Objective: To investigate the intentions of mothers of ageappropriate girls in Qingdao to vaccinate their daughters against human papillomavirus (HPV), so as to provide theoretical guidance for targeted health education in the future. Methods: A multistage random sampling method was adopted to conduct a crosssectional study among 2 244 mothers of girls aged 12-14 years in Qingdao from March to December 2023. The Mann-Whitney U test was used for group comparisons, and Logistic regression was performed to analyze the factors that influenced maternal intention to vaccinate their ageappropriate daughters against HPV. Results: Among the surveyed mothers, 89.22% (n=2 002) intended to vaccinate their daughters against HPV, and 68.58% (n=1 539) had fully vaccinated or had plans to complete it for themselves. The knowledge score of mothers intended to vaccinate their daughters was 10 (8, 11). The multivariate Logistic regression analysis showed that mothers aged >45 years (OR=0.19), those with an annual family income of 60 000-<150 000 yuan (OR=0.65), 150 000-<300 000 yuan (OR=0.58), 300 000-500 000 yuan (OR=0.22), and those with higher knowledge scores (OR=0.90) were more likely to vaccinate their daughters (P<0.05). Mothers with a junior college or undergraduate degree (OR=1.66), those who never or occasionally screened for HPV (OR=1.58), those who were intended to be vaccinated, not planning to complete the fullcourse vaccination, or overaged and unvaccinated (OR=7.13), those who were not concerned about their daughters HPV infection (OR=2.54), and those whose daughters were not in adolescence (OR=1.93) were less intended to vaccinate their daughters (P<0.05). The primary reasons for vaccine hesitancy were vaccine safety concerns (65.06%), followed by the belief of mothers that "the children is to young, and can be vaccinated when they are older" (13.25%). Conclusions Mothers of eligible girls in Qingdao have relatively higher intentions to vaccinate their daughters against HPV, and willingness is influenced by factors such as the mothers vaccination status, knowledge level, and daughters development stage. It is recommended to strengthen targeted health education, improve the cognitive level and acceptance of mother, and increase the vaccination rate of HPV vaccines.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

As an indispensable trace element in the human body,copper plays an important role in various physiological and biochemical reactions.The dyshomeostasis of copper leads to the disorder of copper metabolism and the occurrence of related diseases.Cuproptosis,a newly proposed regulatory cell death mode,is different from the known apoptosis,pyroptosis,necroptosis,and ferroptosis.Recent studies have found that the dyshomeostasis of copper has been observed in a variety of cancers.Therefore,targeting copper for disease treatment may become a new strategy and a new idea.This article systematically summarizes the fundamental properties of copper,copper dyshomeostasis-related diseases (Menkes syndrome,Wilson's disease,and cancer) and their treatment,and reviews the research progress in cuproptosis.
Humans ; Copper/metabolism* ; Homeostasis ; Neoplasms/metabolism* ; Hepatolenticular Degeneration/metabolism* ; Menkes Kinky Hair Syndrome/metabolism*

Objective:To evaluate early residual myocardial ischemia after successful percutaneous coronary intervention (PCI) in patients with coronary artery disease by using myocardial perfusion imaging (MPI) and investigate independent influencing factors of early residual myocardial ischemia.Methods:From January 2020 to December 2022, 127 patients (107 males, 20 females; age (60.3±9.6) years) with coronary artery disease who underwent PCI complete revascularization at the First People′s Hospital of Changzhou were consecutively enrolled prospectively. All patients underwent rest and stress MPI within 1-3 months after PCI. Reversible myocardial perfusion defect in the blood supply area of the culprit vessels in stress and rest MPI was defined as early residual myocardial ischemia after PCI. Accordingly, the culprit vessels undergoing PCI were divided into residual ischemic group and non-ischemic group. Differences of cardiovascular examination between two groups were compared ( χ2 test), such as proportion of culprit vessels with severe stenosis (≥90%), proportion of bifurcation lesions, and proportion of diffuse coronary disease. Logistic regression analyses were performed to identify influencing factors for early residual myocardial ischemia. Results:Among 148 culprit vessels undergoing PCI in 127 patients, early residual myocardial ischemia was present in 49 vessels (33.1%, 49/148). The proportion of culprit vessels with severe stenosis before PCI in residual ischemia group was higher than that in non-ischemia group (69.4%(34/49) and 49.5%(49/99); χ2=5.27, P=0.022). The proportion of bifurcation lesions in residual ischemic group was also higher than that in non-ischemic group (28.6%(14/49) and 10.1%(10/99); χ2=8.23, P=0.004), with a slightly higher proportion of diffuse coronary disease compared to non-ischemic group (14.3%(7/49) and 4.0%(4/99); χ2=3.62, P=0.057). Multivariate logistic regression analysis showed that bifurcation lesion (odds ratio ( OR)=4.087, 95% CI: 1.615-10.344, P=0.003) and diffuse coronary disease ( OR=4.208, 95% CI: 1.115-15.878, P=0.034) were independent influencing factors for early residual myocardial ischemia. Conclusions:Early residual myocardial ischemia is still present in about 1/3 of the culprit vessels after PCI complete revascularization. Bifurcation lesion and diffuse coronary disease are independent influencing factors for early residual myocardial ischemia in culprit vessels.

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*

OBJECTIVE: To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism. METHODS: Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L). RESULTS: DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells. CONCLUSION CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.
Female ; Humans ; Cell Line, Tumor ; HeLa Cells ; Neoplastic Stem Cells/metabolism* ; RNA, Small Interfering/metabolism* ; Uterine Cervical Neoplasms/metabolism*

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.
Humans ; Integrative Medicine ; Brain/pathology* ; Cerebral Small Vessel Diseases/pathology* ; Stroke/complications* ; Cognitive Dysfunction/complications* ; Magnetic Resonance Imaging

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
Humans ; Venous Thromboembolism/etiology* ; Multiple Myeloma/diagnosis* ; Risk Assessment ; Risk Factors ; ROC Curve ; Retrospective Studies

Sclera is an important tissue to maintain the structure and function of eyes.Its unique biomechanical properties influence the occurrence and development of ocular diseases. The biomechanical properties of sclera are mainly determined by extracellular matrix(ECM), which contains different types of collagen fibers, proteoglycan and other substances. In many ocular diseases, the change of the content and arrangement of these scleral ingredients as well as scleral biomechanics can be called scleral remodeling. In recent years, studies have shown that the scleral remodeling is a complex and dynamic process in many ocular diseases,with many key molecules and signaling pathways participating and regulating. Those key molecules and signaling pathways influencing the scleral remodeling of ocular diseases are reviewed, and the availability of scleral intervention in the treatment of ocular diseases is explored.