Objective: To explore the longitudinal associations between dietary macronutrients and lung function in schoolaged children, so as to provide the nutritional research evidence for promoting children s lung health. Methods: In November 2021, two primary schools located in Chengdu, Sichuan Province were selected from the Southwest China Childhood Nutrition and Growth (SCCNG) cohort by a stratified cluster random sampling method, enrolling a total of 1 112 school aged children aged 8 to 13 years. At baseline, the dietary and sociodemographic characteristics of the children were assessed. One year later, the forced vital capacity (FVC) of the children was measured and converted into Z scores (FVC- Z ), while the vital capacity index (VCI) was also calculated. Generalized linear regression analysis was employed to examine the associations between dietary macronutrients and lung function, considering interactions with gender and age, followed by stratified analysis. Results: After adjusting for confounding factors, the analysis results of the generalized linear regression model showed that the carbohydrate energy ratio was negatively correlated with FVC- Z ( β =-0.02) and VCI ( β =-0.16), while the fat energy ratio showed a positive correlation with FVC- Z ( β =0.03) and VCI ( β =0.23) ( P <0.05). The protein energy ratio was positively correlated with FVC- Z ( β =0.09) and VCI ( β =0.60) specifically in girls ( P <0.05). Additionally, there was an interaction effect of age on the associations between macronutrients and lung function ( P <0.01); in children aged 8-9 and 10-11, the carbohydrate energy supply ratio was negatively correlated with FVC- Z ( β =-0.04, -0.03) and VCI ( β =-0.29, -0.21), and fat energy supply ratio was positively correlated with FVC- Z ( β =0.07, 0.05) and VCI ( β =0.46, 0.32) ( P <0.05). Conclusions There are age and sex differences in the association of dietary macronutrients with lung function, with a low carbohydrate, high fat diet promoting lung function in children. Additionally, protein intake appears to have a positive influence on the lung function of girls. The early school age period may represent a critical window for dietary interventions aimed at promoting lung health.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Objective Mitochondrial reactive oxygen species(mtROS)could cause damage to pancreatic β-cells,rendering them susceptible to oxidative damage.Hence,investigating the potential of the mitochondria-targeted antioxidant(Mito-TEMPO)to protect pancreatic β-cells from ferroptosis by mitigating lipid peroxidation becomes crucial. Methods MIN6 cells were cultured in vitro with 100 μmol/L sodium palmitate(SP)to simulate diabetes.FerroOrange was utilized for the detection of Fe2+fluorescence staining,BODIPY581/591C11 for lipid reactive oxygen species,and MitoSox-Red for mtROS.Alterations in mitophagy levels were assessed through the co-localization of lysosomal and mitochondrial fluorescence.Western blotting was employed to quantify protein levels of Acsl4,GPX4,FSP1,FE,PINK1,Parkin,TOMM20,P62,and LC3.Subsequently,interventions were implemented using Mito-TEMPO and Carbonyl cyanide 3-chlorophenylhydrazone(CCCP)to observe changes in ferroptosis and mitophagy within MIN6 cells. Results We found that SP induced a dose-dependent increase in Fe2+and lipid ROS in MIN6 cells while decreasing the expression levels of GPX4 and FSP1 proteins.Through bioinformatics analysis,it has been uncovered that mitophagy assumes a crucial role within the ferroptosis pathway associated with diabetes.Additionally,SP decreased the expression of mitophagy-related proteins PINK1 and Parkin,leading to mtROS overproduction.Conversely,Mito-TEMPO effectively eliminated mtROS while activating the mitophagy pathways involving PINK1 and Parkin,thereby reducing the occurrence of ferroptosis in MIN6 cells.CCCP also demonstrated efficacy in reducing ferroptosis in MIN6 cells. Conclusion In summary,Mito-TEMPO proved effective in attenuating mtROS production and initiating mitophagy pathways mediated by PINK1 and Parkin in MIN6 cells.Consequently,this decreased iron overload and lipid peroxidation,ultimately safeguarding the cells from ferroptosis.

