ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

Histone deacetylase 3 (HDAC3) is an epigenetic modification enzyme that plays a crucial role in the development and progression of diabetes and its complications. Studies have reported that increased HDAC3 activity is associated with pancreatic β-cell dysfunction in type 1 diabetes, while in type 2 diabetes, HDAC3 affects insulin resistance and signaling by regulating the metabolism of the liver, adipose tissue, and muscle. Additionally, HDAC3 plays a key role in diabetic complications such as cardiomyopathy, retinopathy, and nephropathy. Selective inhibition of HDAC3 has the potential to improve insulin sensitivity, reduce chronic inflammation, and enhance pancreatic cell function, offering a promising new therapeutic strategy for diabetes and its complications.

OBJECTIVE: To analyze the clinical efficacy of manual reduction combined with 3D printing small splint external fixation and synchronous manual reduction combined with traditional small splint external fixation in the treatment of humeral shaft. METHODS: Between January 2021 and December 2022, 40 patients with humeral shaft fractures were treated with 3D printing small splints and traditional small splints. They were divided into 3D group and traditional group according to different fixation methods. Among them, there were 15 males and 5 females in the 3D group, aged from 20 to 52 years old with an average of (36.3±15.6) years old. In the traditional group there were 17 males and 3 females, aged from16 to 51 years old with an average of (32.9±17.2) years old. The occurrence of complications, duration of fracture healing, rate of fracture healing, subjective evaluation scores for brace comfort at 1 week and 4 weeks, as well as the Constant-Murley shoulder function score and Mayo elbow function score at 8 weeks and 16 weeks were compared between the two groups. RESULTS: All patients were followed up for 16 weeks. The 3D group did not experience any complications, while there were two cases of complications in the traditional group. However, this difference was not found to be statistically significant (χ²=2.105, P=0.146). The fracture healing time of the 3D group (90.1±4.5) days was significantly shorter compared to that of the traditional group (93.3±3.8) days (P<0.05). The subjective evaluation scores for brace comfort in the 3D group (53.7±2.3) points and (62.8±1.1) points were significantly higher than those in the traditional group (45.6±2.4) points and (52.3±1.4) points at 1 and 4 weeks after reduction (P<0.05). After 8 weeks of reduction, the Constant-Murley shoulder function score in the 3D group was(68.1±5.3) points, which demonstrated a statistically significant improvement compared to the traditional group(54.3±4.9) points (P<0.05). However, at 16 weeks post-reduction, there were no significant differences observed between the two groups (P>0.05). The Mayo elbow function score of the 3D group (84.1±7.5) points was significantly superior to that of the traditional group (79.5±6.8) points at 8 weeks post-reduction (P<0.05). However, there was no statistically significant difference between the two groups at 16 weeks post-reduction (P>0.05). CONCLUSION For humeral shaft fractures with conservative treatment indications, manual reduction combined with 3D printed small splints is a good choice for treatment. The patient's comfort level is higher, which can not only reduce the occurrence of complications, but also improve the fracture healing rate and joint function to a certain extent, and improve the patient's quality of life.
Humans ; Female ; Male ; Adult ; Middle Aged ; Humeral Fractures/physiopathology* ; Printing, Three-Dimensional ; Splints ; Adolescent ; Young Adult ; Fracture Healing

OBJECTIVE: To investigate the effect of non-chemotherapy strategy of retinoic acid (ATRA) combined with arsenic trioxide (ATO) on the survival of patients with acute promyelocytic leukemia (APL). METHODS: The data of APL patients with complete information diagnosed in the hematology department of our hospital from June 2009 to November 2024 were retrospective analyzed. All patients in the non-CHT group received ATRA-ATO induction, consolidation and maintenance therapy. Patients in the CHT group received ATRA-ATO+chemotherapy induction therapy, followed by 3 cycles of ATRA-ATO+CHT consolidation therapy and 6-10 cycles of ATRA-ATO maintenance therapy. The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS), remission rate, differentiation syndrome (DS) and safety. RESULTS: There were 182 patients with APL and 15 patients with early death (ED), accounting for 8.24%, which was related to age and risk stratification. There was no significant difference in remission rate between the non-CHT group and the CHT group (P =0.486). As of February 2025, the median follow-up time of patients was 39.5 months. The EFS of the non-CHT group was significantly better than that of the CHT group (P =0.038). There was no significant difference in OS between the two groups (P =0.442). Subgroup analysis showed that EFS in the non-CHT was longer in standard-risk patients (P =0.012). There was no significant difference in EFS (P =0.585) and OS (P =0.473) between the CHT and non-CHT groups in high-risk patients. The incidence of mild DS was 23.6% in the non-CHT group and 23.1% in the CHT group, respectively, with no statistically significant difference(P =0.937). Compared with CHT group, the incidence of serious adverse events was lower in the non-CHT group. CONCLUSION The non-chemotherapy regimen of ATRA combined with ATO is a feasible method to cure APL patients.
Humans ; Leukemia, Promyelocytic, Acute/drug therapy* ; Arsenic Trioxide/therapeutic use* ; Tretinoin/administration & dosage* ; Retrospective Studies ; Female ; Treatment Outcome ; Male ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Middle Aged ; Remission Induction

