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.

Objective To analyze the epidemic status of breast cancer globally and in China based on gender(female),age,and human development index(HDI)according to the Global cancer statistics 2022 published by the International Agency for Research on Cancer.Methods The epidemiological data of breast cancer from 185 countries and territories were sourced from the GLOBOCAN 2022 database.The HDI data were compiled based on the Human development report 2022 published by the United Nations Development Programme.The epidemiological data were stratified by age,gender,and HDI to describe the prevalence of breast 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 The data of 175 countries and territories were included.The number of breast cancer incident cases worldwide was 2 297 000 in 2022,ranking the 2nd only to lung cancer,with an SIR of 46.8 per 100 000(ranking the 1st in the world).The number of breast cancer deaths globally was 666 000,ranking the 4th among all cancer deaths,with an SMR of 12.7 per 100 000(ranking the 2nd worldwide).In China,the number of breast cancer incident cases was 357 000,ranking the 6th among all cancers,accounting for 15.5％of the global breast cancers,with an SIR of 33.0 per 100 000(ranking the 2nd among all cancers in China).The number of breast cancer deaths in China was 75 000,ranking the 7th among all cancer deaths,accounting for 11.3％of the global breast cancer deaths,with an SMR of 6.1 per 100 000(ranking the 6th among all cancer deaths in China).For females around the world,the number of breast cancer incidents and deaths,SIR,and SMR ranked the 1st among all cancers.For Chinese females,both the incident number of breast cancer and SIR ranked the 2nd,while the deaths and SMR ranked the 5th and the 4th,respectively.SIR was positively correlated with HDI(r=0.76,P＜0.01),M/I was negatively correlated with HDI(r=-0.89,P＜0.01),while SMR was not correlated with HDI(r=-0.09,P=0.23).The incidence of breast cancer worldwide and in China increased with age from 25 to 29 years old.The number of breast cancer deaths in the world increased with age from 30 years old,peaked at 50-59 years old,and declined after 70 years old.The breast cancer deaths in China showed 2 small peaks at the age of 50-54 and 65-69 years old,and gradually decreased after 70 years old.The age-dependent trend of SIR varied in different countries and territories with different HDI levels,as well as globally and in China,whereas SMR continued to increase with age.Conclusion The disease burden of breast cancer is serious globally and in China.Especially in females,both SIR and SMR rank the 1st in the world;although they rank the 2nd and the 4th,respectively,in China,the number of incidents and deaths cannot be ignored.HDI is positively correlated with SIR and negatively correlated with M/I,however,with no correlation with SMR.The SIR in countries and territories with different HDI levels changes differently with age,while SMR increases with age in all.

Objective To analyze the prescription patterns of Professor Chen Bin in treating chronic superficial gastritis(CSG)with data mining methods.Methods Prescription data from effective medical records of outpatients with CSG treated by Professor Chen Bin at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from October of 2022 to April of 2023 were collected.R language,SPSS,and IBM SPSS Modeler were used to perform frequency statistics,association rule analysis,and systematic cluster analysis on the prescription data,and then the medication and prescription patterns of Professor Chen Bin in treating CSG were explored.Results A total of 64 outpatient prescriptions formulated by Professor Chen Bin were included,involving 95 Chinese herbal medicines.The top 10 frequently-used herbs were Glycyrrhizae Radix et Rhizoma Praeparata cum Melle(Zhigancao),Bupleuri Radix(Chaihu),Pinelliae Rhizoma Praeparatum(Fabanxia),Jujubae Fructus(Dazao),Zingiberis Rhizoma(Ganjiang),Codonopsis Radix(Dangshen),Scutellariae Radix(Huangqin),Paederiae Herba(Jishiteng),Citri Reticulatae Pericarpium(Chenpi),and Taraxaci Herba(Pugongying).Most of the herbs were warm,cold,and mild in nature,and were sweet in flavor.And the herbs mainly had the meridian tropism of spleen,stomach,and liver meridians,and had the primary therapeutic effects of strengthening the spleen and replenishing qi,regulating qi,and resolving dampness.Based on the results of association rule analysis,a total of 21 core herb combinations were screened out,and cluster analysis yielded 4 clustered prescriptions.Combining the results of high-frequency herb statistics and cluster analysis and based on the traditional Chinese medicine theory,the core herbs for treating CSG was identified as Zhigancao,Chaihu,Fabanxia,Dazao,Ganjiang,Dangshen,Huangqin,Jishiteng,Chenpi,and Pugongying.Conclusion In treating CSG,Professor Chen Bin adheres to the treatment principle of replenishing qi and regulating the pivot,and the therapeutic methods of regulating qi movement,strengthening the spleen and harmonizing the stomach are applied with Xiaochaihu Decoction as the fundamental prescriptions.His view of treatment by focusing on the spleen and stomach,emphasizing the combination of herbs with cold and warm properties and based on syndrome differentiation will provide a reference for the clinical application of traditional Chinese medicine in treating CSG.