Objective To explore the correlation between thyroid antibody levels and early renal injury in patients with type 2 diabetes mellitus(T2DM)combined with Hashimoto's thyroiditis(HT).Methods A total of 375 T2DM patients hospitalized in The Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2022 were selectedas the study subjects,and 197 healthy people were selected as the control subjects.The patients with T2DM were divided into simple T2DM group(n=191)and T2DM combined with HT group(HT,n=184).According to the urinary albumin/creatinine ratio(UACR)level,T2DM patients with HT were divided into microalbuminuria subgroup(MUAlb,30≤UACR≤300 mg/g,n=70)and normal albuminuria subgroup(NUAlb,UACR<30 mg/g,n=114).According to whether the thyroid antibody was positive,they were divided into thyroid peroxides antibody[TPOAb(+)]subgroup(n=56),thyroglobulin antibody[TGAb(+)]subgroup(n=40)and TGAb and TPOAb double antibody positive subgroup(n=88).Results Compared with the NC group,the smoking,drinking,urinary creatinine,alpha 1-microglobulin,UACR,FPG,HbA1c,LDL-C,TC,and TG in the HT and T2DM groups increased(P<0.05),while HDL-C decreased(P<0.05).Compared with the NUAlb subgroup,the MUAlb subgroup showed age,DM duration,FPG,HbA1c,TGAb,TPOAb,thyroid stimulating hormone(TSH)increased(P<0.05),while FT3 and eGFR decreased(P<0.05).Spearman correlation analysis showed that UACR was positively correlated with age,HbA1c,TPOAb,TGAb,TSH(P<0.01),and negatively correlated with FT3(P<0.01).The UACR of the TGAb(+)+TPOAb(+)subgroup was higher than that of the TGAb(+)and TPOAb(+)subgroups(P<0.05).Logistic regression analysis showed that TSH,TGAb,TPOAb,and HbA1c were risk factors for MUAlb,while FT3 was a protective factor for MUAlb.Conclusions In T2DM with HT patients with normal thyroid function,TPOAb and TGAb are closely related to the occurrence of early renal injury.

OBJECTIVES: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1. METHODS: Male SD rats were randomly divided into 6 groups (n=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence. RESULTS: The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P<0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P<0.01), and they were decreased after WSP and SASP treatment (all P<0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P<0.01), and it was decreased after WSP and SASP treatment. CONCLUSIONS WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.
Animals ; Male ; Rats ; Antineoplastic Agents/therapeutic use* ; Colitis, Ulcerative/chemically induced* ; Colon/pathology* ; Disease Models, Animal ; Interleukin-6/pharmacology* ; Propolis/therapeutic use* ; Rats, Sprague-Dawley ; Sulfasalazine/therapeutic use* ; TRPV Cation Channels ; Tumor Necrosis Factor-alpha/pharmacology*

Objective:To investigate the status quo of potentially inappropriate medication (PIM) among elderly hypertensive patients in community general practice clinic and related influencing factors.Methods:A total of 767 prescriptions for elderly hypertensive patients in a community health service center in Beijing from October 2020 to August 2021 were reviewed. The prevalence of PIM was assessed based on the criteria of potentially inappropriate medications for older adults in China(2017). Logistic regression analysis was employed to analyze the influencing factors for PIM. Results:The survey showed that 198 elderly patients had PIM with 244 person-doses. The top three drugs with high rate of PIM were benzodiazepine-estazolam (64 person-doses), clopidogrel (53 person-doses) and insulin (35 person-doses). Univariate analysis showed that PIM was significantly associated with types of medication;and underlying diseases hypertension with hyperlipidemia, coronary heart disease, type 2 diabetes, osteoarthritis, upper respiratory tract infection and insomnia (χ 2=82.58, 13.65, 17.74, 7.52, 10.34, 68.19,respectively,all P<0.05). Multivariate logistic regression analysis showed that the types of medication, hypertension complicated with upper respiratory tract infection, and insomnia were independent influencing factors for PIM ( OR=1.55, 2.47, 9.05; P<0.05). Conclusion:The study shows that PIM is more common in elderly hypertensive patients in community general practice clinics,which is associated with types of medication, hypertension complicated with upper respiratory tract infection and insomnia. It is suggested that general practitioner working in community clinics should be aware of PIM, minimize the number of prescription drugs, and choose new drugs or non-drug treatments to reduce the occurrence of PIM.

Ossifying fibroma (OF) and fibrous dysplasia (FD) are two fibro-osseous lesions with overlapping clinicopathological features, making diagnosis challenging. In this study, we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations (CNAs) using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples. Freshly frozen tissue specimens from OF (n = 29) and FD (n = 28) patients were obtained for analysis. Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection (LCM), with ~30-50 cells (5 000-10 000 µm
DNA Copy Number Variations ; Diagnosis, Differential ; Fibroma, Ossifying/genetics* ; Fibrous Dysplasia of Bone/genetics* ; Galactosyltransferases ; Humans ; Jaw ; Neoplasm Recurrence, Local ; Nuclear Proteins

