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*

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective To investigate the in vitro anti-hepatitis B virus(HBV)effects of icariside Ⅱ(ICS Ⅱ)and its impact on mitochondrial fission.Methods HBV-positive hepatocellular carcinoma HepAD38 cells were used as the cellular model.The cytotoxicity of ICS Ⅱ was assessed via CCK8 assay.The secretion levels of HBV surface antigen(HBsAg)and HBV e antigen(HBeAg),as well as HBV DNA copy numbers,were measured by ELISA and qPCR after treatment with ICS Ⅱ alone or ICS Ⅱ in combination with entecavir(ENT).The effects of ICS Ⅱ on mitochondrial morphology and motility were observed using confocal laser scanning microscopy and transmission electron microscopy(TEM).After ICS Ⅱ treatment,Western blot was performed to analyze the expression levels of key proteins involved in mitochondrial dynamics.Additionally,intracellular reactive oxygen species(ROS)production was evaluated via fluorescence staining.Results The CCK8 assay results showed that ICS Ⅱ treatment at 25 μmol/L had no significant effect on cell proliferation after 72 h.ICS Ⅱ significantly inhibited the secretion levels of HBsAg and HBeAg,with the respective inhibition rates reaching 54.90％and 39.65％(P＜0.05).Additionally,ICS Ⅱ alone reduced HBV DNA copy numbers by 15.19％,while ENT alone achieved a 34.11％inhibition rate.Notably,ICS Ⅱ in combination with ENT reduced HBV DNA copy numbers by 55.81％(P＜0.05).Furthermore,ICS Ⅱ induced mitochondrial shortening and enhanced mitochondrial motility in HepAD38 cells(P＜0.05).ICS Ⅱ significantly increased the expression levels of mitochondrial motility-related proteins,including Mfn1,Fis1,and phosphorylated Drp1(ser 616)(P＜0.05),while no significant changes were observed in the expression levels of Mfn2,total Drp1,or Drp1(ser 637)(P＞0.05).Additionally,ICS Ⅱ significantly suppressed the production of intracellular ROS in HepAD38 cells(P＜0.05).Conclusion ICS Ⅱ inhibits HBV replication in HepAD38 cells,and the underlying mechanism may be associated with the promotion of mitochondrial fission and suppression of ROS production.

Objective:To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD).Methods:The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children′s Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed.Results:The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant.Conclusions:β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

Objective To investigate the diagnostic value of contrast-enhanced ultrasound(CEUS)combined with serum Smad ubiquitin regulatory factor 1(SMURF1)detection for thyroid cancer.Methods A total of 144 suspected thyroid cancer patients admitted to Lishui branch of Zhongda Hospital Affiliated to Southeast University from February 2019 to February 2020 were selected as the study subjects.Based on the histopathological results,they were divided into the thyroid cancer group(76 cases)and the benign group(68 cases).All patients underwent contrast-enhanced ultrasound examination and serum SMURF1 level detection;the diagnostic value of contrast-enhanced ultrasound parameters,serum SMURF1 detection alone,and the combination of the two methods for thyroid cancer were analyzed.Results Contrast-enhanced ultrasound parameters peak intensity(PI),mean perfusion intensity(SImean)and maximum perfusion intensity(SImax)in the thyroid cancer group were lower than those in the benign group,and the level of SMURF1 mRNA was higher than that in the benign group(P<0.05).The sensitivity of contrast-enhanced ultrasound parameter SImax in the diagnosis of thyroid cancer was 82.89%,the specificity was 72.06%,the accuracy was 77.78%,and the Kappa value was 0.552.The sensitivity of serum SMURF1 in the diagnosis of thyroid cancer was 65.79%,the specificity was 94.12%,the accuracy was 79.17%,and the Kappa value was 0.589.The sensitivity,specificity,accuracy and Kappa value of SImax combined with serum SMURF1 in the diagnosis of thyroid cancer were 97.37%,85.29%,91.67%and 0.832,respectively,which were higher than those of SImax and SMURF1 alone(P<0.05),the AUC of the combination of the two methods was 0.927,which was significantly higher than that of the two methods alone(Zcombined vs.SImax=3.999,P<0.001;Zcombined vs.SMURF1=3.270,P=0.001).Conclusion Contrast-enhanced ultrasound combined with serum SMURF1 detection can improve the diagnostic efficiency of thyroid cancer,which may avoid the over-diagnosis on the premise of ensuring the effective diagnosis of thyroid cancer patients.

