This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.
Humans ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child, Preschool ; Transplantation, Homologous ; Child ; Leukemia, Myeloid, Acute/genetics* ; Oncogene Proteins, Fusion/genetics*

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective:To observe the effect of auricular pressure beans(APN)combined with Compound Tung-Leaf Burn Oil(CTBO)on perioperative anxiety and pain in patients undergoing circumcision.Methods:This study included 100 patients undergo-ing circumcision with the disposable circumcision anastomosis stapler in our hospital from August 2023 to November 2023,of whom 50 received routine circumcision nursing care(the control group)and other 50 APN combined with compound CTBO in addition(the ob-servation group).We compared between the two groups the anxiety scores before any intervention,30 minutes before and 24 hours and 10 days after operation,the pain scores 24 hours postoperatively and at the first change of wound dressing,the frequency of 3-day post-operative sleep awakenings,the incidence of complications,and the satisfaction of the patients.Results:Totally,94 patients com-pleted the study,46 in the observation and 48 in the control group.The anxiety scores exhibited no statistically significant difference between the two groups of patients before any intervention(P>0.05),but were markedly lower in the observation than in the control group at 30 minutes before and 24 hours and 10 days after surgery(P<0.05),and so were the pain scores24 hours after surgery and at the first change of wound dressing(P<0.05),and the frequency of 3-day postoperative sleep awakenings(P<0.05).The satis-faction rate of the patients was remarkably higher(P<0.05)while the incidence of complications significantly lower in the observation group than in the control(P<0.05).Conclusion:Auricular pressure beans combined with Compound Tung-Leaf Burn Oil can ef-fectively alleviate perioperative anxiety,reduce postoperative pain and improve satisfaction of the patients undergoing circumcision.

Objective To investigate the efficacy and safety of subcutaneous immunotherapy(SCIT)using dust mites in children with allergic asthma.Methods In a prospective randomized controlled study,98 children with dust mite-induced allergic asthma were randomly divided into a control group(n=49)and an SCIT group(n=49).The control group received inhaled corticosteroid treatment,while the SCIT group additionally received a standardized three-year SCIT regimen.The two groups were compared based on peripheral blood eosinophil percentage,visual analogue score(VAS),total medication score,Asthma Control Test/Childhood Asthma Control Test scores,fractional exhaled nitric oxide(FeNO),and lung function before treatment,and at 6 months,1 year,2 years,and 3 years after treatment.Adverse reactions were recorded post-injection to evaluate the safety of SCIT.Results Compared with pre-treatment levels,the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils,VAS,total medication score,and FeNO,while lung function significantly improved,and asthma control levels were better 3 years after treatment(P<0.05).Compared with the control group,the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment(P<0.05).A total of 2 744 injections were administered,resulting in 157 cases(5.72%)of local adverse reactions and 4 cases(0.15%)of systemic adverse reactions,with no severe systemic adverse events.Conclusions SCIT is an effective and safe treatment for allergic asthma in children.

AIM To establish a GC-MS method for the simultaneous content determination of sixteen pesticide residues in Lycii Fructus and perform safety assessment.METHODS The analysis was performed on DB-5MS chromatographic column(30 m×0.25 mm,0.25 μm)subjected to the programmed heating,with splitless injection of 1.0 μL dissolved sample at a flowing rate of 1.0 mL/min.Other parameters were as follows:injection port temperature of 250℃,electron impact ionization(EI),electron energy of 70 eV;ion source temperature of 230℃,multi-reaction monitoring mode,and collision gas.of high-purity N2.Pesticide residues with relatively high dietary risk were analyzed and discussed with regard to residue levels,dietary intake risk,risk ranking and cumulative exposure assessment.RESULTS Sixteen pesticides showed good linear relationships within their own ranges(r≥0.994 4),whose average recoveries were 70%-114%,with the RSDs of less than 2%.The highest average cyfluthrin residue of 0.999 2 mg/kg in Lycii Fructus of production regions and the highest average cypermethrin residue of 0.088 4 mg/kg in Lycii Fructus commodities were both detected.In Lycii Fructus of production regions with chronic hazard index(HI)value of 0.012 9 and acute HI value of 0.065 5 and their commodities with chronic HI of 0.001 2 and acute HI of 0.005 4,the pesticide residue of cypermethrin was the leading cause of chronic and acute dietary risk,and additionally,pyridaben within maximum residue limit(MRL)was the only detectectable highly toxic pesticide among the other most concerning pestcides of deltamethrin,pyridaben,chlorpyrifos,dichlorvos and methidathion.CONCLUSION There exist pesticide residues within MRL values in some samples of Lycii Fructus and the use of cypermethrin should be well-controlled.

