ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Chiropractic therapy is a therapeutic approach for regulating the spine and is widely employed in clinical practice for multiple disorders, including constipation. The theory of "bone strengthening and tendon softening" originated from Huang Di Nei Jing, holding that bones maintain normal anatomical forms and relative positional relationships, and tendons are supple and free from damage. Only when the structures and functions of both are normal can the human body sustain normal physiological activities. In accordance with this theory, clinical treatment mainly aims at adjusting the relationship between tendons and bones and restoring the balance between them to address diseases. Based on the theory of "bone strengthening and tendon softening" and taking the essence of "tendons" as the starting point, this article explored the pathogenic mechanism of outlet obstructive constipation and the clinical application of chiropractic therapy in the treatment of outlet obstructive constipation. Pathological changes of the musculotendinous meridians and abnormal spinal structures are significant pathogenic factors for outlet obstructive constipation. Therefore, in clinical practice, spinal techniques such as guided manipulation, massage, and reconstructive techniques can be used to soften muscles, correct bones, and regulate intestinal stagnation.

Objective: To investigate the coexistence of comorbidity of myopia, overweight/obesity and depressive symptoms among middle school students in Quzhou and its associated factors, so as to provide evidence for integrated prevention and control of common multiple health issues in students. Methods: From September to November 2023, a total of 5 867 middle school students from 6 counties (cities and districts) in Quzhou City were selected by stratified random cluster sampling. Physical and visual examinations were conducted, and the Center for Epidemiological Studies - Depression Scale (CES-D) along with a questionnaire on health status and influencing factors were completed. Multivariate Logistic regression was used to analyze the related factors of coexistence of myopia, overweight/obesity, and depressive symptoms among middle school students, and a nomogram model was constructed based on the results. Results: A total of 161 middle school students in Quzhou City were identified as having comorbid myopia, overweight/ obesity and depressive symptoms, with a detection rate of 2.74%. The results of multivariate Logistic regression analysis showed that the coexistence of myopia, overweight/obesity and depressive symptoms increased among middle school students with older age ( OR =1.11), a greater number unhealthy dietary behaviors (1,2,≥3; OR =2.40, 2.70, 4.63), insufficient sleep( OR =1.78) and alcohol consumption ( OR =2.11)(all P <0.05). Compared with no homework after class, those whose homework duration after class was 1 to < 2 hour had a lower risk of comorbidity of myopia, overweight/obesity and depressive symptoms ( OR =0.53, P <0.05). The results of the nomogram model showed that the AUC (95% CI ) was 0.71 (0.67-0.74). Conclusions The coexistence of myopia, overweight/obesity and depressive symptoms among middle school students in Quzhou City is related to age, sleeping, alcohol consumption, poor dietary behavior and the duration of after school homework. The nomogram model can assist in the early screening and intervention of multiple health issues among students.

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with adult T-cell leukemia/lymphoma (ATLL) in Ningde City, Fujian Province. METHODS: We retrospectively collected 23 cases diagnosed with adult T-cell leukemia/lymphoma in the Hematology Department of Ningde Hospital Affiliated to Ningde Normal University from 2014 to 2023, the clinical characteristics of patients were summarized and the prognosis was analyzed. The survival of patients treated with chemotherapy alone and chemotherapy combined with antiviral therapy was compared. RESULTS: All 23 patients were from the coastal endemic area of Fujian (Ningde City), 12 males and 11 females. The median age of onset was 59 (range: 31-84) years old. The clinical types were acute (18 cases) or lymphomatous (5 cases), and no smoldering or chronic type was seen. The most common clinical manifestations were, in order of prevalence, 20 cases of leukocytosis, 19 cases of lymph node enlargement, 13 cases of skin lesions, 13 cases of hypercalcemia. There was an elevation of lactate dehydrogenase (LDH) levels in more than 90% of cases, and β₂-microglobulin levels were elevated in 11 cases. Twelve of the 23 patients were treated with chemotherapy (partly in combination with antiviral therapy), one underwent allogeneic hematopoietic stem cell transplantation. The median overall survival of all patients was 2.3(0.2-13) months. Median survival was 3(2-11) months in the chemotherapy combined with antiviral therapy group, while that of the chemotherapy alone group was 2(0.2-13) months. CONCLUSION The clinical manifestations of adult T-cell leukemia/lymphoma in Ningde city, Fujian province are characteristic and the prognosis is unfavorable. Antiviral therapy may contribute to an improvement in the prognosis.
Humans ; Retrospective Studies ; Middle Aged ; Leukemia-Lymphoma, Adult T-Cell/diagnosis* ; Male ; Adult ; Female ; Prognosis ; Aged ; Antiviral Agents/therapeutic use* ; Aged, 80 and over ; China

