BACKGROUND: The proportion of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is relatively high in China. However, these patients currently lack significant benefits from available neoadjuvant treatment options. This study aims to explore the potential application value of neoadjuvant targeted therapy by evaluating its efficacy and safety in patients with EGFR-mutant resectable lung adenocarcinoma. METHODS: A multicenter retrospective study was used to analyze the treatment effect of patients with stage IIA-IIIB EGFR-mutant lung adenocarcinoma who underwent surgical resection after receiving neoadjuvant targeted therapy from July 2019 to October 2024. RESULTS: A total of 24 patients with EGFR-mutant lung adenocarcinoma from three centers were included in this study. All patients successfully underwent surgery and achieved R0 resection of 100.0%. The objective response rate (ORR) was 83.3% (20/24) . The major pathologic response (MPR) rate was 37.5% (9/24), with 2 patients (8.3%) achieving pathological complete response (pCR). During neoadjuvant therapy, 13 out of 24 patients (54.2%) experienced adverse events of grade 1-2, with no occurrences of ≥ grade 3. The most common treatment-related adverse events were rash (n=4, 16.7%), mouth sores (n=2, 8.3%), and diarrhea (n=2, 8.3%). The median follow-up time was 33.0 months, no deaths occurred in all patients, and the overall survival (OS) rate was 100.0%. The 1-year disease-free survival (DFS) rate was 91.1%, and the 2-year DFS rate remained at 86.2%. CONCLUSIONS The application of neoadjuvant targeted therapy in patients with EGFR-mutant resectable lung adenocarcinoma is safe and feasible, and is expected to become a highly promising neoadjuvant treatment option for the patients with EGFR-mutant lung adenocarcinoma.
Humans ; ErbB Receptors/metabolism* ; Male ; Female ; Middle Aged ; Adenocarcinoma of Lung/surgery* ; Neoadjuvant Therapy ; Lung Neoplasms/surgery* ; Aged ; Retrospective Studies ; Mutation ; Adult

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

OBJECTIVES: To explore the mechanism of Gandou Fumu Decoction (GDFMD) for improving Wilson's disease (WD) in tx-J mice. METHODS: With 6 syngeneic wild-type mice as the control group, 30 tx-J mice were randomized into WD model group, low-, medium- and high-dose GDFMD treatment groups, and Fer-1 treatment group. Saline (in control and model groups) and GDFMD (3.48, 6.96 or 13.92 g/kg) were administered by gavage, and Fer-1 was injected intraperitoneally once daily for 14 days. Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue; ALT, AST, albumin, AKP levels were determined to assess liver function of the mice. Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4, ACSL4, ALOX15, FTH1, FLT, TFR1, FAS, SCD1, and ACOX1, and Fe²⁺, MDA, ROS, SOD, GSH and 4-HNE levels were analyzed to assess oxidative stress. RESULTS: The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT, AST and AKP, decreased albumin level, increased Fe²⁺, MDA, ROS, 4-HNE levels, decreased SOD and GSH levels (P<0.05), lowered protein expressions of ACOX1, GPX4, FTH1, FLT, FAS, and SCD1, and increased protein contents of TFR1, ACSL4 and ALOX15 in the liver. Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models, decreased the levels of Fe²⁺, MDA and ROS, increased SOD and GSH levels, and reversed the changes in hepatic protein expressions. CONCLUSIONS GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Mice ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Hepatolenticular Degeneration/drug therapy* ; Hepatocytes/metabolism* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Fatty Liver/metabolism* ; Arachidonate 15-Lipoxygenase/metabolism* ; Coenzyme A Ligases/metabolism* ; Liver/metabolism* ; Male

