Objective:To analyze the change characteristics of creatinine level in the early stage of patients with diquat (DQ) poisoning, and to explore the early risk factors and the value of prognosis.Methods:A retrospective analysis was carried out on patients with DQ admitted to the the first affiliated hospital of Zhengzhou University from January 2020 to June 2022. The DQ patients were divided into death group and the survival group according to the 28 days survival status after posioning. The basic data and serum indexes and blood gas analysis of the patients on day 1 (D1), day 3 (D3) and day 5 (D5) were collected. The difference of clinical features between the two groups was analyzed, the variables were screened by multiple logistic regression analysis, and the predictive value of the variables was evaluated by drawing receiver operating characteristic curve (ROC curve).Results:A total of 88 patients were included, including 40 patients in the survival group and 48 patients in the death group. The toxic dose in death group was significantly higher than that in survival group [100(40.00, 120.00) mL vs. 50.00(20.00, 90.00) mL, P=0.003]. The higher the toxic dose, the higher the fatality rate. All 4 patients with oral doses greater than 200 mL died. Compared with the survival group, the levels of alanine aminotransferase (ALT) (D3, D5), creatinine (CR) (D3, D5), blood amylase (AMY) (D5) and oxygen partial pressure (PaO 2) (D5) in the death group were significantly higher than those in the survival group (all P<0.05). Multiple Logistic regression analysis showed that CR (D3) and AMY(D5) were independent risk factors for death after poisoning, and PaO 2(D5) was independent protective factor. ROC curve showed that the areas under ROC curve of CR (D3), AMY (D5) and PaO 2 (D5) were 0.814, 0.741 and 0.702, respectively. Conclusion:The higher the oral dose, the higher the death rate. After admission, CR(D3), AMY (D5) and PaO 2 (D5) were independent factors influencing the prognosis of DQ poisoning. In particular, CR (D3) is more effective in predicting death after poisoning.

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

Objective To analyze the mechanism of action of seaweed-kunbu in the treatment of breast cancer through network pharmacology. Methods The active ingredients and their targets of seaweed-kunbu were retrieved through the TCMSP database. Relevant targets for breast cancer were obtained through the GeneCards and OMIM databases, and "drug-disease target" network diagram was constructed using Cytoscape software. Protein-protein interaction (PPI) network analysis was performed using the String platform. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R language. Molecular docking technology was used to verify the binding ability of key compounds to targets, and functional verification was carried out through in vitro experiments. Results A total of 11 effective compounds were obtained from seaweed-kunbu in this study, among which 10 were related to breast cancer. There were 150 highly relevant intersecting targets between seaweed-kunbu and breast cancer, and 10 core genes including Serine/threonine kinase 1 (AKT1), p53 tumor protein (TP53), tumor necrosis factor (TNF), interleukin6 (IL6), vascular endothelial growth factor A (VEGFA), JUN, caspase 3 (CASP3), interleukin1B (IL1B), MYC and human epidermal growth factor receptor (EGFR) were screened out. GO analysis indicated that these compounds may be involved in biological processes such as signal transduction, apoptosis, cell proliferation, and inflammatory response. KEGG pathway analysis showed that the main enriched signaling pathways were PI3K/Akt, MAPK and TNF. Molecular docking and in vitro experimental results demonstrated that fucosterol, the main chemical component of seaweed-kunbu, had an antiproliferative effect on triple-negative breast cancer BT-549 cells. Conclusion Seaweed-kunbu may treat breast cancer through multiple targets and pathways, and its main chemical component fucosterol can effectively inhibit the proliferation activity of BT-549 cells.

Objective:To study the incidence and risk factors of early hyperglycemia in extremely preterm infants (EPIs).Methods:From January 2018 to December 2021, EPIs with gestational age (GA) <28 w born in our hospital and admitted to the neonatal department were retrospectively studied. According to the occurrence of early hyperglycemia (within 1 w after birth), the infants were assigned into hyperglycemia group and non-hyperglycemia group. Univariate and logistic regression were used to analyze the risk factors of early hyperglycemia in EPIs.Results:A total of 218 cases of EPIs were enrolled, including 70 (32.1%) in the hyperglycemia group and 148 (67.9%) in the non-hyperglycemia group. The incidence of early hyperglycemia in EPIs with GA<25 w was 10/20 and 11/16 in EPIs with birth weight (BW) ≤700 g. The GA and BW of the hyperglycemia group were significantly lower than the non-hyperglycemia group ( P<0.05). More infants in the hyperglycemia group had 1-min and 5-min Apgar≤7 than the non-hyperglycemia group ( P<0.05). Logistic regression analysis showed that increased BW ( OR=0.995, 95% CI 0.993~0.997, P<0.05) was a protective factor for early hyperglycemia in EPIs, while male gender ( OR=2.512,95% CI 1.232~5.123, P<0.05), vasoactive drug use during the first week of life ( OR=2.687, 95% CI 1.126~6.414, P<0.05), maternal hypertension during pregnancy ( OR=14.735, 95% CI 1.578~137.585, P<0.05) were risk factors for early hyperglycaemia in EPIs. Conclusions:Early hyperglycemia are common among EPIs. Low BW, male gender, vasoactive drug use during the first week of life and maternal hypertension during pregnancy may increase the risk of early hyperglycemia.

Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macro-phages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative acti-vation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.

Objective:To study the predictive value of total serum bilirubin (TSB) and the ratio of bilirubin to albumin (B/A) in neonatal acute bilirubin encephalopathy (ABE).Methods:Neonates with extremely severe hyperbilirubinemia (TSB≥425 μmol/L) treated in the Nanjing Maternal and Child Health Hospital, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Northwest Women and Children's Hospital, Yinchuan Maternal and Child Health Hospital and Liaocheng People's Hospital from March 2018 to August 2019 were selected as prospective subjects for this study. According to the score of brain injury induced by bilirubin, the subjects were divided into ABE group and non-ABE group, and the predictive value of TSB peak and B/A for neonatal ABE were analyzed.Results:A total of 194 infants with extremely severe hyperbilirubinemia were recruited in this study, including 20 in ABE group and 174 in non-ABE group. The peak value of bilirubin ranged from 427 to 979 μmol/L. The optimal critical values of TSB peak value and B/A for ABE prediction were 530 μmol/L and 9.48, respectively. The sensitivity and specificity of ABE prediction were 85.0% and 92.8% when combined with TSB peak and B/A values.Conclusions:TSB peak combined with B/A value can effectively identify neonatal ABE. When the TSB peak value was greater than 530 μmol/L and the B/A value was greater than 9.48, the neonates had a higher risk of neonatal ABE.

Objective:To explore the efficacy and safety of sivelestat, a neutrophil elastase (NE) inhibitor, in the treatment of acute lung injury (ALI) in the intensive care unit (ICU).Methods:A retrospective analysis was performed on 171 patients with ALI in the ICU of the First Affiliated Hospital of Zhengzhou University from June 2020 to June 2021, including 77 patients in the sivelestat group and 94 patients in the conventional treatment group. Acute physiology and chronic health evaluation (APACHE) Ⅱ score, Murray lung injury score, oxygenation index (PaO 2/FiO 2 ratio), inflammatory cytokines (IL-6, IL-10, TNF-α), ventilator-free days (VFD), the length of ICU stay, and the 28-day mortality were collected to assess the efficacy of sivelestat. At the same time, adverse reactions and laboratory test results within 30 days after the use of sivelestat were recorded to assess the safety. Results:Compared with conventional treatment, oxygenation index, Murray lung injury scores, IL-6, IL-10, and TNF-α were significantly improved after 7 days of sivelestat treatment. Compared with the conventional treatment group, the VFD was significantly longer ( P = 0.0119) and the length of ICU stay was significantly shorter ( P = 0.0269) in the sivelestat group. The mortality was 14.29% in the sivelestat group and 22.34% in the conventional treatment group and, with no statistically significant. In the meantime, sivelestat did not increase adverse reactions within 30 days after treatment. Conclusions:Sivelestat treatment is safe and more effective than conventional treatment for ALI patients in the ICU.

Objective:To explore the relationships between the gut microbiota in patients with cervical and endometrial cancers and the severity of radiation enteritis they suffered during radiotherapy.Methods:Feces samples were collected from 37 patients with cervical or endometrial cancer who received radical radiotherapy (RR) and postoperative radiotherapy (PR). Symptoms were recorded according to the grades of diarrhea and proctitis stated in CTCAE 5.0. The grade of symptoms was considered a high grade (HG) in the case of ≥ 2 and a low grade (LG). The 16S rRNA sequencing technology was used for DNA analysis of the samples.Results:The α diversity of gut microbiota was significantly higher in patients with LG symptoms (LG group) than that in patients with HG symptoms (HG group, P<0.05) and the β diversity also differed between the two groups (stress<0.2) before radiotherapy. Meanwhile, the Ruminococcus gnavus was significantly higher in the HG group than that in the LG group before radiotherapy ( P<0.05), and thus it may serve as a biomarker for the prediction of the severity of radiation enteritis in the patients before radiotherapy. The gut microbiota in the LG and HG groups showed different changes after three weeks of radiotherapy. In addition, RR patients showed higher gut microbiota diversity and less severe radiation enteritis than PR patients. Meanwhile, Faecalibacterium prausnitzii was significantly higher in RR patients than that in PR patients before radiotherapy ( P<0.05), which may correlate negatively with radiation toxicity. Conclusions:The characteristics of gut microbiota in patients with cervical and endometrial cancers were closely related to the severity of radiation enteritis they suffered during radiotherapy. Furthermore, prior treatment such as surgery might reduce radiation tolerance of the patients.