Colon cancer is a complex disease characterized by the impairment of body,qi and spirit,as well as the establishment of a tumor immune microenvironment(TIME)induced by chronic stress.Chronic stress is classified as a micro-level mental disorder,while TIME serves as the biological foundation for qi disorders.The observable manifestation of colon cancer is the tangible representation of physical disease.The interconnected mechanism of"chronic stress-TIME-colon cancer"aligns with the traditional Chinese medicine's understanding of disease as involving the interplay between the body,qi and spirit.In treatment,we should cooperate to improve the"regulating mind"of chronic stress and reshape the"invigorating qi"of TIME,and finally achieve the purpose of shape treatment to delay the progression of colon cancer.The paper is to provide new insights into the treatment of colon cancer with traditional Chinese medicine.

Objective To evaluate the efficacy of a combined immunosuppression regimen in modulating rejection in genetically modified pig-to-macaque xenogeneic heart transplantation.Methods Two xenogeneic heart transplantation models were constructed using genetically modified pigs and macaques.Dynamic monitoring of recipient peripheral blood immune parameters and observation of graft pathological changes were performed.Results Regimen 1,featuring B-cell depletion,T-cell inhibition,and C3 complement suppression,reduced lymphocyte levels but failed to control acute humoral rejection and macrophage infiltration.Regimen 2,adding C5 complement inhibition and interleukin-6 inhibition to Regimen 1,more effectively lowered lymphocyte levels,inhibited acute humoral rejection and complement activation,and decreased antibody deposition.However,a late-phase cytokine storm and residual T cells emerged.Conclusions Regimen 2 reduces the hyperacute and acute rejection risks through multi-target intervention.Yet,it requires balancing medication complexity and safety.This indicates the need to optimize cellular immune regulation and adjust the plan through dynamic multidimensional monitoring.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:This study aims to explore how urban medical groups can empower the scientific research development of primary hospitals through collaborative efforts, providing experience reference for the research construction of medical consortiums.Methods:Taking the Shenzhen Dapeng New District Medical and Health Group as an example, the study examined the impact of the group′s establishment on the research capabilities of primary hospitals in terms of research spirit, team and facilities. It summarized the group′s efforts to promote primary hospital research outcomes through various measures, including establishing funds, building mechanisms, setting up platforms and implementing stratified training.Results:The number of research projects approved by the group had significantly increased, with participation in national key research and development projects as sub-centers for cohort studies. The publication volume of SCI papers had continuously climbed. The integration of research and clinical practice had promoted the introduction of new technologies, significantly enhancing diagnostic and treatment capabilities and public satisfaction.Conclusions:Urban medical groups can address challenges such as the scarcity of research resources in primary hospitals through collaborative mechanisms, offering a replicable pathway for research capacity improvement. However, there is still room for improvement, including deepening the cultivation of scientific research talents and improving the support system to promote the sustainable development of primary hospital research.

Objective:This study aims to explore how urban medical groups can empower the scientific research development of primary hospitals through collaborative efforts, providing experience reference for the research construction of medical consortiums.Methods:Taking the Shenzhen Dapeng New District Medical and Health Group as an example, the study examined the impact of the group′s establishment on the research capabilities of primary hospitals in terms of research spirit, team and facilities. It summarized the group′s efforts to promote primary hospital research outcomes through various measures, including establishing funds, building mechanisms, setting up platforms and implementing stratified training.Results:The number of research projects approved by the group had significantly increased, with participation in national key research and development projects as sub-centers for cohort studies. The publication volume of SCI papers had continuously climbed. The integration of research and clinical practice had promoted the introduction of new technologies, significantly enhancing diagnostic and treatment capabilities and public satisfaction.Conclusions:Urban medical groups can address challenges such as the scarcity of research resources in primary hospitals through collaborative mechanisms, offering a replicable pathway for research capacity improvement. However, there is still room for improvement, including deepening the cultivation of scientific research talents and improving the support system to promote the sustainable development of primary hospital research.