While cranial radiotherapy effectively kills tumor cells and significantly prolongs patient survival, it often leads to progressive cognitive decline. To date, the specific mechanisms underlying radiation-induced cognitive decline have not been fully elucidated, which greatly limits the development of related therapeutic strategies. Therefore, this article provides a comprehensive analysis of post-radiation changes in neurogenesis, neuronal synaptic plasticity, myelin injury plasticity, and parenchymal cells such as microglia in the brain, systematically elucidates the potential mechanisms of radiation-induced cognitive decline, and summarizes feasible therapeutic approaches. These findings provide a solid foundation for developing novel strategies to mitigate radiation-induced cognitive decline.

Objective The aim of this study was to investigate whether downregulation of FK506 binding protein 4(FKBP4)could inhibit the malignant progression of non-small cell lung cancer(NSCLC)by blocking the PI3K/Akt/mTOR signaling pathway.Methods NSCLC A549,H1975,H358 and PC-9 cell lines,as well as human bronchial epithelial cells(HBE)were routinely cul-tured.The expression of FKBP4 in these cells was detected by qRT-PCR,and NSCLC cell lines with the most significant different ex-pression of FKBP4 compared with HBE cells was screened.FKBP4 siRNA and NC siRNA were transfected into A549 cells,which were divided into the si-FKBP4 group and NC group.CCK-8 assay was used to detect the proliferative ability of si-FKBP4 group and NC group,flow cytometry was used to detect the apoptosis rate,scratch healing assay was used to detect the migration ability,Transwell assay was used to detect the invasion ability,and Western blot was used to detect the total and phosphorylation protein expression of PI3K and its downstream effectors Akt and mTOR.Results The expression of FKBP4 in A549 cells,H1975 cells,H358 cells and PC-9 cells were significantly higher than those in HBE cells(P<0.05),and its expression in A549 cells was the highest(P<0.001).Downregulation of FKBP4 could inhibit the proliferation,invasion and migration of A549 cells and promote the apoptosis of A549 cells(P<0.001).In addition,downregulation of FKBP4 also could inhibit the phosphorylation of PI3K,Akt and mTOR,resulting in bloc-king the PI3K/Akt/mTOR signaling pathway.Conclusion Downregulation of FKBP4 can inhibit the proliferation,invasion and mi-gration of NSCLC cells by blocking the PI3K/Akt/mTOR signaling pathway,and promote the apoptosis of NSCLC cells.

Objective To investigate the acupoint selection patterns for treating diabetic cardiac autonomic neuropathy(DCAN)using data mining techniques,providing evidence for clinical practice.Methods Literature on acupuncture treatment for DCAN was retrieved from CNKI,Wanfang,VIP,and PubMed.The publication dates of the included literature ranged from the inception of each database to April 2024.Descriptive analysis,association rule analysis,and cluster analysis were performed on acupoint prescriptions,with the selection patterns of meridians and acupoints were summarized.Results A total of 27 articles were included,involving 18 acupoints.The top 10 high-frequency acupoints were Neiguan(PC6),Xinshu(BL15),Pishu(BL20),Zusanli(ST36),Sanyinjiao(SP6),Shenmen(HT7),Taixi(KI3),Lingtai(GV10),Shendao(GV11),and Shenshu(BL23).The primary meridians selected were the bladder meridian of foot-taiyang and the pericardium meridian of hand-jueyin.Specific acupoint categories predominantly included back-shu points and five transport points.Association rule and cluster analyses identified core acupoint combinations centered on Xinshu,Neiguan,Pishu,and Zusanli.Conclusion The core acupoint combination for treating DCAN with acupuncture comprises Xinshu,Neiguan,Pishu,and Zusanli.

