Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Objective To observe the effects of Ditan Yizhi Decoction on Wnt/β-catenin signaling pathway and mitochondrial autophagy in vascular dementia(VD)rats.Methods Totally 70 male SD rats were randomly selected as the sham-operation group,with only the common carotid artery isolated and not ligated,and the rest of the rats were used to prepare a rat model of VD by the modified bilateral common carotid artery permanent ligature method.The successfully modeled rats were randomly divided into model group,donepezil group,agonist group and Ditan Yizhi Decoction low-,medium-and high-dosage groups and were given corresponding interventions for 4 weeks.Morris water maze experiment was used to assess the learning and memory ability of rats,HE staining and Nissl staining were used to observe the morphology of hippocampal tissue,transmission electron microscopy was used to observe the ultrastructure of hippocampal neuron,Western blot was used to detect the expressions of PINK1,Parkin,p62,Beclin-1,LC3BⅡ/Ⅰ,β-catenin,GSK-3β,p-GSK-3β protein.Results Compared with the sham-operation group,rats in the model group had a prolonged escape latency(P<0.01),a reduced number of crossing platforms(P<0.01);neuronal gaps in the CA1 area of the hippocampus were enlarged,with irregular cell morphology and blurred borders,neuronal solidification,Nissl bodies dissolution and fragmentation,reduced quantity,mitochondrial cristae disorder,and disruption of the structure of the bilayer membrane,with a greater number of autophagosomes in the surroundings;the expressions of PINK1,Parkin,Beclin-1,LC3BⅡ/I,β-catenin,p-GSK-3β/GSK-3β protein were significantly increased(P<0.01),and p62 protein expression was significantly decreased(P<0.01).Compared with the model group,the escape latency of rats in donepezil group,agonist group and Ditan Yizhi Decoction low-,medium-and high-dosage groups were significantly shortened(P<0.01),and the number of crossing platforms significantly increased(P<0.05,P<0.01);the number of neurons in the hippocampal CA1 region increased,with normal morphology and orderly arrangement,Nissl bodies were abundant,and transmission electron microscopy showed that mitochondrial morphology recovered,rupture decreased,and autophagosomes around mitochondria decreased,the protein expressions of PINK1,Parkin,Beclin-1,LC3BⅡ/Ⅰ,β-catenin and p-GSK-3β/GSK-3β in hippocampal tissue were significantly decreased(P<0.01),the protein expression of p62 significantly increased(P<0.05,P<0.01).Conclusion Ditan Yizhi Decoction can improve learning memory ability and neuronal morphology in VD rats,and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway to inhibit mitophagy.

Objective To predict the mechanism of herbal couple Curcumae Rhizoma-Sparganii Rhizoma(CR-SR)in modulation of angiogenesis against lung cancer based on network pharmacology and molecular docking technology,and validate by zebrafish model.Methods The active ingredients and potential targets for anti-lung cancer and antiangiogenesis of CR and SR were screened by network pharmacology.The targets were intersected with those screened from the OMIM database and GeneCards database for lung cancer and antiangiogenesis.Herbal couple-lung cancer and herbal couple-antiangiogenesis of protein-protein interaction(PPI)network was constructed by taking intersecting targets to screen the common and core targets of the herbal couple in lung cancer and anti-angiogenesis.Herbal couple-lung cancer and herbal couple-antiangiogenesis of Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses were performed by Metascape database.The binding ability and the amino acid residues involved of core targets to major components were evaluated by molecular docking technique.In vitro,CCK-8 method was applied to investigate the effects of herbal couple and single drugs on the cell viability of human umbilical vein endothelial cells(HUVECs).Zebrafish embryos were randomly divided into blank control group,different concentration of drug pairs and single drug group,and positive drug control group,and the number of intersegmental vessels of zebrafish in each group was counted after 72 hour.The mRNA expression levels of angiogenesis-related genes,VEGFA,VEGFR2,VEGFR3,EGFR,etc.,were detected by qRT-PCR.Results 106 herbal couple-lung cancer common targets and 130 herbal couple-antiangiogenesis common targets were screened by network pharmacology.Meanwhile,85 of targets were identical.GO function enrichment analyses of herbal couple-lung cancer resulted in 1648 GO analysis entries,KEGG pathway enrichment analyses resulted in 186 signaling pathways.GO function enrichment analyses herbal couple-antiangiogenesis resulted in 1844 GO analysis entries,KEGG pathway enrichment analyses resulted in 188 signaling pathways.The molecular docking results showed a better affinity between the target and the components,and the forces between them mainly included hydrogen bonding and hydrophobic interactions.In vitro cellular experiments demonstrated that the two drugs were used as a drug pair to enhance the inhibitory effect on the cell viability of HUVECs.The zebrafish experiments indicated that the toxicity order of herbal couple and single drugs was CR>CR-SR>SR.The results of transgenic zebrafish vascular fluorescence model confirmed that CR-SR and single drugs had anti-angiogenic activity,with the anti-angiogenic activity order of herbal couple and single drugs was CR-SR>SR>CR.The results of qRT-PCR showed that CR-SR drug pairs and single drugs significantly reduced the expression levels of angiogenesis-related genes VEGFA,VEGFR2,EGFR,MMP9,etc.,and had anti-angiogenic effects.Conclusion CR-SR and single drugs had anti-lung cancer effects on multiple identical targets and regulated multiple identical signaling pathways,and their combination had a synergistic effect.The treatment of lung cancer may be through the regulation of angiogenesis-related target VEGFA,VEGFR2,EGFR,etc.,in order to play an anti-angiogenic effect.

