BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the in vivo microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key "switch" in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged

Objective:To evaluate the efficacy and safety of Chinese medicine Jianpi Antai formula in infertile women undergoing in vitro fertilization-embryo transfer(IVF-ET).Methods:A total of 300 infertile women who underwent 2 frozen embryo transfer procedures at the Reproductive Medicine Center,Sir Run Run Shaw Hospital were included in the study.The participants were randomly divided into study group and control group.The study group received routine medication plus the Jianpi Antai formula during the period of embryo transfer,while the control group received routine medication only.The general condition,embryo implantation rate,clinical pregnancy rate,live birth rate,and the blood routine and liver and kidney function were evaluated and compared between two groups.Results:There were 277 cases who completed the study,including 134 in the study group and 143 in the control group.The embryo implantation rate(68.7%vs.55.9%),the clinical pregnancy rate(56.7%vs.44.8%)and the live birth rate(50.7%vs.37.8%)in the study group were all higher than those in the control group(all P＜0.05).Subgroup analysis revealed that in patients of advanced age(≥35 years)and those with decreased ovarian reserve function(anti-Müllerian hormone＜1.68 ng/mL),the embryo implantation rate,clinical pregnancy rate,and live birth rate in the study group were all higher than those in the control group(all P＜0.05).During the follow-up period,there were no abnormalities in the basic vital signs of both groups,and no adverse events were reported.Conclusion:Jianpi Antai formula can safely improve the embryo implantation rate in infertile women undergoing IVF-ET,reduce the embryo miscarriage rate,increase the live birth rate as well as improve the clinical outcomes.

Histone deacetylases(HDACs)can deacetylate histones,leading to tighter DNA binding,and thereby playing a role in inhibiting gene transcription.On the contrary,histone deacetylase inhibitors(HDACis)can promote chromatin relaxation,enabling various transcription factors to bind specifically to DNA and activate transcription genes.Dental stem cells(DSCs)are human adult stem cells.These cells have the characteristics of less damage and low immune rejection during sampling,and are especially important seed cells in the process of osteogenesis,odontogenesis and other differentiation.A large number of experimental studies have shown that HDACs and HDACis together play important roles in cell division and differentiation,signal transduction,regulation of cellular inflammation and other life processes.This review summarizes the research progress of HDACs and HDACis in regulating osteogenic and odontogenic differentiation of DSCs,aiming to provide insights into the study of the interaction between HDACs and HDACis,and potentially guide clinical application of DSCs in the treatment of tooth and bone injury.

Objective To study the effects and mechanisms of tetramethylpyrazine(TMP)on tumor necrosis factor-α(TNF-α)-induced inflammatory injury in human coronary artery endothelial cells(HCAEC).Methods HCAEC were randomly divided into four groups:the control group(no treatment),the model group(treated with TNF-α,50 ng/mL for 24 hours),the TMP group(pre-treated with TMP,80 μg/mL for 12 hours followed by TNF-α treatment for 24 hours),and the SIRT1 inhibitor group(pre-treated with TMP and the specific SIRT1 inhibitor EX527 for 12 hours followed by TNF-α treatment for 24 hours).Cell viability was assessed using the CCK-8 method,lactate dehydrogenase(LDH)activity was measured using an LDH assay kit,reactive oxygen species(ROS)levels were observed using DCFH-DA staining,expression of pyroptosis-related proteins was detected by Western blot,and SIRT1 expression was analyzed using immunofluorescence staining.Results Compared to the control group,the model group showed decreased cell viability,increased LDH activity,ROS level and expression of pyroptosis-related proteins,and decreased SIRT1 expression(P<0.05).Compared to the model group,the TMP group exhibited increased cell viability,decreased LDH activity,ROS level and expression of pyroptosis-related proteins,and increased SIRT1 expression(P<0.05).In comparison to the TMP group,the SIRT1 inhibitor group showed decreased cell viability,increased LDH activity,ROS level and expression of pyroptosis-related proteins,and decreased SIRT1 expression(P<0.05).Conclusions TMP may attenuate TNF-α-induced inflammatory injury in HCAEC,which is associated with the inhibition of pyroptosis and activation of the SIRT1 signaling pathway.

