OBJECTIVES: To compare the efficacy of transcatheter tricuspid valve replacement (TTVR) using Lux-Valve and Lux-Valve Plus in patients with severe tricuspid regurgitation. METHODS: A total of 28 consecutive patients with severe tricuspid regurgitation who underwent TTVR with Lux-Valve (n=14) or Lux-Valve Plus (n=14) in the First Affiliated Hospital of the Air Force Medical University from August 2019 to November 2023 were enrolled. Transthoracic echocardiography was performed in all patients before and 6 months after the TTVR. The ultrasound indexes were compared before and 6 months after the TTVR in all patients and between Lux-Valve and Lux-Valve Plus groups. RESULTS: Compared with the Lux-Valve group, the Lux-Valve Plus group showed significantly reduced intraoperative bleeding and shorter postoperative hospital stays (both P<0.05). Six months after the TTVR, none of the patients exhibited more than a mild tricuspid valve regurgitation, and none of the patients had moderate or above perivalvular leakage except for one patient in the Lux-Valve Plus group who had a separation of the clamping member from the anterior tricuspid leaflet. The incidence of perivalvular leakage was significantly lower in the Lux-Valve Plus group (14.29%, 2/14) than in the Lux-Valve group (64.29%, 9/14, P<0.05). At 6 months after operation, the right chamber volume and right ventricle middle transverse diameter were reduced (both P<0.05); the peak blood flow velocity across the tricuspid valve, peak pressure gradient across the tricuspid valve, mean blood flow velocity of tricuspid valve, mean pressure gradient across the tricuspid valve and velocity time integral were increased in both groups (all P<0.05).Compared with the Lux-Valve group, the Lux-Valve Plus group showed higher left ventricular ejection fraction at 6 months postoperatively (P<0.05), while the rest of the indicators were not statistically different (all P>0.05). CONCLUSIONS The efficacy of using Lux-Valve and Lux-Valve Plus for TTVR in patients with severe tricuspid regurgitation is comparable. Six months after the TTVR, the right side of the heart has undergone reverse remodeling.While Lux-Valve Plus offers greater minimally invasive benefits, valve selection should consider device-specific characteristics and differences in individual patients.
Humans ; Tricuspid Valve Insufficiency/surgery* ; Male ; Female ; Heart Valve Prosthesis Implantation/methods* ; Middle Aged ; Aged ; Tricuspid Valve/surgery* ; Heart Valve Prosthesis ; Treatment Outcome ; Echocardiography ; Adult ; Cardiac Catheterization/methods*

Objective:To investigate the awareness of Chinese gastroenterologists regarding the treatment targets of inflammatory bowel disease (IBD) as defined by the STRIDE-Ⅱ consensus and to identify challenges encountered in clinical practice.Methods:A nationwide cross-sectional survey was conducted via an online questionnaire distributed to gastroenterologists between February 16 and March 31, 2024. The survey encompassed demographic data, recognition and adherence to the STRIDE-Ⅱ consensus, perceived importance of IBD treatment targets, and clinical challenges.Results:A total of 203 valid questionnaires were collected from 28 provinces (autonomous regions/municipalities). The majority of participants (177/203, 87.2%) reported routinely referencing the STRIDE-Ⅱ consensus in IBD management. Over 90% of physicians identified endoscopic mucosal healing as the core treatment target. Additionally, approximately 80% emphasized the importance of clinical remission, endoscopic remission, quality-of-life improvement, disability prevention, and normalization of growth in pediatric patients. The challenges reported by more than half of physicians in acheiving the goals of the treatment process included lack of a standardized definition for mucosal healing (69.5%), management of psychological comorbidities (89.2%), drug failure (74.4%), penetrating Crohn's disease (72.4%), perianal fistulizing Crohn's disease (65.0%), and IBD management during pregnancy (61.1%).Conclusions:Chinese gastroenterologists demonstrate high awareness and adherence to the STRIDE-Ⅱ consensus, prioritizing mucosal healing as the cornerstone of IBD management. However, numerous challenges remain in clinical practice, particularly regarding operational definitions of therapeutic endpoints and complex disease phenotypes.

