ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

Objective To explore the effect of targeted silencing wild-type p53-induced phosphatase 1(Wip1)on paclitaxel(PTX)chemosensitivity of ovarian cancer cell line A2780.Methods The ovarian cancer cell lines A2780 served as the research object,the stable cell line Wip1-sgRNA with low expression of Wip1 was constructed by infecting cell line A2780 with lentivirus(Wip1-sgRNA group),while the control cell line was NC-sgRNA(NC-sgRNA group).The cells were treated with PTX at appropriate time and divided into the Wip1-sgRNA+PTX group and NC-sgRNA+PTX group.The CCK8 method was used to detect the cell proliferation ability,the flow cytometry was used to detect the cell apoptosis,and the Transwell invasion assay was used to detect the cell invasion ability.Results Compared with the NC-sgRNA group,the expression lev-els of Wip1 mRNA and protein in the Wip1-sgRNA group were significantly down-regulated(P＜0.001).Un-der the condition of PTX gradient treatment for the same time,the cell survival rate of the Wip1-sgRNA group was significantly lower than that of the NC-sgRNA group(P＜0.001).The half maximal inhibitory concentration(IC50)of PTX in cells of the Wip1-sgRNA group at 48 h was significantly lower than that of the NC-sgRNA group(P＜0.001).Compared with the NC-sgRNA group,the proliferation ability of the Wip1-sgRNA group was significantly weakened(P＜0.001),the rate of cellular apoptosis was significantly in-creased(P＜0.001),and the number of transmenbrane cells was significantly decreased(P＜0.001).After PTX treatment,the proliferation ability was weakened compared with corresponding control groups,the rate of cellular apoptosis was significantly increased,and the number of transmenbrane cells was significantly de-creased;additionally,compared with the NC-sgRNA+PTX group,the cellular proliferation ability of the Wip1-sgRNA+PTX group was significantly weakened(P＜0.001),the rate of cellular apoptosis was signifi-cantly increased(P＜0.001),and the number of transmenbrane cells was significantly decreased(P＜0.001).Conclusion Wip1 gene silencing could increase the chemosensitivity of human ovarian cancer cell lines A2780 to PTX.

Objective To analyze the evaluation indicators of pre-hospital first aid for adult patients with acute severe trauma to provide the evidence-based basis for the initiation of "zero channel" in first aid work.Methods The literatures such as expert consensus,clinical research,guideline and systematic review were retrieved from PubMed,Medline,Embase,Cochrane Central Register of Controlled Trials,and China Knowledge Network by computer.The retrieval time was from January 2013 to November 2023.After screen-ing the literatures according to the standard,the quality evaluation and evidence grading were conducted by a-dopting different tools.Results A total of 8 literatures were included,including 4 clinical studies,2 expert consensus and 2 systematic reviews.Finally,10 evidence-based evidences for the initiation of "zero channel" in adult patients with acute severe trauma were summarized.Conclusion This study summarizes the relevant in-dicators of "zero channel" initiation in the adult patients with acute severe trauma,which is helpful for clinical medical staff to start the first aid "zero channel" in time and increase the success rate of rescue.

AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Objective:To explore the latent classes of recurrence risk perception in ischemic stroke patients and their relationship with health behaviors.Methods:Convenience sampling was used to select 312 patients with ischemic stroke from two ClassⅢ Grade A hospitals of Guangzhou from December 2022 to June 2023 as the research subject. Before discharge, the General Information Questionnaire, Recurrence Risk Perception Scale for Patients with Stroke, and Health Behavior Scale for Stroke Patients were used for investigation. One month later, the Health Behavior Scale for Stroke Patients was used for follow-up. Latent class analysis and multiple Logistic regression analysis were used to explore the latent classes of recurrence risk perception and their influencing factors, while multiple linear regression was used to analyze the relationship between latent classes of recurrence risk perception and health behavior at 1-month follow-up.Results:A total of 312 questionnaires were distributed, and 302 valid questionnaires were collected, with an effective response rate of 96.79%. One month later, 261 study subjects completed follow-up. The recurrence risk perception in ischemic stroke patients were divided into four classes of overall low perceived accuracy, light consequence-heavy disease-moderate perceived accuracy, heavy self-care-light diet-upper moderate perceived accuracy, and overall high perceived accuracy. Age, educational level, place of residence and monthly average income were influencing factors for different latent classes ( P<0.05). Compared with patients with overall low perceived accuracy, patients with heavy self-care-light diet-upper moderate perceived accuracy, as well as those with overall high perceived accuracy, showed better health behavior after discharge, with a statistically significant difference ( P<0.05) . Conclusions:Medical and nursing staff should provide targeted nursing interventions based on the common characteristics and individual differences of different classes of patients, helping patients correctly perceive the recurrence risk, improve health behavior, and prevent stroke recurrence.

