Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

OBJECTIVES: To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms. METHODS: Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points post-modeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells. RESULTS: At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU⁺PDGFR-α⁺ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU⁺Olig2⁺ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001). CONCLUSIONS Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxia-ischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.
Animals ; Rats, Sprague-Dawley ; Magnetic Resonance Imaging/methods* ; Rats ; White Matter/injuries* ; Animals, Newborn ; Female ; Multimodal Imaging ; Male ; Hypoxia-Ischemia, Brain/pathology*

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Background and purpose:Follow-up data of 6 737 patients undergoing surgery for gastric cancer were collected based on hospital registration,and the 1-,3-and 5-years observed overall survival(OS)rates and disease-free survival(DFS)rates were analyzed to provide real-world research evidence for the prevention and control of gastric cancer and policy making in China.Methods:A total of 6 737 gastric cancer patients who underwent surgical treatment at Fudan University Shanghai Cancer center from 2015 to 2020 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was November 30,2023.Kaplan-Meier method was applied in evaluating the 1-,3-and 5-year OS rate and DFS rate,and survival data were described by different subgroups including age group,gender,treatment period,tumor staging,and pathological characteristics.Results:With a median follow-up time of 50.99 months,the 5-year OS rate of surgically resected gastric cancer patients was 70.37%,and 5-year DFS rate in Ⅰ-Ⅲ stage cases was 69.46%.The 5-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 94.32%,82.56%,51.01%and 23.97%,respectively.The differences in survival among patients with different age,tumor location,gross classification,Borrmann classification and Laurence classification were significant.Conclusion:Staging is an important factor directly affecting the survival of gastric cancer patients.Screening and early diagnosis and treatment in large population,especially high-risk group,should be strengthened to further improve the patients'survival.

A high performance liquid chromatography (HPLC) method utilizing correction factors was established for the quantitative detection of related substances in flumazenil. Separation was achieved using an Agilent Pursuit XRs C18 column (250 mm × 4.6 mm, 5 μm) with an isocratic elution of dilute phosphoric acid, methanol, and tetrahydrofuran as the mobile phases. Correction factors calculated from a standard curve method were applied to determine the impurity content. The quantification of impurities in flumazenil was conducted using both external standard and correction factor methods, followed by validation and comparison of the two. For the identification of degradation products, a forced degradation approach was employed to prepare a flumazenil degradation solution, and the resulting impurities were confirmed by LC-MS analysis. The separation of flumazenil and its impurities was found to be efficient. The limits of quantification for impurities A, B, D, and E were established at 0.169 9, 0.314 7, 0.143 9, and 0.270 8 ng, respectively, with the limits of detection at 0.055 8, 0.096 9, 0.048 8, and 0.089 0 ng. These impurities demonstrated a strong linear relationship across the concentration ranges of 0.034 9-7.847 0, 0.038 7-8.710 7, 0.034 6-7.794 1, and 0.032 4-7.292 8 µg·mL^-1, respectively (n = 7). The method achieved average recoveries between 98.25% and 99.42%, with an RSD of less than 2.0% (n = 9), indicating high accuracy. The external standard and correction factor methods were used to determine the related substances in flumazenil, and the results of the two methods were consistent. The established HPLC method is characterized by its high accuracy, sensitivity, and repeatability, and is suitable for determining related substances in flumazenil.