Objective To explore the medication rules of Professor Li Huilin in treating Hashimoto's thyroiditis(HT)complicated with hypothyroidism using data mining techniques based on the R language.Methods Prescription data of the patients with HT complicated with hypothyroidism treated by Professor Li Huilin in outpatient clinics from March 2023 to March 2024 were collected.A database was established using Microsoft Excel 2021,and R language was employed to analyze the frequency,efficacy,properties and flavors,and meridian tropism of the medicinals from Chinese herbal prescriptions.Additionally,correlation analysis,association rule analysis,and cluster analysis were performed on the medicines from Chinese herbal prescriptions.Results A total of 57 Chinese herbal prescriptions involving 125 medicinals with 782 medication frequencies were included.The top 10 frequently-used medicinals were Glycyrrhizae Radix et Rhizoma Praeparata cum Melle(Zhigancao),Angelicae Sinensis Radix(Danggui),Atractylodis Macrocephalae Rhizoma(Baizhu),Astragali Radix(Huangqi),Bupleuri Radix(Chaihu),Cinnamomi Ramulus(Guizhi),Leonuri Herba(Yimucao),Paeoniae Radix Alba(Baishao),Poria(Fuling),and Fici Simplicissimae Radix(Wuzhimaotao).Most of the medicinals had therapeutic action of tonifying deficiency.The analysis of properties and flavors showed that the majority of medicinals were mild or warm in nature,and sweet in flavor.The top three meridians having the tropism of medicinals were the liver,lung,and spleen meridians.Correlation analysis identified five strongly-correlated herbal combinations.Association rule mining revealed a core herbal combination consisting of seven medicinals of Zhigancao,Huangqi,Danggui,Chaihu,Codonopsis Radix(Dangshen),Baizhu,and Cyperi Rhizoma(Xiangfu).Cluster analysis of medicinals with a frequency of≥5 yielded five groups of herbal combination.Conclusion For the treatment of HT complicated with hypothyroidism,Professor Li Huilin follows the principle of addressing the root cause of the disease,and focuses on strengthening the spleen and replenishing qi.Moreover,attention is given to soothing the liver and regulating qi,harmonizing qi and blood simultaneously,and treating symptoms and root cause simultaneously.

Objective To explore the protective effect of miR-374c-5p on hydrogen peroxide(H2O2)-induced apoptosis of human umbilical vein endothelial cells(HUVECs).Methods HUVECs were cultured in vitro and the harvested cells were divided into four groups:control group,H2O2 group,H2O2+miR-374c-5p mimics trans-fection group,and H2O2+miR-374c-5p inhibitor transfection group.Cell activity was assessed by CCK-8 prolifer-ation rate assay,apoptosis was detected by TUNEL staining microscopy.Expression of miR-374c-5p and Fas mRNA by RT-qPCR,and Fas protein in HUVECs by was detected by Western blot.Results Proliferation of HUVECs was significantly inhibited(P＜0.001);H2O2 was significantly increased as compared with the H2O2 in-tervention group(P＜0.001);Proliferation in H2O2+miR-374c-5p inhibitor transfection group was significantly increased as compared to H2O2 intervention group(P＜0.001).Conclusions miR-374c-5p protectes the HUVECs against apoptosis induced by H2O2.

