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.

Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

Objective:To investigate the current level of awareness among Chinese gastroenterologists regarding small intestinal bacterial overgrowth (SIBO).Methods:From March 7th to April 14th, 2024, an online survey questionnaire was sent to qualified clinical physicians specializing in gastroenterology in various levels of general hospitals across the country through the official channels of national academic organizations such as the Gastroenterology Branch of the Chinese Medical Association, the Gastrointestinal Motility Group of the Gastroenterology Branch of the Chinese Medical Association, and the Functional Gastrointestinal Disorders Collaborative Group of the Gastroenterology Branch of the Chinese Medical Association, as well as through the national medical continuing education project cooperation platform. The questionnaire content includes basic information, awareness of consensus guidelines on functional gastrointestinal disorders (FGID) and SIBO, understanding of SIBO and its diagnosis and treatment strategies, et al. The influencing factors of physicians′ cognitive level regarding SIBO were analyzed based on the questionnaire results. Statistical methods employed descriptive statistical method and partial correlation analysis.Results:A total of 511 valid questionnaires were collected, among them, 78.1% (399/511) of the respondents practiced in tertiary hospitals, and 90.2% (461/511) of the respondents were aware of the definition of SIBO. However, only 9.0% (46/511) could accurately identify all the key points of the relevant consensus guidelines. Educational background (undergraduate and master′s degree vs. doctor degree, OR=0.265, 0.528, 95% confidence interval(95% CI): 0.155 to 0.454, 0.322 to 0.865), professional title (junior title vs. senior title, OR=0.577, 95% CI: 0.344 to 0.968), and the number of SIBO cases handled per year (less than 50 cases vs. more than 200 cases, OR=0.144, 95% CI: 0.043 to 0.479) were independent influencing factors that affect the cognitive level of specialist physicians regarding SIBO and the guidelines (all P<0.05). The results of hydrogen and methane breath test (HMBT) was the main reference indicator for diagnosing SIBO in the respondents (79.8%, 408/511), but only 8.4%(43/511) of the specialists were familiar with the principle of HMBT, and 65.9% (337/511) were not clear about the differences in diagnostic thresholds among different consensus or guidelines. Rifaximin was the most commonly used therapy (87.5%, 447/511), but there was significant heterogeneity in the selection of dosage and treatment course. According to the survey, 17.6% (90/511) of the clinicians believed that comprehensive assessment of the patient′s clinical condition was not necessary for the diagnosis and treatment of FGID. Conclusion:Gastroenterologists are familiar with the basic concepts of SIBO, but their understanding of the diagnostic criteria application and the latest research progress is limited.

Objective·To construct a framework nucleic acid-based linear amplification platform for the sensitive and quantitative detection of bladder cancer-related microRNAs(miRNAs),facilitating early screening and accurate diagnosis of bladder cancer.Methods·This study combined a plasma fluorescence-enhanced chip with high-performance tetrahedral framework nucleic acid(tFNA)probes,targeting miRNAs as biomarkers,to construct a framework nucleic acid-based linear signal amplification platform for precise and high-throughput quantitative analysis of multiple targets.First,atomic force microscope(AFM)was used to verify the efficient synthesis of tFNA.The signal linear amplification capability of the reporter unit was verified by polyacrylamide gel electrophoresis(PAGE)and total internal reflection fluorescent microscope(TIRFM).The performance of the sensing interface substrates was compared,and the golden island chip with signal amplification was selected.The specificity of the detection system was verified by an interface specificity experiment.Five bladder cancer-related miRNAs were selected to construct standard curves for quantitative detection.Results·The efficient synthesis of tetrahedral monomer and dimer structures was verified by AFM.PAGE and TIRFM characterization verified the linear amplification of fluorescence signals from 1 to 6 valence fluorescence reporter units.In order to achieve further signal amplification,the plasma island chip and the traditional glass chip were compared.The results showed that the gold island chip exhibited a plasmonic effect,which significantly enhanced the near-infrared(NIR)fluorescence,with a signal amplification of up to 13.6 times compared to the glass chip.The specificity verification experiment showed that the signal-to-noise ratio of the system ranged from 7 to 10,demonstrating high specificity.Based on the high specificity of the system,along with the good interface regulation ability and linear amplification of the framework nucleic acid-based interface,dual-color parallel detection of the targets was finally realized.The working range was 100 fmol/L-10 nmol/L(R2≥0.991),and the detection limit was as low as 100 fmol/L.Conclusion·The establishment of this platform opens new avenues for highly sensitive quantitative analysis of biomarkers.Furthermore,the developed framework nucleic acid-based detection platform holds great potential for clinical diagnosis and prognosis of bladder cancer and other major diseases.Through early detection and precise subtype diagnosis,doctors can formulate more personalized treatment plans for patients,improving treatment efficacy and reducing unnecessary treatment plans and associated side effects.Therefore,this liquid biopsy technology not only provides new possibilities for early screening of bladder cancer but also serves as reference for research and clinical applications in other types of cancer.

