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.

Aim To investigate the effects of edaravone(EDA)on depression-like behaviors in a rat model of post-stroke depression(PSD)and to explore the un-derlying mechanisms.Methods SD rats were ran-domly divided into:sham operation group(Sham),cerebral ischemia group(CI),post-stroke depression(PSD),fluoxetine(10 mg·kg-1)group,and EDA(5,15 mg·kg-1)group.A PSD rat model was estab-lished using the suture method combined with 56 d of chronic unpredictable mild stimulation.Drug treatment was given once daily for 28 d after stimulation.Body weight and sucrose water preference were measured during the stimulation period,and serum TNF-α,IL-1 β,IL-6,MDA,SOD levels,and hippocampal tissue HO-1 and GPX4 protein expression were detected at the end of stimulation.Results Compared with the sham group,the rat neurological function scores of the remaining groups increased(P＜0.01).Compared with the PSD group,EDA increased the body weight and sucrose water preference of the rats(P＜0.01),significantly decreased the serum TNF-α,IL-1β and IL-6 levels,decreased the MDA level,increased the SOD level(P＜0.01),and up-regulated hippocampal HO-1 and GPX4 protein expression(P＜0.01).Con-clusions EDA improves depression-like behaviors and inhibits peripheral inflammation and oxidative stress in-jury in PSD rats,and its mechanism may be related to the activation of HO-1/GPX4 pathway to inhibit oxida-tive stress.

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*

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.

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.

Aim To investigate the effects of m6A demethylase ALKBH5 on cardiomyocytes pyroptosis in mice with myocardial infarction(MI).Methods The MI model of left anterior descending coronary artery ligation surgery was established by knocking down ALKBH5 using adeno-associated virus,and the hypox-ia model of mouse cardiomyocytes(HL-1)was estab-lished by knocking down small interfering RNA.The effects of ALKBH5 on the pyroptosis of MI mice and hypoxic HL-1 cells were observed.Subsequently,mechanism studies were conducted at the cellular lev-el,and the binding of ALKBH5 and IGF2BP2 to NL-RP3 mRNA was detected through RNA pull down and RNA immunoprecipitation(RIP)experiments.The MeRIP-qPCR method was used to determine the effects of ALKBH5 on the mRNA m6A level of NLRP3.Acti-nomycin D for RNA stability experiments were conduc-ted to detect the effects of ALKBH5 and IGF2BP2 on the stability of NLRP3 mRNA.Results Knocking down ALKBH5 in vivo and in vitro both inhibited NL-RP3 inflammasome activation and alleviated pyroptosis in MI mice and hypoxic HL-1 cells.Mechanistically,the results showed that NLRP3 mRNA could bind to ALKBH5 protein in HL-1 cells;knocking down ALK-BH5 could increase the m6A level of NLRP3 and re-duce the stability of NLRP3 mRNA;subsequently,it was confirmed that NLRP3 mRNA and IGF2BP2 pro-tein bound to each other;knocking down IGF2BP2 in-creased the mRNA stability of NLRP3.The Rescue ex-periment showed that knocking down IGF2BP2 re-versed the decrease in NLRP3 mRNA expression caused by knocking down ALKBH5.Conclusions ALKBH5 mediated m6A modification of NLRP3 pro-motes cardiomyocytes pyroptosis in mice with myocardi-al infarction.

Background and Aims:The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma(PTC)and is widely used to guide surgical extent and risk stratification.However,other genetic variants are increasingly identified in clinical practice,and their association with lymph node metastasis(LNM)remains unclear.Most existing studies have compared BRAFV600E-mutated cases with BRAF wild-type cases without stratifying specific mutation types,potentially affecting the accuracy of risk assessment.This study aimed to compare the lymph node metastatic features between PTC patients with different common genetic alterations and those with the BRAFV600E mutation.Methods:A retrospective analysis was conducted on 4 795 PTC patients who underwent surgery and genetic testing at Fudan University Shanghai Cancer Center from January 2019 to January 2025.Patients with a single genetic alteration were included and grouped accordingly.Propensity score matching(PSM)was used to control for confounding factors including age,sex,and T stage.The number of metastatic lymph nodes and N stage were compared between each mutation group and the BRAFV600E group.Results:After PSM,patients in the CCDC6-RET and NCOA4-RET fusion groups had significantly higher numbers of metastatic lymph nodes and N1b stage rates compared to the BRAFV600E group(all P<0.05).No significant differences were observed between the ETV6-NTRK3 fusion or RAS mutation groups and the BRAFV600E group in terms of lymph node metastasis or N stage(all P>0.05).Conclusion:PTC patients harboring CCDC6-RET or NCOA4-RET fusions exhibit a significantly higher lymph node metastatic burden than those with the BRAFV600E mutation,suggesting more aggressive behavior.In contrast,ETV6-NTRK3 and RAS-mutated PTCs show similar metastatic profiles to BRAFV600E-mutated cases.Preoperative genetic profiling may help identify patients at high risk of metastasis and guide individualized lymph node dissection strategies.