Pulmonary disease is one of the major threats to human health. However, the current clinical treatment drugs for lung diseases generally have problems such as low lung delivery efficiency, fast clearance rate and obvious toxic side effects. Recently, membrane biomimetic nanocarriers have attracted more and more attention. Due to their advantages of high targeting, long cycle time, good biocompatibility and strong immune escape ability, membrane biomimetic nanocarriers have become a major research hotspot in targeted therapy of lung diseases. In this review, we discuss the main preparation methods of membrane biomimetic nanoparticles, the characteristics of membrane biomimetic nanocarriers from different cell sources and their application in the targeted therapy of lung diseases. At the same time, according to the characteristics of different membranes, the shortcomings, current technical limitations and future prospects are discussed. This review is expected to provide references for the design of membrane biomimetic nanocarriers and their potential applications in the treatment of lung diseases.

OBJECTIVE: To retrospectively analyze efficacy of single structure internal fixation and double structure internal fixation in the treatment of ipsilateral femoral shaft and neck fracture, and analyze their indications. METHODS: From June 2015 to December 2020, 21 patients with ipsilateral femoral shaft and femoral neck fracture were treated, including 14 males and 7 females, aged 23 to 69 years old with an average of(38.1±12.9) years old. According to different femoral shaft fracture sites, some patients were fixed with cephalomedullary implant for both femoral neck and the femoral shaft(single structure, InterTan or PFNA Ⅱ), some patients were fixed with cannulated screws for the femoral neck and a retrograde locking nail for the femoral shaft (dual structure), and postoperative function and complications were recorded during follow-up. In 10 cases of single-structure fixation, the femoral necks were all basicervical fractures, and the femoral shaft fractures were located in the proximal isthmus;11 cases were double-structure fixation, 9 cases in 11 were basal type of femoral neck, 2 cases in 11 were neck type, and the femoral shaft fractures were located in the isthmus and the distal isthmus. RESULTS: All patients were followed up for 12 to 27 months. No femoral head necrosis, deformity, delay or nonunion occurred in the patients with single-structure fixation, and no delayed union or nonunion occurred in femoral shaft fractures;At the final follow-up, Harris score of patients with single-structure fixation was 91.8±4.1, with 8 cases were excellent and 2 cases were good. The fractures of patients with dual-structure fixation achieved good union without femoral head necrosis, except 1 case of femoral shaft fracture had delayed union;At the final follow-up, Harris score of patients with dual-structure fixation was 92.4±5.9, 7 cases were excellent, 3 cases were good, and 1 case was fair. CONCLUSION Good reduction and fixation is the key to the treatment of such fractures. Both the single-structure fixation and the dual-structure fixation are good methods, and it should be selected according to the locations of femoral shaft and femoral neck fractures. Single-structure fixation is a good choice for femoral shaft fractures located at the proximal isthmus and basal femoral neck fractures. For isthmus and distal femoral shaft fractures combined with ipsilateral femoral neck fractures, dual-structure fixation is recommended.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Femur Neck ; Retrospective Studies ; Femoral Neck Fractures/complications* ; Femoral Fractures/complications* ; Fracture Fixation, Internal/methods* ; Femoral Fractures, Distal ; Treatment Outcome ; Fracture Fixation, Intramedullary/methods*

ObjectiveTo construct ¹³¹Ⅰ-labeled hepatoma nucleic acid nanotrain and to explore its feasibility as a new nuclide carrier targeting hepatoma. MethodsThree short nucleic acid chains self-assembled to a long nucleic acid chain after being annealed， and ¹³¹Ⅰ-NT was obtained by radioiodine labeling using chloramine T method. The labeling efficiency and radiochemical purity of the nanoparticles were measured by paper chromatography. The stability of the labeled products in vitro at different temperatures and different storage solvents was detected. The specific uptake of nanoparticles by hepatocellular carcinoma cells was observed by laser confocal microscopy， and the radioactive uptake ratio of ¹³¹Ⅰ-NT combined with human hepatocellular carcinoma cell HepG2 and normal hepatocyte L02 was measured. The biodistribution of ¹³¹Ⅰ-NT was obtained through injecting ¹³¹Ⅰ-NT into HepG2 tumor-bearing mice via tail vein. ResultsThe labeling rate of ¹³¹Ⅰ-NT was （93.05±0.74） %， and the radiochemical purity post purification was （98.35±0.32） %. Its radiochemical purity in PBS and pure serum at 4℃ for 24 h was （92.77±0.04） % and （89.43±0.2） %， respectively. The radioactivity uptake rate of HepG2 cells was higher than that of L02 cells after ¹³¹Ⅰ-NT was incubated with two kinds of cells for 2 h significantly. After injection of ¹³¹Ⅰ-NT through tail vein， the radioactive uptake per gram of tumor tissue were （4.9±0.55）%ID/g， （10.12±0.32）%ID/g and （4.25±0.31）%ID/g at 30 min， 1 h and 2 h， respectively. The T/M ratio was 7.33±2.04， 36.54±12.72 and 44.93±7.90 respectively. ConclusionsThe ¹³¹Ⅰ-labeled long chain nucleic acid nanotrain was constructed successfully， which possesses relatively high stability in vitro ， and high targeting ability to HepG2 cells in vitro and HepG2 tumor-bearing mouse model. Our study demonstrated that ¹³¹Ⅰ-NT may be a potential radionuclide carrier targeting human liver cancer， which provides a new idea for the targeted radionuclide diagnosis and treatment of hepatocellular carcinoma.