Objective:To explore the predictive value of multimodal ultrasound (MMU) for upper urinary tract damage (UUTD) in children with neurogenic bladder (NB).Methods:This was a case-series study.From January 2022 to December 2023, 87 children with NB admitted to the First Affiliated Hospital of Zhengzhou University were examined by MMU.During the filling of bladder, vesical volume (VV), bladder wall thickness (BWT), shear wave velocity (SWV) of the anterior wall, resistance index (RI), and vascularization index (VI) were measured.After the emptying of bladder, VV and anterior wall SWV were measured, and ultrasound bladder compliance (△C) was calculated.The anterior posterior diameter (APD) of the renal pelvis and ureteral diameter (UD) were also measured.According to the upper/lower urinary tract dysfunction classification criteria, NB children were divided into a UUTD group and a non-UUTD (NUUTD) group.The differences in clinical data and related examinations between the 2 groups were analyzed to screen out independent risk factors, and an early warning model was established based on these factors.The prediction efficiency of the model and the urodynamic study (UDS) for UUTD was compared.Results:(1) There were 47 children in the UUTD group and 40 children in the NUUTD group.There was no significant difference in gender, age and body mass index between the 2 groups (all P>0.05).(2) In the UUTD group, the total glomerular filtration rate (tGFR) was (70.45±16.17) mL/min, the incidence of hydronephrosis was 38.30%, and the incidence of ureteral dilatation was 23.40%.No morphological changes were found in the imaging examination of the urinary system in the NUUTD group, and its tGFR was (100.55±16.27) mL/min.There was a significant difference in tGFR between the 2 groups ( P<0.05).(3) The filling VV, emptying VV, mean BWT, filling SWV, emptying SWV, VI, mean RI, △C, maximum cystometric capacity (MCC), maximum detrusor pressure during filling (Pdet.max), bladder compliance (BC), and detrusor leak point pressure (DLPP) in the NUUTD group were (218.43±87.53) mL, (14.62±6.14) mL, (3.08±0.65) mm, (2.64±0.54) m/s, (1.88±0.41) m/s, (6.20±1.04)%, 0.68±0.04, (147.58±49.18) mm 2·s, (309.50±66.54) mL, (59.83±19.79) cmH 2O(1 cmH 2O=0.098 kPa), (25.80±10.34) mL/cmH 2O, and (34.00±6.16) cmH 2O, respectively.Compared with the NUUTD group, the UUTD group showed decreased filling VV [(167.21±85.63) mL], △C [(78.49±31.86) mm 2·s], VI [(5.01±0.81) %], MCC [(255.32±75.10) mL], and BC [(12.57±6.44) mL/cmH 2O], and increased emptying VV [(19.50±7.65) mL], mean BWT [(4.02±0.82) mm], filling SWV [(3.99±1.07) m/s], emptying SWV [(2.15±0.35) m/s], mean RI (0.70±0.08), Pdet.max [(75.94±26.23) cmH 2O], and DLPP [(48.13±12.61) cmH 2O] (all P<0.05).(4) The decreased BC ( OR=0.841, 95% CI: 0.562-1.256, P=0.045), △C ( OR=0.427, 95% CI: 0.202-0.904, P=0.026) and VI ( OR=0.461, 95% CI: 0.091-2.325, P=0.010) and the increased DLPP ( OR=1.139, 95% CI: 0.894-1.451, P=0.040), filling SWV ( OR=1.895, 95% CI: 1.082-3.321, P=0.007) and mean BWT ( OR=1.191, 95% CI: 0.850-1.669, P=0.025) were independent risk factors for UUTD.Among MMU parameters, filling SWV had the highest prediction efficiency for UUTD, with a threshold of 3.33 m/s, sensitivity of 72.34% and specificity of 92.50%. Conclusions:MMU can well predict the occurrence of UUTD in children with NB, and filling SWV has the highest prediction efficiency.