OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Aim To investigate the protective effects of curcumin(CUR)on crystal-induced renal injury and its underlying mechanism in the mouse model of neph-rolithiasis.Methods The mouse model of stone for-mation was established via successive intraperitoneal injection of glyoxylate.Proximal tubular epithelial cell line HK-2 treated with calcium oxalate monohydrate(COM)was used as an in vitro model.The protective role of CUR on nephrolithiasis was tested by determina-tion of tubular injury,crystal deposition and adhesion,levels of inflammatory cytokines.In vitro,the effects of CUR on the cell viability and inflammatory factors of HK-2 cells were measured.The proteins in the Toll-like receptor 4(TLR4)/nuclear factor κB(NF-κB)and nuclear factor erythroid 2-related factor 2(NRF2)/hemeoxygenase-1(HO-1)signaling path-ways were measured by Western blot for confirming the relationship between CUR and these pathways.Final-ly,NRF2 inhibitor ML385 and TLR4 activator CCL-34 were respectively used on COM-induced HK-2 cells ex-posed to CUR for the conduction of gain-of-function and loss-of-function assays.Results CUR improves the damage in the mouse model of kidney stone forma-tion,inhibits inflammation and antioxidative effects;promotes the viability of HK-2 cells induced by COM,and inhibits the expression of inflammatory factors.CUR suppresses the expression of proteins in the TLR4/NF-κB pathway,promotes the transfer of NRF2 from the cytoplasm to the nucleus,and enhances the ex-pression of HO-1.ML385 and CCL-34 respectively counteract the anti-inflammatory effects of CUR on COM-induced HK-2 cells.Conclusions Taken togeth-er,our study demonstrates the protective effect of CUR on the deposition of kidney stone and consequent tubu-lar injury.CUR through regulation of the TLR4/NF-κB and NRF2/HO-1 pathways improves renal injury.

Purpose: Protective ileostomy and colostomy are performed in patients undergoing low anterior resection with a high leakage risk. We aimed to compare surgical, medical, and daily care complications between these 2 ostomies in order to make individual choice. Methods: Patients who underwent low anterior resection for rectal tumors with protective stomas between January 2011 and September 2018 were enrolled. Stoma-related complications were prospectively recorded by wound, ostomy, and continence nurses. The cancer stage and treatment data were obtained from the Taiwan Cancer Database of our Big Data Center. Other demographic data were collected retrospectively from medical notes. The complications after stoma creation and after the stoma reversal were compared. Results: There were 176 patients with protective colostomy and 234 with protective ileostomy. Protective ileostomy had higher proportions of high output from the stoma for 2 consecutive days than protective colostomy (11.1% vs. 0%, P<0.001). Protective colostomy resulted in more stoma retraction than protective ileostomy (21.6% vs. 9.4%, P=0.001). Female, open operation, ileostomy, and carrying stoma more than 4 months were also significantly associated with a higher risk of stoma-related complications during diversion. For stoma retraction, the multivariate analysis revealed that female (odds ratio [OR], 4.00; 95% confidence interval [CI], 2.13–7.69; P<0.001) and long diversion duration (≥4 months; OR, 2.33; 95% CI, 1.22–4.43; P=0.010) were independent risk factors, but ileostomy was an independent favorable factor (OR, 0.40; 95% CI, 0.22–0.72; P=0.003). The incidence of complication after stoma reversal did not differ between colostomy group and ileostomy group (24.3% vs. 20.9%, P=0.542). Conclusion We suggest avoiding colostomy in patients who are female and potential prolonged diversion when stoma retraction is a concern. Otherwise, ileostomy should be avoided for patients with impaired renal function. Wise selection and flexibility are more important than using one type of stoma routinely.

Objective To preliminarily explore the correlation between traditional Chinese Medicine(TCM)syndrome types of patients with polycystic ovary syndrome(PCOS)and their lifestyle and emotional factors such as diet,sleep and exercise,thus to provide more information for guiding the treatment and lifestyle correction for patients with PCOS.Methods A questionnaire survey was conducted in 234 patients who were diagnosed with PCOS and meet the inclusion and exclusion criteria of the study at Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,from January 2020 to February 2023.The collection of relevant information covered general information,diet,sleep,exercise,and psychological state.And then the patients were differentiated as four TCM syndrome types,namely spleen deficiency and phlegm-damp type,kidney deficiency and liver constraint type,kidney deficiency and blood stasis type,phlegm blended with blood stasis type according to the symptoms as well as tongue manifestation and pulse condition.The distribution of the TCM syndrome types in PCOS was investigated,and the lifestyle factors of general information,diet,sleep,exercise,and emotions in PCOS patients with various TCM syndrome types were analyzed by statistical methods,aiming to explore the relationship between the lifestyle factors and TCM syndrome types.Results(1)The analysis of the distribution of TCM syndrome types showed that among the 234 PCOS patients,104 cases(accounted for 44.4%)were differentiated as spleen deficiency and phlegm-damp type,which was the predominant type,and then came kidney deficiency and liver constraint type(85 cases,accounting for 36.3%),phlegm blended with blood stasis type(28 cases,accounting for 12.0%),and kidney deficiency and blood stasis type(17 cases,accounting for 7.3%)in descending order.(2)The correlation of TCM syndrome types with lifestyle factors such as diet,sleep and exercise and emotional factors showed that statistically significant differences were presented in the body mass index(BMI),dietary preference,five-flavor preference,having or not having exercise habits,exercise frequency,duration of exercise,exercise mode,exercise intensity,time from going to bed to falling asleep,duration of sleep,emotions being or not being calm,presence of anxiety or not,and presence of impatience and irritability or not in PCOS patients with various TCM syndrome types(P＜0.05 or P＜0.01).However,there were no statistically significant differences in the age,education level,occupation,family history,history of weight loss,dietary condition,sleep quality,time to fall asleep,frequency of staying up late,depression,obsessive-compulsive disorder,forgetfulness,fatigue,and self-consciousness of high pressure from work and study in PCOS patients with various TCM syndrome types(P＞0.05).Conclusion Healthy lifestyle is of great practical significance for the prevention and treatment of PCOS.The investigation of the correlation of TCM syndrome types with diet,sleep,exercise and psychological state of PCOS patients reveals the possible risk factors for TCM syndromes in PCOS,which will enable the practitioners to perform targeted lifestyle correction for PCOS patients with different TCM syndrome types,and has positive significance for targeted diagnosis and treatment of PCOS patients with different TCM syndrome types.

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.