OBJECTIVE To explore the efficacy and safe ty of Tripterygium wilfordii polyglycoside combined with finerenone in the treatment of diabetic nephropathy （DN）. METHODS This study selected 104 DN patients admitted to the Nephrology Department of Handan Central Hospital from January 2023 to May 2024 as the subjects and randomly assigned them into the control group （52 cases） and the combination group （52 cases）. All patients received basic treatment such as lipid-lowering and blood glucose control. On this basis， patients in the control group received finerenone， while those in the combination group received a combination therapy of T. wilfordii polyglycoside and finerenone. Both groups underwent treatment for a duration of three months. The two groups were compared in terms of clinical efficacy， renal function indicators [24-hour urine protein excretion （24 h UPE）， urinary albumin-to-creatinine ratio （UACR）， urinary albumin excretion rate （UAER） ] ， inflammatory factors [high mobility group box 1 protein （HMGB1）， interleukin-6 （IL-6）， nuclear factor-κB （NF-κB）， high-sensitivity C reactive protein （hs-CRP） ] ， and oxidative stress indicators [total antioxidant capacity （T-AOC）， superoxide dismutase （SOD）， advanced oxidation protein products （AOPP）， malondialdehyde （MDA） ] before and after treatment. Additionally， the occurrence of adverse drug reactions was recorded. RESULTS In terms of efficacy， the total effective rate of patients in the combination group was higher than that of the control group （ P ＜0.05）. After treatment， the levels of 24-h UPE， UACR， UAER， HMGB1， IL-6， NF-κB， hs-CRP， AOPP and MDA in the two groups were significantly lower than those in the same group before treatment； the levels of T-AOC and SOD in the two groups were significantly higher than those in the same group before treatment， with the combination group showing superior changes in the above indicators compared to the control group at the corresponding time point （ P ＜0.05）. In terms of safety， there was no statistical significance in the total incidence of adverse drug reactions between the two groups （ P ＞0.05）. CONCLUSIONS Compared to finerenone monotherapy， the combination therapy of T. wilfordii polyglycoside and finerenone demonstrates significant efficacy in treating DN. It effectively reduces proteinuria levels， alleviates inflammatory reaction， mitigates oxidative stress， and does not increase the risk of adverse reactions.

Objective:To investigate the clinical value of 18F-NaF PET/CT coronary plague imaging in evaluating the long-term prognosis of patients with coronary artery disease (CAD). Methods:A retrospective cohort study was conducted among 54 patients (37 males and 17 females, aged (57.2±9.8) years) diagnosed with CAD from a multicenter study between September 2015 and October 2022. All patients underwent 18F-NaF PET/CT and coronary angiography (CAG) within 1 week, and the PET/CT imaging was performed at the First Hospital of Shanxi Medical University. Major adverse cardiovascular events (MACE) were followed up. ROC curves were established to obtain the optimal thresholds of SUV max and accumulated SUV max of all lesions of main coronary artery branches (S-SUV max) for predicting MACE. Cox proportional risk model and Kaplan-Meier method (log-rank test) were used to analyze the predictive value of PET parameters for MACE. Differences in metabolic parameters between 2 groups were compared by Mann-Whitney U test. Results:The median follow-up time of the 54 patients was 6.0(1.8, 6.6) years, and 13(24.1%) patients developed MACE, including 7 deaths, 5 myocardial infarction and 1 severe arrhythmia. S-SUV max in MACE group was significantly higher than that in the non-MACE group (2.64(2.08, 4.49) vs 1.83(0.95, 2.90); Z=-2.04, P=0.041). ROC curve showed that the optimal threshold of S-SUV max for MACE prediction was 2.05 (AUC=0.690). Multivariate Cox analysis showed that S-SUV max was a strong predictor of MACE (hazard ratio ( HR)=2.434(95% CI: 1.547-3.828), P<0.001). ROC curve showed that the optimal threshold of SUV max to predict MACE was 0.55 (AUC=0.659), and univariate Cox analysis showed that SUV max was a factor to predict MACE ( HR=10.192 (95% CI: 2.667-38.953), P=0.001). In 25 patients with incomplete revascularization (ICR), Kaplan-Meier analysis showed that the incidence of MACE in patients with positive 18F-NaF uptake (single medium stenosis (40%-70%) with SUV max≥0.55) was significantly higher than that in patients with negative 18F-NaF uptake (5/14 vs 0/11; χ2=6.07, P=0.014). Conclusions:18F-NaF PET/CT can be used as an independent predictor of MACE in patients with CAD and can quantitatively assess the long-term progression of moderate coronary artery stenosis. In the future, it is expected to be a new non-invasive way to guide the revascularization treatment decision of multi-vessel CAD.

