OBJECTIVE To establish a method for the determination of the concentrations of anti-tumor lead compounds purine benzamides PLB-E and PLB-P in rat plasma by HPLC and apply to study pharmacokinetics. METHODS The established HPLC was used to determine the plasma drug concentrations of rats at different time points after intravenous administration of 5, 10, 20 mg·kg–1 (low, medium, high doses) of PLB-E and PLB-P, and the pharmacokinetic parameters of each compound were calculated using DAS 3.3.0 software. RESULTS PLB-E and PLB-P had good linear relationship in the range of 2–120, 3–60 μg·mL–1, respectively(r2>0.999). The RSD of inter-day and intra-day precision were <15%. The extraction recoveries were 87.48%–92.84% and 88.24%–92.60%, respectively. The main pharmacokinetic parameters of PLB-E and PLB-P after a single intravenous injection of 5, 10, 20 mg·kg–1 were as follows, the average Cmax was (20.30±2.39), (40.63±3.40), (63.62±7.55)mg·L–1 and (13.21±1.40), (24.87±1.33), (32.83±0.65)mg·L–1, respectively. AUC(0-∞) were (104.67±48.39), (177.42±84.11), (194.32±91.48)mg·h·L–1 and (106.75±54.21), (179.90±93.59), (253.56±126.17)mg·h·L–1, respectively. Tmax of each dose was 0.08 h. CONCLUSION The HPLC method established in this study meets the requirements for the determination of biological samples through methodological verification, which is applicable to the determination of the concentration of PLB-E and PLB-P in rat plasma and the pharmacokinetic study. The pharmacokinetic process of PLB-E and PLB-P in rats conforms to the two-compartment model, and conforms to the nonlinear kinetic elimination.

Objective:To explore the clinical efficacy of simultaneous or staged video-assisted thoracoscopic surgery (VATS) anatomic segmentectomy for bilateral double primary lung cancer (DPLC).Methods:A retrospective cohort study was conducted. The clinical data of 76 patients with bilateral DPLC who underwent VATS anatomic segmentectomy in Luzhou Traditional Chinese Medicine Hospital from February 2020 to August 2022 were retrospectively analyzed, and they were classified into the simultaneous bilateral thoracoscopic surgery group (the simultaneous group, 44 cases) and the staged thoracoscopic surgery group (the staged group, 32 cases) on the basis of the surgical methods. The intraoperative conditions, perioperative indexes and postoperative complications of the two groups were compared.Results:There were no statistically significant differences in the gender, age, pathological type,postoperative TNM staging of both groups (all P > 0.05). The anesthesia awakening time of the first and second stages of surgery in the staged group was (11±3) min and (13±4) min, which was shorter than that in the simultaneous group [(16±4) min] ( t values were 5.27 and 3.51, both P < 0.05). The number of drainage tubes placed in the simultaneous group was less than that in the sum of two stages of the staged group [(1.9±0.5) tubes vs. (2.2±0.5) tubes, t = 3.40, P = 0.001]. The duration of thoracic drainage tube retention, the postoperative total drainage flow, the days of hospitalization, the first postoperative landing time, and the total treatment cost in the first and second stages of surgery in the staged group were lower than those in the simultaneous group (all P < 0.05), while the postoperative total drainage flow, the days of hospitalization, and the total treatment cost in the sum of two stages of the staged group were higher than those in the simultaneous group (all P < 0.05). The total incidence of complications in the simultaneous group was higher than that in the staged group 1 month after surgery [18.18% (8/44) vs. 3.13% (1/32)], and the difference was statistically significant ( χ2 = 4.02, P = 0.045). The scores of activities of daily living, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and blood oxygen saturation in the simultaneous group were lower than those in the staged group (all P < 0.05). Conclusions:Staged VATS anatomic segmentectomy for bilateral DPLC has few complications and good ability to perform activities of daily living, whereas the treatment cost of simultaneous bilateral thoracoscopic surgery is low. Clinicians may recommend prioritizing simultaneous bilateral thoracoscopic surgery after comprehensively considering the patients ' physical and economic conditions.