Background and purpose:Thyroid cancer is the most common malignant endocrine tumor,particularly prevalent among the Asian population.The overall survival for thyroid cancer patients is relatively high,but there are significant survival differences among patients.Based on long-term hospital-based cancer registry database,this study analyzed the 10-year observed overall survival(OS)rate of thyroid cancer cases and the distribution of causes of death,providing real-world evidences to further survival management of thyroid cancer in China.Methods:A total of 55343 thyroid cancer patients who underwent treatment at Fudan University Shanghai Cancer center from 2005 to 2021 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 October 31,2024.Kaplan-Meier method was applied in evaluating the OS rate,and survival data were described by different subgroups as age group,gender,treatment period,tumor staging and pathological characteristics.The standardized mortality ratio(SMR)and absolute excess risk(AER)were calculated using general Shanghai population as the reference,and the mortality risk was described by gender,age at diagnosis and histological subtype.Results:With a median follow-up time of 63.01 months,the overall 1-,3-,5-and 10-year OS rates of thyroid cancer patients were 99.67%(95%CI:99.62%-99.72%),99.11%(95%CI:99.03%-99.19%),98.48%(95%CI:98.36%-98.60%)and 95.81%(95%CI:95.50%-96.11%),respectively.The 10-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 97.99%(95%CI:97.70%-98.28%),89.80%(95%CI:87.24%-92.37%),77.84%(95%CI:70.76%-84.92%)and 62.95%(95%CI:55.37%-70.54%),respectively.The differences in OS among patients with different age,gender and histological classification were significant.1256(2.27%)deaths occurred,of which 18.63%,50.88%and 7.32%were attributable to thyroid cancer,other cancers and cardiovascular disease(CVD),respectively.Compared with the general population,patients with different subtypes of thyroid cancer had higher all-cause mortality rates,progressively increasing with papillary,follicular,medullary and anaplastic thyroid carcinoma/poorly differentiated carcinoma.Compared with general population,the death risk was 2.24 times higher in papillary thyroid cancer patients(95%CI:2.06-2.44),9.94 times higher in follicular thyroid cancer patients(95%CI:6.79-14.09),12.16 times higher in medullary thyroid cancer patients(95%CI:8.05-17.69),and the highest risk was observed in patients with anaplastic thyroid carcinoma/poorly differentiated carcinoma[SMR=79.67(95%CI:58.38-106.31),AER=766.01/1 000 person-years].Conclusion:The 10-year long survival data and cause of death for thyroid cancer patients with different histological types were reported in China based on a large single institution hospital-based cancer registry database.Staging and histological characteristics were the most important factors directly affected the survival.Early diagnosis and individualized treatment are crucial for improving prognosis.

Background and Aims:The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma(PTC)and is widely used to guide surgical extent and risk stratification.However,other genetic variants are increasingly identified in clinical practice,and their association with lymph node metastasis(LNM)remains unclear.Most existing studies have compared BRAFV600E-mutated cases with BRAF wild-type cases without stratifying specific mutation types,potentially affecting the accuracy of risk assessment.This study aimed to compare the lymph node metastatic features between PTC patients with different common genetic alterations and those with the BRAFV600E mutation.Methods:A retrospective analysis was conducted on 4 795 PTC patients who underwent surgery and genetic testing at Fudan University Shanghai Cancer Center from January 2019 to January 2025.Patients with a single genetic alteration were included and grouped accordingly.Propensity score matching(PSM)was used to control for confounding factors including age,sex,and T stage.The number of metastatic lymph nodes and N stage were compared between each mutation group and the BRAFV600E group.Results:After PSM,patients in the CCDC6-RET and NCOA4-RET fusion groups had significantly higher numbers of metastatic lymph nodes and N1b stage rates compared to the BRAFV600E group(all P<0.05).No significant differences were observed between the ETV6-NTRK3 fusion or RAS mutation groups and the BRAFV600E group in terms of lymph node metastasis or N stage(all P>0.05).Conclusion:PTC patients harboring CCDC6-RET or NCOA4-RET fusions exhibit a significantly higher lymph node metastatic burden than those with the BRAFV600E mutation,suggesting more aggressive behavior.In contrast,ETV6-NTRK3 and RAS-mutated PTCs show similar metastatic profiles to BRAFV600E-mutated cases.Preoperative genetic profiling may help identify patients at high risk of metastasis and guide individualized lymph node dissection strategies.