OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

OBJECTIVE: To evaluate the effects of posterior cruciate ligament(PCL) resection on soft tissue elasticity and knee stability in total knee arthroplasty(TKA). METHODS: Six adult cadaveric knee specimens (involving 10 knees) were included in the study. With the assistance of the robotic system(TiRobot Recon, TINAVI, Beijing), total knee arthroplasty (TKA) was performed sequentially using cruciate retaining (CR) prostheses and posterior stabilizing (PS) prostheses. Between the two surgical procedures, the femoral and tibial osteotomy surfaces were not altered;only the posterior cruciate ligament (PCL) was resected and the intercondylar fossa was treated. After installing the femoral trial component, a soft tissue balance solver was used to apply tension ranging from 30 N to 90 N in 5 N increments at 0°, 10°, and 90° of knee flexion. Meanwhile, the medial and lateral joint gaps were measured synchronously. Based on the tension-gap coupling data, the equivalent elastic coefficients of the medial and lateral soft tissue sleeves at different knee flexion angles, as well as the range of the joint line convergence angle (JLCA) under fixed varus-valgus stress, were calculated. Additionally, the gap balance status under 80 N of tension was analyzed. Self-control comparisons of each indicator were conducted before and after PCL resection to analyze the change patterns. RESULTS: After PCL resection, in the fully extended position (knee flexion 0°). The medial equivalent elastic coefficient was 32.2 (25.7, 63.3) N·mm^-1 for the CR prosthesis and 27.7 (22.0, 51.9) N·mm^-1 for the PS prosthesis, and the statistically significant difference (P=0.013). The range of JLCA was 0.41°(0.26, 0.55)° for the CR prosthesis, which was smaller than 0.75° (0.40, 0.98)° for the PS prosthesis, and the difference was statistically significant(P=0.041). At 90° of knee flexion, the medial joint gap was 10.7(10.1, 11.7) mm for the CR prosthesis, which was smaller than 12.1(10.9, 15.1) mm for the PS prosthesis, with a statistically significant difference(P=0.011). No statistically significant differences were observed in other joint gaps. CONCLUSION PCL resection reduces the rigidity of the medial soft tissues in the fully extended knee and increases the medial joint gap in the flexed position, thereby affecting knee stability and balance. This finding suggests that PS and CR prostheses may require different morphological designs, and there should be differences in indications and osteotomy strategies between CR-TKA and PS-TKA. CR-TKA is more suitable for patients with preoperative medial soft tissue laxity.
Humans ; Posterior Cruciate Ligament/physiopathology* ; Knee Joint/physiopathology* ; Arthroplasty, Replacement, Knee ; Elasticity ; Male ; Female ; Middle Aged ; Aged ; Biomechanical Phenomena ; Adult

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Electrical impedance tomography(EIT)is a non-invasive imaging technique that generates cross-sec-tional images of chest by measuring changes in impedance as electric currents passing through human body.In peri-operative respiratory management,EIT provides a real-time,consecutive monitoring of lung ventilation and perfusion status,guiding respiratory management of perioperative patients including medication for COPD and asth-ma,personalized PEEP settings for specific patient populations,lung protection for pediatric perioperative cases,and predicting postoperative pulmonary complications.Application of EIT in the perioperative period helps clinicians to manage patient respiratory status more accurately,reduces complications and improves outcomes.Through real-time monitoring and individualized treatment guidance,EIT enhances the safety and effectiveness of perioperative respiratory management,becoming an essential part of the operating room.This review summarises the application of EIT in the perioperative period,aiming to provide reference for the clinical application of EIT.

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Objective : High performance liquid chromatography⁃mass spectrometry (LC⁃MS/MS) system was used to accurately determine 22 bile acids in serum , liver, amniotic fluid and placenta of pregnant mice , and a LC⁃MS/ MS method was established for efficient detection and analysis of bile acids in serum , liver, amniotic fluid and placenta of mice. Methods : Pregnant mice serum , liver, amniotic fluid and placenta samples were processed , with 0. 1% glacial acetic acid in 4 mmol/L ammonium acetate aqueous solution as mobile phase A and pure methanol as mobile phase B , the flow rate was 0. 4 ml/min , a gradient elution program was used to elute with Phenomenex Gemini 3 μm NX⁃C18 110A ( 100 mm × 2. 0 mm) chromatographic column elution , and mass spectrometry detection system used an electrospray ion source for negative ion multiple reaction monitoring. Results : The linear relationship of 22 bile acids in the quantitative range was good. The RSD of inter⁃day and intra⁃day precision at low , medium and high concentrations was 0. 5% - 7. 4% , the matrix effect was 88% - 110% , and the extraction recovery was 84% - 108% . Conclusion In this experiment , LC⁃MS/MS was established to detect 22 bile acids in serum , liver, amniotic fluid and placenta of pregnant mice. The method not only has high sensitivity and selectivity , but also can stably detect a large number of samples.