Objective To investigate the prognostic value of echocardiography indicators combined with se-rum recombinant human arginase 1(ARG1)and glucose-6-phosphate dehydrogenase(G6PD)in children with sepsis.Methods A total of 116 children with sepsis admitted to the hospital from May 2022 to June 2023 were enrolled in the study as the sepsis group.According to the severity of sepsis,the children were further divided into general sepsis group(52 cases),severe sepsis group(38 cases)and septic shock group(26 cases).Ac-cording to the prognosis of the children,the children with sepsis were divided into good prognosis group(84 cases)and poor prognosis group(32 cases).A total of 116 healthy children who underwent physical examina-tion in the hospital during the same period were enrolled as the control group.The left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic volume(LV-EDV)and early diastolic mitral flow peak velocity(E)were detected by using color Doppler ultrasound.Ser-um ARG1 and G6PD levels were detected by using enzyme-linked immunosorbent assay(ELISA).The echo-cardiographic indexes and serum ARG1 and G6PD levels were compared between the sepsis group and the con-trol group,and among sepsis children with different disease severity and different prognosis.The receiver op-erating characteristic(ROC)curve was used to analyze the predictive value of echocardiographic indexes com-bined with serum ARG1 and G6PD for poor prognosis in children with sepsis.Results Compared with the control group,the sepsis group had significant reductions in LVEF,E,and G6PD(P＜0.05)and significant increases in LVEDD,LVEDV,and ARG1(P＜0.05).With the aggravation of sepsis,the levels of LVEF,E,and G6PD in children with sepsis gradually decreased(P＜0.05),while the levels of LVEDD,LVEDV,and ARG1 gradually increased(P＜0.05).Compared with the good prognosis group,the poor prognosis group had significantly lower levels of LVEF,E,and G6PD(P＜0.05)and significantly higher levels of LVEDD,LV-EDV,and ARG1(P＜0.05).ROC curve analysis showed that the AUC of echocardiographic indexes com-bined with serum ARG1 and G6PD in predicting poor prognosis of children with sepsis was 0.971,and the sensitivity and specificity were 84.4％and 83.2％,respectively.Conclusion The levels of LVEF,E,and G6PD in children with sepsis significantly decreases,and the levels of LVEDD,LVEDV,and ARG1 signifi-cantly increases.Echocardiographic parameters combined with serum ARG1 and G6PD have high predictive value for poor prognosis in children with sepsis.

Purpose To investigate the abnormal brain development in fetuses with isolated mild to moderate ventriculomegaly(VM)during the second and third trimesters of pregnancy by using semi-quantitative fetal total maturation score(fTMS).Materials and Methods A retrospective analysis was performed on 45 normal fetuses and 78 abnormal fetuses who underwent fetal MRI in the General Hospital of Ningxia Medical University from January 2018 to October 2022.fTMS was used to score all images.Linear regression was used to assess the relationship between fTMS and gestational age between normal and abnormal fetuses and to analyze the differences between fetuses with isolated mild and moderate VM and controls.Results In the control group,fetal fTMS was significantly positively correlated with gestational age(r=0.939,P<0.05).The linear regression equation between fTMS(Y)and gestational age(X)was as follows:Y=-28.1+1.25X.In the mild and moderate isolated VM groups,fTMS was positively correlated with gestational age(r=0.945,0.906,P<0.05).The linear regression equations of fTMS(Y)and gestational age(X)were:Y=-28.46+1.24X,Y=-25.57+1.13X.The average fTMS of healthy fetus,mild VM and moderate VM were(10.55±4.25)points,(10.13+4.08)points and(9.22±3.77)points,respectively.There was no significant difference in fTMS between the 49 fetuses with mild isolated VM and the control group(t=1.651,P>0.05).There was significant difference in fTMS between the 29 fetuses with moderate isolated VM and the control group(t=2.306,P<0.05).Conclusion fTMS is suitable for routine clinical use and sensitive to differences in brain maturation between fetuses with isolated moderate VM and healthy controls.

Human myelination begins in the fifth month of fetal development and continues after birth.Myelin development plays a key role in establishing and maintaining information conduction,coordination and communication within the brain,so prenatal quantitative assessment of myelin development is important.In recent years,many MRI techniques for myelin imaging have been developed and implemented,and quantitative MRI assessment of fetal myelin development has received increasing attention.In this review,we discuss the known structural and functional changes in the development of the myelin sheath of the fetal central nervous system,and review the research progress and future expectations of quantitative fetal MRI imaging.

