OBJECTIVE To investigate the reversal effect of Qingfei huayu jiedu formula （QFHYJDF） on drug resistance in non-small cell lung cancer （NSCLC） cells based on the microRNA-641 （miR-641）/extracellular signal-regulated kinase （ERK） signaling pathway. METHODS The human parental NSCLC cell line A549 was used to establish gefitinib-resistant cells A549/GR by combining concentration gradient increment with high-concentration pulse strategy. After screening for optimal intervention concentration and duration， the resistant cells were divided into a control serum group （treated with 20% blank serum for 48 h）， QFHYJDF-containing serum group （treated with 20% QFHYJDF-containing serum for 48 h）， and the normally cultured group （normally cultured for 48 h）. The cell relative viability， total apoptosis rate， as well as the expression levels of miR-641， neurofibromin 1 （NF1）， ERK1/2， and phosphorylated ERK1/2 （p-ERK1/2）， were assessed in each group. RESULTS Compared with the normally cultured group and the control serum group， the QFHYJDF-containing serum group exhibited significantly decreased cell relative viability and significantly increased total apoptosis rate （ P ＜0.05）. Moreover， the expression of NF1 protein was significantly up-regulated， while the expression levels of miR-641 and p-ERK1， p-ERK2 proteins were significantly down-regulated in the QFHYJDF-containing serum group （ P ＜0.05）. CONCLUSIONS QFHYJDF can inhibit proliferation and promote apoptosis of gefitinib-resistant lung cancer cells， which may be associated with up-regulating NF1 protein expression， down-regulating miR-641 expression， and inhibiting the activity of the ERK signaling pathway.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Objective:To observe the efficacy of eculizumab in children with atypical hemolytic uremic syndrome.Methods:It was a single-center observational study. The clinical data of children diagnosed with atypical hemolytic uremic syndrome and treated with eculizumab in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2023 to May 2024 were retrospectively collected. Eculizumab was used at the conventional dose based on the children 's weight. Event-free survival (no death or end-stage renal disease) rate, complete remission rate and recurrence rate of thrombotic microangiopathy in children with atypical hemolytic uremic syndrome after eculizumab treatment were analyzed. The complete remission time of estimated glomerular filtration rate, hemoglobin, platelet, lactic dehydrogenase, urine routine and the adverse reactions during the treatment were observed. Whole exome sequencing was used to conduct genetic testing based on blood samples of the children and their parents.Results:There were 4 children enrolled in the study. Four children were all Han Chinese, including 3 males and 1 female. The median age of onset was 8 years (ranging from 7 to 10 years). Two patients had complement gene abnormalities, both of which were homozygous deletions of complement factor H-related 1 and complement factor H-related 3. All the patients were free of plasma exchange or perfusion after treatment with eculizumab, and the 6-month event-free survival rate and thrombotic microangiopathy complete remission rate were both 4/4. The complete remission time was 19 (14-28) days. The time for the complete recovery of platelets, lactate dehydrogenase, estimated glomerular filtration rate and hemoglobin in 4 children was 4 (1-5), 19 (14-28), 10 (5-14) and 29 (20-42) days, respectively. Except for 1 patient whose urine routine fluctuated between negative and weakly positive expression, the other 3 patients had normal urine routine. All the patients discontinued eculizumab. Two patients without gene mutations discontinued eculizumab after 7 doses, and there was no recurrence during the 1-year follow-up after drug withdrawal. Two patients with genetic abnormalities discontinued eculizumab after 26 weeks of treatment, and no recurrence was found during the 3-month follow-up after drug withdrawal. One patient developed rash approximately 7 days after receiving the third dose of eculizumab. The rash was relieved after anti-allergic treatment, and there was no recurrence after the continued use of eculizumab.Conclusion:Eculizumab is effective and safe in the treatment of children with atypical hemolytic uremic syndrome. Discontinuation of eculizumab can be considered in patients without gene mutations when their condition is stable, but close monitoring and follow-up are needed after drug withdrawal.