Objective:To discuss the effects of bone marrow-derived mesenchymal stem cells(BMSCs)transplantation on mitophagy in the vascular dementia(VaD)rats through reactive oxygen species(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)signaling,and to clarify its mechanism.Methods:Forty-five male adult SD rats were randomly divided into sham operation group,model group,unloaded group,BMSCs group,and MSCs+ML385(Nrf2 inhibitor)group(combination group),and there were 9 rats in each group.After intraperitoneal anesthesia,the VaD models were established in all groups except sham operation group.Morris water maze test was used to detect the learning and memory abilities of the rats in various groups;HE staining was used to observe the histopathological morphology of brain tissue of the rats in various groups;Nissl staining was used to observe the changes of Nissl bodies in hippocampus region of brain tissue of the rats in various groups;transmission electron microscope was used to observe the ultrastructure of hippocampus region of the rats in various groups;fluorescence probe method was used to detect the ROS levels in hippocampus neurons in various groups;Western blotting method was used to detect the expression levels of Nrf2,heme oxygenase-1(HO-1),PTEN-induced putative kinase 1(PINK1),parkin RBR E3 ubiquitin protein ligase(Parkin),Beclin-1,ubiquitin-binding protein p62(P62),and microtubule-associated protein 1A/1B-light chain 3(LC3-Ⅱ/LC3-Ⅰ)ratio in brain tissue of the rats in various groups.Results:The Morris water maze results showed that compared with sham operation group,the escape latency of the rats in model group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).Compared with model group,the escape latency of the rats in BMSCs group was significantly decreased(P<0.01),while the number of crossing time and residence time were significantly increased(P<0.01).Compared with BMSCs group,the escape latency of the rats in combination group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).The HE staining results showed that hippocampus neurons of the rats in sham operation group were normal in quantity and morphology,with uniform staining and clear structure.Compared with sham operation group,the hippocampus tissue of the rats in model group showed sparse arrangement,disordered structure,reduced neuronal quantity,varied morphology,uneven staining,nuclear pyknosis,and partial neuronal necrosis.Compared with model group,the neuronal damage of the rats in hippocampus regio in BMSCs group was alleviated,with restored morphology and improved neuronal loss.Compared with BMSCs group,the neurons of the rats in hippocampus region in combination group showed irregular morphology,disordered structure,unclear cell boundaries,uneven staining,and nuclear pyknosis.The Nissl staining results showed that the hippocampal neurons in sham operation group were tightly arranged with intact morphology,obvious nucleoli,and abundant darkly stained Nissl bodies.Compared with sham operation group,the neurons in hippocampus region of the rats in model group showed pyknosis,vacuolization,and sparse Nissl bodies.Compared with model group,the BMSCs group showed reduced neuronal pyknosis,relatively intact morphology,and increased Nissl bodies.Compared with BMSCs group,the combination group showed neuronal pyknosis,loss of morphological integrity,and fragmented Nissl bodies.The transmission electron microscope results showed that mitochondria in sham operation group exhibited oval shape with intact double-membrane structure and cristae.Compared with sham operation group,the mitochondria in model group showed swelling,disrupted membranes,broken cristae,and numerous autophagosomes.Compared with model group,the BMSCs group showed improved mitochondrial structure and reduced autophagosomes.Compared with BMSCs group,the combination group showed swollen mitochondria,disrupted membranes,broken cristae,and visible autophagosomes.The fluorescence probe results showed that compared with sham operation group,the ROS levels in the hippocampus neurons in brain tissue of the rats in model group were significantly increased(P<0.01);compared with model group,the ROS levels in hippocampus neurons in brain tissue of the rats in BMSCs group were significantly decreased(P<0.01);compared with BMSCs group,the ROS levels in hippocampus neurons in brain tissue of the rats in combination group were significantly increased(P<0.01).The Western blotting results showed that compared with sham operation group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in model group were significantly decreased(P<0.01);compared with model group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in BMSCs group were significantly increased(P<0.01);compared with BMSCs group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in combination group were significantly decreased(P<0.01);compared with sham operation group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,and LC3-Ⅱ/LC3-Ⅰ ratio of the rats in model group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01);compared with model group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in BMSCs group were significantly decreased(P<0.01),while the expression level of P62 protein was significantly increased(P<0.01);compared with BMSCs group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in combination group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01).Conclusion:BMSCs can alleviate the hippocampal neuronal pathological changes and improve cognitive function in the VaD rats,and its mechanism may be related to the regulation of ROS/Nrf2 signaling pathway to inhibit mitophagy.

