Human lactate dehydrogenase A (LDHA) is an NADH-dependent oxidoreductase that catalyzes the conversion of pyruvate to lactate, playing a crucial role in the aerobic glycolysis of tumor cells. Additionally, LDHA is responsible for catalyzing the conversion of glyoxylate to oxalate in the liver, excessive accumulation of which leads to hyperoxaluria. Representative LDHA inhibitors reported to date include GNE-140, NCATS-SM1441, and CHK-336. In this study, NCATS-SM1441 was used as the lead compound. Based on the analysis of its cocrystal binding mode with LDH, the key carboxythiazole and aromatic pharmacophores were retained, while the original substituted pyrazole linker was replaced with urea linker moieties to simplify the structure. As a result, nine urea derivatives were designed and synthesized. Subsequently, on the basis of structure-activity relationship and molecular docking studies, nine target triazole compounds were further designed. Ultimately, triazole compound 25 was found to exhibit the most potent LDHA inhibitory activity (IC50 = 1.59 μmol/L) in vitro. Molecular dynamics simulations were employed to analyze the interactions between compound 25 and key amino acid residues. Finally, the prediction of physicochemical properties and the evaluation of cell viability were performed for compound 25. The study provides an experimental basis for future development of novel LDHA inhibitors with improved drugability.

Objective:This study aimed to systematically evaluate the efficacy of glucagon-like peptide-1(GLP-1) receptor agonists and multi-target analogs on weight reduction and cardiometabolic outcomes in non-diabetic individuals with obesity, and to compare the efficacy and safety across different GLP-1 receptor agonists.Methods:Randomized controlled trials(RCTs) published between January 2000 and March 2025 were identified through a systematic search of CNKI, Wanfang, Web of Science, PubMed, and Cochrane databases. Two reviewers independently screened the studies, extracted data, and assessed methodological quality. Meta-analysis was performed using RevMan 5.4.1 software. Results:A total of 16 RCTs involving 11 032 non-diabetic individuals with obesity were included. Meta-analysis showed that GLP-1 receptor agonists significantly reduced body weight(ΔWeight=-8.71 kg, 95% CI -10.68 to -6.74, P<0.001) and BMI(ΔBMI=-3.01 kg/m 2, 95% CI -3.77 to -2.25, P<0.001), as well as improved systolic blood pressure(ΔSBP=-4.13 mmHg, 1 mmHg=0.133 kPa, 95% CI -4.87 to -3.39, I2=60%) and diastolic blood pressure(ΔDBP=-1.39 mmHg, 95% CI -2.32 to -0.46, I2=95%). Tirzepatide showed the most pronounced effects on both weight and blood pressure reduction. In addition, GLP-1 receptor agonists significantly lowered LDL-C, TC, and TG, while moderately increasing HDL-C levels. In terms of safety, GLP-1 receptor agonists were associated with an increased risk of gastrointestinal adverse events, but did not significantly increase the risk of hypoglycemia. Conclusion:GLP-1 receptor agonists are effective in reducing weight, BMI, and blood pressure, and in improving lipid profiles in non-diabetic individuals with obesity. However, gastrointestinal side effects should be closely monitored. Given the variability in efficacy and safety among various GLP-1 receptor agonists, personalized treatment approaches are recommended.

Objective:To analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021, and to explore the effects of age, period, and cohort on pancreatic cancer incidence and mortality.Methods:Data from the Global Burden of Disease Study (GBD) 2021 database were used to analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021. The Joinpoint software was applied to analyze the time trends of standardized incidence and mortality rates, and to calculate the average annual percentage change. An age-period-cohort model was constructed to analyze the effects of age, period, and birth cohort on the trends of pancreatic cancer incidence and mortality. The disease burden of pancreatic cancer deaths attributed to risk factors such as hyperglycemia and smoking was analyzed.Results:In 2021, the incidence of pancreatic cancer in China was 8.34/100 000, and the mortality rate was 8.41/100 000, representing increases of 150.45% and 145.19%, respectively, compared to 1992 (3.33/100 000 and 3.43/100 000) . By sex, the incidence (9.93/100 000) and mortality (9.91/100 000) rates in males in 2021 were higher than those in females (6.68/100 000 and 6.83/100 000) . From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China showed upward trends, with average annual increases of 0.80% and 0.62%, respectively, both of which were statistically significant (both P<0.001) . Age effect results indicated a general increasing trend in pancreatic cancer incidence, with a steady rise in the 15-49 age group, a sharp increase after the age of 50, and a peak in the over 85 age group at 68.64/100 000. The mortality rate showed a slow increase in the 15-79 age group, with a marked rise and peak in the 80-84 age group at 196.51/100 000. Period effect results showed an overall upward trend in the period relative risk ( RR) for pancreatic cancer incidence, with the highest risk in 2017-2021 ( RR=1.09, 95% CI: 1.05-1.13, P=0.012) , compared to the reference period 2002-2006 ( RR=1) . The RR for pancreatic cancer mortality showed a fluctuating trend, with the highest risk in 2012-2016 ( RR=1.60, 95% CI: 1.07-2.38, P=0.021) , compared to the reference period 2002-2006 ( RR=1) . The results of cohort effect showed that the incidence and mortality risk of pancreatic cancer in China generally increased with the increase of years. With the 1952-1956 birth cohort as the reference cohort ( RR=1) , the incidence ( RR=1.18, 95% CI: 0.99-1.40, P=0.032) and mortality ( RR=1.63, 95% CI: 0.12-11.53, P=0.042) risk of pancreatic cancer were the highest in the 1987-1991 birth cohort, and showed decreasing trends after the 1992-1996 birth cohort. The proportion of pancreatic cancer deaths attributable to high blood glucose showed an increasing trend, while those attributable to smoking showed a decreasing trend. Conclusions:From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China have continued to rise, with males having higher incidence and mortality rates than females. Age, period, and cohort all significantly influence the trends in pancreatic cancer incidence and mortality. The trend in pancreatic cancer deaths attributable to high blood glucose is increasing.