Objective:To identify the influencing factors for acute kidney injury (AKI) in patients undergoing interventional embolization of intracranial aneurysms under general anesthesia and develop a predictive model.Methods:In this retrospective study, the clinical data from patients who underwent elective interventional embolization of intracranial aneurysms at Hospital Affiliated to Nanjing Medical University from January 2019 to December 2023 were collected. All the patients were divided into AKI group and non-AKI group based on whether AKI occurred postoperatively. The general data, preoperative laboratory parameters, and intraoperative parameters of the patients were obtained through the electronic medical record system and operation-anesthesia management system. The variables screened using LASSO regression were included in the multivariate logistic regression analysis to identify the risk factors for AKI following embolization of cerebrovascular aneurysms. Based on the results, a predictive model was established and evaluated.Results:A total of 428 patients were collected, with 73 in AKI group and 355 in non-AKI group. LASSO regression for variable selection and multivariate logistic regression analysis showed that serum creatinine concentration, duration of surgery and age were independent risk factors, and the glomerular filtration rate and hemoglobin concentration were protective factors for AKI after interventional embolization of intracranial aneurysms ( P<0.05). The area under the receiver operating characteristic curve of the prediction model was 0.860 (95% confidence interval 0.815 to 0.905), with a sensitivity of 0.880 and a specificity of 0.718. The calibration curve showed a mean absolute error of 0.014. The Hosmer-Lemeshow goodness-of-fit test indicated that there was no statistically significant difference between the predicted and observed values of the model ( χ2=3.29, P=0.915). The clinical decision curve demonstrated that the net benefit rate for patients was higher when the threshold probability ranged from 0 to 0.83. Conclusions:The glomerular filtration rate, serum creatinine concentration, hemoglobin concentration, duration of surgery and age are influencing factors for AKI following interventional embolization of intracranial aneurysms, and the prediction model established based on these factors demonstrates good predictive performance.

ObjectiveTo retrospectively analyze the epidemiological trends of birth defects in perinatal infants in Fengxian District, Shanghai from 2018 to 2022, so as to provide a scientific evidence for the formulation of related prevention and control strategies. MethodsBased on the data from the National Birth Defects Surveillance System, statistical analysis was conducted on the perinatal birth defects from monitored hospitals within the region from 2018 to 2022. ResultsFrom 2018 to 2022, a total of 20 870 perinatal infants delivered in the monitored hospitals in Fengxian District, with 472 cases with birth defects, showing a significant increase in the prevalence of birth defects (PRR=1.49, 95%CI: 1.39‒1.59). The risk of birth defects increased with maternal age, especially for advanced maternal age (PRR=1.58, 95%CI: 1.12‒2.25). Infants born to mothers with gestational diabetes had a higher prevalence of birth defects compared to those without gestational diabetes (PRR=1.99, 95%CI: 1.46‒2.70). Infants with birth defects were more likely to be born prematurely (PRR=2.07, 95%CI:1.56‒2.76). The top three types of birth defects were congenital heart disease (CHD), other anomalies of the external ear, and polydactyly. ConclusionThe prevalence of birth defects in Fengxian District monitored hospitals showed an upward trend from 2018 to 2022. Advanced maternal age and gestational diabetes were identified as risk factors for birth defects. CHD is the leading type of birth defect in Fengxian District over the five-year period. To reduce the prevalence of birth defects, it is crucial to implement comprehensive prevention and treatment measures for CHD.

Objective To investigate the protective effect of Naoluoxintong(NLXT)on mouse hippocampal neuronal HT22 cells in the oxygen-glucose deprivation/reoxygenation(OGD/R)model,focusing on its impact on mitochondrial function and the role of the cal-cium/calmodulin-dependent protein kinase kinase β(CaMKKβ)in it.Methods HT22 cell were cultured to establish OGD/R model,and the cell were divided into normal group(Control),model group(OGD/R),NLXT group(OGD/R+10％NLXT),positive drug dl-3-n-butylphthalide(NBP)group(OGD/R+NBP 50μmol/L)after the screening of the optimal concentrations of different con-centrations of NLXT-containing serum(0-20％)in interfering with the HT22 cells by the CCK-8 assay.Then,using CCK-8 assay to detect the cell survival rate of each group,inverted fluorescence microscope to observe the morphology of each group,flow cytometry to detect the apoptosis rate of each group,and the kit to detect the activity or content of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)in each group.Nest,the CaMKKβ inhibitor(STO-609,5μmol/L)was introduced,HT22 cells were di-vided into Control group,OGD/R group,OGD/R+10％NLXT group,OGD/R+NBP group,OGD/R+STO-609group,OGD/R+STO-609+NLXT group.The mitochondrial membrane potential in each group was observed by using JC-1 fluorescent probe,and the end products Na+-K+-ATP,Ca+-Mg+-ATPase activity were detected by the kit.The expression changes of CaMKKβ protein in cells of each group were detected by Western blot,the changes of mitochondrial DNA copy number and CaMKKβ mRNA expression in cells of each group were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results The optimal concentration of NLXT-containing serum was 10％,which resulted in the most significant effects.Compared with the OGD/R group,NLXT intervention significantly increased cell viability(P＜0.05)and restored cellular morphological characteristics.Compared with the Control group,the OGD/R group showed significantly increased apoptosis(P＜0.05),elevated MDA levels,and decreased activities of SOD and GSH,alongside a reduction in mitochondrial membrane potential,ATP activity,and mitochondrial DNA copy number.Further-more,CaMKKβ protein and mRNA expression were downregulated(P＜0.05).Compared with the OGD/R group,the NLXT and NBP groups antagonized these effects and upregulated CaMKKβ protein and mRNA expression(P＜0.05).Additionally,the application of the CaMKKβ inhibitor STO-609 significantly attenuated the protective effects of NLXT on mitochondrial function and neurons(P＜0.05).Conclusion NLXT exerts neuroprotective effects by activating the CaMKKβ to enhance mitochondrial function after OGD/R in HT22 cells.