Objective:To summarize the clinical manifestations and diagnostic methods of adult neuronal intranuclear inclusion disease (NIID), improve understanding of the disease, and avoid misdiagnosis.Methods:Clinical data of 8 adult NIID patients in the Hunan region were collected, and their clinical manifestations, cranial imaging, genetic testing, skin biopsy, and other characteristics were analyzed.Results:Among the 8 patients, 4 were males and 4 were females; The initial symptoms of 2 patients were dizziness, 2 were mental abnormalities, 2 were stroke like attacks, 1 was urinary incontinence, and 1 was limb tremor; Six patients experienced slow progression of the disease, while two patients experienced sudden progression after several years of slow progression; The GGC repeat amplification mutation in the 5′untranslated region of the NOTCH2NLC gene, as well as the lace like sign in the brain cortex medullary junction on diffusion-weighted imaging (DWI) and the presence of eosinophilic transparent inclusion bodies in the nucleus on skin biopsy, were helpful in diagnosing NIID.Conclusions:The clinical manifestations of NIID are highly heterogeneous, and some patients have rare initial clinical symptoms, which are prone to misdiagnosis and missed diagnosis. It is necessary to combine imaging, genetic testing, and skin biopsy to confirm the diagnosis; Some patients may experience sudden progression and poor prognosis after years of slow progression.

Purpose To analyze the multimodal imaging manifestations of phosphaturic mesenchymal tumor.Materials and Methods A retrospective analysis was performed on ten patients with phosphaturic mesenchymal tumor confirmed by pathology and molecular imaging from November 2012 to June 2022 in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology.The imaging features of CT in four cases,of MRI in seven cases,and of nuclear medicine in ten cases were reviewed,along with the clinical characteristics of all patients.Results The main clinical symptoms of ten patients,eight cases had pain,four cases had weakness,and nine cases had multiple fractures.Laboratory tests results:ten cases showed decreased blood phosphorus,six cases showed decreased blood 25-hydroxyvitamin D and ten cases showed elevated blood alkaline phosphatase.The lesions were heterogeneous in four cases on CT scans and in six cases on MRI scans.Calcification was common,and some had cysts and fatty components.After enhancement,seven cases showed moderate to obvious uneven enhancement.99Tcm-MDP SPECT showed increased uptake of multiple bones and joints in eight cases,18F-FDG PET/CT showed no or slight increase in lesion metabolism in eight cases,68Ga-DOTATATE PET/CT showed significantly high uptake at the lesion site in ten cases.Conclusion Phosphaturic mesenchymal tumor patients typically present with pain,fractures and hypophosphatemia.The conventional imaging features are characterized by small and concealed lesions and complex components.Particularly,68Ga-DOTATATE PET/CT imaging exhibits high sensitivity for the tumor detection.

