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.

Objective: To investigate the effects of Erianin on cell proliferation and apoptosis in human oral squamous cell carcinoma (OSCC) cells, providing a research foundation for the clinical treatment of OSCC. Methods: Erianin was applied to OSCC cells (CAL27 and SCC9) at concentrations of 0, 2.5, 5, and 10 μmol/L. The inhibitory effect of Erianin on OSCC cell proliferation was evaluated using CCK-8 and soft agar colony formation assays. Western blotting (WB) was employed to analyze the expression levels of anti-apoptotic proteins B-cell lymphoma-extra large (Bcl-xL), B-cell lymphoma-2 (Bcl-2), myeloid cell leukemia-1 (Mcl-1), and apoptotic protein cleaved-Caspase 3 (c-Caspase 3) in OSCC cells. Caspase 3 activity was further assessed using a caspase 3 activity detection kit to examine the pro-apoptotic effect of Erianin in OSCC cells. Mcl-1 overexpression was induced in CAL27 cells via plasmid transfection, and the influence of Mcl-1 on the effects of Erianin in CAL27 cells was analyzed by WB and caspase 3 activity measurement. All animal experiments were approved by the Ethics Committee of Hunan Cancer Hospital. A CAL27 xenograft mouse model was established and randomly divided into two groups (n = 5): the treatment group received intraperitoneal injection of Erianin (25 mg/kg), while the control group was injected with phosphate-buffered saline (PBS) as the vehicle. Immunohistochemistry (IHC) was used to detect the expression levels of Ki67 and Mcl-1 in the tumor tissues. Results: Erianin inhibited the proliferation of CAL27 and SCC9 cells in a dose-dependent manner and downregulated the protein expression of Mcl-1, with minimal effects on Bcl-2 and Bcl-xL. Furthermore, Erianin induced apoptosis in OSCC cells, as evidenced by increased expression of c-Caspase 3 and enhanced caspase 3 activity (P<0.001). Overexpression of Mcl-1 inhibited the Erianin-induced increase in c-Caspase 3 protein levels and caspase 3 activity. In vivo results were consistent with the in vitro findings. After Erianin treatment, CAL27 cell growth in nude mice was suppressed (P<0.001), and the expression levels of the proliferation marker Ki67 and the anti-apoptotic protein Mcl-1 in the tumor tissues were downregulated (P<0.001). Conclusion Erianin exhibits potent anti-tumor effects, effectively inhibiting the proliferation of OSCC cells and inducing apoptosis. The underlying mechanism may involve the downregulation of the pro-survival protein Mcl-1.

[Objective] To determine the blood group of a patient with ABO forward and reverse typing discrepancies using PacBio third-generation sequencing (TGS) technology, and to explore the application of serological methods and molecular biological methods in identifying chimeric blood groups. [Methods] The blood group serology testing was utilized. PCR amplification and Sanger sequencing of exons 1-7 of the ABO gene were conducted. The full-length sequencing of the ABO gene and haplotype analysis were carried out by PacBio third-generation sequencing technology. Short tandem repeat typing was also performed. [Results] Serological testing suggested a suspected B subtype, which appeared mixed field of vision with anti-B antibodies and showed 2+mf strength agglutination. Sanger sequencing revealed a homozygous ABO^* O. 01. 01 genotype with the c. 261delG mutation in exon 6. PacBio TGS identified a predominant ABO^* O. 01. 01/ABO^* O. 01. 01 genotype and a low proportion of ABO^* B. 01. Nine locis of twenty short tandem repeat (STR) locis showed three or four types of genotypes in STR analysis, confirming chimerism. [Conclusion] The sample was a B/O blood group chimerism. The low proportion of ABO^* B. 01 chimerism was the true cause for the serological mixed field of vision. The PacBio third-generation sequencing technology can not only determine the ABO gene haplotype but also detect a low proportion gene chimerism in ABO blood groups.

