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.

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.

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*

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

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 safety and learning curve of Da Vinci robotic single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in the treatment of obesity patients. Methods: A descriptive case series study was performed. Clinical data of obesity patients who were treated with Da Vinci robotic SADI-S in China-Japan Union Hospital of Jilin University from March 2020 to May 2021 were analyzed retrospectively. Case inclusion criteria: (1) uncomplicated obese patients with body mass index (BMI)≥37.5 kg/m(2); (2) patients with BMI of 28 to <37.5 kg/m(2) complicated with type 2 diabetes or two metabolic syndrome components, or obesity comorbidities; (3) patients undergoing SADI-S by Da Vinci robotic surgery system. Those who received other bariatric procedures other than SADI-S or underwent Da Vince robotic SADI-S as revisional operation were excluded. A total of 77 patients were enrolled in the study, including 31 males and 46 females, with median age of 33 (18-59) years, preoperative body weight of (123.0±26.2) kg, BMI of (42.2±7.1) kg/m(2) and waistline of (127.6±16.3) cm. According to the order of operation date, the patients were numbered as 1-77. The textbook outcome (TO) and Clavien-Dindo grading standard were used to analyze the clinical outcome of each patient and to classify surgical complications, respectively. The standard of textbook outcome was as follows: the operative time less than or equal to the 75th percentile of the patient's operation time (210 min); the postoperative hospital stay less than or equal to the 75th percentile of the patient's postoperative hospital stay (7 d); complication grade lower than Clavien grade II; no readmission; no conversion to laparotomy or death. The patient undergoing robotic SADI-S was considered to meet the TO standard when meeting the above 5 criteria. The TO rate was calculated by cumulative sum analysis (CUSUM) method. The curve was drawn by case number as X-axis and CUSUM (TO rate) as Y-axis so as to understand the learning curve of robotic SADI-S. Results: The operative time of 77 robotic SADI-S was (182.9±37.5) minutes, and the length of postoperative hospital stay was 6 (4-55) days. There was no conversion to laparotomy or death. Seven patients suffered from complications (7/77, 9.1%). Four patients had grade II complications (5.2%), including one with duodeno-ileal anastomotic leakage, one with abdominal bleeding, one with peritoneal effusion and one with delayed gastric emptying; two patients were grade IIIb complications (2.6%) and both of them were diagnosed with gastric leakage; one patient was grade IV complication diagnosed with postoperative respiratory failure (1.3%), and all of them were cured successfully. A total of 51 patients met the textbook outcome standard, and the TO rate was positive and was steadily increasing after the number of surgical cases accumulated to the 46th case. Taking the 46th case as the boundary, all the patients were divided into learning stage group (n=46) and mastery stage group (n=31). There were no significant differences between the two groups in terms of gender, age, weight, body mass index, waist circumference, ASA classification, standard liver volume, operative time and morbidity of postoperative complication (all P>0.05). The percent of abdominal drainage tube in learning stage group was higher than that in mastery stage group (54.3% versus 16.1%, P<0.05). The length of postoperative hospital stay in learning stage group was longer than that in mastery stage group [6 (4-22) d versus 6 (5-55) d, P<0.05)]. Conclusion: The Da Vinci robotic SADI-S is safe and feasible with a learning curve of 46 cases.
Adult ; Anastomosis, Surgical ; Diabetes Mellitus, Type 2/surgery* ; Female ; Gastrectomy/methods* ; Gastric Bypass/adverse effects* ; Humans ; Learning Curve ; Male ; Middle Aged ; Obesity/surgery* ; Obesity, Morbid/surgery* ; Retrospective Studies ; Robotic Surgical Procedures

Objective:To investigate the clinical outcome and influencing factor of one-anastomosis duodenal switch (OADS) for obesity.Methods:The retrospective cohort study was conducted. The clinical data of 104 obesity patients who underwent OADS in the China-Japan Union Hospital of Jilin University from October 2018 to June 2021 were collected. There were 42 males and 62 females, aged 33(range, 18?66)years. The clinical outcome of each patient was evaluated using Textbook Outcome (TO). Observation indicators: (1) treatment situations for patients; (2) TO situa-tions; (3) analysis of factors affecting postoperative TO. Follow-up was conducted using outpatient examination or telephone interview to detect postoperative complication of patients up to November 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using chi-square test. Multivariate analysis was conducted using the binary Logistic regression model. Results:(1) Treatment situations for patients. All 104 patients under-went OADS without conversion to laparotomy or death of patient. The operation time and duration of postoperative hospital stay of the 104 patients were (187±39)minutes and 6(range, 4?55)days, respectively. Two of the 104 patients were readmitted. The experiences of surgeons on OADS was (53±30)cases. There were 82 patients underwent OADS using the Da Vinci robotic surgical system, while there were 22 patients underwent OADS using laparoscopic surgery system. The complication rate of 104 patients was 7.69%(8/104). Cases with stage Ⅱ, stage Ⅲb and stage Ⅳ complications of the Clavien Dindo classification were 5, 2 and 1, respectively. (2) TO situation. Of the 104 patients, 62 cases achieved TO, while 42 cases did not achieve TO. The operation time, retention time of abdominal drainage tube, duration of postoperative hospital stay, experiences of surgeons on OADS, number of OADS for surgeons using Da Vinci robotic surgical system were (166±26)minutes, 0(range, 0?7)days, 6(range, 4?7)days, 62±28, 54 in patients achieved TO, versus (218±34)minutes, 3 (range, 0?11)days, 8(range, 5?55)days, 38±27, 28 in patients not achieved TO, showing significant differences in the above indicators between them ( t=?8.81, Z=?3.63, ?5.33, t=4.27, χ2=6.27, P<0.05). Cases with complications were 0 in patients achieved TO, versus 8 in patients not achieved TO, showing a significant difference between them ( P<0.05). (3) Analysis of factors affecting postoperative TO. Results of multivariate analysis showed that the experiences of surgeons on OADS was an independent influencing factor for postoperative TO in patients undergoing OADS ( odds ratio=1.04, 95% confidence interval as 1.01?1.06, P<0.05). Conclusions:OADS is safe and feasible for obesity patients with low postoperative complication incidence and satisfactory clinical outcome. The experiences of surgeons on OADS is an independent influencing factor for postoperative TO in patients undergoing OADS.

The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 μm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 μg·cm~(-2) and 74.3%, respectively, which indicated that its release kinetics was in line with the first-order kinetic model.This study preliminarily proved that the reservoir microneedle could effectively increase the drug loading with good mechanical properties and release perfor-mance.
Drug Delivery Systems/methods* ; Drug Liberation ; Indocyanine Green ; Morphinans ; Needles ; Polyethylene Glycols