Objective By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.

DNA polymerase theta (Polθ), also known as DNA polymerase θ, is the member of the DNA polymerase A family and plays a crucial role in the repair of DNA double-strand breaks (DSB). Polθ has 3 distinct structural domains: the N-terminal helicase-like domain with a conserved sequence, the C-terminal polymerase domain, and the central domain, which is a disordered sequence connecting these two regions. Notably, Polθ is the only known polymerase in eukaryotes that possesses helicase activity. However, it is also an error-prone polymerase. When DNA DSBs occur, a specialized network consisting of at least 4 pathways, including classical-non homologous end joining (C-NHEJ), homologous recombination (HR), single-strand annealing (SSA), and alternative-end joining (Alt-EJ), is responsible for repairing DNA damage caused by DSBs. In the absence of major DNA repair pathways like HR, cells rely on Alt-EJ pathway mediated by Polθ to repair damaged DNA and maintain genomic stability. Nevertheless, due to the low fidelity of Polθ, Alt-EJ repair often leads to errors. Depletion of Polθ has shown to increases DSB formation and compromise genomic stability. Conversely, overexpression of Polθ has been associated with increases DNA damage markers and impairs cell cycle progression. As a result, the impact of Polθ on genome stability remains controversial. Furthermore, overexpression of Polθ is frequently observed in cancer and is associated with a characteristic mutational signature and poor prognosis. Depleting Polθ in an HR-deficient background has been shown to impair cell viability, suggesting a synthetic lethal (SL) relationship between Polθ and HR factors. In recent years, targeted chemotherapy drugs that inhibit tumor growth have gained significant attention. However, off-target effects and drug resistance pose challenges for clinical application, particularly with poly-ADP-ribose polymerase inhibitor (PARPi). Blocking Polθ activity in HR-deficient tumor cells has been found to reverse PARPi resistance, making Polθ a very promising therapeutic target in cancer treatment. The availability of crystal structures for both helicase and polymerase domain has facilitated the design of potent inhibitors of Polθ. Currently, several highly specific and effective small molecule inhibitors targeting Polθ, such as Novobiocin, RP-6685, and ART558, have been reported to effectively block various cancers with HR deficiency. The initial success of these inhibitors points to new directions for treating BRCA1/2-mutated tumors. Additionally, reducing the Alt-EJ repair pathway mediated by Polθ can improve HR repair efficiency and increase the chance of exogenous gene target integration (TI), suggesting potential new applications for Polθ inhibitors. This article reviews the recent research progress on the molecular function of Polθ and its involvement in the Alt-EJ pathway modification mechanism, providing insights for a deeper understanding of this field.

Transcatheter aortic valve replacement(TAVR)has become one of the effective methods for treating patients with aortic valve disease.With the continuous maturity of technology,innovation of instruments and increasing experience,the indications for TAVR has been expanded.Following international trends,the number of TAVR in China has steadily increased with each passing year.In 2023,the long-term follow-up results of TAVR in low-risk AS patients further confirm the long-term benefits of TAVR.The relevant research on TAVR for patients with aortic regurgitation and patients with bicuspid aortic stenosis provide evidence support for the expansion of TAVR indications.At the same time,the development of valve devices and new technological innovations are emerging in an endless stream,and the new concept of full life cycle management is increasingly being valued.Especially in China,the development of local devices is progressing rapidly,and multiple devices have entered the clinical research stage.The clinical manifestations and research results are worth pursuing.

Refractory prolactinoma is the most common pituitary neuroendocrine tumor.Dopamine receptor agonists(DA)are the primary choice for drug treatment.Most patients with prolactinomas respond well to DA.However,a minority of prolactinomas patients still show resistance to DA.Although drug-resistant and refractory prolactinomas are rare in clinical practice,their treatment is extremely challenging.Even a combination of drug therapy,multiple surgeries,and radiotherapy may not yield satisfactory outcomes.Therefore,standardizing the diagnosis and treatment process and pathway for refractory prolactionmas and exploring more effective multidisciplinary collaborative treatment strategies are urgent problems to be solved.In the clinical management of refractory prolactinomas,it is often necessary to consider the patient's condition comprehensively,replace other types of DA,or consider surgery,radiotherapy,and immunotherapy,which requires multidisciplinary diagnosis and treatment.This review synthesizes the latest literature at home and abroad to systematically discuss the latest advances in drug therapy,surgery,and radiotherapy treatments for refractory prolactionmas,aiming to provide new ideas for basic research,clinical diagnosis and treatment.

