Objective To investigate the role and regulatory mechanism of LINC00657 in the progression of cervical cancer. Methods Bioinformatics analysis predicted potential binding sites between LINC00657 and miR-30a-5p and between miR-30a-5p and Skp2. These sites were verified by using RNA immunoprecipitation and dual-luciferase reporter experiments. LINC00657, miR-30a-5p, and Skp2 mRNA expression levels in cervical cancer tissues and cell lines were assessed by utilizing RT-qPCR. Western blot analysis was employed to examine the protein levels of Skp2 in cells and subcutaneous xenograft tumor models in nude mice. Immunohistochemistry was applied to analyze Skp2 expression in animal tissues. The cellular processes of cervical cancer cell lines were evaluated through CCK-8, scratch, and Transwell assays. Results LINC00657 and Skp2 presented binding sites for miR-30a-5p. In cervical cancer, LINC00657 and Skp2 showed high expression levels (P<0.05), whereas miR-30a-5p displayed low expression (P<0.05). Functional experiments demonstrated that linc00657 upregulates Skp2 expression, a process that is dependent on its sequestration of miR-30a-5p. Conclusion LINC00657 promoted the malignant progression of cervical cancer by upregulating Skp2 expression through specifically sequestering miR-30a-5p, thereby relieving its inhibitory effect on the target gene Skp2.

Objective To compare the effects of non-invasive intermittent oxygen-driven nebulization,non-invasive intermittent air-driven nebulization,and non-invasive simultaneous air-driven nebulization on the dynamic changes of partial pressure of carbon dioxide(PtCO2),pulse oxygen saturation(SpO2),and heart rate during nebulization,as well as the therapeutic effects in patients with acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods A total of 99 patients with acute exacerbation of COPD requiring non-invasive mechanical ventilation and nebulization were randomly divided into a control group,an experimental group one,and an experimental group two,with 33 patients in each group.The control group was given non-invasive intermittent oxygen-driven nebulization,the experimental group one was given non-invasive intermittent air-driven nebulization,and the experimental group two was given non-invasive simultaneous air-driven nebulization.The changes in PtCO2,SpO2,and heart rate at 0 min,5 min,10 min,15 min during nebulization,5 min,10 min,and 15 min after nebulization were recorded.The values of arterial blood gas PaCO2 and PaO2 were recorded every morning from before treatment to the 7th day of treatment.The length of hospital stay in the three groups was also recorded.Results The comparison of PtCO2 during nebulization among the three groups showed that there were statistically significant differences in the main effect of time and the interaction effect of time and group(P<0.001).The PtCO2 values in the control group showed a linear relationship with time(F=10.166,P=0.003),increasing over time;the PtCO2 values in the experimental group one showed a linear relationship with time(F=10.544,P=0.003),decreasing over time;the PtCO2 values in the experimental group two showed a linear rela-tionship with time(F=20.003,P<0.001),decreasing over time.A one-way ANOVA was conducted on the PtCO2 values at each time point in the three groups.The PtCO2 value at 15 min of nebulization in the control group was higher than that in the experimental group one and the experimental group two.There were statistically signifi-cant differences in the difference in PtCO2 before and after nebulization(dPtCO2)between the experimental group one and the experimental group two and the control group(P<0.05).A one-way ANOVA was conducted on the PtCO2 values at each time point during the observation period after nebulization.The results showed that there were statistically significant differences in PtCO2 at 0 min and 5 min after nebulization among the three groups(P<0.05),while there were no statistically significant differences in PtCO2 at 10 min and 15 min after nebulization among the three groups(P>0.05).The comparison of SPO2 during nebulization among the three groups showed that there were statistically significant differences in the interaction effect of time and group(P<0.05).The SPO2 values in the experimental group one decreased over time.The SPO2 values at 10 min and 15 min of nebulization in the control group were higher than those in the experimental group one and the experimental group two.All three groups could improve PaCO2 in arterial blood gas with the treatment days(P<0.05).Conclusions All three nebu-lization treatment methods can achieve good therapeutic effects.However,non-invasive intermittent oxygen-driven nebulization can increase PtCO2 and SPO2 during nebulization;non-invasive intermittent air-driven nebulization can decrease PtCO2 and SPO2 during nebulization;non-invasive simultaneous air-driven nebulization can decrease PtCO2 and maintain stable SPO2 during nebulization.Therefore,non-invasive simultaneous air-driven nebulization is a relatively safer nebulization inhalation method and is worthy of clinical promotion.