Objective To assess the incidence of contrast-induced nephropathy(CIN)in patients with chronic thromboembolic pulmonary hypertension(CTEPH)after receiving balloon pulmonary angioplasty(BPA),and to evaluate the effect of the contrast agents on renal function.Methods A total of 143 CTEPH patients,who received BPA at the China-Japan Friendship Hospital of China from December 2018 to May 2022,were enrolled in this study.The clinical data,hemodynamic indicators,and serum creatinine(SC)concentrations within one week before and 48-72 h after BPA were collected.The estimated glomerular filtration rate(eGFR)was calculated according to the Modification of Diet in Renal Disease(MDRD)formula.The SC concentration and eGFR changes before and after each BPA procedure were compared.The incidence of CIN and its risk factors were evaluated,and the changes in hemodynamics,SC and eGFR after the initial and last time of BPA treatment were analyzed.Results A total of 192 BPA procedures were performed in 115 CTEPH patients,including 88 BPA procedures in males and 103 BPA procedures in females.The mean amount of contrast agent used for each BPA was(145.58±47.26)mL.After BPA,12 patients developed 13 times of CIN,with an incidence of 6.8％.There was no significant differences(P＞0.05)in the baseline characteristics and SC concentration before BPA between CIN patients and non-CIN patients.In terms of the hemodynamic indexes,the mixed venous oxygen saturation(SvO2)in CIN patients was significantly lower than that in non-CIN patients(58.58％±10.38％vs.66.15％±8.02％,P=0.002),and no statistically significant differences(P＞0.05)in the other hemodynamic indexes existed between CIN group and non-CIN group.No statistically significant differences in SC concentration and eGFR existed before and after each BPA procedure.In patients who had received several BPA procedures,significant improvements in the SC[(78.09±18.760)μmol/L vs.(82.26±21.37)μmol/L,P＜0.001]and eGFR[(86.08±21.22)mL/(min·1.73 m2)vs.(82.07±22.05)mL/(min·1.73 m2),P=0.007]was achieved when compared with their baseline values.Conclusion CTEPH patients may develop CIN after receiving BPA treatment.After receiving several BPA treatments the patient's clinical symptoms and hemodynamics can be improved,and the patient's renal function is also significantly improved.

Objective:To evaluate the long-term effectiveness of lingual mucosal graft ureteroplasty (LMGU) for managing long-segment (≥5 cm) ureteral strictures in a multi-institutional cohort of patients.Methods:A multi-center retrospective case series study was conducted on clinical data from 42 patients undergoing LMGU for long-segment ureteral strictures (≥5 cm) across five institutions between February 2017 and June 2024. The cohort comprised 31 males and 11 females, with an age of (43.4±12.0) years (range: 15 to 64 years) and a body mass index of (24.6±2.6) kg/m2 (range: 16.0 to 30.0 kg/m2). Strictures involved the left ureter in 24 cases and right ureter in 18 cases, demonstrating a stricture length of (6.4±1.5) cm (range: 5.0 to 11.5 cm). Surgical interventions included either onlay ureteroplasty or augmented anastomotic ureteroplasty, selected according to intraoperative findings. Intraoperative parameters, postoperative complications, and follow-up outcomes were analyzed.Results:Laparoscopic surgery was performed in 22 cases and robot-assisted surgery in 20 cases. Among the 42 patients, 22 underwent onlay ureteroplasty while 20 received augmented anastomotic ureteroplasty. The graft length was (5.9±1.8) cm (range: 3.0 to 12.0 cm), operative time (191.5±55.6) minutes (range: 105.0 to 350.0 minutes), and intraoperative estimated blood loss (86.7±73.6) ml (range: 10.0 to 400.0 ml). All procedures were successfully completed without conversion to open surgery. The postoperative hospital stay was (7.6±2.0) days (range: 4.0 to 15.0 days), with double-J stent removal at 6 to 8 weeks postoperatively. During a follow-up of (49.1±25.0) months (range: 12.0 to 99.0 months), no stricture recurrence was observed in any patient.Conclusion:LMGU is a safe, feasible, and effective long-term technique for managing long-segment (≥5 cm) ureteral strictures.