Objective To explore the clinical value of endoscopic ultrasonography(EUS)combined with serum serine protease inhibitor Kazal 1(SPINK1)and secretory phosphoprotein 1(SPP1)in early diagnosis of esophageal cancer.Methods 276 patients from June 2021 to May 2023 were selected as the study objects.92 cases of esophageal cancer diagnosed by operation and pathology were esophageal cancer group,another 89 patients diagnosed as benign esophageal lesions through tissue biopsy were selected as the benign lesion group,and 95 healthy individuals who underwent physical examinations were collected as the healthy control group,general information such as age and gender of subjects in three groups were collected and organized;using pathological results as the gold standard,the accuracy of EUS in diagnosing esophageal cancer was verified;the expression of serum SPINK1 and SPP1 was compared among the esophageal cancer group,benign lesion group,and healthy control group;the relationship between the expression of serum SPINK1 and SPP1 in esophageal cancer patients and their clinical and pathological characteristics was explored;efficacy of EUS combined with serum SPINK1,SPP1 levels for early diagnosis of esophageal cancer was analyzed using receiver operator characteristic curve(ROC curve).Results Compared with the gold standard,the results of EUS examination showed that 81 cases were diagnosed with esophageal cancer,79 cases were diagnosed with benign lesions,11 cases were missed diagnosed,and 10 cases were misdiagnosed,with an accuracy rate of 88.40%(160/181);Compared with the healthy control group and the benign lesion group,the expression levels of serum SPINK1 and SPP1 in the esophageal cancer group were obviously increased,the expression levels of serum SPINK1 and SPP1 in the benign lesion group were significantly higher than those in the healthy control group,the differences were statistically significant(P<0.05);Serum SPINK1 expression was linked to tumor diameter>2 cm,presence of lymph node metastasis,lymph node positivity,and tissue grading level 3 in patients(P<0.05).Serum SPP1 expression level was related to tumor diameter>2 cm,presence of lymph node metastasis,lymph node positivity,and estrogen receptor positivity of patients(P<0.05);ROC curve showed that the area under the curve(AUC)of EUS,serum SPINK1,SPP1 levels,and their combination in the early diagnosis of esophageal cancer was 0.862,0.834,0.782,and 0.926,respectively,the clinical efficacy of the combination of the three in the early diagnosis of esophageal cancer was superior to that of EUS,serum SPINK1,and SPP1 alone(Z=2.30,Z=3.70,Z=4.23,P=0.022,P=0.000,P=0.000).Conclusion The expression levels of serum SPINK1 and SPP1 in esophageal cancer patients are abnormally up-regulated.The combination of EUS and serum SPINK1 and SPP1 has high clinical value in early diagnosis of esophageal cancer.

Child ; Humans ; Hemangioma/surgery* ; Wrist Joint

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To analyze the short-term effect of individual atmospheric PM_2.5 exposure on the diversity, enterotype, and community structure of gut microbiome in healthy elderly people in Jinan, Shandong province. Methods: The present panel study recruited 76 healthy elderly people aged 60-69 years old in Dianliu Street, Lixia District, Jinan, Shandong Province, and followed them up five times from September 2018 to January 2019. The relevant information was collected by questionnaire, physical examination, precise monitoring of individual PM_2.5 exposure, fecal sample collection and gut microbiome 16S rDNA sequencing. The Dirichlet multinomial mixtures (DMM) model was used to analyze the enterotype. Linear mixed effect model and generalized linear mixed effect model were used to analyze the effect of PM_2.5 exposure on gut microbiome α diversity indices (Shannon, Simpson, Chao1, and ACE indices), enterotype and abundance of core species. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 352 person-visits. The age of 76 subjects was (65.0±2.8) years old with BMI (25.0±2.4) kg/m². There were 38 males accounting for 50% of the subjects. People with an educational level of primary school or below accounted for 10.5% of the 76 subjects, and those with secondary school and junior college or above accounting for 71.1% and 18.4%. The individual PM_2.5 exposure concentration of 76 subjects during the study period was (58.7±53.7) μg/m³. DMM model showed that the subjects could be divided into four enterotypes, which were mainly driven by Bacteroides, Faecalibacterium, Lachnospiraceae, Prevotellaceae, and Ruminococcaceae. Linear mixed effects model showed that different lag periods of PM_2.5 exposure were significantly associated with a lower gut α diversity index (FDR<0.05 after correction). Further analysis showed that PM_2.5 exposure was significantly associated with changes in the abundances of Firmicutes (Megamonas, Blautia, Streptococcus, etc.) and Bacteroidetes (Alistipes) (FDR<0.05 after correction). Conclusion: Short-term PM_2.5 exposure is significantly associated with a decrease in gut microbiome diversity and changes in the abundance of several species of Firmicutes and Bacteroidetes in the elderly. It is necessary to further explore the underlying mechanisms between PM_2.5 exposure and the gut microbiome, so as to provide a scientific basis for promoting the intestinal health of the elderly.
Aged ; Humans ; Male ; Middle Aged ; Feces/microbiology* ; Gastrointestinal Microbiome ; Particulate Matter ; RNA, Ribosomal, 16S/genetics* ; Female