Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry* ; Endangered Species ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/economics* ; China

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules (QFG) in inhibiting colitis-associated colorectal cancer (CAC) development via RNA sequencing (RNA-seq) and 16S ribosomal RNA (rRNA) correlation analysis. METHODS: CAC was induced in BALB/c mice using azoxymethane (AOM) and dextran sulfate sodium (DSS), and QFG was administered orally to the treatment group. The effects of QFG on CAC were evaluated using disease index, histology, and serum T-cell ratios. RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change. Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence. The link between microbiota and CAC-related markers was explored using linear discriminant analysis effect size and Spearman correlation analysis. RESULTS: Long-term treatment with QFG prevented AOM/DSS-induced CAC formation, reduced levels of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), IL-6, and interferon γ (IFN-γ), and increased CD3⁺ and CD4⁺/CD8⁺ T cells ratio, without causing hepatic or renal toxicity. A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances. Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/nuclear factor kappa-B (NF-κB) pathway as key for QFG's treatment against CAC. Furthermore, QFG decreased the abundance of Bacilli, Bacillales, Staphylococcaceae, Staphylococcus, Lactobacillales, Aerococcus, Alloprevotella, and Akkermansia, while increasing Clostridiales, Lachnospiraceae, Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Muribaculaceae, which were highly correlated with CAC-related markers or NOD2/NF-κB pathway. CONCLUSION By mapping the relationships between CAC, immune responses, microbiota, and key pathways, this study clarifies the mechanism of QFG in inhibiting CAC, highlighting its potential for clinical use as preventive therapy.

Objective To evaluate the value of miniprobe endoscopic ultrasound(EUS)in guiding endoscopic treatment of small-diameter(maximum diameter less than 1 cm)and low-grade(G1 grade)rectum neuroendocrine neoplasm(R-NEN),and to provide evidence and clues for its clinical application and further research.Methods The clinical data of 85 cases of low-grade(G1 grade)R-NEN with a maximum diameter of less than 1 cm who underwent endoscopic treatment in our center from January 2014 to December 2020 were retrospectively analyzed.The patients were divided into the EUS group(37 cases)and control group(48 cases)according to whether EUS was performed before endoscopic treatment.The positive rate of incision margin,the incidence of complications,the recurrence rate,the hospital stay,the cost of hospitalization and endoscopic therapy were compared between the two groups.Results The positive rate of incision margin in the EUS group was significantly lower than that in control group(P<0.05).There was no significant difference in the incidence of complications,tumor recurrence rate,hospital stay or hospital costs between the two groups(P>0.05).There was statistically significant difference in the endoscopic therapy between the two groups(P<0.05).Conclusion Evaluating the lesion depth of small-diameter and low-grade(G1 grade)R-NEN before surgery by miniprobe EUS and selecting endoscopic surgery according to its results of can significantly reduce the residual risk of resection margin tumors.

Objective To compare the effect of palliative mitral valve surgeries and medication therapies for secondary non-ischemic mitral regurgitation. Methods The clinical data of patients with non-ischemic functional mitral regurgitation treated in our hospital between 2009 and 2019 were retrospectively analyzed. Patients with a left ventricular ejection fraction (LVEF)＜40% underwent a dobutamine stress test, and a positive result was determined when the LVEF improved by more than 15% compared to the baseline value. Positive patients were divided into a surgery group and a medication group. The surgery group underwent surgical mitral valve repair or replacement, while the medication group received simple medication treatment. Follow-up on survival and cardiac function status through outpatient or telephone visits every six months after surgery, and patients underwent cardiac ultrasound examination one year after surgery. The main research endpoint was a composite endpoint of all-cause death, heart failure readmission, and heart transplantation, and the differences in cardiac function and cardiac ultrasound parameters between the two groups were compared. Results Ultimately 41 patients were collected, including 28 males and 13 females with an average age of 55.5±11.1 years. Twenty-five patients were in the surgery group and sixteen patients in the medication group. The median follow-up time was 16 months, ranging 1-96 months. The occurrence of all-cause death in the surgery group was lower than that in the medication group (HR=0.124, 95%CI 0.024-0.641, P=0.034). The difference between the two groups was not statistically significant in the composite endpoint (HR=0.499, 95%CI 0.523-1.631, P=0.229). The New York Heart Association (NYHA) grade of the surgery group was better (NYHA Ⅰ-Ⅱ accounted for 68.0% in the surgury group and 18.8% in the medication group, P<0.01) as well as the grade of mitral valve regurgitation (87.5% of the patients in the medication group had moderate or above regurgitation at follow-up, while all the patients in the surgery group had moderate below regurgitation, P<0.01). There was no statistical difference in preoperative and follow-up changes in echocardiograph parameters between the two groups (P＞0.05). Conclusion For non-ischemic functional mitral regurgitation, if the cardiac systolic function is well reserved, mitral valve surgery can improve survival and quality of life compare to simple medication therapy.

