A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Purpose/Significance To summarize the application progress of artificial intelligence (AI) in the field of digestive endoscopy, to analyze the key challenges and look forward to future trends, so as to provide guidance for clinical practice and research. Method/Process Domestic and international literature databases such as PubMed, Web of Science, and CNKI are retrieved. The application research of AI in the auxiliary diagnosis, process optimization and treatment precision of digestive endoscopy is sorted out. Result/Conclusion Although AI has significant clinical value in the field of digestive endoscopy, its application still faces major challenges, and its prospects and limitations need to be further discussed.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Iron is an essential trace element in the human body, crucial in maintaining normal physiological functions. Recent studies have identified iron ions as a significant factor in initiating the ferroptosis process, a novel mode of programmed cell death characterized by iron overload and lipid peroxide accumulation. The iron metabolism pathway is one of the primary mechanisms regulating ferroptosis, as it maintains iron homeostasis within the cell. Numerous studies have demonstrated that abnormalities in iron metabolism can trigger the Fenton reaction, exacerbating oxidative stress, and leading to cell membrane rupture, cellular dysfunction, and damage to tissue structures. Therefore, regulation of iron metabolism represents a key strategy for ameliorating ferroptosis and offers new insights for treating diseases associated with iron metabolism imbalances. This review first summarizes the mechanisms that regulate iron metabolic pathways in ferroptosis and discusses the connections between the pathogenesis of various diseases and iron metabolism. Next, we introduce natural and synthetic small molecule compounds, hormones, proteins, and new nanomaterials that can affect iron metabolism. Finally, we provide an overview of the challenges faced by iron regulators in clinical translation and a summary and outlook on iron metabolism in ferroptosis, aiming to pave the way for future exploration and optimization of iron metabolism regulation strategies.

Objective: To delineate the epidemiologic profile of rifampicin resistant pulmonary tuberculosis (RR-PTB) among students in Chongqing, so as to provide evidence for effectively controlling RR-PTB outbreaks in schools. Methods: Individual level surveillance records of 395 student RR-PTB cases reported from 2015 to 2024 were extracted from the China Information System for Disease Control and Prevention. The Joinpoint regression analysis was employed to quantify temporal trends in the registration rate of student RR-PTB cases, and the comparison of RR-PTB registration rates with different demographic characteristics and different regions was performed using Chi-square test. Results: From 2015 to 2024, a total of 395 student RR-PTB cases were identified, with the registration rate ranged from 0.07 per 100 000 to 1.47 per 100 000, showed a fluctuating upward trend ( AAPC= 35.22%, t =4.13, P <0.01). A turning point was detected in 2017, rates rose during 2015-2017 (APC=295.23%， t =4.62， P < 0.01 ) and plateaued thereafter (APC=-0.47%， t =-0.12， P =0.91). The proportion of RR-PTB cases occurring among students increased both among all RR-PTB cases (1.54% in 2015, 7.48% in 2024) and all student pulmonary tuberculosis cases (0.20% in 2015, 7.17% in 2024), with significant linear trends ( χ 2 trend =33.55,159.98, both P <0.01). The majority of cases were enrolled in senior high school (50.38%), classified as retreatment (53.92%), of Han ethnicity (75.95%), and diagnosed with multidrug resistant tuberculosis(53.16%). There were significant differences in the composition of different ethnicity, registration category and resistance pattern between different years( χ 2=23.47, 17.23, 59.64，all P <0.05). The South-Eastern Wuling Mountainous Region exhibited the highest notification rate (3.96 per 100 000), whereas the western region had the lowest rate ( 0.47 per 100 000). County level jurisdictions reported higher rates than district level ones (2.16 per 100 000 vs 0.63 per 100 000 ). Statistically significant differences were observed in the RR-PTB reported rates among students across different districts and counties( χ 2=418.05,167.05,both P <0.01). Conclusions From 2015 to 2024, the registration rate of detected student RR-PTB cases in Chongqing showed an increasing trend. Students have become one of the key populations for drug resistant TB prevention and control. Intensified health education and active case finding should be implemented to enhance proactive surveillance capabilities.

Objective : To explore the role of semaphoring 6d(SEMA6D) in the malignant progression of triple-negative breast cancer(TNBC). Methods : Bioinformatics and Immunohistochemistry(IHC) were used to analyze the expression level of SEMA6D in TNBC and paracancer non-tumor tissues and its relationship with patients′ clinicopathological features. MDA-MB-231 cell line stably knocking down the expression of SEMA6D was constructed, and the effects of SEMA6D on migration and invasion of TNBC cells were investigated by Wound-healing assays and Transwell assays. cBioPortal and GEPIA2 databases were used to screen out the gene negatively associated with it, namely aurora kinase A(AURKA). Bioinformatics and IHC were used to analyze the expression level of AURKA in TNBC and paracancer non-tumor tissues and its relationship with patients' clinicopathological features. Western blot assay was used to analyze the expression of AURKA and the effect of epithelial-mesenchymal transition(EMT) makers Claudin-1, N-cadherin and Vimentin after knocking downSEMA6D. Results: Bioinformatics analysis and IHC results showed that the expression of SEMA6D in TNBC tissues was significantly lower than that in paracancer non-tumor tissues(bothP<0.05). The expression of AURKA in TNBC tissues was significantly higher than that in paracancer non-tumor tissues(bothP<0.05), SEMA6D and AURKA were significantly negatively correlated in TNBC(P<0.01). Both low expression of SEMA6D and high expression of AURKA were positively correlated with tumor size, tumor histological grade, clinical stage and lymph node metastasis in TNBC patients(allP<0.05). The knockdown ofSEMA6Dsignificantly promoted the migration and invasion ability of TNBC cells(bothP<0.01). Western blot results showed that the knockdown ofSEMA6Dupregulated AURKA expression, promoted the expression of N-cadherin and Vimentin, and inhibited the expression of Claudin-1 in tumor cells. Conclusion Down-regulation of SEMA6D expression in TNBC may be involved in the malignant progression of TNBC through up-regulation of AURKA expression and promotion of EMT.

