Esophageal cancer remains a significant cause of morbidity and mortality from malignant tumors in this region. Biopsy and pathological examination should be strengthened during gastroscopy, and follow-ups and regular check-ups should be given high importance to reduce the incidence and mortality rates of esophageal cancer.

Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

OBJECTIVE: To investigate the effect of inverted-Y urethral function-preserving holmium laser enucleation of the prostate (HoLEP) on stress urinary incontinence after surgery in patients with BPH. METHODS: We retrospectively analyzed the clinical data on 109 cases of BPH treated in our hospital from June 2022 to May 2023 by traditional HoLEP with preservation of the apical prostatic urethral valve (group A, n = 52) or inverted-Y urethral function-preserving HoLEP (group B, n = 57). We recorded the intra- and post-operative parameters, evaluated the urinary incontinence status and post-void symptoms according to the International Continence Society standards, and analyzed the effect of inverted-Y versus traditional HoLEP in improving the postoperative urinary incontinence of the patients. RESULTS: The incidence rate of stress urinary incontinence after catheter removal was significantly lower in group B than in A (10.52% vs 26.92%, P = 0.027), and so was it at 2 weeks after surgery (1.75% vs 11.54%, P = 0.037), and at 1 month postoperatively (0% vs 7.69%, P = 0.033). CONCLUSION For the treatment of BPH, inverted-Y urethral function-preserving HoLEP is superior to traditional HoLEP with preservation of the apical prostatic urethral valve in improving stress urinary incontinence after surgery.
Humans ; Male ; Retrospective Studies ; Lasers, Solid-State/therapeutic use* ; Prostatic Hyperplasia/surgery* ; Urethra/surgery* ; Postoperative Complications/prevention & control* ; Urinary Incontinence, Stress/etiology* ; Prostatectomy/adverse effects* ; Aged ; Urinary Incontinence ; Prostate/surgery*

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*

Objective:To summarize the clinical characteristics of patients with renal angiomyolipoma(RAML)combined with inferior vena cava(IVC)tumor thrombus,and to explore the feasibility of par-tial nephrectomy and thrombectomy in this series of patients.Methods:The clinical data of patients diagnosed with RAML combined with IVC tumor thrombus in the Department of Urology of the Peking University Third Hospital from April 2014 to March 2023 were retrospectively analyzed,and demographic and perioperative data of RAML patients with IVC tumor thrombus were recorded and collected from Elec-tronic Medical Record System,including age,gender,surgical methods,and follow-up time,etc.The clinical characteristics between classic angiomyolipoma(CAML)patients with IVC tumor thrombus and epithelioid angiomyolipoma(EAML)patients with IVC tumor thrombus were compared to determine the clinical characteristics of these patients.Results:A total of 11 patients were included in this study,in-cluding 7 patients with CAML with IVC tumor thrombus and 4 patients with EAML with IVC tumor thrombus.There were 9 females(9/11,81.8％)and 2 males(2/11,18.2％),with an average age of(44.0±17.1)years.9 patients(9/11,81.8％)experienced clinical symptoms,including local symp-toms including abdominal pain,hematuria,abdominal masses,and systemic symptoms including weight loss and fever;2 patients(2/11,18.2％)with RAML and IVC tumor thrombus did not show clinical symptoms,which were discovered by physical examination.Among the 11 patients,10 underwent radical nephrectomy with thrombectomy,of whom,3 underwent open surgery(3/10,30.0％),2 underwent laparoscopic surgery(2/10,20.0％),and 5 underwent robot-assisted laparoscopic surgery(5/10,50.0％).In addition,1 patient underwent open partial nephrectomy and thrombectomy.The patients with EAML combined with I VC tumor thrombus had a higher proportion of systemic clinical symptoms(100％vs.0％,P=0.003),more intraoperative bleeding[400(240,3 050)mL vs.50(50,300)mL,P=0.036],and a higher proportion of tumor necrosis(75％vs.0％,P=0.024)compared to the patients with CAML combined with I VC tumor thrombus.However,there was no statistically significant difference in operation time[(415.8±201.2)min vs.(226.0±87.3)min,P=0.053]between the two groups.Conclusion:Compared with the patients with CAML and IVC tumor thrombus,the patients with EAML and IVC tumor thrombus had a higher rate of systemic symptoms and tumor necrosis.In addi-tion,in the selected patients with CAML with IVC tumor thrombus,partial nephrectomy and tumor thrombectomy could be performed to better preserve renal function.

Objective:To analyze the clinicopathological features,prognostic value and surgical treat-ment experience in patients with adrenocortical carcinoma with venous tumor thrombus.Methods:We collected relevant data of the patients with adrenocortical carcinoma who had undergone surgery in Peking University Third Hospital from 2018 to 2023.The patients were divided into venous tumor thrombus group and non-tumor thrombus group.The Wilcoxon rank sum test was used to compare the quantitative varia-bles.The chi-squared test and Fisher's exact test were used to compare the categorical variables.The Kaplan-Meier method was used to estimate the survival rate.Results:A total of 27 patients with adreno-cortical carcinoma were included,of whom 11 cases(40.7％)had venous tumor thrombus.In the pa-tients with venous tumor thrombus,8 patients were female and 3 were male.The median age was 49(36,58)years.The median body mass index was 26.0(24.1,30.4)kg/m2.Seven patients presented with symptoms at their initial visit.Six patients had a history of hypertension.Elevated levels of cortisol were observed in 2 cases.Three tumors were found on the left side,while 8 were found on the right side.Median tumor diameter was 9.4(6.5,12.5)cm.On the left,there was a case of tumor thrombus limit-ed to the central vein of the left adrenal gland without invasion into the left renal vein,and two cases of tumor thrombus growth extending into the inferior vena cava below the liver.One case of tumor thrombus on the right adrenal central vein did not invade the inferior vena cava.Four cases of tumor thrombus inva-ded the inferior vena cava below the liver and three cases extended to the posterior of the liver.Ten pa-tients were in European Network for the Study of Adrenal Tumors(ENSAT)stage Ⅲ and one was in ENSAT stage Ⅳ.Open surgery was performed in 6 cases,laparoscopic surgery alone in 4 cases and ro-bot-assisted laparoscopic surgery in 1 case.Two patients underwent ipsilateral kidney resection.Median operative time was 332(261,440)min.Median intraoperative bleeding was 900(700,2 200)mL.Median hospital stay was 9(5,10)days.Median survival time for the patients with tumor thrombus was 24.0 months and median time to recurrence was 7.0 months.The median survival and recurrence time of 16 patients without tumor thrombus were not reached.The patients with tumor thrombus had worse 3-year overall survival(OS)rate(40.9％vs.71.4％;Log-rank,P=0.038)and 2-year recurrence-free sur-vival(RFS)(9.1％vs.53.7％;Log-rank,P=0.015)rates compared with the patients with non-tumor thrombus.Conclusion:Patients with adrenocortical carcinoma with venous tumor thrombus have poor prognosis.Different adrenal tumor resections and venous tumor thrombus removal procedures based on different tumor thrombus locations are safe and effective in treating this disease.