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*

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Rice (Oryza sativa L.), as a thermophilic crop, is highly susceptible to cold stress during its growth process. Chilling injury at the plumule stage and seedling stage often affects the morphological development and leads to yield reduction of rice. The exploration and utilization of cold tolerance genes are among the most direct and effective approaches to address cold stress in rice. To identify quantitative trait loci (QTLs) associated with cold tolerance at plumule and seedling stages, in this study, we measured the seedling rates and survived seedling rates of the indica rice cultivar 'HZ', the japonica cultivar 'Nekken2', and their 120 recombinant inbred lines (RILs) under cold stress. A previously constructed high-density genetic linkage map was used for the mapping of the QTLs conferring cold tolerance at the plumule and seedling stages. A total of 4 QTLs for plumule-stage cold tolerance and 9 QTLs for seedling-stage cold tolerance were detected, with the maximum limit of detection reaching 5.20. Notably, a genetically overlapping QTL for both plumule and seedling stages was identified on chromosome 8, spanning a physical interval of 24 432 953-25 295 129 bp. Candidate genes within the detected QTL intervals were screened, and quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the gene expression during the plumule and seedling stages. The results revealed that LOC_Os03g06570, LOC_Os03g07100, LOC_Os06g08280, LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540 exhibited significantly differential expression between the parental lines. These genes were either significantly downregulated or upregulated under cold stress. Among them, the first three gene (LOC_Os03g06570, LOC_Os03g07100, and LOC_Os06g08280) were hypothesized to be key candidates regulating the cold tolerance of rice seedlings, while the latter three genes (LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540) were identified as comprehensive regulators of cold tolerance during both plumule and seedling stages. These findings lay a foundation for the fine mapping and cloning of cold tolerance genes at the plumule and seedling stages, providing valuable insights for breeding cold-tolerant rice varieties.
Quantitative Trait Loci/genetics* ; Oryza/growth & development* ; Seedlings/growth & development* ; Cold Temperature ; Chromosome Mapping ; Gene Expression Regulation, Plant

Human epidermal growth factor receptor 2 (HER2) is a key therapeutic target for breast cancer. With the wide application of anti-HER2 and HER2 antibody-drug conjugates such as trastuzumab, pertuzumab, trastuzumab emtansine, and trastuzumab deruxtecan, the survival of patients with advanced HER2-positive breast cancers have been significantly improved. However, the subsequent drug-induced interstitial lung disease (DILD) has gradually become an important complication affecting the therapeutic effect and safety. However, the clinical understanding of interstitial lung disease (ILD) caused by this type of drugs is still insufficient, the management lacks unified standards, and the molecular mechanism has not been fully clarified. This study, through two clinical cases of severe DILD, explores the pathogenesis, treatment strategies, risk factors and follow-up monitoring requirements of ILD caused by HER2-targeted drugs, providing a scientific basis for optimizing the clinical diagnosis and treatment plan.

ObjectiveTo explore the effects of exosomal CXCL on the biological behavior of cervical cancer cells and its underlying mechanisms. MethodsChemokine CXCL was first screened through bioinformatics databases. The GEPIA database was analyze CXCL expression in cervical cancer tissues and adjacent normal cervical tissues. Western blot was performed to detect CXCL expression levels in cervical cancer cells （Caski） and normal cervical epithelial cells （H8）. The successful isolation of exosomes was confirmed by nanoparticle tracking analysis， transmission electron microscopy （TEM） and Western blot. ELISA was employed to detect the expression level of exosomes CXCL was determined by ELISA. After CXCL knockdown via siRNA transfection， cells were divided into three groups： blank control， negative control and experimental groups. Cell proliferation was evaluated using the CCK-8 assay， while cell migration and invasion were assessed by Transwell assays. ResultsExosomal CXCL expression was significantly upregulated in cervical cancer cells compared with normal cervical epithelial cells （P<0. 01）， and also markedly elevated in cervical cancer tissues compared with adjacent normal tissues. After low expression of CXCL knockdown significantly reduced CXCL expression in both cancer cells and their derived exosomes（P<0. 05）. Low expression markedly inhibited the proliferation， invasion and migration abilities ConclusionSilencing exosomal CXCL may inhibit the malignant biological behavior of cancer cells.

