ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） on cell proliferation， apoptosis， cancer stem cell （CSC） marker expression， and metabolism in non-small cell lung cancer （NSCLC） cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs （gefitinib or osimertinib） in NSCLC cells were evaluated using the cell counting kit-8 （CCK-8） and Annexin V-FITC/propidium iodide （PI） double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional （3D） cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers， sex determining region y box protein 2 （SOX2） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）， were detected by quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Changes in intracellular reactive oxygen species （ROS） levels were detected by ROS staining， and the redox ratio was detected by femtosecond laser labeling free imaging （FLI）. ResultsUnder both two-dimensional （2D） and 3D culture conditions， compared with the blank group and EGFR-TKI group， the combination group showed significantly reduced cell viability and increased apoptosis rate （P<0.05）. Compared with the EGFR-TKI group， the mRNA and protein levels of CSC markers were significantly downregulated in the combination group （P<0.05）. Additionally， the redox ratio was significantly elevated （P<0.05）， and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells， Scutellariae Radix enhances the redox ratio and increases ROS levels， thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.

OBJECTIVE To establish the characteristic chromatogram of the volatile oil in the standard decoction of Qingshang juantong decoction， and preliminarily infer the main active components of volatile oil that affect the clinical therapeutic effect. METHODS The volatile oil in the standard decoction of Qingshang juantong decoction was extracted by steam distillation. The ultra-high performance liquid chromatography （UPLC） characteristic chromatograms of 15 batches of samples were established by the Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）， and the similarity evaluation was carried out. The volatile oil of standard decoction was identified by UPLC coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. Then the volatile oil components were analyzed by GC-MS. RESULTS The similarities of UPLC characteristic chromatograms for volatile oil of 15 batches of Qingshang juantong decoction were between 0.949 and 0.997. A total of 12 common peaks were obtained. According to the UPLC-Q-TOF/MS， the main components were methyl eugenol， E-ligustilide， E-butylidenephthalide and so on. A total of 23 components were identified by GC-MS， which were mainly 3，4，5-trimethoxy- methylbenzene， patchouli alcohol， Z-ligustilide and so on. CONCLUSIONS The characteristic chromatograms of the volatile oil in the standard decoction of Qingshang juantong decoction is established， and it is inferred that methyl eugenol， ligustilide， E- butylidenephthalide， patchouli alcohol， 3，4，5-trimethoxy-methylbenzene might be the main active components affecting the clinical therapeutic effect of the volatile oil of Qingshang juantong decoction.

Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases.MethodsBased on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (Dmd^Mu/+) mice were obtained after genotype identification. Male hemizygous Dmd^Mu/+(Dmd^Mu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting.An acute inflammation model was established in Dmd^Mu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry.Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (Dmd^Mu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of Dmd^Mu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P<0.05). Compared with wild-type mice of the same background, Dmd^Mu/Y mice at 3 and 9 months of age showed significant weight loss (P<0.01) and decreased muscle tension (P<0.05). 9-month-old Dmd^Mu/Y mice exhibited significant pathological changes in skeletal muscle and myocardium, including widening of intermuscular space. Under normal condition, compared with wild-type mice, the proportion of neutrophils and monocytes in the peripheral blood of 3-month-old Dmd^Mu/Y mice was significantly lower than that of wild-type mice (P<0.01). After lipopolysaccharide stimulation, the proportion of neutrophils in peripheral blood of 3-month-old Dmd^Mu/Y mice remained significantly lower compared to that of wild-type mice (P<0.01). The proportion of neutrophils in peripheral blood of 9-month-old Dmd^Mu/Y mice significantly decreased after lipopolysaccharide induction (P<0.01), with a trend of change observed in monocytes between groups.Conclusion The successful construction of the Dmd gene mutant mouse model has confirmed the vital function of Dmd gene in maintaining normal muscle tissue morphology and muscle tone. It preliminarily indicated that Dmd gene deletion could significantly reduce the proportion of neutrophils in peripheral blood, offering a new perspective for the study of immune system alterations in Duchenne muscular dystrophy patients.

Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

Objective:To explore the prevalence of sleep problems among residents in the city of Ruian during the outbreak of novel coronavirus pneumonia(COVID-19),and to investigate whether the presence of sleep prob-lems was related to the infection of COVID-19.Methods:Totally 4 810 community residents(1116 residents tested positive for COVID-19 and 3 694 residents tested negative for COVID-19)were chosen by stratified convenience sampling.All participants were assessed with the Sleep Self-Rating Scale(SRSS,total score ≥23 SRSS screen-pos-itive),Generalized Anxiety Scale(GAD-7,total score ≥5 GAD-7 screen-positive)and 9-item Patient Health Ques-tionnaire(PHQ-9,total score ≥5 PHQ-9 screen-positive).Results:The screen-positive rates of SRSS,GAD-7 and PHQ-9 were 30.5％,33.7％and 27.2％,respectively.Logistic regression analysis showed that the infection of CO-VID-19 was significantly associated with the SRSS screen-positive(OR=1.73,95％CI:1.48-2.03),after con-trolling for the confounding variables of gender,age group,GAD-7 screen-positive and PHQ-9 screen-positive.Conclusion:The prevalence of sleep problems was higher in the residents tested positive for COVID-19 than in those tested negative for COVID-19.The occurrence of sleep problems may be directly associated with the infection of COVID-19.

ObjectiveTo compare and observe the effect of Reduning injection （mainly clearing heat）， Shenfu injection （mainly warming Yang） combined with gefitinib on the proliferation， apoptosis， stemness characteristics and metabolism of lung cancer cells. MethodDifferent non-small cell lung cancer （NSCLC） cell lines were selected and intervened with gefitinib （5， 10， 20 μmol·L^-1）， Reduning injection （0.6%， 0.9%）， Shenfu injection （0.6%， 0.9%）， gefitinib combined with Reduning injection， and gefitinib combined with Shenfu injection. Cell proliferation in each group was detected by cell counting kit-8 （CCK-8） assay， and cell apoptosis was detected by flow cytometry. The mRNA and protein expressions of lung cancer stem cell markers sex determining region Y-box 2 （Sox2） and aldehyde dehydrogenase family 1 member A1 （ALDH1A1） were determind by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The redox ratio of lung cancer cells was observed by femtosecond label-free imaging （FLI） and energy metabolism instrument was used to determine the glycolysis level in cells. ResultCompared with the blank group， Reduning injection reduced the survival rate of lung cancer cells （P<0.05）， increased the apoptosis rate （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， and up-regulated the redox ratio of cells （P<0.05）， while Shenfu injection exerted no remarkable effect on the above indexes. In addition， compared with gefitinib alone， Reduning injection combined with gefitinib inhibited the survival rate of lung cancer cells （P<0.05）， promoted the cell apoptosis （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， up-regulated the redox ratio of cells （P<0.05）， and lowered the proton efflux rate of glycolysis （P<0.05）， while Shenfu injection combined with gefitinib failed to affect these indexes of lung cancer cells significantly. ConclusionReduning injection may inhibit stemness characteristics of tumor cells by regulating their metabolism to enhance the proliferation-inhibiting and pro-apoptotic effects of gefitinib on lung cancer cells， while Shenfu injection had no significant enhancing effect on gefitinib. This indicates that epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） should be used in combination with heat-clearing Chinese medicines.

Purpose: Anxiety, depression, and poor quality of life (QOL) were considered important concerns that hindered the rehabilitation of breast cancer survivors. A number of studies have investigated the effects of physical activity, but they have not reached the same conclusions. This review aimed to identify the effects of physical activity on QOL, anxiety, and depression in breast cancer survivors. Methods: PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, SinoMed, CNKI, Vip, and WanFang databases were searched for the time period between January 1, 2012, and April 30, 2022. Studies were included if they were randomized controlled trials of the effects of physical activity on QOL, anxiety, or depression in breast cancer survivors. The tools of the Joanna Briggs Institute were used to assess the quality of the included studies. R software version 4.3.1 was used for meta-analysis. Results: A total of 26 studies, involving 2105 participants, were included in the systematic review. Among these, 20 studies involving 1228 participants were included in the meta-analysis. Compared with the control group, the results indicated that physical activity can significantly improve QOL(Hedges' g = 0.67; 95% CI 0.41–0.92) and reduce anxiety (Hedges' g = −0.28; 95% CI −0.46 to −0.10) in breast cancer survivors. However, the effect of physical activity on depression (Hedges' g = −0.46; 95% CI −0.99 to 0.06) was not statistically significant. Conclusions Physical activity was an effective intervention to improve QOL and reduce anxiety in breast cancer survivors, as well as showed positive trends in depression, although without statistical significance. More well-designed studies are required to clarify the effects of different types of physical activities on the QOL, anxiety, and depression among breast cancer survivors.