ObjectiveTo observe the clinical efficacy of Tongdu Huoxue decoction in the treatment of acute lumbar disc herniation （LDH）. MethodA total of 316 patients with acute LDH admitted to the orthopedic outpatient department of Hubei Provincial Hospital of Traditional Chinese Medicine and Honghu City Hospital of Traditional Chinese Medicine from January 2020 to June 2023 were randomly divided into two groups. 156 cases in the control group （two cases with stopped follow-up） were treated with meloxicam tablets， while 153 cases in the observation group （five cases with stopped follow-up） were treated with Tongdu Huoxue decoction. Both groups were treated for three months. The clinical efficacy， McGill Pain Score Scale （SF-MPQ）， Oswestry Dysfunction Index （ODI） score， and the Japanese Orthopaedic Association （JOA） scores of the two groups before and after treatment were compared. The serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） of the patients before and after treatment were determined by using enzyme-linked immunosorbent assay （ELISA）. The NDI-092 type electromyography-evoked potential instrument was adopted to measure the motor conduction velocity and clinical efficacy of the tibial and common peroneal nerves in patients of the two groups before and after treatment， and the clinical safety of the two groups of patients was compared. ResultAfter treatment， the total effective rate in the observation group was 95.4% （146/153）， significantly higher than that in the control group of 76.3% （119/156） （χ² =23.18， P<0.05）. After treatment， both groups showed significant reductions in SF-MPQ and ODI scores， as well as the levels of IL-1β， IL-6， and TNF-α （P<0.05）， with the observation group showing a more significant reduction （P<0.05）. Both groups showed a significant increase in JOA scores and motor conduction velocities of the tibial and common peroneal nerves after treatment （P<0.05）， with the observation group showing a more significant increase （P<0.05）. ConclusionTongdu Huoxue decoction can alleviate lumbar and leg pain in acute LDH， improve lumbar spine function， and suppress inflammatory reactions. It is highly safe and is worthy of clinical promotion.

Objective:To investigate the value of diffusion kurtosis imaging (DKI) combined with quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting axillary lymph node metastasis in breast cancer.Methods:A total of 150 cases of breast cancer confirmed by pathology in the Affiliated Hospital of Jining Medical University were retrospectively analyzed. 68 cases had axillary lymph node (ALN) metastasis and 82 cases had no ALN metastasis. All breast lesions were examined by DKI and DCE-MRI before operation. We analyzed clinical case data, routine MRI features, DKI, and DCE-MRI parameters between two groups, including diffusion kurtosis (MK), mean diffusion rate (MD), volume transfer constant (K trans), extravascular volume fraction (Ve), and rate constant (Kep); The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of quantitative parameters for ALN metastasis of breast cancer. Results:The proportion of lesions with blurred edges in the metastatic group was higher than that in the non ALN metastatic group ( P=0.032); The proportion of uneven and circular enhancement within the ALN metastasis group was relatively high ( P=0.018). The MD value of the ALN transfer group was lower than that of the group without ALN transfer ( P=0.021); The MK value, K trans value, and Kep value were higher than those in the group without ALN metastasis (all P<0.01). The K trans value of DCE-MRI model was the most effective in diagnosing ALN metastasis of breast cancer, and the area under the ROC curve (AUC) was 0.831; The AUC of DCE-MRI model was 0.833, which was higher than that of DKI model (AUC=0.733), and the difference was statistically significant ( Z=2.208; P=0.027). The AUC of DCE-MRI and DKI models were higher than that of conventional MRI models ( Z=3.184, P=0.002; Z=1.917, P=0.046). The sensitivity and accuracy of combined DKI and DCE-MRI models in the diagnosis of ALN metastasis in breast cancer were higher than those of single model. Conclusions:DKI and DCE-MRI models can be used to predict axillary lymph node metastasis in breast cancer. Among them, the K trans value of DCE-MRI model is the most effective in diagnosing axillary lymph node metastasis in breast cancer.

