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.

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.

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 establish the UHPLC fingerprint of Miao Medicine Ficus tikoua Bur., study its spectrum-effect relationship with antioxidant activity, and screen the antioxidant active components. METHODS UHPLC was used to establish the fingerprint of Ficus tikoua Bur.. Evaluation System for Similarity of Chromatographic Fingerprint of Chinese Herbal Medicine (Version 2012) was used to evaluate the similarity and identify the common peaks. SPSS 16.0 and SIMCA 14.1 software were used for hierarchical cluster analysis(HCA) and principal component analysis(PCA). The 1,1-diphenyl-2-picrylhydrazyl(DPPH) free radical scavenging method, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt(ABTS) free radical scavenging method and total antioxidant capacity method were used to evaluate the antioxidant activity of 16 batches of ethanol extracts from Ficus tikoua Bur. Three methods including grey relational analysis(GRA), bivariate correlation analysis and partial least squares regression(PLSR) were used to study the spectrum-effect relationship. RESULTS The UHPLC fingerprints of 16 batches of Ficus tikoua Bur. were established and 13 common peaks were identified. The similarities were 0.613−0.996. At the same time, it was identified that peak 9 was rutin, peak 10 was isoquercetin, and peak 12 was narcissin. The results of HCA showed that the samples were clustered into two categories, which was consistent with the PCA results. Sixteen batches of Ficus tikoua Bur. had different degrees of antioxidant activity. The results of GRA showed that the correlation between 13 common peaks and antioxidant activity was >0.8, and all of them had high correlation. The results of bivariate correlation analysis and PLSR analysis showed that the correlation coefficient and regression coefficient of peak 5, peak 9(rutin), peak 10(isoquercetin), peak 11 and peak 12(narcissin) were positively correlated with antioxidant activity, and the contribution rate was larger(variable importance in projection>1), which were the main active components of antioxidant activity. CONCLUSION All the 16 batches of Ficus tikoua Bur. have good antioxidant activity, and its antioxidant effect is the result of the synergistic action of the internal antioxidant component group. The components corresponding to the common peaks 5, 9, 10, 11, 12 are closely related to their antioxidant activity, revealing the pharmacodynamic material basis of the antioxidant activity of Ficus tikoua Bur.

Myopia is a significant global health issue,and its exact causes are still not fully understood,leaving a lack of effective and propaqable treatment options.The prevalence of myopia among children and adolescents in China remains high,posing challenges for prevention and control efforts.According to the"theory of imbalance of essence and tendon",an imbalance in the essential elements and tendons can impede the passage of eye essence and blood,resulting in delayed expansion and contraction of the eye meridians and tendons,leading to blurred vision.Modern research indicates that during the development of myopia,there are notable changes in the microstructure,activation range,and signaling of various brain regions,providing a biological basis for the"brain-eye"mechanism.Moreover,abnormal activity in the brain nucleus contributes to alterations in choroid blood flow and the impairment of eye muscle regulation,thereby accelerating the progression of myopia,this phenomenon represents the manifestation of the brain-eye imbalance.Consequently,strategies for myopia prevention and control should prioritize nourishing kidney essence,replenishing brain marrow,promoting liver and blood health,and softening the meridians.These measures aim to optimize the functioning of the brain and eyes,maintain the flexibility of eye tendons,enhance eye regulation,sustain the strength of eye tendons,and delay the advancement of eye axis growth and myopia.By enriching the scientific understanding of the appropriate application of traditional Chinese medicine techniques to prevent and control myopia through the brain,this research provides valuable insights for future explorations in this field.

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.

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.