Objective:To investigate the clinical value of 18F-NaF PET/CT coronary plague imaging in evaluating the long-term prognosis of patients with coronary artery disease (CAD). Methods:A retrospective cohort study was conducted among 54 patients (37 males and 17 females, aged (57.2±9.8) years) diagnosed with CAD from a multicenter study between September 2015 and October 2022. All patients underwent 18F-NaF PET/CT and coronary angiography (CAG) within 1 week, and the PET/CT imaging was performed at the First Hospital of Shanxi Medical University. Major adverse cardiovascular events (MACE) were followed up. ROC curves were established to obtain the optimal thresholds of SUV max and accumulated SUV max of all lesions of main coronary artery branches (S-SUV max) for predicting MACE. Cox proportional risk model and Kaplan-Meier method (log-rank test) were used to analyze the predictive value of PET parameters for MACE. Differences in metabolic parameters between 2 groups were compared by Mann-Whitney U test. Results:The median follow-up time of the 54 patients was 6.0(1.8, 6.6) years, and 13(24.1%) patients developed MACE, including 7 deaths, 5 myocardial infarction and 1 severe arrhythmia. S-SUV max in MACE group was significantly higher than that in the non-MACE group (2.64(2.08, 4.49) vs 1.83(0.95, 2.90); Z=-2.04, P=0.041). ROC curve showed that the optimal threshold of S-SUV max for MACE prediction was 2.05 (AUC=0.690). Multivariate Cox analysis showed that S-SUV max was a strong predictor of MACE (hazard ratio ( HR)=2.434(95% CI: 1.547-3.828), P<0.001). ROC curve showed that the optimal threshold of SUV max to predict MACE was 0.55 (AUC=0.659), and univariate Cox analysis showed that SUV max was a factor to predict MACE ( HR=10.192 (95% CI: 2.667-38.953), P=0.001). In 25 patients with incomplete revascularization (ICR), Kaplan-Meier analysis showed that the incidence of MACE in patients with positive 18F-NaF uptake (single medium stenosis (40%-70%) with SUV max≥0.55) was significantly higher than that in patients with negative 18F-NaF uptake (5/14 vs 0/11; χ2=6.07, P=0.014). Conclusions:18F-NaF PET/CT can be used as an independent predictor of MACE in patients with CAD and can quantitatively assess the long-term progression of moderate coronary artery stenosis. In the future, it is expected to be a new non-invasive way to guide the revascularization treatment decision of multi-vessel CAD.