Objective:To evaluate the value of multi-slice spiral CT (MSCT) in the diagnosis of liver metastases with rich blood supply.Methods:The clinical data and imaging data of 19 patients with liver metastases with rich blood supply admitted to the 921st Hospital of the Joint Logistics Support Force of Chinese People′s Liberation Army from September 2018 to September 2023 were retrospectively analyzed, and the number, location, shape, size of the lesions and the images of CT plain scan and dynamic enhanced scan were analyzed.Results:Among the 19 patients, there were 18 multiple cases and 1 single case. A total of 108 lesions were found. There were 62 cases (57.4%) in the right lobe of liver and 87 cases (80.6%) in the peripheral part of liver. The form of circular or quasi-circular, there were 99, irregular shape or lobed 9. The focal diameter was 0.6-6.8 cm. CT plain scan showed that 99 lesions showed slightly low density, and the other 9 lesions showed equal density relative to the background liver. In the dynamic enhanced scan, 108 lesions in arterial stage showed high-density enhancement, 97 lesions showed circular enhancement, and 11 lesions showed nodular enhancement. Among them, 77 lesions had moderate to obvious intensification density. Of the 108 lesions in the portal vein stage, 31 lesions showed moderate to obvious enhancement density, 49 lesions showed slightly low clearance density, and 28 lesions showed continuous enhancement density. In the delayed stage, all 108 lesions showed slightly low density.Conclusions:The main features of liver metastases with rich blood supply are: low density on plain CT scan, annular or nodular enhancement in the arterial phase of enhanced CT scan, and the peak of enhanced density can be in the arterial phase or the portal vein phase. Combined with clinical data, CT can make a correct diagnosis.

Objective To investigate the protective effect of Naoluoxintong(NLXT)on mouse hippocampal neuronal HT22 cells in the oxygen-glucose deprivation/reoxygenation(OGD/R)model,focusing on its impact on mitochondrial function and the role of the cal-cium/calmodulin-dependent protein kinase kinase β(CaMKKβ)in it.Methods HT22 cell were cultured to establish OGD/R model,and the cell were divided into normal group(Control),model group(OGD/R),NLXT group(OGD/R+10％NLXT),positive drug dl-3-n-butylphthalide(NBP)group(OGD/R+NBP 50μmol/L)after the screening of the optimal concentrations of different con-centrations of NLXT-containing serum(0-20％)in interfering with the HT22 cells by the CCK-8 assay.Then,using CCK-8 assay to detect the cell survival rate of each group,inverted fluorescence microscope to observe the morphology of each group,flow cytometry to detect the apoptosis rate of each group,and the kit to detect the activity or content of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)in each group.Nest,the CaMKKβ inhibitor(STO-609,5μmol/L)was introduced,HT22 cells were di-vided into Control group,OGD/R group,OGD/R+10％NLXT group,OGD/R+NBP group,OGD/R+STO-609group,OGD/R+STO-609+NLXT group.The mitochondrial membrane potential in each group was observed by using JC-1 fluorescent probe,and the end products Na+-K+-ATP,Ca+-Mg+-ATPase activity were detected by the kit.The expression changes of CaMKKβ protein in cells of each group were detected by Western blot,the changes of mitochondrial DNA copy number and CaMKKβ mRNA expression in cells of each group were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results The optimal concentration of NLXT-containing serum was 10％,which resulted in the most significant effects.Compared with the OGD/R group,NLXT intervention significantly increased cell viability(P＜0.05)and restored cellular morphological characteristics.Compared with the Control group,the OGD/R group showed significantly increased apoptosis(P＜0.05),elevated MDA levels,and decreased activities of SOD and GSH,alongside a reduction in mitochondrial membrane potential,ATP activity,and mitochondrial DNA copy number.Further-more,CaMKKβ protein and mRNA expression were downregulated(P＜0.05).Compared with the OGD/R group,the NLXT and NBP groups antagonized these effects and upregulated CaMKKβ protein and mRNA expression(P＜0.05).Additionally,the application of the CaMKKβ inhibitor STO-609 significantly attenuated the protective effects of NLXT on mitochondrial function and neurons(P＜0.05).Conclusion NLXT exerts neuroprotective effects by activating the CaMKKβ to enhance mitochondrial function after OGD/R in HT22 cells.