Objective:To explore the feasibility of expectant management in pregnant women with preterm premature rupture of membranes (PPROM) before 28 weeks of gestation.Methods:A retrospective analysis was conducted on the clinical data of 92 pregnant women diagnosed with PPROM before 28 weeks and delivered in Peking University First Hospital from January 2015 to March 2023. These women were divided into the termination group or expectant management group, and the latter was further divided based on whether the rupture of membranes occurred before 24 weeks or after. Clinical data of the women and neonates between the two groups and the two subgroups were analyzed. Additionally, all the subjects were divided based on the presence or absence of severe neonatal complications and clinical data of the mothers and their neonates were also analyzed. Statistical analyses were performed using t-tests, Mann-Whitney U tests, Chi-square tests, or Fisher's exact tests. Results:(1) Among the 92 women with PPROM, 53 (57.6%) chose to terminate the pregnancy, while 39 (42.4%) chose expectant management including ten twins and 29 singletons. (2) Compared to the termination group, the expectant management group had a smaller percentage of multiparous women [7.7% (3/39) vs. 32.1% (17/53), Fisher's exact test, P=0.019], greater gestational age at membrane rupture [24 +6 weeks (18-27 +6) weeks vs.21 +3weeks (14 +2-27 weeks), Z=53.14, P=0.042], and a lower incidence of oligohydramnios after membrane rupture [46.2% (18/39) vs. 84.9% (45/53), χ2=6.56, P=0.031]. (3) All of the 39 women in the expectant group gave birth before 37 weeks with the mean gestational age at delivery of 28 +1weeks (25 +1-36 +1 weeks) and 49 live born babies, among which four neonates died giving the survival rate of 91.8%(45/49). There were no statistically significant differences in gestational age at delivery or neonatal outcomes between women with membrane rupture before 24 weeks and those ruptured between 24 and 27 weeks and 6 days of gestation (all P>0.05), but the expectant duration was significantly longer in the former group [55.0 d (20.0-96.0 d) vs. 9.0 d (0.5-52.0 d ), Z=－4.95, P<0.001]. (4) The 49 neonates were further divided into with ( n=9, including the death) or without ( n=40) severe complication subgroups. Those neonates in the non-severe complication subgroup had a significantly greater gestational age at birth compared to those in the other subgroup [30 +6 weeks (27 +5-36 +4 weeks) vs. 27 +5 weeks (25 +1-31 +5 weeks), Z=－3.42, P=0.001], a longer expectant duration [42.0 d (3.0-80.0 d) vs. 19.0 d (0.5-59.0 d), Z=－2.31, P=0.021], a higher birth weight [(1 630±544) g vs. (1 069±272) g, t=4.56, P=0.009], a lower incidence of neonatal asphyxia [2/9 vs. 70.0% (28/40), Fisher's exact test, P=0.012], a shorter hospital stay [37.5 d (3.0-54.0 d) vs. 67.0 d (60.0-105.0 d), Z=－3.01, P=0.003] and a higher proportion of pregnancies completing two courses of fetal lung maturation [5/9 vs. 17.5% (7/40), Fisher's exact test, P=0.029]. (5) Among the ten twin pregnancies, all the 20 babies developed severe complication resulting a higher proportion of twins in the severe complication group than in the non-severe complication group [50% (20/40) vs. 0/9, Fisher's exact test, P=0.005]. Conclusions:For pregnant women with PPROM before 28 weeks, under the premise of informed consent and thorough evaluation, expectant management can be considered if there are no indications for immediate termination of pregnancy, to achieve a higher neonatal survival rate. However, the incidence of severe complications related to preterm infants remains high in the short term, with most having a good prognosis after treatment in the neonatal intensive care unit. Twin pregnancies and lower gestational age at birth are risk factors for severe complications in preterm infants.

ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling， 40 surviving mice were randomly divided into model group， cisplatin group ［2.5×10^-3 g·kg^-1·（3 d）^-1］， Shenqi Yiliu prescription group （27 g·kg^-1·d^-1）， and a combination group （Shenqi Yiliu prescription group + cisplatin）. The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention， the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators， including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. The TdT-mediated dUTP-biotin nick end labeling （TUNEL） assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， and gasdermin D （GSDMD） in tumor tissues. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in tumor tissues were detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the mice in the blank group， those in the model group were in a poor mental state， sleepy， and lazy， and their fur color was dull， with increased levels of serum ALT and AST in liver function tests （P<0.01）. Compared with the model group， the groups with drug intervention showed improved mental state， inhibited tumor growth to varying degrees， and decreased tumor weight， and the tumor inhibition rate in the combination group was the highest （P<0.01）. HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant， while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test， the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased （P<0.05， P<0.01）. Among them， the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant （P<0.01）. TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention （P<0.05， P<0.01）， especially the cisplatin group and Shenqi Yiliu prescription group （P<0.01）. Western blot， IHC， and IF found that the protein expression levels of NLRP3， Caspase-1， and GSDMD in each group with drug intervention decreased （P<0.05， P<0.01）. Compared with the mice in the cisplatin group， those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology， and the tumor weight of the mice in the combination group decreased （P<0.05）. The levels of ALT and AST in the Shenqi Yiliu prescription group decreased （P<0.05）， and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased （P<0.05， P<0.01）， especially in the combination group （P<0.01）. The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced （P<0.01）. IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced （P<0.01）. The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the expression level of Caspase-1 protein in the combination group decreased （P<0.01）. The decrease in GSDMD protein expression was not significant， and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect， which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis， and relieve the inflammatory response in mice with liver cancer.