Objective:To compare the survival and prognostic factors of intraoperative radiotherapy (IORT) and postoperative radiotherapy (PORT) in female patients, aged≥50 years, diagnosed with node-negative breast cancer (≤ 3 cm in size).Methods:Clinical data of eligible early breast cancer patients between 2010 and 2015 were obtained from the SEER database. Patients were divided into the IORT and PORT groups according to the radiotherapy record and propensity score matching (PSM) was subsequently conducted. Kaplan-Meier curve was used to evaluate the overall survival (OS) and breast cancer-specific survival (BCSS) between two groups and Cox proportional hazard regression analysis was used to explore the risk factors of clinical prognosis.Results:7 068 patients were included after PSM. The median follow-up time was 32.0 months. The 5-year OS rates in the IORT and PORT groups were 96.8% and 93.8%, respectively. Univariate Cox analysis showed that radiotherapy, age, histological grade, T stage, estrogen receptor (ER) status and progesterone receptor (PR) status were the independent risk factors for OS, and histological grade, T stage, ER status, PR status and chemotherapy were the independent risk factors for BCSS. Multivariate Cox regression analysis demonstrated that patients who received IORT had better OS than PORT counterparts ( P=0.020). Besides, patients aged≥60 years obtained worse OS than those aged<60 years ( P=0.003). Patients with T 2 stage or ER-negative tumors had worse OS than those with T 1 stage tumors ( P<0.001) or ER-positive tumors ( P=0.001). Patients with grade Ⅲ-Ⅳ tumors achieved worse BCSS ( P=0.004). Subgroup analysis showed that IORT yielded better OS for elderly patients (≥60 years), grade Ⅲ-Ⅳ tumors, infiltrating duct carcinoma, T 2 stage tumors, ER-positive tumors, PR-positive tumors and patients without chemotherapy. Conclusions:IORT may bring benefit for highly selected patients with low risk of recurrence, which is not inferior to PORT in terms of short-term survival. Prospective studies with longer follow-up time are needed to confirm the findings.

Objective To compare the clinical efficacy of high-flow nasal cannula oxygen therapy (HFNC) with non-invasive positive pressure ventilation (NPPV) in patients with traumatic cervical spinal cord injury complicated with acute respiratory failure (ARF).Methods A prospective randomized controlled trial was performed in EICU of the First Affiliated Hospital of Zhengzhou University from May 2016 to January 2018.One hundred sixty-eight consecutive patients with traumatic cervical spinal cord injury complicated with ARF,who did not respond to conventional oxygen therapy,were assigned to the HFNC or NPPV treatment group sequenced by the random number table.The baseline clinical characteristics of randomized participants and respiratory frequency (RR),PaCO2,mean arterial pressure (MAP) at 1,12,24,48 h after treatment were evaluated.Comfortable scale,tracheal intubation rate within 28 d,duration of mechanical ventilation,length of stay in ICU and mortality rate were compared as well.Results There was no significant differences in baseline clinical characteristics,such as sex,age.between the two groups (P＞0.05).RR and PaCO2 were lower in the HFNC group at all time point.In addition,the HFNC group had significantly lower PaCO2 than the NPPV group at 24 and 48 h after treatment (P＜0.01);Oxygenation index (PaO2/FiO2) was improved in both groups,and the HFNC group had superior oxygenation index than the NPPV group at 12,24,48 h after treatment (P＜0.01).Furthermore,the HFNC group had better comfort scale (6.93±0.71 vs 4.29±0.93,P＜0.01),shorter length of stay in ICU and duration of mechanical ventilation compared to the NPPV group (P＜0.01).There was no significant differences in tracheal intubation rate and mortality rate between the two groups (P＞0.05).Conclusions In addition to the superior efficacy in improving respiratory function and shortening length of stay in ICU,HFNC was well tolerated by patients with traumatic cervical spinal cord injury complicated with ARF,and could be recommended in clinical practice.