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 systematically evaluate the radiation impact of radioactive sources used in online elemental analyzers in cement enterprises on the surrounding environment, and to provide a scientific basis for radiation monitoring and safety management at the application sites of this type of radioactive sources. Methods A statistical analysis was conducted on 15 cement enterprises in Guangxi Province using online elemental analyzers with ²⁵²Cf as the radioactive source. On-site investigation of radiation safety management and on-site monitoring of radiation environment were performed, followed by an evaluation based on the collected data. Results Although the gamma radiation ambient dose equivalent rate and neutron ambient dose equivalent rate increased around the sites using online elemental analyzers with ²⁵²Cf as the radioactive source, they all met the requirements of the Radiological Health Protection Requirements for Instruments with Sealed Sources (GBZ 125—2009). Conclusion Under the current usage and management conditions, the application of this type of radioactive sources has controllable radiation impact on the surrounding environment, and will not pose a threat to public health and environmental safety. However, continuous strengthening of radiation safety management measures and regular radiation monitoring work are still needed to ensure the safe use of radioactive sources, further reducing potential radiation risks and providing strong guarantees for the safe application of radioactive sources in online elemental analyzers in cement enterprises.

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

Objective To establish a liquid chromatography tandem mass spectrometry(LC-MS/MS)method for the determination of polymyxin B and tigecycline in rat plasma and to study the pharmacokinetic profile in rats.Methods Rat plasma was treated with 3％trichloroacetic acid-methanol solution(50∶50)for protein precipitation on a Symmetry C18(150.0 mm × 4.6 mm,3.5 μm)column,with mobile phase:0.1％formic acid in water-0.1％formic acid in acetonitrile at a flow rate of 0.6 mL·min-1,the column temperature was 40 ℃,and the ionization source was electrospray ionization,positive ion detection mode:multiple reaction detection.The method was investigated for its specificity,standard curve and lower limit of quantification,precision and recovery,stability and reproducibility.Results The linear range of tigecycline was 25-2 500 ng·mL-1,the lower limit of quantification was 25 ng·mL-1,and the extraction recovery was 95.89％-107.90％;the linear range of polymyxin B,was 82-8 200 ng·mL-1,the lower limit of quantification was 80 ng·mL-1,and the extraction recovery was 93.84％-97.70％;the linear range of polymyxin B2 was 9-900 ng·mL-1,the lower limit of quantification was 9 ng·mL-1,the extraction recovery was 96.41％-104.80％;the intra-day and inter-day relative standard deviations of each substance were 96.41％-104.80％.The linear range was 9-900 ng·mL-1,the lower limit of quantification was 9 ng·mL-1,and the extraction recoveries were 96.41％-104.80％.The intra-day and inter-day relative standard deviations of each substance were less than 10％,and the stability and reproducibility were good.Conclusion This method is simple,sensitive,and has a short analytical time,and is suitable for the determination of the blood concentration of polymyxin B and tigecycline in rat plasma as well as for pharmacokinetic studies.

Objective:To evaluate the 1-year postoperative efficacy and nutritional indicators of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) in obese patients.Methods:This retrospective observational study included patients with a body mass index (BMI) of ≥40.0 kg/m 2 regardless of other related metabolic diseases and patients with severe type 2 diabetes and a BMI between 27.5 and 40.0 kg/m 2. The clinical data of 66 obese patients who underwent SADI-S at the Bariatric and Metabolic Surgery Department of China-Japan Union Hospital of Jilin University from November 2018 to May 2022 were collected, including 53 cases of da Vinci robotic surgery and 13 cases of laparoscopic surgery. The patients comprised 38 men and 28 women with a median age of 35 (18–61) years and a mean preoperative BMI of 42.93 ± 6.82 kg/m 2. A total of 38 patients had type 2 diabetes, and 46 had hyperuricemia, 45 had hypertension, 35 had hyperlipidemia, 12 had hypercholesterolemia, and 12 had a high low-density lipoprotein (LDL) level. The main observation indicators were (1) intraoperative and postoperative conditions; (2) weight loss outcomes, including body weight, BMI, excess body weight loss (%EWL), and total body weight loss (%TWL) at 3, 6, and 12 months after surgery; (3) effects of treatment on metabolic disease; and (4) changes in nutrient indicators. Results:(1) Intraoperative and postoperative conditions: All patients successfully underwent SADI-S with neither conversion to laparotomy nor death. Four (6.1%) patients developed postoperative complications, and all of them recovered and were discharged after conservative or surgical treatment. (2) Weight loss outcomes: %EWL at 3, 6, and 12 months after surgery was 62.07 ± 26.56, 85.93 ± 27.92, and 106.65 ± 29.65, respectively, and %TWL was 22.67 ± 4.94, 32.10 ± 5.18, and 40.56 ± 7.89, respectively. Body weight and BMI 3 to 12 months after surgery were significantly lower than those before surgery (all P < 0.001). (3) Effect of treatment on metabolic disease: 3 to 12 months after surgery, fasting blood sugar, HbA1c, uric acid, systolic blood pressure, diastolic blood pressure, triglycerides, total cholesterol, LDL, and other indicators were significantly lower than those before surgery (all P < 0.05). Twelve months after surgery, the remission rates of diabetes, hyperuricemia, hypertension, hypertriglyceridemia, hypercholesterolemia, and high LDL were 100% (38/38), 65.2% (30/46), 62.2% (28/45), 94.3% (33/35), 100% (12/12), and 100% (12/12), respectively. (4) Changes in nutrient indicators: Compared with the preoperative nutrient levels, the hemoglobin and hematocrit levels were lower at 3 to 12 months after surgery, the total protein level was lower at 6 to 12 months after surgery, the albumin level was lower at 6 months after surgery, and the ferritin level was lower at 3 months after surgery. The differences were statistically significant (all P < 0.05). The incidence of anemia was 6.1% (4/66), hypoalbuminemia was 4.5% (3/66), and ferritin deficiency was 4.5% (3/66), all of which were improved or normalized through conservative treatment. Twelve months after surgery, 30 (45.5%) patients had vitamin A deficiency, 17 (25.8%) had vitamin E deficiency, 11 (16.7%) had folic acid deficiency, 2 had potassium deficiency (3.0%), 3 (4.5%) had calcium deficiency, 2 (3.0%) had magnesium deficiency, 9 (13.6%) had iron deficiency, and 16 (24.2%) had zinc deficiency. However, no relevant clinical symptoms occurred. Conclusions:SADI-S has a very significant effect on weight loss and alleviation of metabolic diseases. Nutrient deficiencies after SADI-S mainly involve vitamin A, vitamin E, zinc, and folic acid. The long-term efficacy and safety of SADI-S still need further follow-up observation.