Under the Healthy China strategy, the training of preventive medicine professionals should conform to the development of the times and the needs of public health. The article analyzed the problem of "disconnection between medical care and prevention" in teaching the course of Obstetrics and Gynecology for students majoring in preventive medicine, and proposed to strengthen the strategy of "integration of medical care and prevention". Guided by the concepts of "Comprehensive Health", with the cornerstone of cultivating morality and talents, the reform focused on enhancing the post competency of preventive medicine talents. Course content was optimized by reinforcing prevention-focused elements, student-centered teaching method innovation was advocated, and simulation-based training teaching system was established. Moreover, projects integrating science and education were used to improve faculty teaching capacity with tiered and diversified approaches. Course assessment methods were revised and "ideological and political education" was incorporated to establish the education concept of "emphasis on prevention and integration of medical care and prevention". The survey showed that these reform measures effectively improved the comprehensive clinical literacy of preventive medicine students in obstetrics and gynecology, which is of great significance for building a "integration of medical care and prevention" public health talent training model. In the future, the long-term effectiveness of course reform will be ensured from the perspectives of teaching resources, personnel investment, and policy support.

Objective:To investigate the awareness of Chinese gastroenterologists regarding the treatment targets of inflammatory bowel disease (IBD) as defined by the STRIDE-Ⅱ consensus and to identify challenges encountered in clinical practice.Methods:A nationwide cross-sectional survey was conducted via an online questionnaire distributed to gastroenterologists between February 16 and March 31, 2024. The survey encompassed demographic data, recognition and adherence to the STRIDE-Ⅱ consensus, perceived importance of IBD treatment targets, and clinical challenges.Results:A total of 203 valid questionnaires were collected from 28 provinces (autonomous regions/municipalities). The majority of participants (177/203, 87.2%) reported routinely referencing the STRIDE-Ⅱ consensus in IBD management. Over 90% of physicians identified endoscopic mucosal healing as the core treatment target. Additionally, approximately 80% emphasized the importance of clinical remission, endoscopic remission, quality-of-life improvement, disability prevention, and normalization of growth in pediatric patients. The challenges reported by more than half of physicians in acheiving the goals of the treatment process included lack of a standardized definition for mucosal healing (69.5%), management of psychological comorbidities (89.2%), drug failure (74.4%), penetrating Crohn's disease (72.4%), perianal fistulizing Crohn's disease (65.0%), and IBD management during pregnancy (61.1%).Conclusions:Chinese gastroenterologists demonstrate high awareness and adherence to the STRIDE-Ⅱ consensus, prioritizing mucosal healing as the cornerstone of IBD management. However, numerous challenges remain in clinical practice, particularly regarding operational definitions of therapeutic endpoints and complex disease phenotypes.