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 To observe the effect of Ginkgo biloba extract(GBE)on depression like behavior in post stroke depression(PSD)model rats,and explore the mechanism of regulating Toll like receptor 4/nuclear factor-κ B(TLR4/NF-κB)pathway to inhibit neuroinflammation.Methods Rats were randomly divided into 6 groups,sham,cerebral ischemia,PSD,paroxetine,low-dose Ginkgo biloba extract(GBE-L)and high-dose Ginkgo biloba extract(GBE-H)groups,10 rats in each group.Except for the sham group,middle cerebral artery occlusion(MCAO)was performed to prepare a left focal cerebral ischemia model.Except for the sham group and cerebral ischemia group,other groups were subjected to chronic unpredictable mild stress(CUMS)to establish PSD rat model for 8 weeks.After 4 weeks of CUMS,the paroxetine group,GBE-L,and GBE-H were treated with paroxetine 5 mg·kg-1,GBE 50 mg·kg-1,and GBE 100 mg·kg-1,respectively.The sham group,cerebral ischemia group,and PSD group were treated with the same volume of 0.9％NaCl and continuously administered by gavage for 28 d.After 4 weeks and 8 weeks of CUMS,the body weight and sugar preference test were measured.Levels of serum tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)and levels of norepinephrine(NE),serotonin(5-HT),and dopamine(DA)in the cerebral cortex were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of Tlr4,Nfkb1,and nuclear factor κ B-kinase subunit β inhibitory factor(Ikbkb)in the hippocampus of rats were detected by polymerase chain reaction.The protein levels of NF-κB,nuclear factor κB inhibitory protein α(IKBα)and phosphorylation nuclear factor κB inhibitory protein α(p-IKB)in hippocampal tissue were detected by Western blot.Results The body weights of rats in the sham group,cerebral ischemia group,PSD group,paroxetine group,GBE-L group and GBE-H group were(427.10±6.36),(403.10±7.37),(310.10±9.71),(355.00±4.03),(347.90±9.88)and(391.90±5.07)g;sugar preference rate were(93.93±1.78)％,(91.57±1.03)％,(54.72±7.34)％,(88.35±4.36)％,(63.55±12.73)％and(81.04±4.31)％;the levels of NE in the cerebral cortex were(1 951.14±52.86),(1 827.27±23.63),(1 662.12±35.92),(2 033.58±72.28),(1 887.31±33.07)and(2 175.00±42.54)pg·mL-1;the levels of 5-HT in the cerebral cortex were(237.07±8.86),(226.15±10.27),(214.51±3.46),(297.13±5.79),(274.14±7.63)and(285.34±8.72)ng·mL-1;the levels of DA in the cerebral cortex were(1 531.11±47.26),(1 209.89±58.09),(1 143.15±36.31),(1 812.67±51.28),(1 651.56±31.82)and(1 853.33±20.42)pg·mL-1.Compared with the PSD group,GBE significantly increased the body weight of rats(P＜0.01)and increased the preference rate of sugar water in rats,showing the antidepressant like behavioral.GBE significantly reduced the levels of serum TNF-α,IL-1 β(all P＜0.01),increased the levels of NE,5-HT,and DA in the cerebral cortex(all P＜0.01),down regulate the mRNA levels of Tlr4,Nfkb1 and Ikbkb(P＜0.05,P＜0.01),reduced the expression of NF-κB(P＜0.01),and reduced the phosphorylation of IKBα(P＜0.01).Conclusion Ginkgo biloba extract can improve depression-like behavior in PSD model rats,and has antidepressant effect.Its mechanism is related to the inhibition of TLR4/NF-κB pathway,thus reducing neuroinflammation.

In recent years,natural antimicrobial peptides have become an important direction in the development of novel antibiotics.Cecropin has the characteristics of wide antibacterial spectrum,good tolerance and low adverse drug reactions.As the first antimicrobial peptide discovered in the family of Cecropin,Cecropin A has many important biological activities.In this paper,the research on the antibacterial,antifungal,antiparasitic and antitumor activities of Cecropin A and its derivatives in recent years was reviewed,and its application prospect was prospected,in order to provide reference for further research and development of cecropin.

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.

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.