Objective:To explore the chain mediating effect of anxiety and flow experience on perceived stress and mobile phone addiction in nursing college students.Methods:In December 2021, a cross-sectional design survey was conducted on 4 179 freshmen and sophomores in a nursing college in Heilongjiang Province. The Chinese perceived stress scale, generalized anxiety disorder-7, flow state scale, and mobile phone addiction tendency scale were selected separately to assess perceived stress, anxiety symptoms, flow experience and mobile phone addiction. SPSS 26.0 software was used for descriptive analysis, independent sample t-test, Spearman correlation analysis, and AMOS 24.0 software was used for mediating effect test. Results:(1) Among the 3 050 nursing students, there were 714(23.41%) students who were addicted to mobile phones. (2) Spearman correlation analysis indicated that perceived stress(27.31±9.56) was positively correlated with anxiety(7.00(1.00, 10.00), r=0.441, P<0.05), flow experience((12.00±3.40), r=0.517, P<0.05), and mobile phone addiction((42.42±13.05), r=0.476, P<0.05).Anxiety was positively correlated with flow experience ( r=0.430, P<0.01) and mobile phone addiction ( r=0.538, P<0.01).Flow experience was positively correlated with mobile phone addiction ( r=0.490, P<0.01). (3) Anxiety and flow experience played seperate mediating and chain mediating roles between perceived stress and mobile phone addiction, accounting for 26.06%(0.165/0.633), 23.54%(0.149/0.633) and 3.48%(0.022/0.633) of the total effect. Conclusion:Perceived stress not only directly affects the mobile phone addiction of nursing students, but also indirectly affects mobile phone addiction through the independent and chain mediating effects of anxiety and flow experience.

AIM:To investigate whether the expression of perilipin 2(PLIN2)in renal tubular cells could predict a decline in renal function in diabetic kidney disease(DKD)patients,and to explore the potential mechanisms in-volved in renal tubular cell injury induced by PLIN2 during the progression of DKD.METHODS:Control individuals(n=12)and DKD patients(n=51)were enrolled in this retrospective cohort study.Demographic and laboratory data were col-lected.A simplified linear mixed-effects model was applied to assess the estimated glomerular filtration rate(eGFR)slope.The relationship between PLIN2 and renal function decline in DKD patients was predicted by Spearman correlation analysis and a generalized linear model.BKS-db/db diabetic mice and streptozotocin-induced diabetic mice were used.Primary renal tubular cells were treated with glucose and transfected with small interfering RNA or plasmid.Western blot-ting and immunofluorescence staining were used to detect PLIN2 expression.Lipid droplets were stained with oil red O.The oxygen consumption rate(OCR)of mitochondria was measured using an extracellular flux analyser.RESULTS:The expression of PLIN2 was markedly higher in the tubules of DKD patients than in those of control subjects.After 24(12,39)months of follow-up,the eGFR slope of DKD patients was-7.42(-19.77,-2.09)mL/(min·1.73 m2·year).An in-crease in the baseline percentage of PLIN2-positive tubules was significantly associated with the eGFR slope during the fol-low-up period[hazard ratio(HR)=1.90,95%confidence interval(CI):1.00～3.58],indicating that tubular PLIN2 could predict a decrease in renal function in DKD patients.Both the accumulation of lipid droplets and the expression of PLIN2 were markedly greater in the tubules of diabetic mice than in those of control mice.Glucose treatment induced lipid droplet accumulation and PLIN2 expression in renal tubular cells.Knockdown of PLIN2 significantly alleviated glucose-in-duced lipid droplet accumulation,whereas PLIN2 overexpression aggravated glucose-induced lipid droplet accumulation.The decrease in mitochondrial OCR in renal tubular cells induced by glucose treatment was alleviated after PLIN2 knock-down.However,overexpression of PLIN2 directly decreased the mitochondrial OCR.CONCLUSION:The PLIN2 ex-pression in tubules predicts a decline in renal function in patients with DKD.The PLIN2 suppresses mitochondrial aerobic respiration and contributes to the accumulation of lipid droplets in renal tubular cells to promote the progression of DKD.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.