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.

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.

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.

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:We examined the levels of Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling in head and neck squamous cell carcinoma(HNSCC)and their influence on chemotherapy sensitization.Methods:Sixty patients with HNSCC who were treated at Tianjin Medical University Cancer Institute&Hospital,between January 2018 and December 2022,were included in the study.Levels of expressed JAK2,p-STAT3Y705,c-Myc,and Ki-67 in HNSCC tissues were evaluated using immunohistochemical staining,and correlation analysis was performed.The viability of UM-SCC1 cells treated with fedratinib,a JAK2 inhibitor,combined with cisplatin(DDP)and paclitaxel(PTX)was determined using the CCK8 assay.Western blot was performed to detect p-STAT3Y705 expression in tumor tissues and HNSCC cell lines.SCC15 and UM-SCC1 cell lines stably transfected with JAK2 or STAT3 vectors were constructed and verified.Cell activity and cell proliferation capacity were measured to evaluate the detrimental impact of STAT3 overexpression on chemotherapy with fedratinib using Western blot,CCK8,and plate cloning assays.Results:JAK2 expression in HNSCC positively correlated with p-STAT3Y705(r=0.43,P<0.000 1)and c-Myc(r=0.48,P<0.01)expression.High p-STAT3Y705 expression positively correlated with AJCC stage(P<0.000 1)and Ki-67 expression(P<0.05).High STAT3 and p-STAT3 levels were associated with poor prognosis in patients with HNSCC.In vitro,the JAK2 inhibitor fedratinib inhibited HNSCC cell proliferation and enhanced tumor cell sensitivity to DDP and PTX.JAK2 activation promotes STAT3 phosphorylation,and STAT3 overexpression reverses the effects of fedratinib on HNSCC sensitivity to chemotherapy.Conclusions:JAK2/STAT3 signaling is elev-ated in patients with HNSCC.Targeting the JAK2/STAT3 pathway is a potential method for increasing the sensitivity of HNSCC to chemotherapy.

Objective To observe the effects of Ditan Yizhi Decoction on learning and memory ability,structure of hippocampal tissue,neuronal morphology of hippocampus,and the expression of endoplasmic reticulum autophagy-related protein FAM134B in hippocampal tissue;To explore the mechanism of its therapeutic effect on vascular dementia.Methods Totally 32 SD rats were randomly divided into sham-operation group,model group,donepezil group and Ditan Yizhi Decoction group,with 8 rats in each group.The model group,donepezil group and Ditan Yizhi Decoction group were prepared with a modified permanent ligation method of bilateral common carotid arteries to create a rat model of vascular dementia,the common carotid artery was separated in the sham-operation group,but not ligated.After modeling,the donepezil group was given donepezil hydrochloride,Ditan Yizhi Decoction group was given Ditan Yizhi Decoction,and the sham-operation group and model group were given equal volume of distilled water for gavage for 4 consecutive weeks.Morris water maze experiment was used to evaluate the learning and memory ability,HE staining and Nissl staining were used to observe the morphological changes of hippocampus,ultrastructure of hippocampal neurons was observed using transmission electron microscopy,Western blot was used to detect the protein expression of FAM134B and p-FAM134B in hippocampal tissue.Results Compared with the sham-operation group,the escape latency period was prolonged of the rats in model group,and the number of crossing the original platform and the duration of stay in the target quadrant was reduced(P<0.01),the gap between neurons in CA1 region of the hippocampus increased,the cell morphology was irregular,the boundaries were blurred,the neurons shrinked,the Nissl bodies dissolved and broke,the number decreased,the endoplasmic reticulum arrangement was scattered,mitochondria swelled and deformed,and the expressions of FAM134B and p-FAM134B protein in hippocampal tissue increased(P<0.01).Compared with the model group,the escape latency period of rats in donepezil group and Ditan Yizhi Decoction group were significantly shortened,and the number of crossing the original platform and the duration of stay in the target quadrant were increased(P<0.01),the morphology and quantity of neurons in CA1 region of the hippocampus were more regular,with a decrease in neuronal pyknosis,an increase in the number of Nissl bodies,and a reduction in dissolution and fragmentation,the swelling and deformation of the endoplasmic reticulum were restored,and the expression of FAM134B and p-FAM134B protein in hippocampal tissue increased(P<0.01).Moreover,the effects of Ditan Yizhi Decoction group were better than those of the donepezil group(P<0.01).Conclusion Ditan Yizhi Decoction can improve the learning and memory ability and the morphology of neurons in vascular dementia rats.The mechanism may related to increasing the expression and phosphorylation of FAM134B protein,thereby promoting endoplasmic reticulum autophagy.