Lead is one of the most important occupational hazards in China, and occupational exposure is the leading cause of lead poisoning. Lead can be absorbed by the body through air, food, drinking water and skin, and accumulate in multiple organs in the body, posing health risks to humans, especially to lead workers. Many previous studies have shown that lead can affect the function of glial cells such as microglia, astrocytes and oligodendrocytes, resulting in irreversible neurological damage. This article provides an overview of the neurotoxic mechanism induced by lead through glial cells, elucidates that lead can induce neurodegenerative diseases such as Alzheimer′s disease, Parkinson′s disease, and amyotrophic lateral sclerosis, and reviews the relationship between lead and glial cells, in order to provide reference for further research on the neurotoxic mechanism of lead on glial cells.

Lead is one of the most important occupational hazards in China, and occupational exposure is the leading cause of lead poisoning. Lead can be absorbed by the body through air, food, drinking water and skin, and accumulate in multiple organs in the body, posing health risks to humans, especially to lead workers. Many previous studies have shown that lead can affect the function of glial cells such as microglia, astrocytes and oligodendrocytes, resulting in irreversible neurological damage. This article provides an overview of the neurotoxic mechanism induced by lead through glial cells, elucidates that lead can induce neurodegenerative diseases such as Alzheimer′s disease, Parkinson′s disease, and amyotrophic lateral sclerosis, and reviews the relationship between lead and glial cells, in order to provide reference for further research on the neurotoxic mechanism of lead on glial cells.

Objective:To explore the efficacy and safety of endovascular intervention combined with preoperative laparoscopic exploration in the treatment of patients with acute mesenteric artery ischemia.Methods:This was a prospective cohort study (NCT04686981). The study enrolled 31 patients with acute mesenteric artery ischemia from Oct 1, 2020 to Oct 1, 2022. Among them, 26 patients (84%) were male, with a mean age of (67±13) years and a mean time to onset of (21±8) hours. All patients underwent laparoscopic exploration in the hybrid operating room. If the presence of intestinal necrosis or suspected necrosis was clearly determined, the patient would undergo open surgery (mesenteric artery embolization, intestinal resection and intestinal double stoma) as the treatment by gastrointestinal surgeon. If intestinal necrosis or suspected necrosis was not found by laparoscopy, the patient would undergo endovascular intervention by vascular surgeon. The primary observational endpoints of this study were the proportion of patients who were not dependent on total parenteral nutrition and all-cause mortality within 30 days after operation. The secondary observational endpoints were the rate of mesenteric vascular patency within 30 days and the proportion of interventions that were converted to open surgery.Results:Six patients underwent open surgery and 25 patients underwent endovascular intervention, including 13 cases of thrombus reduction alone, 3 cases of stent implantation during the same period after reduction, and 9 cases of stent implantation alone. Twenty-four patients (77%) were completely weaned from the TPN within 30 days after the procedure, and all-cause mortality was observed in 3 cases (9.7%). The patency rate of the mesenteric artery within 30 days after the procedure was 82.1%. The rate of conversion to open surgery after intervention was 16%.Conclusions:Endovascular intervention combined with preoperative laparoscopic exploration can clarify intestinal ischemia in acute mesenteric patients as early as possible, and individualized treatment strategies for each patient by multidisciplinary care team can potentially improve the prognosis of such patients.

ObjectiveTo analyze the trends in life expectancy and cause-eliminated life expectancy of the registered residents in Qingpu District, Shanghai from 2002 to 2021, and to identify the major diseases causing life expectancy loss in the area, so as to provide a theoretical basis for strengthening disease prevention and interventions and optimizing health resources allocation. MethodsUsing the International Classification of Diseases (ICD)-10 classification of death causes, average life expectancy and cause-eliminated life expectancy were calculated with the abbreviated life table and the cause-eliminated life expectancy table. A trend forecast of life expectancy from 2022 to 2029 was made. ResultsFrom 2002 to 2021, the life expectancy of Qingpu District residents showed an increasing trend, with an average annual growth of 0.32 years (AAPC=0.39%, P<0.001). Among the seven major causes of death, the cause-eliminated expected life expectancy for circulatory system diseases showed the most significant upward trend (AAPC=0.53%, P<0.001), rising from the third leading cause of death in 2002 to the first in 2021. The life expectancy loss rate due to circulatory system diseases increased from 3.79% to 7.97%. Respiratory system diseases showed the largest decline, decreasing from the first leading cause of death in 2002 to the fourth in 2021, with the life expectancy loss rate decreasing from 6.83% to 0.99%. ConclusionLife expectancy of the registered residents in Qingpu District has reached a leading level in China. Future efforts should focus on effectively increasing the life expectancy of male residents, strengthening the comprehensive prevention and treatment of chronic diseases such as cerebrovascular diseases, diabetes, and malignant tumors, and improving health promotion policies for residents to achieve a steady long-term increase in regional life expectancy.