Objective:To explore the current status of lipid-lowering therapy, the distribution of low-density lipoprotein cholesterol (LDL-C) levels and the risk assessment of cardiovascular events recurrence in patients with coronary heart disease (CHD) complicated by hypertension.Methods:This was a cross-sectional study. Patients with CHD combined with hypertension were hospitalized in the Department of Cardiology, General Hospital of Chinese People′s Liberation Army from August 5, 2008 to July 22, 2018 were included, and were divided into standard group and substandard group according to whether LDL-C reached the standard. Study data were obtained from inpatient coronary angiography records and electronic medical records database of Department of Cardiology, General Hospital of Chinese People′s Liberation Army, who used data from the first diagnosis of CHD. Clinical data of the selected patients were collected. Multivariate logistic regression model was used to analyze the associated factors of whether LDL-C reached the standard in CHD patients with hypertension.Results:A total of 18 800 patients were selected from 31 provinces/autonomous regions/municipalities directly under the central government in China, with Beijing accounting for the largest proportion (5 692 patients (30.28%)), followed by Hebei (3 621 patients (19.26%)), Henan (1 837 patients (9.77%)), and Shandong (1 618 patients (8.61%)). Among the selected patients, 1 493 had LDL-C<1.4 mmol/L (standard group), and 17 307 had LDL-C≥1.4 mmol/L (substandard group). Only 1 493 patients (7.94%) had LDL-C<1.4 mmol/L. There were 4 518 patients (24.03%), 4 366 patients (23.22%), 6 924 patients (36.83%) and 1 499 patients (7.97%) with LDL-C for 1.4-<2.0, 2.0-<2.5, 2.5-<3.8 and≥3.8 mmol/L levels, respectively. 17 855 patients (95.15%) were treated with statins, but only 1 334 patients (7.10%) were treated with statins and ezetimibe. Of the selected patients, 4 986 patients (26.52%) were at low risk, 6 515 patients (34.65%) were at intermediate risk, and 7 299 patients (38.82%) were at high risk. The combined lipid-lowering treatment rates of statin and ezetimibe in the middle-and high-risk patients were 7.43% (484/6 515) and 7.48% (546/7 299), respectively. The results of multivariate logistic regression analysis showed that increasing age, male, diabetes mellitus, stroke, and history of percutaneous coronary intervention (PCI) were positively associated with LDL-C standards in patients with CHD and hypertension, whereas obesity and acute myocardial infarction (AMI) were negatively associated with LDL-C standards (all P<0.01). Conclusions:The rate of achieving the standard LDL-C in patients with CHD combined with hypertension was low in China. Although the majority of patients had received moderate-intensity statin therapy, the proportion of statin-treated patients combined with ezetimibe was extremely low. The proportion of high-risk patients with recurrent cardiovascular events was higher in patients with CHD and hypertension in China, whereas the proportion of such patients receiving statin combined with ezetimibe lipid-lowering therapy was lower. This study also found that increasing age, male, diabetes mellitus, stroke, and history of PCI were positively associated with LDL-C standards, while obesity and AMI were negatively associated with LDL-C standards in patients with CHD and hypertension.

Objective:To investigate the effects of regular yoga practice on pulmonary function and mechanical parameters of diaphragm.Methods:Eighty regular yoga practitioners, including 40 practicing for≤5 year (yoga≤5 years group) and 40 for>5 year (yoga>5 years group) were recruited in Shanxi Norman Bethune Hospital from January 2024 to April 2024; and 40 sedentary subjects were also recruited as the control group. The diaphragmatic motion was evaluated by two-dimensional ultrasound and speckle tracking ultrasound in all subjects, the parameters, including displacement, fractional thickening, strain and strain rate of diaphragm were observed at rest and deep breathing. At the same time, the pulmonary function tests were performed, the indexes including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1) and one-second rate (FEV 1/FVC) were measured in all subjects. The mechanical parameters of diaphragm and the pulmonary function were compared among three groups. Results:There were no significant differences in gender ( χ2= 0.346), age ( F=1.16), height ( F=0.45), weight ( F=0.11) and body mass index (BMI) ( F=0.07) among the three groups (all P>0.05).At the rest status, there was no significant difference in diaphragm displacement, thickening rate and strain among three groups ( F=1.21, 2.10 and 0.23,all P>0.05); the strain rate of yoga>5 years group was lower than that of other two groups ( t=-4.23、-4.10, all P<0.05); however, there was no significant difference between yoga≤5 years group and control group ( t=-0.06, P>0.05). During deep breathing, the increment of displacement, thickening rate, strain and strain rate of diaphragm in yoga>5 years group was larger than that in other tow groups, while the increment of yoga≤5 years group was larger than that in control group ( F=25.82, 60.99, 17.29 and 52.46, all P<0.05); the increment of FVC, FEV 1 and FEV 1/FVC in yoga>5 years group was larger than other two groups, whilc the increment of yoga≤5 years group was larger than that of sedentary group (F=4.49, 7.32 and 39.71, all P<0.05). The diaphragmatic displacement was positively correlated with FVC ( r=0.290, P<0.05), and diaphragmatic displacement and thickening rate were positively correlated with FEV 1 and FEV 1/FVC (0.333 and 0.448, 0.231 and 0.599, all P<0.05), the strain and strain rate of diaphragm were negatively correlated with FEV 1 and FEV 1/FVC ( r=-0.399 and -0.719, -0.355 and -0.796, all P<0.05). Conclusion:The regular yoga practice can improve the movement capacity and efficiency of diaphragm, improve the pulmonary function, and there is a negative correlation between the strain rate and the mechanical parameters of diaphragm and FEV 1, FEV 1/FVC.