Apurinic/apyrimidinic endonuclease 1(APE 1)is a multifunctional protein that plays important roles in DNA repair and regulation of gene expression.Because APE 1 is overexpressed in various cancers,it can serve as a cancer biomarker for aiding clinical diagnosis,guiding therapy,and monitoring prognosis.On this basis,a label-free fluorescent probe was designed based on the primer exchange reaction(PER)strategy for highly sensitive detection of APE 1 activity.In the absence of APE 1,the structure of catalytic hairpin(HP)was stable and could not form G-quadruplex.Therefore,the background fluorescence of this sensing system was very low due to the dissociation of thioflavin T(ThT).In the presence of APE 1,the apurinic/apyrimidinic(AP)site of HP was cleaved by APE 1 and a short nucleic acid fragment that acted as a primer to initiate PER was generated.After PER reaction,a large number of G-quadruplex were produced,which could specifically bind with ThT and resulted in significant increase of fluorescence signal.The combination of low background design of HP and PER amplification made this biosensor had high sensitivity with a detection limit(3σ)of 0.0008 U/mL.Furthermore,the primer sequence was directly generated by the cleavage of APE 1 without additional addition,which not only increased the specificity of the reaction,but also simplified the experiment procedure.Moreover,the use of label-free fluorescence signal reduced the cost of the experiment,and realized rapid detection of APE 1.Finally,this sensor was used to detect APE 1 in human serum samples with spiked recoveries of 91%-104%,proving great potential in study of biological enzyme.

Objective To analyze the relationship between umbilical cord blood chemokines regulated upon activation normal T cell expressed and secreted(RANTES),C-X-C motif chemokine ligand 12(CXCL12),C-X-C motif chemokine receptor 4(CXCR4)and neonatal septicemia inflammatory response and outcome.Meth-ods A total of 242 children with neonatal septicemia admitted to a hospital from January 2020 to January 2024 were selected as the study subjects,and were divided into non-critical group(101 cases),critical group(79 cases)and extremely critical group(62 cases)according to neonatal critical case score.According to the prognosis,the subjects were divided into good prognosis group and bad prognosis group.The levels of RAN-TES,CXCL12,CXCR4 and inflammatory factors[C-reactive protein(CRP),interleukin-6,IL-1β]in umbilical cord blood of each group were detected.The correlation between RANTES,CXCL12,CXCR4 and inflammato-ry factors in umbilical cord blood of neonatal septicemia was analyzed by Pearson correlation,and the influen-cing factors of poor prognosis of neonatal septicemia were analyzed by multivariate Logistic regression.Re-ceiver operating characteristic(ROC)curve was drawn to analyze the value of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting the poor prognosis of neonatal septicemia.Results The levels of RAN-TES,CXCL12,CXCR4,CRP,IL-6 and IL-1β in umbilical cord blood of extremely critical group were higher than those of critical group and non-critical group,and the differences were statistically significant(P＜0.05).The levels of RANTES,CXCL12 and CXCR4 in umbilical cord blood of neonatal septicemia were posi-tively correlated with CRP,IL-6 and IL-1β(P＜0.05).Multivariate Logistic regression analysis showed that extremely severe,early-onset septicemia,high RANTES,high CXCL12 and high CXCR4 were risk factors for poor prognosis of neonatal septicemia(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting poor prognosis of neonatal septicemia were 0.810,0.814 and 0.763,respectively,and the AUC of three indicators combined prediction was 0.914,which was higher than that of single prediction.Conclusion The increased levels of RANTES,CX-CL12 and CXCR4 in umbilical cord blood of neonatal septicemia are associated with inflammation,aggravation and poor prognosis,and the combination of RANTES,CXCL12 and CXCR4 can predict the risk of poor prog-nosis of neonatal septicemia.

Objective To investigate the characteristics of intestinal flora and its correlation with peripheral blood microinflammatory factors in patients with pulmonary tuberculosis complicated with diabetes mellitus(PTB-DM).Methods A total of 162 patients with PTB-DM admitted to the hospital from September 2022 to September 2024 were selected as the PTB-DM group,and another 150 healthy subjects who underwent physi-cal examinations during the same period in the hospital were selected as the control group.The clinical data of all research subjects was collected.The composition of intestinal flora of the research subjects was analyzed by using 16S rRNA gene sequencing technology.The levels of peripheral blood microinflammatory factors[inter-feron-γ(IFN-γ),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)]in all research subjects were detected.The clinical data,composition of intestinal flora and levels of microinflammatory factors of the PTB-DM group were compared with those of the control group.Spearman correlation analysis was used to analyze the correlation between the relative abundance of intestinal flora and the levels of peripheral blood microin-flammatory factors in patients with PTB-DM.Results The relative abundances of Bacteroidales and Clostridi-ales in the PTB-DM group were significantly lower than those in the control group,while the relative abun-dances of Enterobacterales and Actinobacteriales were significantly higher than those in the control group,and the differences were statistically significant(P<0.05).The levels of IFN-γ,IL-6 and TNF-α in the PTB-DM group were significantly higher than those in the control group,and the differences were statistically signifi-cant(P<0.05).The relative abundances of Bacteroidales and Clostridiales in the PTB-DM group were nega-tively correlated with the levels of IFN-γ,IL-6 and TNF-α.The relative abundances of Enterobacterales and Actinobacteriales were positively correlated with the levels of IFN-γ,IL-6 and TNF-α(all P<0.05).Conclu-sion There is a significant imbalance of intestinal flora in patients with PTB-DM,and the levels of microin-flammatory factors IFN-γ,IL-6 and TNF-α in peripheral blood are significantly increased,and are closely re-lated to the relative abundance of specific flora.