Objective To evaluate the clinical efficacy and safety of Wuwei Wentong Chubi Capsules in patients with rheumatoid arthritis of cold and dampness obstruction syndrome under real world based on clinical medical record information system.Methods Medical history,symptoms and medication information of hospitalized patients with rheumatoid arthritis of cold and dampness obstruction syndrome in the Department of Rheumatology,First Affiliated Hospital of Anhui University of Chinese Medicine were collected from January 2020 to March 2024.According to whether to use Wuwei Wentong Chubi Capsules,patients were divided into treatment group(304 cases)and control group(378 cases).A database was established after improving the information and indicators of two groups of patients.TCM syndrome scores,disease activity scores and laboratory indicators of both groups were compared.Results Compared with before treatment,TCM syndrome score(severe joint pain,morning stiffness,swelling,worsening pain when encountering cold,poor joint flexion and extension,eating less and eating more,lack of breath and lazy speech,weak mouth and thirst,heavy head and body fatigue,loose stools and fatigue)in the treatment group significantly decreased after treatment(P<0.05),the disease activity score,erythrocyte sedimentation rate(ESR),high-sensitivity C-reactive protein(hs-CRP),rheumatoid factor(RF),complement(C3,C4),immunoglobulin(Ig)G,IgM,anti cyclic citrullinated peptide antibody(anti CCP antibody),thyroid stimulating hormone(TSH),anti thyroglobulin antibody(TGAb),and anti thyroid peroxidase antibody(TPOAb)were significantly reduced(P<0.05),and free triiodothyronine(FT3)and free tetraiodothyronine(FT4)increased(P<0.05);after treatment,TCM syndrome score(severe joint pain,morning stiffness,swelling,fatigue and weakness)in the control group significantly decreased,and the disease activity score,ESR,hs-CRP,RF,the levels of anti CCP antibodies,TGAb,and TPOAb were significantly reduced(P<0.05);compared with the control group after treatment,TCM syndrome scores in the treatment group showed more significant improvement(P<0.05)in terms of joint morning stiffness,swelling,poor flexion and extension,exacerbation of cold exposure,eating less and eating more,lack of breath and speech,weak and dry mouth,heavy head and body fatigue and fatigue.Disease activity score,ESR,hs-CRP,RF,the levels of anti CCP antibodies,C3,IgG,TSH and TPOAb decreased more significantly,while FT3 and FT4 increased more significantly(P<0.05);both groups had normal blood routine and liver and kidney function before and after treatment,with no significant difference(P>0.05).According to the analysis of association rules,after using Wuwei Wentong Chubi Capsules,there was a significant improvement in ESR,hs-CRP,RF,C3,IgG,TSH,FT4 and TPOAb indicators,with a degree of improvement greater than 1,indicating a strong association.Conclusion Wuwei Wentong Chubi Capsules can effectively improve the cold and dampness obstruction syndrome and spleen deficiency dampness excess syndrome in patients with rheumatoid arthritis cold dampness obstruction syndrome,reduce disease activity index and immune inflammatory indicators,and have a certain regulatory effect on thyroid immune dysfunction and the clinical application has good safety.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

OBJECTIVES: To investigate the inhibitory effect of pirfenidone (PFD) on growth of bladder cancer xenograft and its regulatory effect on Treg cells in tumor-bearing mice. METHODS: Thirty-two C57BL/6 mice bearing ectopic bladder tumors were randomized into control and PFD groups (n=16). In PFD group, PFD was administered orally at the daily dose of 500 mg/kg, and tumor growth and survival of the mice were monitored. After treatment for 21 days, the tumors and vital organs were harvested for analysis. Immunohistochemistry was used to assess CD3, CD4, CD8, and FOXP3 expressions in the tumors. Flow cytometry and RT-qPCR were used to analyze the percentage of CD4⁺CD25⁺FOXP3⁺ Treg cells and IL-2, IL-10, and IL-35 expressions in the tumors and spleens; organ damage of the mice was examined with HE staining. RESULTS: Compared with the control group, the PFD-treated mice exhibited significantly lower tumor growth rate with smaller tumor volumes at day 21, along with improved survival at day 28. Immunohistochemistry revealed no significant differences in the infiltration of CD3⁺ and CD8⁺ cells between the two groups, but the percentages of CD4⁺ and FOXP3⁺ cells were significantly lower in the tumors of PFD-treated mice. Flow cytometric analysis confirmed a decrease in CD4⁺CD25⁺FOXP3⁺ Treg cells in the tumors from PFD-treated mice, which also had reduced expression levels of IL-2, IL-10 and IL-35 mRNAs in the tumors. No significant differences were found in Treg cell populations or cytokine expressions in the spleen tissues between the two groups. HE staining showed obvious organ damage in neither of the groups. CONCLUSIONS PFD inhibits bladder cancer growth and enhances survival of tumor-bearing mice possibly by suppressing Treg cells in the tumor microenvironment.
Animals ; Urinary Bladder Neoplasms/drug therapy* ; Mice ; T-Lymphocytes, Regulatory/metabolism* ; Mice, Inbred C57BL ; Interleukins/metabolism* ; Interleukin-10/metabolism* ; Cell Line, Tumor ; Interleukin-2/metabolism* ; Xenograft Model Antitumor Assays ; Female