Objective:To establish the characteristic spectrum of Liushenqu standard decoction using ultra-high performance liquid chromatography (UPLC); To determine the contents of related index components; To evaluate the quality of Liushenqu standard decoction.Methods:UPLC method was used to establish characteristic spectrum of Liushenqu standard decoction. Chromatographic Fingerprint Similarity Evaluation System (2012 edition) was used for similarity analysis, the characteristic peak was assigned, and the content of its index components was determined.Results:The characteristic peaks of Liushenqu standard decoction were calibrated and 8 components were identified, namely uridine, adenosine, guanosine, 5-hydroxymethylfurfural, tryptophan, vanillic acid, ferulic acid and shaftaside. The contents of uridine, adenosine, tryptophan ferulic acid and shaftaside in 10 batches of Liushenqu standard decoction were simultaneously determined, and ranged from 0.036 1～0.383 9 mg/g, 0.030 7～0.170 2 mg/g, 0.007 0～0.060 2 mg/g, 0.001 0～0.005 0 mg/g, 0.000 8～0.013 8 mg/g, respectively. The transfer rates ranged from 44.2% to 50.8%, 60.1% to 67.7%, 60.4% to 76.4%, 62.7% to 77.4%, 50.7% to 61.4%, respectively.Conclusion:The established UPLC characteristic spectrum and content determination method are accurate and repeatable, which can provide references for quality control of Liushenqu standard granules.

Objective:This study aimed to systematically evaluate the efficacy of glucagon-like peptide-1(GLP-1) receptor agonists and multi-target analogs on weight reduction and cardiometabolic outcomes in non-diabetic individuals with obesity, and to compare the efficacy and safety across different GLP-1 receptor agonists.Methods:Randomized controlled trials(RCTs) published between January 2000 and March 2025 were identified through a systematic search of CNKI, Wanfang, Web of Science, PubMed, and Cochrane databases. Two reviewers independently screened the studies, extracted data, and assessed methodological quality. Meta-analysis was performed using RevMan 5.4.1 software. Results:A total of 16 RCTs involving 11 032 non-diabetic individuals with obesity were included. Meta-analysis showed that GLP-1 receptor agonists significantly reduced body weight(ΔWeight=-8.71 kg, 95% CI -10.68 to -6.74, P<0.001) and BMI(ΔBMI=-3.01 kg/m 2, 95% CI -3.77 to -2.25, P<0.001), as well as improved systolic blood pressure(ΔSBP=-4.13 mmHg, 1 mmHg=0.133 kPa, 95% CI -4.87 to -3.39, I2=60%) and diastolic blood pressure(ΔDBP=-1.39 mmHg, 95% CI -2.32 to -0.46, I2=95%). Tirzepatide showed the most pronounced effects on both weight and blood pressure reduction. In addition, GLP-1 receptor agonists significantly lowered LDL-C, TC, and TG, while moderately increasing HDL-C levels. In terms of safety, GLP-1 receptor agonists were associated with an increased risk of gastrointestinal adverse events, but did not significantly increase the risk of hypoglycemia. Conclusion:GLP-1 receptor agonists are effective in reducing weight, BMI, and blood pressure, and in improving lipid profiles in non-diabetic individuals with obesity. However, gastrointestinal side effects should be closely monitored. Given the variability in efficacy and safety among various GLP-1 receptor agonists, personalized treatment approaches are recommended.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.