Objective To measure the range of cervical spine mobility in flight trainees and analyze its correlation with flight task performance.Methods A total of 55 participants were enrolled(30 in the experimental group,25 in the control group).An independently developed AI-based digital cervical spine function assessment system was used to measure rotational ranges in yaw,pitch,and roll directions,with comparative analysis performed against contralateral rotation.A subjective scoring scale was designed,and flight instructors of the experimental group were invited to provide performance ratings to explore the relationship between cervical mobility and flight task performance.Results Significant differences were observed between the experimental and control groups in left rotation(P<0.01),right rotation(P<0.05),and flexion(P<0.05).Within the experimental group,significant differences were found between left and right rotation(P<0.01)and between flexion and extension(P<0.01).Correlation analysis between flight performance scores and cervical mobility revealed a significant association between situational awareness and yaw range(r=-0.415,P<0.05).Conclusion The experimental group exhibited significant differences in certain cervical mobility parameters compared to the control group,suggesting that occupational characteristics may influence cervical mobility.The correlation between yaw range and situational awareness implies a potential link between head-neck yaw capability and vestibular-visual system functions,though further validation is required.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective To investigate the inhibitory effect of Ginsenosides Rg1(GS-Rg1)on the proliferation and metastasis of tongue squamous cell carcinoma(TSCC),and its related mechanisms of action.Methods TSCC cells were treated with GS-Rg1 at concentrations of 1.25,2.5,5.0 and 10.0 μmol·L-1 for 48 hours.The proliferation ability of cells at different concentrations was measured by cell counting kit-8(CCK-8)experiment,and the IC5ovalue of GS-Rg1 at CAL-27 for 48 hours was calculated.TSCC cells CAL-27 were divided into control group and GS-Rg1 group.The control group and GS-Rg1 group were treated with 0.9％NaCl and IC50concentration of GS-Rg1 for 48 hours,respectively.The cell cycle distribution of each group was detected by flow cytometry,and the cell metastasis ability of each group was detected by Transwell experiment.Construct TOP/FOP Flash plasmid,transfect control group and GS-Rg1 group,and detect the effect of GS-Rg1 effect on wnt/β-catenin signaling pathway activity in TSCC cell CAL-27 using luciferase assay.Using wnt/β-catenin pathway inhibitor XAV939 treated GS-Rg1 group cells(XAV939+GS-Rg1 group),and wnt/β-catenin pathway activator HLY78 was used to treat GS-Rg1 group cells(HLY78+GS-Rg1 group)and detect changes of wnt/β-catenin signaling pathway activity,the cell proliferation ability,cell cycle distribution,and metastasis ability in XAV939+GS-Rg1 group,HLY78+GS-Rg1 group and GS-Rg1 group.The expression of wnt/β-catenin signaling pathway related proteins β-catenin,and its downstream cell cycle related proteins cellular myelocytomatosis oncogene(cMYC),Cyclin dependent kinase 4(CDK4),andcyclinD1,as well as metastasis related proteins E-cadherin,N-cadherin and matrix metalloproteinase 2(MMP-2)were detected by Western blotting in each group of cells.Results GS-Rg1 significantly inhibited the proliferation ability of TSCC cells CAL-27(P＜0.05),and the IC50value of GS-Rg1 on CAL-27 was(5.46±1.58)μmol·L-1.The ratio of GO/G1 phase cells in the control group and GS-Rg1 group were(60.65±2.16)％and(71.20±2.38)％,respectively;the number of cell transmembrane penetration were 87.33±7.51 and 50.67±3.21,respectively;the luciferase activity were 1.00±0.02 and 0.35±0.06,respectively.Compared with the control group,the GS-Rg1 group showed cell cycle arrest in GO/G1 phase,decreased cell metastasis ability,and the activity of wnt/β-catenin signaling pathway decreased(P＜0.05,P＜0.01).Compared with the GS-Rg1 group,the activity of the wnt/β-catenin signaling pathway was decreased,cell proliferation ability and metastasis ability was decreased(P＜0.05),while the number of GO/G1 phase cells was increased(P＜0.05),the expression of β-catenin,cMYC,CDK4,cyclinD1,E-cadherin and MMP-2 proteins were decreased(P＜0.05),while the expression of N-cadherin protein increased in XAV939+GS-Rg1 group cells.However,the result were opposite in the HLY78+GS-Rg1 group of cells.Conclusion GS-Rg1 downregulates wnt/β-catenin signaling pathway inhibits the proliferation and metastasis ability of TSCC cells.