Objective:To preliminarily explore the role of silent information regulator 3 (SIRT3) in ferroptosis induced by high glucose in renal tubular epithelial cells, and to provide a new theoretical basis and treatment ideas for renal tubular injury in diabetic kidney disease patients.Methods:The single-cell transcriptomic analysis from "Tabula-muris" database was used to evaluate the expression of SIRT3 gene in different cellular subtypes of kidney tissues. HK-2 cells, a human immortalized proximal tubule epithelial cell line, were cultured in vitro and divided into following groups: (1) control group, mannitol group and high glucose group; (2) control group, negative control group, SIRT3 overexpression group, high glucose group and SIRT3 overexpression + high glucose group; (3) control group, negative control group, SIRT3 knockdown group, high glucose group and SIRT3 knockdown + high glucose group; (4) control group, Erastin intervention group and SIRT3 overexpression + Erastin intervention group. Normal glucose was 5.5 mmol/L, high glucose was 30 mmol/L, mannitol was 24.5 mmol/L, Erastin was 10 μmol/L, and the intervention time was 48 h. Cell counting kit-8 proliferation and cytotoxicity assay was used to determine cell viability. Real-time quantitative PCR and Western blotting were performed to assess the expression of SIRT3, kidney injury molecule-1 (KIM-1), and ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) at the mRNA and protein levels. The malondialdehyde, glutathione, and iron levels were measured to evaluate the degree of cellular ferroptosis. DCFH-DA was used to analyze the intracellular reactive oxygen species level, while the JC-1 staining method was employed to evaluate alterations of mitochondrial membrane potential in HK-2 cells. Results:(1) The results of single-cell transcriptomic database analysis demonstrated that SIRT3 gene was expressed at the highest level in the subtypes of proximal tubule epithelial cells of kidney tissues. (2) Compared with the control group, the expression levels of KIM-1 and ACSL4 were higher, and the expression levels of SIRT3 and GPX4 and cell viability were lower in the high glucose group (all P<0.05), while there was no statistically significant difference of the aforementioned indicators between the mannitol group and the control group (all P>0.05). (3) Compared with the high glucose group, HK-2 cell vitality, GPX4 expression and intracellular glutathione were higher, ACSL4 expression, intracellular iron, malondialdehyde and reactive oxygen species were lower, mitochondrial membrane potential partially recovered in SIRT3 overexpression + high glucose group (all P<0.05). Compared with the high glucose group, HK-2 cell vitality and GPX4 expression were lower, ACSL4 expression was higher in SIRT3 knockdown + high glucose group (all P<0.05), and there were no statistically significant differences in intracellular iron, malondialdehyde and glutathione (all P>0.05). (4) Compared with the control group, Erastin intervention group had upregulated ACSL4 expression and downregulated GPX4 expression in HK-2 cells (all P<0.05). Compared with the Erastin intervention group, SIRT3 overexpression + Erastin intervention group had upregulated GPX4 expression and downregulated ACSL4 expression (all P<0.05). Conclusions:High glucose can decrease SIRT3 expression and mitochondrial membrane potential, and increase oxidative stress and ferroptosis in HK-2 cells. Overexpression of SIRT3 may reduce oxidative stress and alleviate mitochondrial dysfunction, thereby mitigating glucose-induced ferroptosis in HK-2 cells.

Objective:To access the therapeutic efficacy of newly-designed digital cholangioscope-assisted bedside one-stage lithotomy and biliary drainage for severe acute cholangitis caused by choledocholithiasis.Methods:Data of 26 patients were retrospectively analyzed, who were admitted into the intensive care unit (ICU), Zhongda Hospital, Southeast University, due to choledocholithiasis induced by severe acute cholangitis and underwent cholangioscope-assisted bedside one-stage lithotomy and biliary drainage from June 2020 to February 2022. Clinical outcomes were analyzed.Results:The time interval from disease onset to endoscopic intervention was 36.2±15.5 hours, with 7.2±4.9 hours from ICU admission to endoscopic intervention. Technical success rate was 100.0% in one-stage stone removal and biliary drainage. Except for one mild pancreatitis, no other complication occurred. Acute physiology and chronic health evaluation (APACHE)Ⅱ and sequential organ failure assessment (SOFA) scores prior to endoscopic intervention were 25.2±6.6 and 11.9±3.5, respectively. APACHE Ⅱ scores at day 1, 3, and 7 after endoscopic intervention were 21.7±6.5, 17.2±6.8 and 12.7±7.7, respectively, and SOFA scores were 10.6±2.9, 8.4±3.0 and 5.4±3.7, respectively, all of them were lower than those before operation ( P<0.001). The lengths of ICU stay and total hospitalization were 9.7±5.0 days and 12.8±4.5 days, respectively. In-hospital mortality occurred in 3 (11.5%) patients. According to a 6-month follow-up, one patient died of pneumonia, and another died of acute myocardial infarction. No acute cholangitis re-occurred in those survivors. Conclusion:Newly-designed digital cholangioscope-assisted bedside one-stage lithotomy and biliary drainage demonstrate significant improvements in prognosis, highlighting its safety in managing severe acute cholangitis.