Objective This study aims to evaluate the effect of vitamin D supplementation in the earliest stages of pregnancy(12-16 weeks)on the development of preeclampsia(PE)in primiparous women.Methods Primiparous women who visited Maternal and Child Care Center of Qinhuangdao from January 1,2019 to January 31,2022 were recruited as study subjects.According to the random number table method,primiparous women were randomly divided into the control group(calcium carbonate D3 tablets)and the experimental group(calcium carbonate D3 tablets+vitamin D).The main observed outcome of the study was the incidence of preeclampsia.Preterm birth,neonatal birth weight,neonatal height at birth,mode of delivery,and neonatal Apgar scores were the secondary observed outcomes.A Logistic regression was used to explore the relationship between vitamin D supplementation and study outcomes.In addition,serum 25 hydroxyvitamin D was measured by ELISA before and after the intervention.Results A total of 586 primiparas were recruited,70 were lost,and 516 were included(264 in the control group and 252 in the experimental group).The incidences of PE,preterm birth,cesarean birth,and birth weight in the experimental group were significantly lower than those of the control group(P<0.05).After the end of the intervention,the serum level of 25 hydroxyvitamin D had increased significantly in both groups(P<0.05),while there was no significant change in calcium ions(P>0.05).Furthermore,serum 25 hydroxyvitamin D levels were significantly higher in the experimental group than in the control group(P<0.05).In addition,the birth length,1-minute Apgar,5-minute Apgar and 10-minute Apgar scores of the experimental group were all higher than the control group(P<0.05).Multivariate Logistic analysis showed that vitamin D supplementation was the independent protective factor for PE[OR=0.336,95%CI(0.120,0.939),P=0.037],cesarean section[OR=0.539,95%CI(0.364,0.798),P=0.002],misoprostol-induced delivery[OR=0.066,95%CI(0.009,0.504),P=0.009],preterm birth[OR=0.487,95%CI(0.238,0.995),P=0.048]and low birth weight[OR=0.391,95%CI(0.189,0.806,P=0.011].Conclusion Vitamin D supplementation reduces the incidence of PE and reduces the incidence of adverse pregnancy and fetal outcomes.

Objective To analyze the incidence and mortality of pancreatic cancer in 2022 globally and in China based on the Global Cancer Statistics 2022 published by the International Agency for Research on Cancer,considering characteristics such as gender,age,and human development index(HDI).Methods Pancreatic cancer data from 185 countries and regions were sourced from the GLOBOCAN 2022 database,and HDI data were compiled based on the Human Development Report 2022 published by the United Nations Development Programme.Cancer data were stratified by age,gender,and HDI to describe the prevalence of pancreatic cancer globally and in China.Pearson correlation analysis was used to evaluate the correlation of standardized incidence rate(SIR),standardized mortality rate(SMR),and mortality-to-incidence ratio(M/I)with HDI.Results In 2022,the number of pancreatic cancer incident cases worldwide was 510 992,ranking 12th among all cancer incidents,with an SIR of 4.7 per 100 000(ranking 15th).The number of pancreatic cancer deaths globally was 467 409,ranking 6th among all cancer deaths,with an SMR of 4.2 per 100 000(ranking 9th).In China,the number of pancreatic cancer incident cases was 118 672(ranking 10th among all cancer incidents),accounting for 23.22%of the global pancreatic cancer incidents,with an SIR of 4.4 per 100 000(ranking 13rd).The number of pancreatic cancer deaths in China was 106 295(ranking 6th among all cancer deaths),accounting for 22.74%of the global pancreatic cancer deaths,with an SMR of 3.9 per 100 000(ranking 8th).The incidence,mortality,SIR,and SMR in males were higher than those in females both globally and in China.SIR and SMR were positively correlated with HDI(r=0.77 and 0.77,both P＜0.001),while M/I was negatively correlated with HDI(r=-0.43,P＜0.001).The incidence,mortality,SIR and SMR of pancreatic cancer showed an increasing trend with age,and rapidly increased from 45-49 years old.Conclusion The disease burden of pancreatic cancer is serious globally and in China.The incidence and mortality of pancreatic cancer show an upward trend with age,and they are higher in males than in females.HDI is positively correlated with SIR and SMR of pancreatic cancer,while negatively correlated with M/I.

Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.

Migraine is a common primary headache,which is the second leading cause of disability worldwide,espe-cially resistant and refractory migraine.Treatments for migraine are diverse.This article summarizes the progress in the prevention and treatment of resistant and refractory migraine,aiming to promote clinicians'understanding of such types of migraine.

Headache is a common disease of the nervous system,with a high risk of disability,but currently the di-agnosis rate of headache remains at a relatively low level,mainly relying on the self-treatment by patients.In recent years,as headache diseases attract more attention,headache nurses are playing an increasingly important role in the management of headache patients,and headache nursing has become an important link in improving the prognosis of patients.This ar-ticle mainly introduces the importance and necessity of headache nursing in the management of headache patients.