Objective:To evaluate the elastic characteristics of the pulmonary trunk and its distal branches in fetuses with tetralogy of Fallot（TOF）by Doppler echocardiography.Methods:A total of 42 fetuses with TOF（TOF group）and 84 gestational age-matched normal fetuses（control group）were prospectively collected from the Second Xiangya Hospital of Central South University from August 2022 to January 2023. The severity of TOF was classified into mild TOF（Z-score≥-2），moderate TOF（-40.05）. Conclusions:Fetuses with TOF present with increased MPA-PAS and decreased stiffness in the distal PA. Histological abnormalities of the pulmonary artery wall in fetuses with TOF have been observed during pregnancy.

A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) method was established for simultaneous determination of seven characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rat plasma, including galangin, kaempferol, kaempferide, pinocembrin, 1,7-diphenyl-4-en-3-heptanone, 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA), and 7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-4-en-3-heptanone(DPHB). The new developed HPLC-MS/MS method was applied to study the pharmacokinetics of the 7 characteristic components in rats with Helicobacter pylori gastritis. A Waters Sunfire C_(18) column(2.1 mm×150 mm, 3.5 μm) was used. The acetonitrile-aqueous solution(containing 0.1% formic acid) was adopted as the mobile phase for gradient elution. Seven components and internal standard(chlorogenic acid) were separated within 12 min. Mass spectrometric detection was performed in multiple reaction monitoring(MRM) mode using electrospray ionization(ESI) source with fast switching between positive and negative ions. The method was verified by specificity, linearity, precision, accuracy, recovery, matrix effect, and stability and met the requirements of pharmacokinetic study on the 7 components in rat plasma. Pharmacokinetic results showed that the average peak time(T_(max)) of the 7 components was 0.31-2.19 h, their elimination half-life(t_(1/2)) was 5.26-16.65 h, and the average residence time(MRT) was 6.29-31.03 h after the oral administration of the active fraction of Alpiniae Officinarum Rhizoma to rats with H. pylori gastritis. The plasma exposure levels of galangin and DHPA were higher than those of the other components. The concentration-time curves of four detected flavonoids showed obvious double peaks. This study elucidated the pharmacokinetic characteristics of 7 characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rats with H. pylori gastritis, providing a scientific basis for the identification of the pharmacodynamic substances of Alpiniae Officinarum Rhizoma for treatment of H. pylori gastritis and the clinical application of Alpiniae Officinarum Rhizoma in the prevention and treatment of H. pylori gastritis.
Animals ; Rats ; Chromatography, High Pressure Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Helicobacter pylori/drug effects* ; Alpinia/chemistry* ; Rats, Sprague-Dawley ; Gastritis/metabolism* ; Helicobacter Infections/metabolism* ; Flavonoids/blood* ; Rhizome/chemistry* ; Liquid Chromatography-Mass Spectrometry