Objective:To evaluate the long-term effectiveness of lingual mucosal graft ureteroplasty (LMGU) for managing long-segment (≥5 cm) ureteral strictures in a multi-institutional cohort of patients.Methods:A multi-center retrospective case series study was conducted on clinical data from 42 patients undergoing LMGU for long-segment ureteral strictures (≥5 cm) across five institutions between February 2017 and June 2024. The cohort comprised 31 males and 11 females, with an age of (43.4±12.0) years (range: 15 to 64 years) and a body mass index of (24.6±2.6) kg/m2 (range: 16.0 to 30.0 kg/m2). Strictures involved the left ureter in 24 cases and right ureter in 18 cases, demonstrating a stricture length of (6.4±1.5) cm (range: 5.0 to 11.5 cm). Surgical interventions included either onlay ureteroplasty or augmented anastomotic ureteroplasty, selected according to intraoperative findings. Intraoperative parameters, postoperative complications, and follow-up outcomes were analyzed.Results:Laparoscopic surgery was performed in 22 cases and robot-assisted surgery in 20 cases. Among the 42 patients, 22 underwent onlay ureteroplasty while 20 received augmented anastomotic ureteroplasty. The graft length was (5.9±1.8) cm (range: 3.0 to 12.0 cm), operative time (191.5±55.6) minutes (range: 105.0 to 350.0 minutes), and intraoperative estimated blood loss (86.7±73.6) ml (range: 10.0 to 400.0 ml). All procedures were successfully completed without conversion to open surgery. The postoperative hospital stay was (7.6±2.0) days (range: 4.0 to 15.0 days), with double-J stent removal at 6 to 8 weeks postoperatively. During a follow-up of (49.1±25.0) months (range: 12.0 to 99.0 months), no stricture recurrence was observed in any patient.Conclusion:LMGU is a safe, feasible, and effective long-term technique for managing long-segment (≥5 cm) ureteral strictures.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Objective:To analyze the risk factors for 6-month prognosis of traumatic spinal cord injury (TSCI).Methods:A retrospective analysis was conducted of the 133 patients with TSCI who had been admitted to Department of Orthopaedics, The First Hospital Affiliated to Jinan University from January 2017 to August 2021. The patients with TSCI were categorized into an improved group ( n=82) and a non-improved group ( n=51) according to the improvements in the American Spinal Injury Association (ASIA) grading between admission and 6 months after injury. To identify the risk factors that might affect the prognosis of TSCI patients at 6 months after injury, univariate and logistic regression analyses were conducted of indicators such as gender, age, length of MRI spinal cord signal change, maximum canal compromise (MCC), maximum spinal cord compression (MSCC), brain and spinal cord injury center(BASIC)score, neutrophil-to-lymphocyte ratio (NLR) within 3 days after injury, ASIA grading within 3 days after injury, mean arterial pressure (MAP) at 3 days after operation, and presence of complications. Results:The univariate analysis showed significant differences between the improved and non-improved groups in length of MRI spinal cord signal change, MCC, MSCC, BASIC, NLR within 3 days after injury, ASIA grading within 3 days after injury, MAP at 3 days after operation, and presence of complications (all P<0.05). The logistic regression analysis showed that NLR ( OR=0.463, 95% CI: 0.287 to 0.748, P=0.002) and ASIA grading ( OR=11.684, 95% CI: 1.684 to 81.086, P=0.013) within 3 days after injury, as well as MAP at 3 days after operation ( OR=2.224, 95% CI: 1.306 to 3.787, P=0.003), were risk factors affecting the 6-month prognosis in TSCI patients. Conclusion:The NLR and ASIA grading within 3 days after injury, and MAP at 3 days after operation are risk factors that may affect the prognosis of TSCI patients at 6 months after injury.

Objective:To investigate the effect of vitamin D supplementation on weight loss efficacy and insulin resistance (IR) in obese patients.Methods:It was a randomized controlled trial. A total of 190 obese patients with vitamin D deficiency were selected from the obesity clinic of Tianjin Union Medical Center from March to December in 2023. The patients were divided into control group (95 cases) and vitamin D group (95 cases) according to random number table. The control group was given energy-limited high-protein diet combined with moderate intensity exercise, and the vitamin D group was supplemented with vitamin D on the basis of the control group, 14 000 U/week for 24 weeks. A total of 25 dropped out of the study from the two groups for various reasons. Finally, 79 cases in the control group and 