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.
Animals ; Mice ; HMGB1 Protein ; Melatonin/therapeutic use* ; Mice, Inbred C57BL ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oxygen/adverse effects* ; Peroxidase ; Receptors, Melatonin ; Retinal Diseases/drug therapy*

Objective:To evaluate the 1-year postoperative efficacy of four bariatric procedures, namely sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S), and biliopancreatic diversion with duodenal switch (BPD/DS) for treating super obesity.Methods:In this retrospective observational study, we analyzed the clinical data of 40 patients with super obesity (body mass index [BMI]≥50 kg/m 2) who had undergone bariatric surgery in the China-Japan Union Hospital of Jilin University from November 2015 to December 2020. The study cohort consisted of 21 men and 19 women of average age 31.7±9.0 years. The preoperative weight and BMI were (159.2±16.9) kg and (53.4±3.0) kg/m 2, respectively. Prior to the surgery, 30 individuals had hypertension, 27 hyperuricemia, 15 type 2 diabetes, 10 abnormally high total cholesterol, 20 abnormally high triglycerides, and 24 abnormally high low-density lipoprotein. We divided the participants into four groups according to the type of operation: SG group ( n=16), RYGB group ( n=9), SADI-S group ( n=9) and BPD/DS group ( n=6). We examined the following factors: weight, BMI, excess weight loss (%), total weight loss (%), and remission of preoperative metabolic diseases (including hypertension, hyperuricemia, type 2 diabetes, and hyperlipidemia) 3, 6, and 12 months after surgery. The variables assessed for hypertension were systolic and diastolic blood pressure; for type 2 diabetes, glycated hemoglobin; and for hyperlipidemia, total cholesterol, triglycerides, and low-density lipoprotein 1-year after the surgery. The safety of surgery was also assessed. Results:All patients successfully completed laparoscopic procedures, none of them requiring conversion to laparotomy. The amount of blood loss during surgery was less than 50 mL. Postoperative hospital stay was 6–16 days. There were no deaths during the perioperative period. However, two postoperative complications occurred in the RYGB group, namely bleeding and anastomotic leakage. No complications were detected in the other groups. At 3, 6, and 12 months after surgery, percentage of excess weight loss was 36.6±11.0, 62.4±15.7, and 68.2±16.0 ( F=21.830, P<0.001) in the SG group; 30.6±6.9, 42.5±5.8, and 50.6±11.1 ( F=13.222, P<0.001) in the RYGB group; 39.7±7.8, 54.6±12.7, and 81.9±12.0 ( F=33.821, P<0.001) in the SADI-S group; and 40.2±4.8, 57.7±11.8, and 82.8±14.9 ( F=21.552, P<0.001), respectively, in the BPD/DS group. The percentage of excess weight loss increased significantly over the 12-month observation period in all groups . Compared with before surgery, hypertension and hyperuricemia in the SG, SADI-S, and BPD-DS groups showed significant improvement after one year (all P<0.05). However, only the SADI-S group exhibited a significant decrease in glycosylated hemoglobin concentrations ( P=0.038). Only the BPD-DS group showed significant decreases in various indicators of hyperlipidemia (all P<0.05). The improvements in obesity-related complication indexes did not reach statistical significance in the RYGB group (all P>0.05). Conclusion:SG, RYGB, SADI-S and BPD/DS are all safe and effective treatments for super obesity. All of these procedures can improve the associated metabolic diseases to a certain extent.