OBJECTIVE：To reference for the rational use of sodium va lproate in clinic. METHODS ：By retrospective analysis，blood concentration monitoring results of sodium valproate and medical record data in 856 patients were collected from the Affiliated Tianyou Hospital of Wuhan University of Science and Technology during Jan. 2016-Dec. 2018. The dosage form of sodium valproate ，monitoring times of therapeutic drugs ，monitoring results of steady-state blood concentration of sodium valproate up to the standard ，dosage adjustment and the combination with carbamazepin ，fluconazol and carbapenem drugs were analyzed. Fisher exact test was used to analyze the factors influencing the steady-state blood concentration of sodium valproate up to the standard. RESULTS ：A total of 1 270 cases of sodium valproate were monitored in 856 patients，involving 407 males and 449 females，with age of （38.2±13.8）years and body mass of （52.3±10.0）kg. Among 1 270 cases of monitoring ，steady-state blood concentration of sodium valproate in 554 cases were in the range of 50-100 µg/mL，and 43.6％ of which reached the standard. The rate of reaching the standard in patients with multiple monitoring was higher than patients with single monitoring ；the dosage of patients with last monitoring reaching the standard was higher than that of patients with the first monitoring reaching the standard. The rate of reaching the standard in Sodium valproate sustained-release tablet group was higher than general Sodium valproate tablet group；the carbamazepin/fluconazol free group was higher than the carbamazepin combination group and fluconazol combination group；the carbapenem free group was higher than the carbapenem combination group （all P＜0.05）. CONCLUSIONS ：Clinical pharmacists should pay attention to the monitoring of sodium valproate treatment drugs ， strengthen the publicity and 3551851542@qq.com education of patients and their families ，and try to use Sodium valproate sustained-release tablets. When patients additionally receive carbapenem drugs like carbamazepin or fluconazol ， the standard level of sodium valproate will be reduced ，then the dosage of sodium valproate should be adjusted.

Parkinson′s disease (PD) is a common neurodegenerative disease. Its main pathological feature is the progressive loss of substantia nigra and other catecholaminergic neurons containing neuromelanin (NM). Therefore, NM may be closely related to the pathogenesis of PD. The content of NM can be detected by NM magnetic sensitive sequence imaging, and then it can be applied to the study of the neuropathological mechanism of NM and PD. This paper focuses on the physiological significance of NM, its role in the pathogenesis of PD and the prospect of NM as a biomarker to assist diagnosis and disease monitoring of PD.

Objective:To evaluate the incidence of deeply infiltrating endometriosis (DIE) among patients of pelvic endometriosis confirmed by pathology and to make analysis of its clinical and pathological characteristics.Methods:From January 1, 2018 to December 31, 2018, clinical data of 240 cases of pelvic endometriosis diagnosed by laparoscopy and pathology hospitalized in Peking University First Hospital were analyzed retrospectively for the characteristics of symptoms, pelvic examination and anatomic distribution of endometriosis foci.Results:(1) Among 240 cases of pelvic endometriosis, 94 were diagnosed with DIE with an incidence of 39.2% (94/240); of them the diagnosis were made preoperatively in 44 cases (46.8%, 44/94). (2) Compared with those without DIE, patients with DIE had higher rates of secondary dysmenorrhea [53.2% (50/94) versus 38.4% (56/146), P=0.033], anal pain [43.6% (41/94) versus 28.1% (41/146), P=0.013], dyspareunea [39.4% (37/94) versus 18.5% (27/146), P=0.001] and frequent bowel movement [33.0% (31/94) versus 15.8%(23/146), P=0.002]. (3) Patients with DIE had higher rates of bad movement of uterus [21.3% (20/94) versus 6.8% (10/146), P=0.001], painful nodularity on uterosacral ligaments [26.6% (25/94) versus 6.2% (9/146), P<0.01], painful nodularity of posterior fornix [19.1% (18/94) versus 4.8% (7/146), P<0.01], blue nodule in vaginal wall [6.4% (6/94) versus 0 (0/146), P=0.003] by pelvic examination compared with those without DIE. (4) Ninety-four patients with DIE had a total of 162 nodules, of those 88 (54.3%, 88/162) located in uterosacral ligaments, 14 (8.6%, 14/162) in the rectum, 7 (4.3%, 7/162) in vaginal wall, 6 (3.7%, 6/162) in ureter, 4 in bladder (2.5%, 4/162), 2 (1.2%, 2/162) in Douglas pouch. Forty-three DIE patients (45.7%, 43/94) had more than one nodules. Patients with DIE had concomitant ovarian endometriosis in 69 cases (73.4%, 69/94), with a total of 103 endometrial cysts. (5) Patients with DIE had a higher rate of obliterated Douglas pouch [76.6% (72/94) versus 19.2% (28/146), P<0.01]. Conclusions:More than one third of patients with pelvic endometriosis have concomitant DIE with a lower rate of preoperative diagnosis. Pelvic pains, bad movement of uterus and painful nodulirity around cervix suggest the presence of DIE.