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Background and purpose:Colorectal cancer(CRC),ranking as the third most common malignant tumor globally,continues to pose a significant public health challenge due to its high incidence and mortality rates.Chemotherapy remains a cornerstone treatment for advanced CRC.However,its efficacy is often severely limited by the emergence of multidrug resistance(MDR).The drug efflux mediated by ABCB1 is a key mechanism underlying chemotherapeutic failure.Although the non-steroidal anti-inflammatory drug tepoxalin exhibits potential antitumor activity,it remains unclear whether it influences CRC progression and chemoresistance by targeting ABCB1.This study aimed to elucidate the mechanism by which tepoxalin suppresses CRC cell growth and reverses chemoresistance through the regulation of ABCB1.Methods:This study employed a multifaceted research strategy:Bioinformatics analysis was conducted using the DepMap,The Cancer Genome Atlas(TCGA),Genotype-Tissue Expression(GTEx)and Human Protein Atlas(HPA)databases to analyze ABCB1 expression profiles and drug sensitivity.In vitro,the cell counting kit-8(CCK-8)assay was used to assess cell proliferation and chemosensitivity,and IC50 values were calculated.A subcutaneous xenograft model in nude mice was established to evaluate the antitumor efficacy in vivo.The drug affinity responsive target stability(DARTS)assay was performed to validate the direct binding between tepoxalin and ABCB1 protein.Transcriptome sequencing and gene set enrichment analysis(GSEA)were utilized to identify downstream signaling pathways.Western blot and immunohistochemistry were applied to detect the expression changes of key proteins.The PI3K-Akt pathway inhibitor copanlisib was used for reverse validation.Statistical analysis was performed using SPSS 20.0 software,and graphs were generated using GraphPad Prism 8.0.1.A value of P＜0.05 was considered statistically significant.Results:ABCB1 was significantly overexpressed in CRC tissues and cell lines(P＜0.05).Cells with high ABCB1 expression exhibited increased sensitivity to tepoxalin(R=-0.323,P＜0.001).Tepoxalin directly bound to the ABCB1 protein and promoted its proteasomal degradation.In vivo,tepoxalin significantly inhibited the growth of xenograft tumors(P＜0.01)and downregulated the expression of ABCB1 and Ki-67 proliferation index in tumor tissues.Transcriptomic analysis revealed that tepoxalin suppressed the PI3K-Akt signaling pathway[GSEA,false discovery rate(FDR)＜0.05],leading to reduced transcriptional expression of ABCB1.This effect was replicated using the PI3K-Akt pathway inhibitor copanlisib.Ultimately,tepoxalin synergistically enhanced the efficacy of 5-fluorouracil(5-FU)through the aforementioned actions.Conclusion:Tepoxalin targets ABCB1 through a dual-track mechanism:it directly binds to and destabilizes the ABCB1 protein while simultaneously downregulating its transcriptional expression via inhibition of the PI3K-Akt pathway.This coordinated action can synergistically inhibit CRC cell growth and effectively reverse chemoresistance,offering a novel potential therapeutic strategy for overcoming drug resistance in CRC.

Background and purpose:Colorectal cancer(CRC),ranking as the third most common malignant tumor globally,continues to pose a significant public health challenge due to its high incidence and mortality rates.Chemotherapy remains a cornerstone treatment for advanced CRC.However,its efficacy is often severely limited by the emergence of multidrug resistance(MDR).The drug efflux mediated by ABCB1 is a key mechanism underlying chemotherapeutic failure.Although the non-steroidal anti-inflammatory drug tepoxalin exhibits potential antitumor activity,it remains unclear whether it influences CRC progression and chemoresistance by targeting ABCB1.This study aimed to elucidate the mechanism by which tepoxalin suppresses CRC cell growth and reverses chemoresistance through the regulation of ABCB1.Methods:This study employed a multifaceted research strategy:Bioinformatics analysis was conducted using the DepMap,The Cancer Genome Atlas(TCGA),Genotype-Tissue Expression(GTEx)and Human Protein Atlas(HPA)databases to analyze ABCB1 expression profiles and drug sensitivity.In vitro,the cell counting kit-8(CCK-8)assay was used to assess cell proliferation and chemosensitivity,and IC50 values were calculated.A subcutaneous xenograft model in nude mice was established to evaluate the antitumor efficacy in vivo.The drug affinity responsive target stability(DARTS)assay was performed to validate the direct binding between tepoxalin and ABCB1 protein.Transcriptome sequencing and gene set enrichment analysis(GSEA)were utilized to identify downstream signaling pathways.Western blot and immunohistochemistry were applied to detect the expression changes of key proteins.The PI3K-Akt pathway inhibitor copanlisib was used for reverse validation.Statistical analysis was performed using SPSS 20.0 software,and graphs were generated using GraphPad Prism 8.0.1.A value of P＜0.05 was considered statistically significant.Results:ABCB1 was significantly overexpressed in CRC tissues and cell lines(P＜0.05).Cells with high ABCB1 expression exhibited increased sensitivity to tepoxalin(R=-0.323,P＜0.001).Tepoxalin directly bound to the ABCB1 protein and promoted its proteasomal degradation.In vivo,tepoxalin significantly inhibited the growth of xenograft tumors(P＜0.01)and downregulated the expression of ABCB1 and Ki-67 proliferation index in tumor tissues.Transcriptomic analysis revealed that tepoxalin suppressed the PI3K-Akt signaling pathway[GSEA,false discovery rate(FDR)＜0.05],leading to reduced transcriptional expression of ABCB1.This effect was replicated using the PI3K-Akt pathway inhibitor copanlisib.Ultimately,tepoxalin synergistically enhanced the efficacy of 5-fluorouracil(5-FU)through the aforementioned actions.Conclusion:Tepoxalin targets ABCB1 through a dual-track mechanism:it directly binds to and destabilizes the ABCB1 protein while simultaneously downregulating its transcriptional expression via inhibition of the PI3K-Akt pathway.This coordinated action can synergistically inhibit CRC cell growth and effectively reverse chemoresistance,offering a novel potential therapeutic strategy for overcoming drug resistance in CRC.