Objective:To reassess the pathogenicity of copy number variants (CNVs) involving chromosomal microdeletions and microduplications classified as variants of uncertain significance (VUS).Methods:This retrospective study analyzed 1 882 pregnant women who underwent invasive prenatal diagnosis for chromosomal microarray analysis (CMA) at the First Medical Center, Chinese PLA General Hospital between January 1, 2018, and December 31, 2022. The results were classified according to the American College of Medical Genetics and Genomics guidelines, with 82 fetuses rated as VUS selected for the study. We analyzed invasive prenatal diagnostic indications, followed up on fetal ultrasound findings, parental origin identification results, and pregnancy outcomes, and reclassified VUS CNVs based on the latest evidence. Descriptive statistical analysis was applied to the data.Results:(1) Among the 82 fetuses with VUS CNVs, prenatal diagnostic indications included fetal structural abnormalities detected by ultrasound (21 cases, 25.6%), abnormal non-invasive prenatal testing (NIPT) results (12 cases, 14.6%), high-risk serum screening (seven cases, 8.5%), advanced maternal age (≥35 years at expected delivery, 28 cases, 34.1%), and other indications (14 cases, 17.1%). Sixteen cases (19.5%) exhibited abnormal phenotypes, with seven pregnancies terminated due to severe structural abnormalities detected by prenatal ultrasound. Seventy-five live births were followed up for 25 (13-66) months. (2) Among the 82 cases, five fetuses had two VUS CNVs detected by CMA, while the remaining 77 had only one, totaling 87 VUS CNVs. Of these, 63 (72.4%) were chromosomal microduplications and 24 (27.6%) were chromosomal microdeletions. The size of the CNV segments ranged from 0.85 (0.05-5.61) Mb, with 82 segments less than 2 Mb. Parental origin identification was refused by 44 cases (53.7%), while 38 (46.3%) underwent the test, revealing eight (21.0%) de novo variants and 30 (78.9%) inherited from either parent (12 maternal and 18 paternal). (3) Among the 87 VUS CNVs, the ratings of 11 CNVs (12.6%) changed after re-evaluation. This included one 4p16.2 microdeletion and two 15q11.2 microdeletions being upgraded to pathogenic, one 16p13.11 microduplication being upgraded to likely pathogenic, one Xp22.31 microduplication and two 2q13 microdeletions being downgraded to likely benign, and four Xp22.31 microduplications being downgraded to benign. (4) Among the 16 fetuses with abnormal phenotypes, seven with prenatal abnormalities terminated pregnancies, including six with structural abnormalities and one with severe fetal growth restriction. After re-evaluation, one case was upgraded to pathogenic, while six remained VUS. Nine live births with postnatal abnormal phenotypes showed no change in classification after re-evaluation. Among the 66 cases (80.5%) without abnormal phenotypes, 10 had their classifications changed after re-evaluation. Conclusions:Fetuses with VUS CNVs often exhibit no significant abnormal phenotypes and have a relatively favorable prognosis, however, further floow-up is still needed. Parental origin identification can provide valuable insights for genetic counseling.

Objective The aim of this study was to investigate whether downregulation of FK506 binding protein 4(FKBP4)could inhibit the malignant progression of non-small cell lung cancer(NSCLC)by blocking the PI3K/Akt/mTOR signaling pathway.Methods NSCLC A549,H1975,H358 and PC-9 cell lines,as well as human bronchial epithelial cells(HBE)were routinely cul-tured.The expression of FKBP4 in these cells was detected by qRT-PCR,and NSCLC cell lines with the most significant different ex-pression of FKBP4 compared with HBE cells was screened.FKBP4 siRNA and NC siRNA were transfected into A549 cells,which were divided into the si-FKBP4 group and NC group.CCK-8 assay was used to detect the proliferative ability of si-FKBP4 group and NC group,flow cytometry was used to detect the apoptosis rate,scratch healing assay was used to detect the migration ability,Transwell assay was used to detect the invasion ability,and Western blot was used to detect the total and phosphorylation protein expression of PI3K and its downstream effectors Akt and mTOR.Results The expression of FKBP4 in A549 cells,H1975 cells,H358 cells and PC-9 cells were significantly higher than those in HBE cells(P<0.05),and its expression in A549 cells was the highest(P<0.001).Downregulation of FKBP4 could inhibit the proliferation,invasion and migration of A549 cells and promote the apoptosis of A549 cells(P<0.001).In addition,downregulation of FKBP4 also could inhibit the phosphorylation of PI3K,Akt and mTOR,resulting in bloc-king the PI3K/Akt/mTOR signaling pathway.Conclusion Downregulation of FKBP4 can inhibit the proliferation,invasion and mi-gration of NSCLC cells by blocking the PI3K/Akt/mTOR signaling pathway,and promote the apoptosis of NSCLC cells.