In order to realize the quantitative assessment of muscle strength in hand function rehabilitation and then formulate scientific and effective rehabilitation training strategies, this paper constructs a multi-scale convolutional neural network (MSCNN) - convolutional block attention module (CBAM) - bidirectional long short-term memory network (BiLSTM) muscle strength prediction model to fully explore the spatial and temporal features of the data and simultaneously suppress useless features, and finally achieve the improvement of the accuracy of the muscle strength prediction model. To verify the effectiveness of the model proposed in this paper, the model in this paper is compared with traditional models such as support vector machine (SVM), random forest (RF), convolutional neural network (CNN), CNN - squeeze excitation network (SENet), MSCNN-CBAM and MSCNN-BiLSTM, and the effect of muscle strength prediction by each model is investigated when the hand force application changes from 40% of the maximum voluntary contraction force (MVC) to 60% of the MVC. The research results show that as the hand force application increases, the effect of the muscle strength prediction model becomes worse. Then the ablation experiment is used to analyze the influence degree of each module on the muscle strength prediction result, and it is found that the CBAM module plays a key role in the model. Therefore, by using the model in this article, the accuracy of muscle strength prediction can be effectively improved, and the characteristics and laws of hand muscle activities can be deeply understood, providing assistance for further exploring the mechanism of hand functions .
Neural Networks, Computer ; Humans ; Hand Strength/physiology* ; Support Vector Machine ; Muscle Strength/physiology* ; Hand/physiology* ; Convolutional Neural Networks

ObjectiveTo understand the development stages and use of policy tools of general practitioner policies in China since it was first proposed, to summarize the experience and explore the shortcomings, so as to provide references for the adjustment and optimization of China’s general practitioner policies. MethodsContent analysis and mathematical statistics analysis were used to conduct a quantitative research on 111 policy documents with 422 policy items involving general practitioners at the national level from 1997 to 2023, through a three-dimensional analysis framework integrating policy tools, human capital process and policy development stages. ResultsCapacity‑building policy tools were most frequently used in general practitioner policies, and the policy tools gradually shifted from mandate to inducement. The general practitioner policies paid less attention to the career selection link, but paid full attention to every segment of human capital links, with a comprehensive application of policy tools observed in the integrated development stage, despite the existence of unbalanced internal distribution. ConclusionIt is suggested to promote the use of incentive policy tools and to explore multiple approaches based on incentive theory; pay attention to the career selection link for guiding the employment of general practitioners; take the appropriateness between the policy tools and human capital process into comprehensive consideration, striking a dynamic balance of the internal structure of general practitioner policies.

ObjectiveTo analyze the characteristics of policy texts related to the physician periodic assessment system in China, providing references for the improvement of the system. MethodsContent analysis was employed, examining 116 policy documents from three dimensions: policy process, policy themes, and policy tools. ResultsA total of 298 codes were obtained. The number of policies related to the periodic assessment of physicians showed an overall trend of increasing first and then decreasing, with the peak annual issuance period between 2011 and 2021, and the average number of policy texts showing a downward trend. Policy documents were summarized into 3 levels: physician periodic assessment work, individual behavior, and institutional systems, encompassing a total of 8 categories of themes. The proportion of supply-oriented, environmental-oriented, and demand-oriented policy tools were 4.03%, 60.40%, and 35.57%, respectively. Moreover, environmental-oriented tools continued to dominate over time, followed by demand-oriented tools, with supply-oriented tools being the least. ConclusionThe policy themes are relatively broad and difficult to implement, focusing on establishing regulations while neglecting resource provision, and failing to continuously improve the construction of the system. It is recommended to clearly define the scope of the periodic assessment management, improve supporting systems, increase resource supply, and continuously promote the execution of assessments and policy revisions.