AIM: To investigate the current status of retinopathy of prematurity(ROP)in premature infants in Xiamen and analyze its influencing factors, aiming to provide a scientific basis for clinical treatment and preventive strategies.METHODS: A retrospective study was conducted on the case data of 363 preterm infants with a gestational age of <32 wk who underwent fundus examination at Xiang'an Hospital of Xiamen University from February 11, 2020 to February 25, 2023. The incidence of ROP was statistically analyzed based on the screening results. All premature infants were divided into ROP group(37 cases, 64 eyes)and non-ROP group(326 cases, 652 eyes). General clinical data and perinatal-related information of the two groups were compared, and multivariate Logistic regression analysis was used to identify factors influencing the occurrence of ROP in premature infants.RESULTS: A total of 363 premature infants were included in this study. The fundus screening results showed that a total of 37 cases(64 eyes)of premature infants were detected with ROP, including 10 cases(10 eyes)monocular and 27 cases(54 eyes)binocular, with an overall incidence of 10.2%(37/363). The severity was determined according to the ROP international classification standard(ROP is divided into 5 stages, with stage I being the least severe and stage V the most severe). Among the 64 eyes, 30 eyes(46.9%)were in stage I, 20 eyes(31.3%)were in stage II, 10 eyes(15.6%)were in stage III, 4 eyes(6.3%)were in stage IV, and there were no cases in stage V. By comparing the clinical data of the two groups, no significant differences were found in gender, mode of delivery, singleton or multiple births, premature rupture of membranes, history of asphyxia, patent ductus arteriosus(PDA), or neonatal respiratory distress syndrome(NRDS)between the two groups(all P>0.05). However, premature infants in the ROP group had significantly younger gestational age and lower birth weight compared to those in the non-ROP group(all P<0.05). Additionally, the ROP group had higher proportions of longer hospital stays, bronchopulmonary dysplasia(BPD), neonatal sepsis, anemia, oxygen therapy for more than 1 wk, oxygen concentration above 40%, and blood transfusion treatment(all P<0.05). Multivariate Logistic regression analysis revealed that combined neonatal sepsis(OR=166.985, 95% CI: 35.239-791.277, P<0.001), anemia(OR=8.111, 95% CI: 2.064-31.871, P=0.003), oxygen use time >1 wk(OR=10.216, 95% CI: 2.543-41.039, P=0.001), oxygen therapy concentration >40%(OR=7.647, 95% CI: 1.913-30.566, P=0.004), and receiving blood transfusion therapy(OR=5.879, 95% CI: 1.412-24.470, P=0.015)were the main risk factors affecting the occurrence of ROP in preterm infants, and the higher birth weight of preterm infants was a protective factor for ROP(OR=0.093, 95% CI: 0.022-0.394, P=0.001).CONCLUSION: The incidence of ROP in premature infants is relatively high, and there are multiple influencing factors. Low birth weight, neonatal sepsis, anemia, oxygen therapy, and blood transfusion treatment are high-risk factors for ROP in premature infants. Clinical attention should be given to such infants, and fundus screening should be conducted in a standardized manner to provide early treatment, thereby further reducing the risk of ROP in premature infants.

Objective: To explore the correlation between allogeneic red blood cell (RBC) transfusion and healthcare-associated infections (HAIs) in patients undergoing coronary artery bypass grafting (CABG) during the perioperative period. Methods: A single-center retrospective cohort of 1,170 patients undergoing isolated CABG was analyzed. Multivariable logistic regression and restricted cubic splines (RCS) were employed to explore the nonlinear association between perioperative RBC transfusion (from intraoperative period to 72 hours postoperatively) and HAIs. Results: Among the 1,170 CABG patients, 109 patients (9.2%) received RBC transfusion during the operation or within 3 days after the operation. The risk of HAIs in those who received ≥4 units of RBCs during and within 3 days after the operation was 6.89 times higher than that in the non-transfusion group (95% CI: 3.65-17.20). Furthermore, there was a nonlinear threshold effect between the blood transfusion volume and postoperative HAIs (inflection point: 7.8 units). When the transfusion volume was ≤7.8 units, the risk of HAIs increased by 61% for each additional unit transfused (OR=1.61, 95% CI: 1.21-2.15). Beyond this threshold, no statistically significant association was observed (P=0.289). Conclusion: Perioperative RBC transfusion in CABG patients is associated with an increased incidence of HAIs. The perioperative blood transfusion volume has a curvilinear relationship with the risk of postoperative HAIs. When the blood transfusion volume is ≤7.8 units, the blood transfusion volume has a dose-dependent relationship with postoperative infection, with higher blood transfusion volumes correlating with greater postoperative infection risk. When the blood transfusion volume is >7.8 units, the relationship between the two is not statistically significant. The preventive effect of reducing RBC transfusion on HAIs requires further validation in the future.