OBJECTIVE: To explore the immunological mechanisms underlying spermatogenetic malfunction in patients with non-obstructive azoospermia (NOA) based on bioinformatics and machine learning, and to screen out the key genes associated with spermatogenesis failure. METHODS: NOA-related datasets were obtained from the GEO database, and the differentially expressed genes identified by differential analysis and weighted gene co-expression network analysis (WGCNA). A model of spermatogenesis scoring was established for analysis of the immunological microenvironment and cell interaction networks related to spermatogenesis failure. The key genes were screened out by machine learning, followed by analysis of their correlation with T cells and macrophages. An NOA mouse model was constructed for validation of transcriptome sequencing. RESULTS: Seventy-five differentially expressed genes were identified for the establishment of the spermatogenesis scoring model. The low spermatogenesis score group showed a higher infiltration of the immune cells, with an increased proportion of T cells and macrophages and a correlation of cell interaction signals with immunity. SOX30, KCTD19, ASRGL1 and DRC7 were identified by machine learning as the key genes related to spermatogenesis, with down-regulated expressions in the NOA group, and their expression levels negatively correlated with the infiltration of T cells and macrophages. The accuracy of the spermatogenesis scoring and machine learning models, as well as the trend of the expression levels of the key genes, was successfully validated with the transcriptome sequencing data on the NOA mouse testis. CONCLUSION The development of NOA is closely associated with enhanced immunological microenvironment in the testis. T cells and macrophages may play important roles in spermatogenesis failure. SOX30, KCTD19, ASRGL1 and DRC7 are potential biomarkers for the diagnosis and treatment of NOA.
Male ; Azoospermia/genetics* ; Machine Learning ; Animals ; Computational Biology ; Mice ; Humans ; Spermatogenesis/genetics* ; Gene Expression Profiling ; Macrophages/immunology* ; Gene Regulatory Networks ; T-Lymphocytes/immunology* ; Transcriptome

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective: To analyze the current status of work-related musculoskeletal disorders (WMSDs), work fatigue and musculoskeletal pain in Chinese occupational population, and to study the relationship between work fatigue and musculoskeletal pain and WMSDs. Methods: A total of 66 961 employees from 323 enterprises in 15 key industries in China were selected as the study subjects using stratified cluster sampling method. The incidence of WMSDs in the past year was investigated using the Chinese version of the Musculoskeletal Disorders Questionnaire, and the work fatigue and musculoskeletal pain were investigated using Borg 6-20 Rating of Perceived Exertion Scale and visual analogue scale. The data were standardized using the age composition data of 18 to 60 years from the seventh national population census. Results: The standardized annual incidence of WMSDs was higher in the front-line workers than that in the administrative and other supportive staff (38.82% vs 36.30%). The detection rates of work fatigue and musculoskeletal pain in the study subjects were 44.54% and 63.08%, respectively. The result of S-curve fitting showed that the risk of WMSDs increased with the level of work fatigue (P<0.01). Among the front-line workers, the average of monthly fatigue frequency in the neck, shoulder, lower back, upper back, wrist/hand, foot and ankle, knee, leg, and elbow were higher in the group with WMSDs compared to those without WMSDs (all P<0.01). The pain degree of musculoskeletal pain was higher in all nine sites in the fatigued group than in the no-fatigue group (all P<0.01). The standardized detection rate of musculoskeletal pain was higher in the fatigued group than in the non-fatigued group (80.38% vs 25.71%). The work fatigue was moderate and positively correlated with musculoskeletal pain in all seven sites except the lower back and elbow, with Kendall Tau-b correlation coefficients ranging from 0.423 to 0.546 (all P<0.01). Conclusion: There is a good correlation between work fatigue and local musculoskeletal pain, work fatigue and WMSDs in Chinese occupational population. Implementing ergonomic interventions to control the development of work fatigue can be an effective measure for preventing WMSDs.

Objective: To determine the association between anthropometric parameters and 20 meter shuttle run test (20 m SRT) score among children and adolescents. Methods: The convenient sampling method was conducted to select 3 192 primary and secondary school students in Baoan District, Shenzhen, based on the street school types school from April to May 2019. Height, weight, 20 m SRT score and general demographic indicators were assessed and collected. Individuals were divided into two groups based on the dose response correlation between different anthropometric parameters (the Z score of height, weight and BMI) and 20 m SRT score analyzed with the restricted cubic spline. The association between the Z score of height and 20 m SRT score was further analyzed using the Spearman correlation analysis. Logistic regression analysis was used to analyze separately the relationship different anthropometric parameters and 20 m SRT score. Results: The Z value of weight and 20 m SRT score showed a non linear dose response association ( P <0.01), the significant but weak linear correlation between the Z value of height and 20 m SRT score ( r=0.06, P <0.05). The prevalence rate on the low level of the Z value of 20 m SRT score in 3 192 children and adolescents was 44.7%, and the gender ( χ 2=14.02, P <0.01) and grade difference ( χ 2=93.28, P <0.01) were both statistically significant. There was no significant relationship between the Z value of height and 20 m SRT score grade among total population, different genders and different grades ( P > 0.05). Compared with the reference group on the Z value of weight ≤-0.23, individuals with the Z value of weight >-0.23 had the low level of 20 m SRT score ( OR =0.61, P <0.05). Compared with the reference group on the Z value of BMI ≤ 0.25, individuals with the Z value of weight >0.25 had the low level of 20 m SRT score ( OR =0.45, P <0.05). Stratified for gender and grade, the above significant relationship on the Z value of weight, Z value of BMI and 20 m SRT score were still observed ( P <0.01). Conclusions The higher height Z value shows on correlations with 20 m SRT score, but the positive association is found between weight and BMI Z value and the 20 m SRT score. The cardiopulmonary fitness improvement may be more effective among children and adolescents when tuking weight and BMI Z scores into consideration.