Objective: To investigate the effects of lactoprotein iron chelates on rats with iron deficiency anaemia (IDA), so as to provide insights into developing and utilizing novel iron supplements. Methods: Seventy weaning female SPF-graded rats of the SD strain were randomly divided into the control group (A), model group (B), ferrous sulfate group (C), lactoferrin group (D), lactoferrin iron chelate group (E), Casein oligopeptide iron chelate group (F) and whey protein oligopeptide iron chelate group (G), with 10 rats in each group. The rats in group A were fed with normal diet, and the others were fed with poor iron diet for IDA modeling. The corresponding interventions were given by intragastric administration once a day. The iron ion concentrations of group C, E, F and G were 2.0 mg/kg, and the protein and oligopeptide concentrations of group D, E, F and G were 2 000 mg/kg. Body weight and hemoglobin of rats were measured weekly during 21-day intervention. At the end, peripheral blood samples were collected, and blood routine, iron metabolism and liver function indicators were determined. Results: After the intervention, among blood routine indicators, the rats in group C, E, F and G showed elevated hemoglobin, red blood cell, mean corpuscular volume and hematocrit, and decreased free protoporphyrin and mean corpuscular hemoglobin concentration when compared with the rats in group B (all P<0.05); among iron metabolism indicators, the rats in group C, E and G showed elevated serum ferritin, the rats in group C, E, F and G showed elevated serum iron, the rats in group C, D, E, F and G showed decreased unsaturated iron binding capacity and total iron binding capacity when compared with the rats in group B (all P<0.05); among liver function indicators, the rats in group E and G showed decreased alanine transaminase when compared with the rats in group B (both P<0.05). Conclusions Lactoprotein alone could not completely improve IDA in rats compared with traditional iron supplement (ferrous sulfate). Lactoprotein iron chelate, especially whey protein oligopeptide iron chelate, could significantly improve IDA, iron reserve and liver function damage in rats.

ObjectiveTo summarize the current situation, hot spots and frontiers of the application of functional near-infrared spectroscopy (fNIRS) in rehabilitation in recent ten years. MethodsLiterature related to the application of fNIRS in rehabilitation was retrieved from the core collection of Web of Science from January, 2003 to December, 2022, and the visualized analysis was performed by CiteSpace 6.1.R6 software. ResultsA total of 828 literatures were included. The annual publication volume was on the rise. The most prolific author was LI Zengyong. The most published country was the United States. And the most published institution was Karolinska Institute. Hot keywords included children, stroke, activation, quality of life, cerebral palsy, etc. The hot keywords of bursting intensity included early intervention, speech perception, cerebral palsy, plasticity, spinal cord injury, physical therapy, visual feedback, Parkinson's disease, etc. Cluster analysis suggested that in the past decade, the application of fNIRS in rehabilitation involved physical therapy, speech therapy, occupational therapy, pre-rehabilitation and early rehabilitation of surgery, mainly focusing on six themes: the rehabilitation of motor dysfunction after stroke, cognitive impairment, hearing and speech dysfunction, children with cerebral palsy, cardiopulmonary function monitoring in severe diseases and long-term nursing of chronic diseases. Among them, the application of fNIRS in neurological rehabilitation of stroke patients occupied a large proportion, which might be the current research hot spot and trend. ConclusionThe application of fNIRS in rehabilitation is on the rise. In the future, more attention should be paid to the application of fNIRS in the study of the injury and recovery mechanism of neurological disorders, especially the effects of various rehabilitation interventions on cortical plasticity and the etiology of neurological disorders.