OBJECTIVE: To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD. METHODS: Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24⁺] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)⁺ TREM2⁺ and Iba1⁺ lysosome-associated membrane protein 1 (LAMP1)⁺ in the hippocampus. RESULTS: Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1⁺LAMP1⁺ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1⁺ TREM2⁺ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1⁺TREM2⁺, and Iba1⁺ LAMP1⁺ was higher compared with that in the model group (P<0.05, P<0.01). CONCLUSION "Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals ; Dementia, Vascular/metabolism* ; Rats ; Rats, Sprague-Dawley ; Microglia/metabolism* ; Male ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Humans ; Remyelination ; Memory ; Hippocampus/cytology* ; Cognition ; Electroacupuncture ; Needles

Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Objective To investigate the relationship between serum histone deacetylase 3(HDAC3),solu-ble programmed death molecule-1(sPD-1)and Omentin-1 levels with periodontal indexes and prognosis after combined periodontal-orthodontic treatment in patients with periodontitis.Methods A total of 102 patients with periodontitis who were treated in a hospital from September 2018 to May 2020 were selected as the study group.Another 95 healthy subjects who underwent periodontal examination in the same period were selected as the control group.After 6 months of combined periodontal-orthodontic treatment,the patients were divided into poor prognosis group(n=39)and good prognosis group(n=63)according to the results of review.Ser-um levels of HDAC3,sPD-1 and Omentin-1 were detected by enzyme-linked immunosorbent assay.The corre-lation between serum HDAC3,sPD-1,Omentin-1 and periodontal indexes in patients with periodontitis was analyzed by Pearson method.The prognostic value of serum HDAC3,sPD-1 and Omentin-1 in patients with periodontitis after treatment was analyzed by receiver operating characteristic(ROC)curve.Results The ser-um levels of sPD-1,sulcus bleeding index(SBI),plaque index(PLI),loss of attachment(AL)and periodontal probing depth(PD)in the study group were significantly higher than those in the control group,while the ser-um levels of HDAC3 and Omentin-1 were significantly lower than those in the control group,with statistical significance(P＜0.05).Serum sPD-1 levels were positively correlated with periodontal indicators SBI,PLI,AL and PD,while serum HDAC3 and Omentin-1 levels were negatively correlated with periodontal indicators SBI,PLI,AL and PD(P＜0.05).Before treatment,PD,PLI,alveolar bone height and serum sPD-1 level in the poor prognosis group were significantly higher than those in the good prognosis group,while serum HDAC3 and Omentin-1 levels were significantly lower than those in the good prognosis group,with statistical signifi-cance(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)predicted the prognosis of periodontitis patients after treatment by the combination of serum HDAC3,sPD-1 and Omentin-1 was better than the AUC predicted by serum HDAC3,SPD-1 and Omentin-1 alone(Z three combination-HDAC3=2.754,Z three combination-sPD-1=3.415,Z three combination-Omentin-1=3.355,P=0.006,0.001,0.001).Conclusion The serum level of sPD-1 in patients with periodontitis is significantly increased,and the serum levels of HDAC3 and Omentin-1 are significantly decreased,which are closely related to periodontal indexes.The combination of the three has a good predictive value for the prognosis of patients with periodontitis after treatment.

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 To explore the improving effects of motion sickness acclimatization training methods,namely sinusoidal vertical oscillation stimulation and sinusoidal vertical oscillation stimulation combined with visual virtual reality(VR)swell stimulation,on cognitive performance of individuals with extremely severe motion sickness.Methods A total of 90 individuals with extremely severe motion sickness screened by the Graybiel score during 6 h navigation were randomly divided into vertical group,vertical+VR group,and control group(n=30).The abilities of vigilance,memory,rapid calculation,information processing and visual manipulation were evaluated before and after the acclimatization training using a self-developed cognitive performance evaluation software.Results On the 1st day of training,the numbers of missed targets of the vertical group and vertical+VR group were increased in the vigilance test;the reaction time was prolonged in the short-term memory,rapid calculation,information processing and visual manipulation tasks;and the efficiency of rapid calculation was reduced.After acclimatization training,the numbers of missed targets were reduced to the baseline level in the vertical and vertical+VR groups,and the reaction time in the short-term memory,rapid calculation,information processing and visual manipulation tasks and the efficiency of rapid calculation were improved.Conclusion Motion sickness caused by vertical oscillation stimulation or vertical oscillation combined with visual VR swell stimulation can decrease vigilance,short-term memory,rapid calculation,information processing and visual manipulation abilities.Motion sickness acclimatization training can significantly improve the above cognitive abilities.