OBJECTIVES: To investigate the effect of Haematococcus pluvialis (HP) on bleomycin (BLM)-induced pulmonary fibrosis in mice and on TGF-β1-induced human fetal lung fibroblasts (HFL1). METHODS: Thirty male C57BL/6 mice were randomly divided into control group, BLM-induced pulmonary fibrosis model group, low- and high-dose HP treatment groups (3 and 21 mg/kg, respectively), and 300 mg/kg pirfenidone (positive control) group. The effects of drug treatment for 21 days were assessed by examining respiratory function, lung histopathology, and expression of fibrosis markers in the lung tissues of the mouse models. In TGF-β1-induced HFL1 cell cultures, the effects of treatment with 120, 180 and 240 μg/mL HP or 1.85 μg/mL pirfenidone for 48 h on expression levels of fibrosis markers were evaluated. Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240 μg/mL HP. RESULTS: HP obviously alleviated BLM-induced lung function damage and fibrotic changes in mice, evidenced by improved respiratory function, lung tissue morphology and structure, inflammatory infiltration, and collagen deposition and reduced expressions of fibrotic proteins. HP at the high dose produced similar effect to PFD. In TGF-β1-induced HFL1 cells, treatment with 240 μg/mL HP significantly reduced the mRNA and protein expression levels of α-SMA and FN. Transcriptome analysis revealed that multiple key genes and pathways mediated the protective effect of HP against pulmonary fibrosis. CONCLUSIONS HP alleviates pulmonary fibrosis in both the mouse model and cell model, possibly as the result of the synergistic effects of its multiple active components.
Animals ; Pulmonary Fibrosis/chemically induced* ; Bleomycin/adverse effects* ; Mice, Inbred C57BL ; Male ; Mice ; Fibroblasts/drug effects* ; Lung/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Myofibroblasts/drug effects* ; Humans ; Pyridones

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

The study introduced the general evaluation indicator system for community health services in Shanghai and its characteristics,analyzing the results of the comprehensive evaluation from the aspects of regions and institutions.From six aspects of financial input,human resource construction, operation mechanism,family doctor system,information system construction and the application of the comprehensive evaluation results,the paper recommended on deepening the reform of community health services.

Purpose To investigate the clinicopathologic characteristics, differential diagnosis, treatment and prognosis of differentia-ted-type vulvar intraepithelial neoplasia ( dVIN) . Methods Clinicopathologic findings and immunophenotypes of 6 cases diagnosed as“dVIN” were retrospectively analyzed, and the relevant literatures were also reviewed. Results 6 patients were all female ranged 53~80 years old with mean age of 62 years old. Clinical aspects included leukoplakia vulvar, pruitis, irritation, pain, ulcer and so on. The histopathological features were hyperplasia of basal and parabasal layer with elongation and anastomosing reteridges. Cells were marked atypia with obvious nucleoli, atypical mitosis, and dyskeratosis. In the middle and surface layer, cells were well differentiated with pronounced intercellular bridges, and eosinophilic cytoplasm, hyperkeratosis and parakeratosis. Oedema and band of infiltration of chronic inflammatory cells of subepidermal could been seen. Immuohistochemistry showed the expression rates of p53 and p16 in totally 6 cases were 83. 3% (5/6), 0 (0/6), respectively. The Ki-67 index was more than 90% in basal and parabasal cells. Four patients were followed up ( mean follow-up 17 months, range 6~36 months) , one patient died at 9 months later after surgery, another patient recurred at 6 months later after surgery, both of the 2 cases were all with invasive lesions after resection, and the rest two cases had no recur in 18 months and 36 months after surgery, respectively. Conclusion dVIN is a high grade squamous intraepithelial lesions of vulvar with low incidence rate, but had more risk of progression. p53, p16 and Ki-67 stain were useful in the diagnosis of dVIN.

Whole esophagus deep burn is an extremely rare upper gastrointestinal tract disease. We report a case of severe burns of involving extensive body skin, eyes, throat, and esophagus. Endoscopic examination revealed acute necrotizing esophagitis and detected a metal foreign body in the stomach. The patient underwent burn wound debridement with analgesia, anti-shock rehydration, anti-infection, and symptomatic treatments, which failed to improve the conditions. The patient died of respiratory and circulatory failure secondary to serious sepsis.
Burns ; complications ; Esophagus ; injuries ; Foreign Bodies ; complications ; Humans ; Male ; Middle Aged ; Stomach

Objective To discuss the technical feasibility and clinical effectiveness of using complex tissue flap pedicled with inferior gluteal artery perforator for repair giant sacrococcygeal pressure sore.Methods Thirty embalmed lower limbs of adult cadavers perfused with red latex were used for anatomical study,and the followings were observed:①The course,branche and distribution of gluteal artery.②The course and distribution of the posterior femoral cutaneous nerve.③Anastomosis between the posterior cutaneous branch of gluteal artery and nutrient vessels of the posterior femoral cutaneous nerve.8 cases aging from 17 years to 56 years were completed during May 2007 to July 2013,6 cases were males and 2 cases were females.The sizes of pressure sore with the depth to Ⅳ degree were ranged from 16 cm × 9 cm to 22 cm × 10 cm.The sizes of flaps were harvested from 32 cm × 10 cm to 25 cm × 9 cm.Results The gluteal artery crossed the edge of the piriformis,the main stem was (3.1 ± 0.4) mm in diameter and gave out 2-5 muscular branches to supply the gluteus maximus.The posterior femoral cutaneous nerve crossed the edge of gluteus maximus and descended between biceps femoris and semitendinosus.Perforating deep fascia point located was (5.9 ± 0.8) cm above the line between medial and lateral femoral epicondyle.The constant anastomosis were formed by the posterior cutaneous branch of gluteal artery,the obturator artery perforator and the direct popliteal artery perforator around the posterior femoral cutaneous nerve.The complex flap survived successfully in all patients.Sutures were removed at 14 days postoperatively and the wounds healed well.All supplied areas were closed by directly suturing.Recurrent sacrococcygeal pressure sore was not observed in all cases with satisfied appearance and normal color during the outpatient follow-up period from 5 months to 5 years.Conclusion The united flap of gluteal myocutaneous flap and the posterior femoral cutaneous neurovascular flap pedicled with inferior gluteal artery perforator can be used to primary repair giant sacrococcygeal pressure sore.Rich blood supply,simple operation technique and high rate survival rate was considered as advantages of the flap.The lower recurrence of pressure sore was due to nice wear resisting with rich layer of anatomical structure in the flap and strong ability of anti-infection.The clinical effect was satisfied.