Objective·To construct a framework nucleic acid-based linear amplification platform for the sensitive and quantitative detection of bladder cancer-related microRNAs(miRNAs),facilitating early screening and accurate diagnosis of bladder cancer.Methods·This study combined a plasma fluorescence-enhanced chip with high-performance tetrahedral framework nucleic acid(tFNA)probes,targeting miRNAs as biomarkers,to construct a framework nucleic acid-based linear signal amplification platform for precise and high-throughput quantitative analysis of multiple targets.First,atomic force microscope(AFM)was used to verify the efficient synthesis of tFNA.The signal linear amplification capability of the reporter unit was verified by polyacrylamide gel electrophoresis(PAGE)and total internal reflection fluorescent microscope(TIRFM).The performance of the sensing interface substrates was compared,and the golden island chip with signal amplification was selected.The specificity of the detection system was verified by an interface specificity experiment.Five bladder cancer-related miRNAs were selected to construct standard curves for quantitative detection.Results·The efficient synthesis of tetrahedral monomer and dimer structures was verified by AFM.PAGE and TIRFM characterization verified the linear amplification of fluorescence signals from 1 to 6 valence fluorescence reporter units.In order to achieve further signal amplification,the plasma island chip and the traditional glass chip were compared.The results showed that the gold island chip exhibited a plasmonic effect,which significantly enhanced the near-infrared(NIR)fluorescence,with a signal amplification of up to 13.6 times compared to the glass chip.The specificity verification experiment showed that the signal-to-noise ratio of the system ranged from 7 to 10,demonstrating high specificity.Based on the high specificity of the system,along with the good interface regulation ability and linear amplification of the framework nucleic acid-based interface,dual-color parallel detection of the targets was finally realized.The working range was 100 fmol/L-10 nmol/L(R2≥0.991),and the detection limit was as low as 100 fmol/L.Conclusion·The establishment of this platform opens new avenues for highly sensitive quantitative analysis of biomarkers.Furthermore,the developed framework nucleic acid-based detection platform holds great potential for clinical diagnosis and prognosis of bladder cancer and other major diseases.Through early detection and precise subtype diagnosis,doctors can formulate more personalized treatment plans for patients,improving treatment efficacy and reducing unnecessary treatment plans and associated side effects.Therefore,this liquid biopsy technology not only provides new possibilities for early screening of bladder cancer but also serves as reference for research and clinical applications in other types of cancer.

Objective:To investigate the current level of awareness among Chinese gastroenterologists regarding small intestinal bacterial overgrowth (SIBO).Methods:From March 7th to April 14th, 2024, an online survey questionnaire was sent to qualified clinical physicians specializing in gastroenterology in various levels of general hospitals across the country through the official channels of national academic organizations such as the Gastroenterology Branch of the Chinese Medical Association, the Gastrointestinal Motility Group of the Gastroenterology Branch of the Chinese Medical Association, and the Functional Gastrointestinal Disorders Collaborative Group of the Gastroenterology Branch of the Chinese Medical Association, as well as through the national medical continuing education project cooperation platform. The questionnaire content includes basic information, awareness of consensus guidelines on functional gastrointestinal disorders (FGID) and SIBO, understanding of SIBO and its diagnosis and treatment strategies, et al. The influencing factors of physicians′ cognitive level regarding SIBO were analyzed based on the questionnaire results. Statistical methods employed descriptive statistical method and partial correlation analysis.Results:A total of 511 valid questionnaires were collected, among them, 78.1% (399/511) of the respondents practiced in tertiary hospitals, and 90.2% (461/511) of the respondents were aware of the definition of SIBO. However, only 9.0% (46/511) could accurately identify all the key points of the relevant consensus guidelines. Educational background (undergraduate and master′s degree vs. doctor degree, OR=0.265, 0.528, 95% confidence interval(95% CI): 0.155 to 0.454, 0.322 to 0.865), professional title (junior title vs. senior title, OR=0.577, 95% CI: 0.344 to 0.968), and the number of SIBO cases handled per year (less than 50 cases vs. more than 200 cases, OR=0.144, 95% CI: 0.043 to 0.479) were independent influencing factors that affect the cognitive level of specialist physicians regarding SIBO and the guidelines (all P<0.05). The results of hydrogen and methane breath test (HMBT) was the main reference indicator for diagnosing SIBO in the respondents (79.8%, 408/511), but only 8.4%(43/511) of the specialists were familiar with the principle of HMBT, and 65.9% (337/511) were not clear about the differences in diagnostic thresholds among different consensus or guidelines. Rifaximin was the most commonly used therapy (87.5%, 447/511), but there was significant heterogeneity in the selection of dosage and treatment course. According to the survey, 17.6% (90/511) of the clinicians believed that comprehensive assessment of the patient′s clinical condition was not necessary for the diagnosis and treatment of FGID. Conclusion:Gastroenterologists are familiar with the basic concepts of SIBO, but their understanding of the diagnostic criteria application and the latest research progress is limited.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.