Objective:To investigate the risk factors of infection with polymyxin resistant and carbapenemase-resistant Klebsiella pneumoniae（PR-CRKP）. Methods:A total of 170 patients with CRKP infection admitted in the Third Affiliated Hospital of Soochow University from July 2020 to October 2023 were enrolled，including 123 cases of CRKP infection and 47 cases of PR-CRKP infection. The general conditions，exposure of antibacterial drugs 6 months before admission，laboratory test indicators at admission，antibacterial drug use when target bacteria were detected，length of hospital stay and time of invasive procedures in two groups were retrospectively analyzed. The risk factors of PR-CRKP infection were analyzed with univariate and multivariate logistic regression. SPSS 26.0 software was used to analyze the data.Results:Univariate analysis showed that compared with the CRKP group，the average age of patients in PR-CRKP group was older（ Z = -2.186， P = 0.029），the proportion of patients with exposure history to semisynthetic penicillins，carbapenems，polymyxins，and quinolones 6 months before admission was higher（ χ 2= 3.930，5.414，11.939，8.478，all P < 0.05），the proportion of infections diagnosed at admission and blood urea nitrogen levels（ χ 2= 7.268， Z = -2.406， P = 0.007 and 0.016）was higher，the hemoglobin level（ t = 2.641， P = 0.009）was lower，the length of hospital stay was longer，the rates of tracheal intubation，urinary catheter，and deep vein catheterization were higher（ Z = -4.243，-4.660，-5.341，-4.583，all P < 0.001），the duration of carbapenem and polymyxin B use was longer（ Z = -4.757，-7.554，both P < 0.001），the proportion of combined quinolone-resistant Escherichia coli（QREC）and carbapenem-resistant organism（CRO）infections and bloodstream infections，and the rate of admission to intensive care units was higher（ χ 2 = 33.737，42.041，5.426，12.991， P < 0.05 or < 0.01）. Multivariate analysis showed that time to polymyxin B use（ OR = 1.179， 95%CI 1.059-1.312， P = 0.003），combined QREC infection（ OR = 5.357， 95%CI 2.100-13.669， P < 0.001）and combined CRO infection（ OR = 3.302， 95%CI 1.146-9.514， P= 0.027）were independent risk factors for PR-CRKP. Conclusion:Prolonged use of polymyxin B is an independent risk factor for PR-CRKP，and mixed QREC and CRO infection can increase the risk of PR-CRKP.

In recent years, the application of complex interventions in fields such as public health, clinical research, and education has become a trend. Due to the complexity of interventions, target populations, or implementation contexts, complex intervention research can help clarify the mechanism of interventions, determine factors such as contexts related to outcome changes, and evaluate the feasibility and scalability of intervention plans. Based on the update of the complex intervention guidelines and research examples, this article summarizes the complex interventions' characteristics and core elements of the update, combs the development of the complex interventions research framework, and explains the specific content of the research phase, with a view to providing reference for the rational development of complex intervention research in the domestic nursing field.

Objective:To study the risk factors of axillary lymph node metastasis by analyzing the acoustic image characteristics of the automated breast volume scanner (ABVS) of breast cancer masses.Methods:The imaging features of ABVS of 212 patients with breast cancer, unilaterally and singly, confirmed by pathological examination admitted in Hangzhou First People’s Hospital from Jan. 2016 to Dec. 2018 were retrospectively analyzed. There were 83 cases with axillary lymph node metastasis (metastatic group) and 129 cases without (non-metastatic group) . The correlation of clinical and the imaging features of ABVS with axillary lymph node metastasis was analyzed using univariate analysis and multivariate logistic regression. ROC curve was used to analyze the cut-off value of the maximum diameter of the mass in predicting the breast cancer axillary lymph node metastasis. The sensitivity, specificity, positive predictive value, and negative predictive value of each risk factor were analyzed for predicting breast cancer axillary lymph node metastasis.Results:The retraction phenomenon and micro-calcification of breast cancer in the metastatic group (60.2%, 65.1%) were higher than those in the non-metastatic group (43.4%,37.2%) ( P=0.017 vs P<0.001) . The maximum diameter of the breast cancer in the metastatic group was bigger than in the non-metastatic group ( Z=2.18, P=0.029) . Multivariate logistic regression analysis showed that the micro-calcification of breast cancer ( OR=2.522, P=0.003) was an independent predictor of lymph node metastasis in breast cancer. The area under the curves and the cut-off value of the maximum diameter of the mass in predicting the breast cancer axillary lymph node metastasis were 0.589 and 2.85 cm. The sensitivity was 34.9%, the specificity was 82.9%, the positive predictive value was 56.9%, and the negative predictive value was 66.5%. The sensitivities of micro-calcification and retraction phenomenon to predict the occurrence of axillary lymph node metastasis in breast cancer patients were 65.1% and 60.2%, specificities were 62.8% and 56.6%, positive predictive values were 52.9% and 47.2%, and negative predictive values were 73.6% and 68.9%. Conclusion:The study suggests that the maximum diameter, micro-calcification, and retraction phenomenon of masses are associated with the occurrence of the axillary lymph node metastasis in breast cancer.