Objective:To identify the influencing factors for acute kidney injury (AKI) in patients undergoing interventional embolization of intracranial aneurysms under general anesthesia and develop a predictive model.Methods:In this retrospective study, the clinical data from patients who underwent elective interventional embolization of intracranial aneurysms at Hospital Affiliated to Nanjing Medical University from January 2019 to December 2023 were collected. All the patients were divided into AKI group and non-AKI group based on whether AKI occurred postoperatively. The general data, preoperative laboratory parameters, and intraoperative parameters of the patients were obtained through the electronic medical record system and operation-anesthesia management system. The variables screened using LASSO regression were included in the multivariate logistic regression analysis to identify the risk factors for AKI following embolization of cerebrovascular aneurysms. Based on the results, a predictive model was established and evaluated.Results:A total of 428 patients were collected, with 73 in AKI group and 355 in non-AKI group. LASSO regression for variable selection and multivariate logistic regression analysis showed that serum creatinine concentration, duration of surgery and age were independent risk factors, and the glomerular filtration rate and hemoglobin concentration were protective factors for AKI after interventional embolization of intracranial aneurysms ( P<0.05). The area under the receiver operating characteristic curve of the prediction model was 0.860 (95% confidence interval 0.815 to 0.905), with a sensitivity of 0.880 and a specificity of 0.718. The calibration curve showed a mean absolute error of 0.014. The Hosmer-Lemeshow goodness-of-fit test indicated that there was no statistically significant difference between the predicted and observed values of the model ( χ2=3.29, P=0.915). The clinical decision curve demonstrated that the net benefit rate for patients was higher when the threshold probability ranged from 0 to 0.83. Conclusions:The glomerular filtration rate, serum creatinine concentration, hemoglobin concentration, duration of surgery and age are influencing factors for AKI following interventional embolization of intracranial aneurysms, and the prediction model established based on these factors demonstrates good predictive performance.

Objective To investigate the correlation between levels of low-density lipoprotein cholesterol(LDL-C)and atrial fibrillation in a hypertensive population.Methods Hypertension screening was performed in the Wuyuan County of Jiangxi Province from June to August 2022.Data were collected using face-to-face questionnaire surveys,physical measurements,and biochemical tests.Logistic regres-sion analysis was used to analyze the effect of LDL-C on atrial fibrillation.The restricted cubic spline method was used to fit the correlation curve.Results A total of 14 314 patients with hypertension were included in the analysis,with an average age of 65.7±9.2 years.There were 570 patients detected with atrial fibrillation(the rate of atrial fibrillation was 4.0％).The rates of atrial fibrillation for LDL-C＜1.80 mmol/L,1.80-＜2.60 mmol/L,2.60-＜3.40 mmol/L and≥3.40 mmol/L were 10.2％(67/654),5.7％(216/3 807),3.3％(189/5 805),and 2.4％(98/4 048),respectively.Logistic regression analysis showed that,compared with LDL-C＜1.80 mmol/L group,LDL-C 1.80-＜2.60 mmol/L group,2.60-＜3.40 mmol/L group,and ≥ 3.40 mmol/L group had a lower risk of atrial fibrillation(OR=0.53,95％CI:0.39-0.72,P＜0.001;OR=0.32,95％CI:0.23-0.45,P＜0.001;OR=0.22,95％CI:0.16-0.32,P＜0.001).Curve-fitting results showed that LDL-C levels were negatively associated with the risk of atrial fibrillation.Subgroup analysis showed that LDL-C level was negatively associated with the risk of atrial fibrillation in patients without a history of stroke(OR=0.51,95％CI:0.44-0.58,P＜0.001),while the association was not statistically significant in patients with a history of stroke(OR=0.80,95％CI:0.54-1.19,P=0.273).Conclusion In hyperten-sive patients without a history of stroke,LDL-C levels negatively correlated with the risk of atrial fibrillation.