Objective To discuss the safety and efficacy of arterial embolization combined with local ablation in the treatment of recurrent and refractory chest wall tumors.Methods The clinical data of 11 patients with chest wall tumor that recurred after surgery and progressed after treatment were retrospectively analyzed.On the basis of the original treatment regimen,DSA-guided arterial embolization and CT-guided local ablation were employed.VAS score of pain relief and postoperative complications were recorded,and the therapeutic efficacy was evaluated Results All the patients were follow up for a median time of 18.5 months.Successful DSA-guided arterial embolization was accomplished in all patients.Seven patients(9 lesions in total)initially received CT-guided radiofrequency ablation(RFA),and tumor reoccurred in 2 patients,who had to receive RFA once more.Four patients(5 lesions in total)initially received CT-guided microwave ablation(MWA),and tumor reoccurred in one patient,who had to receive MWA again.According to mRECIST criteria,the 6-month,12-month and 18-month objective response rates(ORR)were 72.7%(8/11),45.5%(5/11)and 18.2%(2/11)respectively,the 6-month,12-month and 18-month overall survival rates were 81.8%(9/11),63.6%(7/11)and 27.3%(3/11)respectively,with a median survival time of 13.2 months.The postoperative one-month and 3-month VAS scores were(2.42±1.25)points and(1.91±1.24)points respectively,which were strikingly lower than preoperative(6.78±1.13)points,the differences were statistically significant(P＜0.05).After surgery,3 patients developed pleural effusion,which disappeared after puncture and drainage treatment,and 2 patients developed fever,which was improved after symptomatic treatment.One patient died of respiratory failure six months after treatment.Conclusion Arterial embolization combined with local ablation can improve the symptoms of pain and prolong the survival time of patients with chest wall tumors.This combination therapy is less traumatic and clinically safe,and it can be used as an effective treatment for patients with recurrent and refractory chest wall tumors.

BACKGROUND:Our previous studies found that the polypeptide of Cornus cervi Colla can promote bone growth,which has a good application prospect in the treatment of bone diseases.However,how Cornus cervi Colla works in the body and the principle are not clear. OBJECTIVE:To study the in vivo distribution and tracing of Cornus cervi Colla using fluorescence labeling and tracer technique. METHODS:Cornus cervi Colla was fluorescently labeled using fluorescein isothiocyanate,and the labeling results were detected by fluorescence imaging and UV spectral scanning.Successfully labeled Cornus cervi Colla was injected into mice by gavage,and the absorption of Cornus cervi Colla into blood was detected by laser confocal microscopy,and the distribution of Cornus cervi Colla in mice was detected by small animal in vivo imager.The distribution of Cornus cervi Colla in the mice was detected by laser confocal microscopy.Samples were taken from serum and bone at the time of the strongest fluorescence,and gel electrophoresis was carried out on serum and bone tissue protein solutions,and the components of Cornus cervi Colla absorbed into target organs were determined by secondary mass spectrometry. RESULTS AND CONCLUSION:The fluorescent markers were successfully separated by dextran gel chromatography,and the fluorescence imaging and ultraviolet spectrum scanning proved that the labeling was successful,and the fluorescence substitution degree of FITC-labeled Cornus cervi Colla was 0.953%.The fluorescence intensity of the components of Cornus cervi Colla in the blood showed that Cornus cervi Colla was most distributed in serum after oral administration for 2 hours.The fluorescence images of mice at different times were the same as those of bilateral femur and tibia,indicating that Cornus cervi Colla could play a role by entering the bone.Compared with UniProt database,secondary mass spectrometry showed that the peptide was a characteristic fragment of decorin.It is proved that decorin in Cornus cervi Colla can enter the bone to play a therapeutic role.