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

AIM:This study aims to investigate the role of ferroptosis in the myocardium of mice with lipopoly-saccharide(LPS)-induced sepsis and in the injury of H9c2 rat cardiomyocytes,and to explore the regulatory function of microRNA-351-5p(miR-351-5p)in this context.METHODS:An in vivo model of sepsis-induced cardiomyopathy was established in mice through intraperitoneal injection of LPS.Twenty-four mice were randomly divided into negative control(NC)group,LPS group,and LPS+ferroptosis inhibitor ferrostatin-1(Fer-1)group.Hematoxylin-eosin(HE)staining was conducted to assess cardiac injury,and plasma levels of creatine kinase(CK)and lactate dehydrogenase(LDH)were also measured.Additionally,the levels of Fe2+and malondialdehyde(MDA)in plasma were quantified,and the mRNA levels of acyl-CoA synthetase long chain family member 4(ACSL4)and prostaglandin-endperoxide synthase 2(PTGS2)were de-tected by RT-qPCR.In vitro,H9c2 cardiomyocytes were stimulated with LPS to create cellular models,followed by treat-ment with Fer-1,inhibitor NC,or miR-351-5p inhibitor.Cell viability was evaluated using CCK8 assay,intracellular re-active oxygen species(ROS)were measured by flow cytometry,intracellular Fe2+levels were assessed using a fluorescence probe,and the protein expression of glutathione peroxidase 4(GPX4)and ACSL4 was analyzed by Western blot.The MDA and reduced glutathione(GSH)levels were measured using commercial kits.MicroRNA(miRNA)sequencing was performed on the LPS-stimulated H9c2 cardiomyocyte models,with differential miRNAs identified and subsequently vali-dated using RT-qPCR.RESULTS:The mice in LPS group exhibited significant myocardial tissue dysregulation com-pared with NC group,with enlarged space,increased plasma CK and LDH levels(P<0.05),elevated Fe2+and MDA levels in myocardial tissues(P<0.05),and increased mRNA levels of ACSL4 and PTGS2(P<0.05).In contrast,the mice in LPS+Fer-1 group demonstrated improved myocardial tissue structure,reduced space,decreased plasma CK and LDH levels(P<0.05),and lower Fe2+and MDA levels in myocardial tissues(P<0.05),along with decreased mRNA level of PTGS2(P<0.05).In H9c2 cardiomyocytes,cell viability,intracellular GSH level,and GPX4 protein level were significantly reduced in LPS group compared with NC group(P<0.05),while ROS,MDA,Fe2+,and ACSL4 protein levels were elevated(P<0.05).The cells in LPS+Fer-1 group showed increased viability,intracellular GSH level,and GPX4 protein level compared with LPS group(P<0.05),alongside reduced ROS,MDA,Fe2+,and ACSL4 levels(P<0.05).miRNA sequencing revealed a significant decrease in several miRNAs,with miR-351-5p showing the most pro-nounced reduction.In LPS+miR-351 inhibitor group,H9c2 cell viability significantly declined(P<0.05),and the levels of GSH and GPX4 were notably lowered(P<0.05),while ROS,MDA,Fe2+and ACSL4 protein levels were significantly elevated(P<0.05).However,in LPS+miR-351 inhibitor+Fer-1 group,the cell viability increased(P<0.05),and the GSH level rose significantly(P<0.05),with corresponding decreases in intracellular ROS,Fe2+and ACSL4 protein levels(P<0.05).CONCLUSION:Inhibition of ferroptosis attenuated sepsis-induced myocardial injury,and inhibition of miR-351-5p promotes sepsis-induced ferroptosis of H9c2 cardiomyocytes.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.

Objective:To explore the perioperative safety and postoperative efficacy of prophylactic jejunal nutrition tube placement during early gastric body cancer pylorus-preserving gastrectomy (PPG).Methods:The clinical data of 29 gastric cancer patients treated by Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2024 were retrospectively analyzed. There were 17 males (58.6%) and 12 females (41.4%), aged from 43 to 74 years, with an average age of (58.9 ± 8.3) years, and an average body mass index (BMI) of (24.3 ± 3.0) kg/m 2. According to the type of catheterization, all cases were divided into jejunal nutrition tube group ( n=12) and gastric tube group( n=17). The main outcome was the incidence of delayed gastric emptying within one month after surgery in both groups. Statistical analysis was conducted using SPSS26.0 software. Results:Patients in the jejunal feeding tube group resumed oral liquid intake, soft diet and regular diet significantly earlier postoperatively compared to those in the gastric tube group, with statistically significant differences ( P<0.05). Conversely, the time to removal of the tube was significantly earlier in the gastric tube group than in the jejunal feeding tube group ( P<0.05). However, the proportion of patients requiring reinsertion of a gastric or jejunal feeding tube postoperatively was significantly higher in the gastric tube group (7 cases) compared to the jejunal feeding tube group (0 case) ( P<0.05). In the jejunal feeding tube group, there were 4 cases occurred DGE, in the gastric tube group, there were 8 cases occurred DGE. There were no statistically significant differences between the two groups in either the overall incidence of DGE or the distribution of DGE severity grades. On postoperative 7th day , the Gastric Outlet Obstruction Scoring System (GOOSS) grade was significantly better in the jejunal feeding tube group than in the gastric tube group ( P<0.05), and all patients in the jejunal feeding tube group had resumed liquid intake, compared to only 58.8% in the gastric tube group. Conclusions:Compared with gastric tube placement, intraoperative prophylactic jejunal feeding tube placement for PPG has significant advantages in perioperative safety and postoperative recovery, but large-sample prospective studies are still needed for further verification.