Objective:To evaluate the 1-year postoperative efficacy of four bariatric procedures, namely sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S), and biliopancreatic diversion with duodenal switch (BPD/DS) for treating super obesity.Methods:In this retrospective observational study, we analyzed the clinical data of 40 patients with super obesity (body mass index [BMI]≥50 kg/m 2) who had undergone bariatric surgery in the China-Japan Union Hospital of Jilin University from November 2015 to December 2020. The study cohort consisted of 21 men and 19 women of average age 31.7±9.0 years. The preoperative weight and BMI were (159.2±16.9) kg and (53.4±3.0) kg/m 2, respectively. Prior to the surgery, 30 individuals had hypertension, 27 hyperuricemia, 15 type 2 diabetes, 10 abnormally high total cholesterol, 20 abnormally high triglycerides, and 24 abnormally high low-density lipoprotein. We divided the participants into four groups according to the type of operation: SG group ( n=16), RYGB group ( n=9), SADI-S group ( n=9) and BPD/DS group ( n=6). We examined the following factors: weight, BMI, excess weight loss (%), total weight loss (%), and remission of preoperative metabolic diseases (including hypertension, hyperuricemia, type 2 diabetes, and hyperlipidemia) 3, 6, and 12 months after surgery. The variables assessed for hypertension were systolic and diastolic blood pressure; for type 2 diabetes, glycated hemoglobin; and for hyperlipidemia, total cholesterol, triglycerides, and low-density lipoprotein 1-year after the surgery. The safety of surgery was also assessed. Results:All patients successfully completed laparoscopic procedures, none of them requiring conversion to laparotomy. The amount of blood loss during surgery was less than 50 mL. Postoperative hospital stay was 6–16 days. There were no deaths during the perioperative period. However, two postoperative complications occurred in the RYGB group, namely bleeding and anastomotic leakage. No complications were detected in the other groups. At 3, 6, and 12 months after surgery, percentage of excess weight loss was 36.6±11.0, 62.4±15.7, and 68.2±16.0 ( F=21.830, P<0.001) in the SG group; 30.6±6.9, 42.5±5.8, and 50.6±11.1 ( F=13.222, P<0.001) in the RYGB group; 39.7±7.8, 54.6±12.7, and 81.9±12.0 ( F=33.821, P<0.001) in the SADI-S group; and 40.2±4.8, 57.7±11.8, and 82.8±14.9 ( F=21.552, P<0.001), respectively, in the BPD/DS group. The percentage of excess weight loss increased significantly over the 12-month observation period in all groups . Compared with before surgery, hypertension and hyperuricemia in the SG, SADI-S, and BPD-DS groups showed significant improvement after one year (all P<0.05). However, only the SADI-S group exhibited a significant decrease in glycosylated hemoglobin concentrations ( P=0.038). Only the BPD-DS group showed significant decreases in various indicators of hyperlipidemia (all P<0.05). The improvements in obesity-related complication indexes did not reach statistical significance in the RYGB group (all P>0.05). Conclusion:SG, RYGB, SADI-S and BPD/DS are all safe and effective treatments for super obesity. All of these procedures can improve the associated metabolic diseases to a certain extent.

Objective : To investigate the protective effect of obeticholic acid (OCA) on di(2⁃ethylhexyl) phthalate (DEHP)Ⅳinduced cholestasis in mice. Methods : Animal experiment 1 : Female ICR mice were randomly divided into 3 groups: the control group, DEHP low⁃dose group [50 mg/(kg d)]and DEHP high⁃dose group [200 mg/ ( kg d)] . All mice were administered with DEHP by gavage for 18 days. Animal experiment 2: Female ICR mice were randomly divided into 4 groups: the control group, OCA group, DEHP model group[200 mg/(kg ·d)] and DEHP + OCA group. All mice were administered with DEHP by gavage for 18 days and the duration of OCA was 12 - 18 days. Serum and liver tissues of mice were collected. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid ( TBA) levels, liver TBA levels, protein expression of farnesoid X receptor (FXR) and mRNA levels of FXR and SHP were detected. HE staining was used to observe the pathological changes in liver tissues. Results : Experiment 1: Compared with the control group, the liver weight, liver coefficient and the TBA concentrations in serum and liver significantly increased only in DEHP[200 mg/(kg ·d)] group(P < 0. 01), indicating that the modeling was successful. Animal experiment 2: Compared with the DEHP model group, the liver weight and liver coefficient significantly decreased after OCA treatment, and the TBA concentrations in serum and liver both decreased (P < 0. 01) .Compared with the control group, the protein expression level and its mRNA level of FXR decreased after DEHP[200 mg/(kg ·d)]treatment; Compared with the DEHP model group, the protein expression of FXR and the mRNA levels of FXR and SHP significantly increased after OCA treatment(P < 0. 05) . Conclusion DEHP exposure can induce cholestatic liver injury in mice, and OCA posttreatment has a protective effect on DEHP⁃induced cholestasis in mice.