BACKGROUND:Osteonecrosis of the femoral head is a common and disabling disease,which is mainly characterized by microcirculation disorders and bone cell metabolism disorders.Luzhongjiangu decoction was developed by Shandong Academy of Chinese Medicine and used in the form of soup in the clinic,which has good efficacy in the treatment of osteonecrosis of the femoral head.However,its mechanism of action has not been clarified. OBJECTIVE:To study the effect mechanism of Luzhongjiangu decoction on intestinal flora in rats with osteonecrosis of the femoral head based on 16S rDNA sequencing technique. METHODS:The model of osteonecrosis of the femoral head was established in Wistar rats by intragastric administration of retinoic acid.The therapeutic effect of Luzhongjiangu decoction was evaluated by serum hormone,bone histopathology and serum hormone levels.16s rDNA sequencing technique was used to detect the intestinal flora of rats in the blank control group,model group and middle-dose Luzhongjiangu decoction group.The corresponding library was constructed and OTU clustering and microbial community diversity and abundance analysis were carried out to determine the composition of intestinal flora and the changes of species and diversity among groups. RESULTS AND CONCLUSION:Luzhongjiangu decoction could significantly increase the expression of osteocalcin,osteopontin and other osteogenic related factors,alleviate the destruction of bone trabeculae,increase bone mineral density,and had a significant therapeutic effect on osteonecrosis of the femoral head,of which the middle dose group showed the most significant effect.The results of intestinal flora sequencing showed that Luzhongjiangu decoction improved the flora disorder of rats with osteonecrosis of the femoral head to some extent,and screened out different colonies such as Bacillus,Desulfurizans,Desulfurization,Isobacteria,Bifidobacterium and so on;it could up-regulate the abundance of beneficial bacteria such as Bifidobacterium,down-regulate the abundance of harmful bacteria such as Desulfovibrio,and improve the structure of intestinal flora.Functional prediction analysis indicated that Luzhongjiangu decoction could mainly affect amino acid metabolism and energy metabolism.Correlation analysis showed that the differential bacteria of Bifidobacterium and Intestinimonas in the middle dose group of Luzhongjiangu decoction were positively correlated with vitamin D3,estradiol and calcitonin,and negatively correlated with prostaglandin E2.In the model group,Escherichia-Shigella,Desulfovibrio,Globicatella and Streptococcus were positively correlated with prostaglandin E2 and negatively correlated with vitamin D3,estradiol and calcitonin.To conclude,Luzhongjiangu decoction may play a role in the treatment of osteonecrosis of the femoral head by regulating the structure of intestinal flora,up-regulating the abundance of beneficial bacteria and affecting the secretion of vitamin D3,estradiol,calcitonin and prostaglandin E2.

Objective To investigate the relationship between serum miR-505,miR-15 and endoscopic activity of ulcerative colitis(UC).Methods 98 patients with UC from May 2020 to May 2022 were selected as the observation group,and 80 patients with irritable bowel syndrome(IBS)were selected as the control group during the same period.The modified Mayo score was used to evaluate the endoscopic activity in patients with UC,and the relationship among the changes of serum miR-505 and miR-15 levels and the endoscopic activity in patients with UC was analyzed.Results The level of serum miR-505 in observation group was lower than that in control group,while the level of miR-15 in observation group was higher than that in control group(P<0.05).The level of serum miR-505 in patients with active UC was lower than that in patients with the healing stage,while the level of serum miR-15 in patients with active UC was higher than that in patients with healing stage(P<0.05).The serum miR-505 level of E3 type was lower than that of E2 type and E1 type,and the serum miR-15 level of E3 type was higher than that of E2 type and E1 type(P<0.05).The Mayo score of type E3 was higher than that of type E2 and E1(P<0.05).Pearson correlation analysis showed that serum miR-505 was negatively correlated with Mayo score(r =-0.51,P<0.05),while serum miR-15 was positively correlated with Mayo score(r = 0.54,P<0.05).Receiver operator characteristic curve(ROC curve)results showed that the cut-off value of miR-505 was 0.93,and the area under the curve(AUC)for evaluating the endoscopic activity of patients with UC was 0.67(95%CI:0.659～0.785),and the sensitivity and specificity were 73.24%and 68.55%,respectively.The cut-off value of miR-15 was 0.85,and the AUC for evaluating the endoscopic activity of patients with UC was 0.69(95%CI:0.672～0.814),and the sensitivity and specificity were 76.38%and 69.72%,respectively.The AUC for the joint evaluation of UC by both was 0.82(95%CI:0.809～0.912),and the sensitivity and specificity were 84.56%and 68.49%,respectively.Conclusion Serum miR-505 levels decrease and serum miR-15 levels increase in UC patients than IBS,and the level is closely related to patients'pathological conditions and endoscopic activity.Combined detection of serum miR-505 and miR-15 has a good value in evaluating endoscopic activity in UC patients.