Objective:To investigate the role of platelet-derived zyxin in promoting tumor migration by platelets.Methods:The gene expression profile of platelets was analyzed from cancer patients by using the GEO database.Isolated platelets from wild-type(WT)and Zyx-/-mice were co-cultured with B16F10 cells labeled with green fluorescence to investigate the influence of zyxin deficiency on tumor cell migration,invasion,and wound healing.Optical microscopy was employed to evaluate the impact of zyxin deficiency on epithelial-mesenchymal transition(EMT)in B16F10 cells induced by platelets.Employing specific markers to label platelets,fluorescence confocal microscopy was utilized to investigate the impact of platelet-derived zyxin on the binding between tumor cells and platelets.And an aggregometer was employed to observe the influence of zyxin deficiency on tumor cell-induced platelet aggregation.Results:Compared to platelets from healthy volunteers,zyxin was upregulated in platelets from cancer patients.Zyx-/-mouse platelets exhibited a significant reduction in tumor cell invasion and migration,impaired wound healing,and delayed tumor cell EMT compared to WT mouse platelets.Additionally,zyxin deficiency attenuated the interaction between platelets and tumor cells,and diminished the capacity for tumor cell-induced platelet aggregation.Conclusion:Platelet-derived zyxin deficiency diminishes platelet-tumor cell interactions and weakens the ability of tumor cell-induced platelet aggregation,ultimately suppressing tumor cell migration.

AIM To analyze the dynamic change patterns of aflatoxin B1,aflatoxin B2,aflatoxin G1,aflatoxin G2,T-2 toxin and deoxynivalenol contents during the fermentation of Massa Medicata Fermentata.METHODS The analysis was performed on a 40 ℃ thermostatic Waters ACQUITY UPLC HSS T3 column(100 mm×2.1 mm,1.8 μm),with the mobile phase comprising of 0.01％formic acid-[acetonitrile-methanol(1∶1)]flowing at 0.3 mL/min,and electron spray ionization source was adopted in positive ion scanning with multiple reaction monitoring mode.RESULTS Six mycotoxins showed good linear relationships within their own ranges(R2＞0.998 0),whose average recoveries were 76.1％-119.3％with the RSDs of 0.49％-9.27％,and except for deoxynivalenol,their contents demonstrated the trends of growing out of nothing and gradually increasing.CONCLUSION The risk of mycotoxin infection exists in the fermentation of Massa Medicata Fermentata.This simple,efficient,rapid and sensitive method can provide a reference for whole-process monitoring the fermentation process for Massa Medicata Fermentata.

BACKGROUND:Studies have shown that vascular factors have an important impact on the occurrence of diabetic foot.OBJECTIVE:To investigate the important role of angiopoietin-like protein 4 in the formation of diabetic foot.METHODS:(1)Bioinformatics analysis was performed on the gene expression profile data of diabetic foot patients to find the key genes.The skin samples of diabetic foot patients and healthy people were collected for hematoxylin-eosin staining,immunohistochemical staining,and qRT-PCR experiments to detect the expression of angiopoietin-like protein 4.(2)The immortalized human skin fibroblast cell line and primary human umbilical vein endothelial cells were cultured.The two kinds of cells were divided into control group and exogenous angiopoietin-like protein 4 supplemented group.The migration ability and proliferation ability of fibroblasts were detected by scratch assay and CCK-8 assay.The proliferation ability of endothelial cells was detected by Ki67 assay.RESULTS AND CONCLUSION:(1)Bioinformatics analysis results showed that the down-regulation of angiopoietin-like protein 4 gene might be the key gene leading to the formation of diabetic foot.(2)Hematoxylin-eosin staining exhibited that compared with normal skin,angiopoietin-like protein 4 was weakly expressed in diabetic foot skin,and the mRNA level was decreased(P＜0.01).(3)Scratch assay results demonstrated that compared with the control group,fibroblast migration ability was significantly enhanced in the angiopoietin-like protein 4 group.CCK-8 assay showed that the absorbance value of fibroblasts in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours(P＜0.01,P＜0.001).It is suggested that angiopoietin-like protein 4 can enhance the migration and proliferation of fibroblasts.(4)Ki67 assay results demonstrated that the number of Ki67 positive cells in the angiopoietin-like protein 4 group was significantly more than that in the control group.CCK-8 assay results showed that the absorbance value of endothelial cells in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours(P＜0.05,P＜0.001).(5)All findings suggest that angiopoietin-like protein 4 can enhance the proliferation of endothelial cells treated with high glucose.

Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.

Objective:To investigate the role of platelet-derived zyxin in promoting tumor migration by platelets.Methods:The gene expression profile of platelets was analyzed from cancer patients by using the GEO database.Isolated platelets from wild-type(WT)and Zyx-/-mice were co-cultured with B16F10 cells labeled with green fluorescence to investigate the influence of zyxin deficiency on tumor cell migration,invasion,and wound healing.Optical microscopy was employed to evaluate the impact of zyxin deficiency on epithelial-mesenchymal transition(EMT)in B16F10 cells induced by platelets.Employing specific markers to label platelets,fluorescence confocal microscopy was utilized to investigate the impact of platelet-derived zyxin on the binding between tumor cells and platelets.And an aggregometer was employed to observe the influence of zyxin deficiency on tumor cell-induced platelet aggregation.Results:Compared to platelets from healthy volunteers,zyxin was upregulated in platelets from cancer patients.Zyx-/-mouse platelets exhibited a significant reduction in tumor cell invasion and migration,impaired wound healing,and delayed tumor cell EMT compared to WT mouse platelets.Additionally,zyxin deficiency attenuated the interaction between platelets and tumor cells,and diminished the capacity for tumor cell-induced platelet aggregation.Conclusion:Platelet-derived zyxin deficiency diminishes platelet-tumor cell interactions and weakens the ability of tumor cell-induced platelet aggregation,ultimately suppressing tumor cell migration.

Objective:To investigate the efficacy of radiotherapy in postoperative metastatic human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer treated with pyrotinib, and to identify potential subgroups that may benefit from this strategy.Methods:The clinical data of 187 patients with postoperative distant metastatic HER2-overexpressing breast cancer who received pyrotinib at the First Affiliated Hospital of Bengbu Medical University from January 2018 to July 2022 were retrospectively analyzed. The Kaplan-Meier method was used to assess changes in survival outcomes in patients undergoing radiotherapy. Univariate and multivariate analyses were conducted to identify prognostic factors, and the log-rank test was used to determine potential subgroups that may benefit from radiotherapy.Results:Among the 187 patients, 76 received radiotherapy. The median follow-up duration for the entire population was 16.9 months (range: 3.1-37.9 months), and the 2-year overall survival (OS) was 75.0%. Multivariate analysis showed that age, metastatic status, and radiotherapy were independent factors affecting OS (3.86-6.76, P<0.05). Further subgroup analysis showed that radiotherapy significantly improved OS in patients aged ≥50 years, those with oligometastases or bone metastases, those not receiving endocrine therapy, and those resistant to trastuzumab ( P<0.05). Conclusions:Radiotherapy, in addition to pyrotinib, can enhance the survival rate of patients with postoperative metastatic HER2-overexpressing breast cancer. The benefits of radiotherapy may be more pronounced in patients with a low tumor burden, inadequate systemic treatment, and drug resistance.

Objective To investigate the prevalence of chronic somatic comorbidities in schizophrenic patients in Shanghai communities,and to explore the factors influencing comorbidities.Methods Based on Shanghai community-based severe mental disorders cohort,5 422 patients with schizophrenia(SCZ)were included in the study.12 common chronic somatic diseases,defined by patients'self-report,were selected to analyze the prevalence of comorbidity,and Logistic regression model was used to analyze the factors influencing the number of somatic comorbidities.Results The total prevalence of somatic comorbidity was 37.0%in 5 422 patients with SCZ,with the highest prevalence of hypertension(22.6%)and diabetes mellitus(13.1%)among 12 somatic diseases selected.Older age was the main factor associated with chronic somatic comorbidities in community schizophrenic patients.The risk of 1-2 comorbidities in patients aged≥60 years was 3.34(95%CI:2.74-4.07)times higher than those aged<45 years,while the risk of≥3 comorbidities was 3.27(95%CI:2.11-5.09)times higher,correspondingly.Female gender,marriage,smoking,and longer duration of illness were also risk factors for comorbidity.Women after menopause had higher risk of comorbidity than perimenopausal women.Conclusion Cardiovascular and metabolic diseases were common somatic comorbidities among schizophrenic patients in Shanghai communities.Older age,female gender,marriage,smoking,and longer duration of illness were risk factors for increasing number of comorbidities.

Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.