Under the Healthy China strategy, the training of preventive medicine professionals should conform to the development of the times and the needs of public health. The article analyzed the problem of "disconnection between medical care and prevention" in teaching the course of Obstetrics and Gynecology for students majoring in preventive medicine, and proposed to strengthen the strategy of "integration of medical care and prevention". Guided by the concepts of "Comprehensive Health", with the cornerstone of cultivating morality and talents, the reform focused on enhancing the post competency of preventive medicine talents. Course content was optimized by reinforcing prevention-focused elements, student-centered teaching method innovation was advocated, and simulation-based training teaching system was established. Moreover, projects integrating science and education were used to improve faculty teaching capacity with tiered and diversified approaches. Course assessment methods were revised and "ideological and political education" was incorporated to establish the education concept of "emphasis on prevention and integration of medical care and prevention". The survey showed that these reform measures effectively improved the comprehensive clinical literacy of preventive medicine students in obstetrics and gynecology, which is of great significance for building a "integration of medical care and prevention" public health talent training model. In the future, the long-term effectiveness of course reform will be ensured from the perspectives of teaching resources, personnel investment, and policy support.

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Objective To investigate the effect of radiation on cardiomyocyte apoptosis and its related mechanism.Methods Rat H9C2 cardiomyocytes were divided into blank control group,X-ray irradiation group(X-ray group),X-ray irradiation+microRNA(miRNA)-134-5p inhibitor group(X-inhibitor group)and X-ray irradiation+miRNA-134-5p inhibitor negative control group(X-NC group).H9C2 cardiomyocytes were irradiated with 6 Gy X-ray,and the changes of various indexes were detected 48 h after irradiation.Cell viability was detected by cell counting kit 8 assay.The apoptosis rate was detected by flow cytometry and Hoechst 33342 staining.The level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescence probe.The mitochondrial membrane potential was detected by JC-1 method.The activity of superoxide dismutase(SOD)and the level of malondialdehyde(MDA)in cells were measured by kits.The expression of miRNA-134-5p was detected by quantitative polymerase chain reaction.The protein expression of brain-derived neurotrophic factor(BDNF),protein kinase B(Akt),phosphorylated Akt(p-Akt),Bcl2 and Bax was detected by Western blotting.Results Compared with the blank control group,in the X-ray group the levels of ROS and MDA were significantly increased,the activity of SOD was significantly decreased,the decreased percentage in mitochondrial membrane potential was significantly increased,the number of micronuclei of DNA damage was significantly increased,and the apoptosis rate was significantly increased(all P＜0.01).Compared with the X-ray group,all the indexes of the X-inhibitor group were reversed(P＜0.05 or P＜0.01),while there was no significant difference in the above parameters in the X-NC group(all P＞0.05).Compared with the blank control group,the X-ray group had a significant increase in the miRNA-134-5p level and significant reductions in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01).Compared with the X-ray group,the X-inhibitor group had a significant reduction in the level of miRNA-134-5p and significant increases in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01),and there was no significant difference in all parameters in the X-NC group(all P＞0.05).Conclusion X-ray irradiation can induce oxidative stress,mitochondrial damage,and DNA damage,eventually leading to apoptosis in rat cardiomyocytes,and the mechanism may involve miRNA-134-5p/BDNF/Akt signaling pathway.