Objective:To reassess the pathogenicity of copy number variants (CNVs) involving chromosomal microdeletions and microduplications classified as variants of uncertain significance (VUS).Methods:This retrospective study analyzed 1 882 pregnant women who underwent invasive prenatal diagnosis for chromosomal microarray analysis (CMA) at the First Medical Center, Chinese PLA General Hospital between January 1, 2018, and December 31, 2022. The results were classified according to the American College of Medical Genetics and Genomics guidelines, with 82 fetuses rated as VUS selected for the study. We analyzed invasive prenatal diagnostic indications, followed up on fetal ultrasound findings, parental origin identification results, and pregnancy outcomes, and reclassified VUS CNVs based on the latest evidence. Descriptive statistical analysis was applied to the data.Results:(1) Among the 82 fetuses with VUS CNVs, prenatal diagnostic indications included fetal structural abnormalities detected by ultrasound (21 cases, 25.6%), abnormal non-invasive prenatal testing (NIPT) results (12 cases, 14.6%), high-risk serum screening (seven cases, 8.5%), advanced maternal age (≥35 years at expected delivery, 28 cases, 34.1%), and other indications (14 cases, 17.1%). Sixteen cases (19.5%) exhibited abnormal phenotypes, with seven pregnancies terminated due to severe structural abnormalities detected by prenatal ultrasound. Seventy-five live births were followed up for 25 (13-66) months. (2) Among the 82 cases, five fetuses had two VUS CNVs detected by CMA, while the remaining 77 had only one, totaling 87 VUS CNVs. Of these, 63 (72.4%) were chromosomal microduplications and 24 (27.6%) were chromosomal microdeletions. The size of the CNV segments ranged from 0.85 (0.05-5.61) Mb, with 82 segments less than 2 Mb. Parental origin identification was refused by 44 cases (53.7%), while 38 (46.3%) underwent the test, revealing eight (21.0%) de novo variants and 30 (78.9%) inherited from either parent (12 maternal and 18 paternal). (3) Among the 87 VUS CNVs, the ratings of 11 CNVs (12.6%) changed after re-evaluation. This included one 4p16.2 microdeletion and two 15q11.2 microdeletions being upgraded to pathogenic, one 16p13.11 microduplication being upgraded to likely pathogenic, one Xp22.31 microduplication and two 2q13 microdeletions being downgraded to likely benign, and four Xp22.31 microduplications being downgraded to benign. (4) Among the 16 fetuses with abnormal phenotypes, seven with prenatal abnormalities terminated pregnancies, including six with structural abnormalities and one with severe fetal growth restriction. After re-evaluation, one case was upgraded to pathogenic, while six remained VUS. Nine live births with postnatal abnormal phenotypes showed no change in classification after re-evaluation. Among the 66 cases (80.5%) without abnormal phenotypes, 10 had their classifications changed after re-evaluation. Conclusions:Fetuses with VUS CNVs often exhibit no significant abnormal phenotypes and have a relatively favorable prognosis, however, further floow-up is still needed. Parental origin identification can provide valuable insights for genetic counseling.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective:This study aimed to investigate the clinical value of glucocorticoids in patients with neutropenic severe pneumonia at moderate to high risk according to the Pneumonia Severity Index (PSI) in patients with hematologic diseases.Methods:Clinical data were collected from 534 patients at the Fujian Medical University Union Hospital from October 2016 to December 2018. We evaluated the changes in inflammatory cytokines, treatment failure, in-hospital mortality, and other outcomes, adjusting for potential confounders through propensity score matching.Results:Patients were categorized into glucocorticoids ( n=176) and control ( n=358) groups. The glucocorticoid group demonstrated higher levels of C-reactive protein, procalcitonin, and interleukin-6, alongside higher PSI scores. The differences in comorbidities diminished, except for inflammatory cytokine levels, with a notable reduction in inflammatory cytokines observed in the glucocorticoid group, after matching 125 pairs based on propensity scores. Late treatment failure was more prevalent in the glucocorticoid group (39.2% vs 24.8%, P=0.015), but this was primarily caused by radiographic progression. The incidences of respiratory failure, mechanical ventilation, and septic shock were similar between the groups. Logistic regression analyses revealed that glucocorticoids reduced the risk of treatment failure ( OR=0.367, 95% CI 0.165-0.818, P=0.014). The 30-day in-hospital mortality rates were comparable (8.0% in glucocorticoids vs 7.2% in controls, P=0.811), with indications that glucocorticoids may exert a protective effect on mortality. The PSI score was determined as the sole independent risk factor for 30-day in-hospital mortality ( OR=1.077, 95% CI 1.032-1.123, P=0.001). No evidence indicated that glucocorticoids increased the incidence of hyperglycemia, gastrointestinal bleeding, or 30-day infection recurrence. Conclusion:Glucocorticoids reduce inflammatory cytokine levels and are potentially related to decreased treatment failure and mortality in patients with neutropenic pneumonia classified as PSI Ⅳ and Ⅴ among hematological patients.