Objective To observe the effects of Qigui Buxue Decoction combined with timed press-needle therapy on myelosuppression and cancer-related fatigue in chemotherapy patients with non-small cell lung cancer(NSCLC)of lung-spleen qi deficiency type.Methods A total of 124 NSCLC patients with lung-spleen qi deficiency type admitted to the Department of Radiotherapy and Chemotherapy at Cangzhou Integrated Traditional Chinese and Western Medicine Hospital in Hebei Province from January 2022 to June 2024 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 62 cases in each group.Both groups received platinum-based two-drug combination chemotherapy.The control group received timed press-needle therapy in addition to chemotherapy,while the observation group received Qigui Buxue Decoction in addition to the control group's treatment.The treatment course was 3 weeks,with a total of 2 courses.After 2 courses of treatment,changes in blood routine,lymphocyte subsets(CD3+,CD4+,CD8+,NK cells),CD4+/CD8+ratio,and the incidence of myelosuppression were observed.Changes in Piper Fatigue Scale and Karnofsky Performance Scale(KPS)scores before and after treatment were compared between the two groups.Results(1)After treatment,the white blood cell count in the observation group significantly improved(P＜0.05),and the observation group showed significantly better improvement in white blood cell count compared to the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the levels of CD3+,CD4+,CD4+/CD8+,and NK cells in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(3)The incidence of myelosuppression in the observation group was 58.06%(36/62),while it was 77.42%(48/62)in the control group.The incidence of myelosuppression in the observation group was significantly lower than that in the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the Piper Fatigue Scale scores,including behavioral,emotional,physical,and total scores,significantly improved in both groups(P＜0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P＜0.05).The cognitive scores of the Piper Fatigue Scale showed slight improvement in both groups,but there was no statistically significant difference compared to before treatment(P＞0.05).(5)After treatment,the KPS scores and TCM syndrome scores significantly improved in both groups(P＜0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P＜0.05).Conclusion Qigui Buxue Decoction combined with timed press-needle therapy can effectively improve myelosuppression,enhance immune function,and alleviate cancer-related fatigue in NSCLC patients with lung-spleen qi deficiency type after chemotherapy,thereby improving their quality of life.This approach is worthy of clinical promotion.

Objective To compare the clinical efficacy of the transforaminal endoscopic lumbar discectomy(TELD)approach with that of the interlaminar endoscopic lumbar discectomy(IELD)approach,both performed using a single-channel spinal endoscope,in the treatment of L4-L5 degenerative lumbar lateral recess stenosis(DLLRS).Methods A retrospective analysis was conducted on 78 patients with L4-L5 DLLRS who underwent single-channel endoscopic spinal surgery at our institution between March 2020 and March 2024.Patients were classified into the TELD group(lateral transforaminal approach,n=34)and the IELD group(interlaminar approach,n=44).Propensity score matching(PSM)was performed in a 1∶1 ratio using age,sex,body mass index(BMI),and duration of symptoms as covariates,yielding 25 matched pairs for final comparative analysis.Perioperative outcomes were systematically compared between groups.Visual analog scale(VAS)scores for low back pain and leg pain,as well as the Oswestry Disability Index(ODI),were evaluated preoperatively and at 3 days,3 months,6 months,and 1 year postoperatively.Lumbar computed tomography(CT)scans obtained 3 days after surgery were used to measure the lateral recess angle(LRA)and assess the extent of decompression.Spinal stability was evaluated using dynamic lumbar radiographs at 3 months postoperatively.Clinical outcomes were assessed 1 year after surgery based on the modified MacNab criteria.Results Both groups showed significant reductions in VAS scores for low back and leg pain,as well as in ODI scores,at all postoperative time points compared to baseline values(P<0.05).However,no statistically significant differences were observed between the two groups(P>0.05).Lumbar CT scans performed on postoperative day 3 demonstrated a significant increase in LRA in both groups relative to preoperative measurements(P<0.05).Although the magnitude of increase was greater in the IELD group,the intergroup difference did not reach statistical significance(P>0.05).At 3 months postoperatively,dynamic lumbar radiographs revealed no deterioration in spinal stability in either group compared to preoperative conditions,with no significant difference between groups(P>0.05).According to the modified MacNab criteria at 1 year postoperatively,the excellent and good outcome rate was 88.0%in the TELD group and 92.0%in the IELD group,with no statistically significant difference between the groups(P>0.05).Conclusions Both the TELD and IELD techniques are safe and effective for managing L4-L5 DLLRS,yielding comparable clini-cal outcomes.The selection of surgical approach should be guided by the anatomical location of ventral disc protru-sions,as well as the degree of facet joint hypertrophy and neural compression.