Objective To predict the potential distribution areas of three kinds of Stemonae Radix in China;To provide reference for the cultivation site selection of three kinds of Stemonae Radix;To reduce the confusion of Stemonae Radix medicinal materials in the selection of planting areas.Methods Totally 130 pieces of geographical distribution information of Stemona tuberosa Lour.,52 pieces of geographical distribution information of Stemona japonica(Bl.)Miq.,and 52 pieces of geographical distribution information of Stemona sessilifolia(Miq.)Miq.were combined with 91 environmental variables and 3 topographic factors.The maximum entropy(MaxEnt)model and geographic information system software ArcGIS 10.2 were used to predict the potential distribution areas of the three kinds of Stemonae Radix.Results Stemona tuberosa Lour.is mainly distributed in the southern provinces,including eastern Sichuan,western Chongqing,eastern Guangdong,southwestern Fujian,Taiwan,Hainan,southern Yunnan and the junction of Guizhou,Guangxi and Yunnan provinces.The high suitable area is about 293 983 km2,and the medium suitable area is about 519 667 km2.Stemona japonica(Bl.)Miq.is mainly distributed in the plain area of the middle and lower reaches of the Yangtze River,including northwestern and eastern Zhejiang,northern Jiangxi,eastern Hubei,southern Anhui,southern Jiangsu and northern Fujian.The high suitable area is about 140 320 km2,and the medium suitable area is about 188 752 km2.Stemona sessilifolia(Miq.)Miq.is mainly distributed in the North China Plain,including northeastern Hubei,southern Henan,central Anhui,western Jiangsu and central Shandong.The high suitable area is about 198 568 km2,and the medium suitable area is about 198 626 km2.Conclusion The results have important guiding significance for the standardized cultivation of three kinds of Stemonae Radix,and also provide reference for the cultivation of Stemonae Radix.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To investigate the clinical application of three-dimensional intracavitary/free-hand interstitial brachytherapy technique in radical radiotherapy for cervical cancer. Methods A retrospective study was conducted on the clinical data of patients with cervical cancer who underwent radical radiotherapy using CT-guided three-dimensional intracavitary/free-hand interstitial brachytherapy technique in The Affiliated Cancer Hospital of Nanjing Medical University from April 2019 to September 2021. The short-term efficacy and adverse reactions were analyzed, and the independent predictors affecting short-term efficacy were evaluated by logistic risk regression model. Results A total of 182 patients were included, and all patients successfully completed the treatment. Clinical efficacy assessment performed 3 months after treatment revealed an overall response rate of 90.65%; the incidence of grade 3 and 4 adverse reactions in the lower gastrointestinal tract was 4.4% during treatment. After reclassifying stage IIIC patients according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system and including factors affecting the stage, it was found that the tumor volume before brachytherapy was the main factor affecting the clinical efficacy of patients at this stage (P = 0.004). Conclusion As a key method in radical radiotherapy for cervical cancer, three-dimensional intracavitary/free-hand interstitial brachytherapy technique is safe and effective and can be quickly popularized in primary hospitals beyond regional cancer centers for cervical cancer brachytherapy.