Objective To explore the clinical significance of serum cytokine expression in the hepatitis B surface antigen(HBsAg)sero-clearance in patients with severe hepatitis B.Methods A nested case-control trial was conducted on 14 inpatients with severe hepatitis B admitted in our hospital from 2006 to 2020.Of them,7 patients(aged 36.57±3.15 years)achieved HBsAg sero-clearance within 1 year after the onset of hepatitis B flares(with abrupt rise of ALT level to＞5 times the upper limit of normal during HBV infection)and were assigned into HBsAg clearance group,while the other 7 patients(aged 34.14±2.97 years)only obtained HBsAg decreased less than 1 g within 1 year after the onset(HBsAg non-clearance group).Then,multiplex liquid-chip assay based on Luminex xMAP was used to detect the expression levels of 48 cytokines such as IFN-γ and IL-2 in serum samples of these 14 patients.Results The serum levels IFN-γ,IL-2Ra and SDF-1α were significantly lower in the HBsAg clearance group than the HBsAg non-clearance group(P＜0.05),but no statistical differences were observed in other 39 cytokines between the 2 groups.And there were 5 cytokines having no mutual expression in both groups.The copy number of HBV DNA was positively correlated with serum HGF(r=0.675,P=0.008)and SDF-1α levels(r=0.587,P=0.027),while negatively with IP-10(r=-0.600,P=0.023)and MIG level(r=-0.640,P=0.014).Meanwhile,a positive correlation was found between HBsAg titer and IL12-p70 level(r=0.593,P=0.025),and a negative correlation between HBsAg titer and TNF-α level(r=-0.609,P=0.021).In addition,the serum total bilirubin level was positively correlated with the expression of SCGF-β(r=0.543,P=0.045).Conclusion Three differentially expressed cytokines and some cytokines related to HBV DNA level and HBsAg titer are found,which may provide new insights into the underlying immunological mechanism of HBV virus clearance caused by hepatitis flares.Meanwhile,it also provides potential biomarkers for HBsAg serological clearance in patients with severe hepatitis B.

Background Previous research on chlorinated paraffins (CPs) in fine particulate matter (PM_2.5) has predominantly focused on short- and medium-chain chlorinated paraffins (SCCPs and MCCPs), and few studies could simultaneously determine short-, medium-, and long-chain chlorinated paraffins (LCCPs). Simultaneous extraction and determination of SCCPs, MCCPs, and LCCPs in PM_2.5 could provide technical support for their environmental monitoring and human health risk assessment. Objective To establish a method based on QUEChERS pretreatment method in conjunction with ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry for simultaneously determining the levels of SCCPs, MCCPs, and LCCPs in PM_2.5. Methods The extraction solvents, extraction salts, and extraction steps of a QuEChERS method were optimized. The extraction efficiencies of the target substances were compared under 4 extraction solvents [acetonitrile, dichloromethane, and n-hexane solvents in sequence; acetonitrile: dichloromethane: n-hexane = 1: 1: 2 (v/v/v) mixed solvent; 1% acetic acid-acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent; acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent], 2 dehydrated salts (anhydrous MgSO₄+NaCl and anhydrous Na₂SO₄+NaCl), 2 purification salts (C18 and PSA), and 4 vortex time (5, 7.5, 10, and 12.5 min) conditions. Then internal standard was utilized to estimate linear range and detection limit of the refined QuEChERS approach. Results The linearities of SCCPs, MCCPs, and LCCPs were good in the range of 10~1000 ng·mL⁻¹ with the correlation coefficients all greater than 0.96. The method detection limits (MDLs) ranged from 0.01 to 0.29 ng·m⁻³. The spiked recoveries of SCCPs, MCCPs, and LCCPs at the low, medium, and high concentrations were 77.38%-81.64%, 93.11%-99.78%, and 87.41%-101.39%, respectively, and the relative standard deviations (RSDs) were 2.90%-12.84%. This method was used to determine the CPs levels in 11 PM_2.5 samples from Shijiazhuang. The positive rates of ∑SCCPs, ∑MCCPs, and ∑LCCPs were all 100%, the concentration ranges were 0.24-2.18 ng·m⁻³ (mean 0.84 ng·m⁻³), 0.17-1.67 ng·m⁻³ (mean 0.70 ng·m⁻³), and 0.01-0.16 ng·m⁻³ (mean 0.04 ng·m⁻³), respectively, and the percentages to ΣCPs were 52.95%, 44.39%, and 2.66%, respectively. Conclusion The method established in this study is simple, time-saving, solvent saving, and can simultaneously detect SCCPs, MCCPs, and LCCPs in PM_2.5, which is suitable for the determination of PM_2.5 samples in large quantities, and can also provide a reference for the detection methods of other halogenated organic compounds in PM_2.5.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.