86 cases in the vitamin D group were included in the analysis. Independent sample t test and rank sum test were used to compare serum 25 hydroxyvitamin D [25 (OH) D] level, body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin and glycated hemoglobin (HbA 1c) between the two groups at baseline and after intervention. Homeostasis model insulin resistance index (HOMA-IR) was used to evaluate the degree of insulin resistance (IR), and the effects of vitamin D supplementation on weight loss efficiency and IR in those patients were analyzed. Results:There was no significant differences in serum 25(OH)D level between the two groups before intervention ( P>0.05); the serum 25(OH)D level in the vitamin D group was significantly higher than that in the control group after intervention [(30.90±7.55) vs (16.00±4.34) μg/L] ( t=-15.35, P<0.001). The body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin, HbA 1c, and HOMA-IR were all significantly lower after the intervention than those before the intervention in both groups [control group: (93.32±13.47) vs (98.95±14.31) kg, (33.74±5.09) vs (35.80±5.52) kg/m 2, (39.77±11.87) vs (44.12±12.79) kg, (183.76±40.95) vs (204.01±32.18) m 2, 5.00 (4.55, 5.67) vs 5.24 (4.68, 6.42) mmol/L, 16.78 (13.94, 24.30) vs 22.56 (15.95, 31.2) mU/L, 5.55%±0.53% vs 6.05%±0.99%, 4.11 (3.14, 5.57) vs 5.51 (3.61, 8.49); vitamin D group: (88.14±17.66) vs (104.43±22.02) kg, (31.02±5.10) vs (36.66±5.98) kg/m 2, (35.51±12.87) vs (46.67±13.33) kg, (166.50±49.50) vs (213.64±40.14) m 2, 4.70 (4.35, 5.07) vs 5.17 (4.77, 6.30) mmol/L, 13.18 (9.87, 18.84) vs 21.67 (15.78. 32.74) mU/L, 5.43%±0.48% vs 6.21%±1.22%, 2.88 (1.99, 4.21) vs 5.19 (3.82, 9.27)], and the body weight, body mass index, adiposity, visceral fat area, fasting blood glucose, fasting insulin, and HOMA-IR were all significantly lower in vitamin D group than those in the control group [(88.14±17.66) vs (93.32±13.47) kg, (31.02±5.10) vs (33.74±5.09) kg/m 2, (35.51±12.87) vs (39.77±11.87) kg, (166.50±49.50) vs (183.76±40.95) m 2, 4.70 (4.35, 5.07) vs 5.00 (4.55, 5.67) mmol/L, 13.18 (9.87, 18.84) vs 16.78 (13.94, 24.30) mU/L, and 2.88 (1.99, 4.21) vs 4.11 (3.14, 5.57), respectivley] (all P<0.05). The IR remission rate was significantly higher in the vitamin D group than that in the control group after the intervention (37.3% vs 15.3%) ( χ2=8.071, P=0.002). Conclusion:Supplementation of vitamin D on the basis of energy-limited high-protein diet combined with moderate intensity exercise can significantly improve the efficacy of weight loss and IR in obese patients with vitamin D deficiency.

Objective To evaluate the bioequivalence of two formulations of minocycline hydrochloride capsules administered orally after fasting administration and fed administration.Methods An open-label,randomized,two-period,self-crossover design was employed to assess the bioequivalence study.Twenty-eight healthy subjects were enrolled in both fasting and fed groups,with each period involving a single administration of either the reference formulation or the test formulation of 50 mg,separated by a washout period of 7 days.The concentration of minocycline in human plasma was determined by HPLC-MS/MS and was used for calculating pharmacokinetic parameters and evaluating the bioequivalence of the test formulation and reference formulation.Results After oral administration of test and reference formulations of minocycline under fasting condition,the Cmax Values of minocycline were(541±137)ng·mL-1 for the test formulation and(558±140)ng·mL-1for the reference formulation.The AUC0-t values were(8 347±1 986)h·ng·mL-1 for the test and(8 205±1 790)h·ng·mL-1 for the reference.The t1/2 values were(18.2±2.84)h for the test and(18.0±3.05)h for the reference.After oral administration of the test and reference formulations of minocycline under fed condition,the Cmax values of minocycline were(349±72.1)ng·mL-1 for the test and(352±73.2)ng·mL-1for the reference.The AUC0-twere(6 428±1 077)h·ng·mL-1 for the test and(6 588±1 118)h·ng·mL-1 for the reference.The t1/2values were(18.5±3.10)h for the test and(18.4±3.21)h for the reference.Under fasting condition,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test and reference formulations were(90.84%,101.46% ),(95.2%,102.8% ),and(95.31%,102.71% ),respectively.Under fed conditions,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test formulation and the reference formulation were(94.71%,103.42% ),(95.40%,99.83% ),and(95.79%,100.02% ),respectively.Conclusions Bioequivalence of the two minocycline formulations was demonstrated after fasting administration and fed administration in a healthy Chinese population.