Objective:To evaluate the mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in the treatment of obesity and type 2 diabetes mellitus.Methods:The cohort of this retrospective observational study comprised 118 obese patients with body mass index (BMI) ≥40 kg/m 2 with or without other related metabolic diseases and BMI of (27.5-40.0) kg/m 2 with type 2 diabetes mellitus (T2DM) who had been treated with SADI-S. Patients who had undergone modified surgery or been followed up for less than 1 year were excluded. Clinical data of the included patients [56 men and 62 women aged (34.5±9.7) years], who had undergone SADI-S in China-Japan Union Hospital, Jilin University from October 2018 to August 2022, were collected. Their mean preoperative body mass was (125.9±25.0) kg and BMI (42.8±6.8) kg/m 2. The 60 patients with T2DM had a mean fasting blood glucose of (9.9±3.2) mmol/L and HBA1c of (8.4±1.7) % before surgery. The main outcome measures were mid-term weight loss after surgery (body mass, BMI, excess weight loss, and total weight loss) 1, 2, 3, and 4 years after surgery and efficacy regarding diabetes mellitus (fasting blood glucose, glycated hemoglobin and diabetes remission rate at 1, 2, and 3 years after surgery). Outcomes were defined as follows. Complete remission: HbA1c <6% or fasting blood glucose <6 mmol/L without hypoglycemic medication; partial remission: HBA1c <6.5% or fasting blood glucose <7 mmol/L without hypoglycemic medication; significant improvement: HBA1c <7.0%, stable decrease of at least 1% compared with preoperative HBA1c, and postoperative dose of hypoglycemic medication significantly less; ineffective: no change in HBA1c and no reduction in dosage of hypoglycemic medication. Other outcome measures included intraoperative and postoperative adverse effects and postoperative nutritional indexes. Results:SADI-S was successful in all patients. There was no significant bleeding, conversion to open surgery, or perioperative death. The operation time was (186.1±41.5) minutes, and the postoperative hospital stay 6 (5–7) days. Surgical complications occurred in four patients, comprising peritoneal effusion, internal jugular vein thrombosis, anastomotic leakage, and gastric fistula. Body weight and BMI 1, 2, 3 and 4 years were significantly lower post- than pre-operatively (all P<0.05). Excess weight loss was (81.9±16.2) %, (82.2±15.5) %, (88.3±20.1) %, and (83.2±18.1) % at 1, 2, 3, and 4 years postoperatively, respectively. Total weight loss was (39.7±8.7) %, (40.6±10.6) %, (42.2±11.5) % and (45.4±10.2) %, respectively. The mean fasting blood glucose concentrations of the 60 patients with T2DM were (5.1±1.0) mmol/L, (5.0±0.7) mmol/L, and (5.4±0.9) mmol/L 1, 2 and 3 years postoperatively, respectively. The values for glycosylated hemoglobin were (4.9±0.6) %, (4.8±0.5) %, and (5.1±0.8) %, respectively, all of which are significantly lower than preoperatively (all P<0.05). The complete remission rate of diabetes was 95.0% (38/40), 90.0% (36/40), and 9/13 1, 2, and 3 years postoperatively, respectively. Additionally, the partial remission rate and significant improvement rate were both 100%. Two years postoperatively, the incidence of anemia was 27.8% (10/36), of hypoproteinemia 11.8% (4/34), and of ferritin deficiency 25.8% (8/31), all of which were improved by conservative treatment such as blood transfusion, iron supplementation, and adjustment of diet. Conclusion:SADI-S has a significant mid-term beneficial effect on weight loss and diabetes remission status in patients with obesity and type 2 diabetes.

Objective To propose a cell phone fingertip video-based heart rate extraction algorithm to relieve the influences of environmental factors.Methods Firstly,the fingertip video was captured and extracted at a frame rate of 30 frames/s,and the images were separated into three channels:R,G,and B.The brightness changes of the three channels were compared,the G channel,which was the most sensitive to the fingertip blood flow signal,was selected as the signal source,and the brightness change information was extracted to generate a volumetric pulse waveform with a duration of 10 s.Secondly,the waveform underwent signal processing such as digital filtering,removal of baseline drift and Fourier transform,then the heart rate was predicted based on the position information of the maximum spectral peak.Finally,the heart rate prediction efficacy by the proposed algorithm was validated on Brno University of Technology Smartphone PPG Database(BUT PPG dataset).Results The predicted heart rate by the algorithm and the actual value had the mean square deviation,root mean square deviation and mean absolute error being 3.71,1.92 and 1.2 beats/min,respectively.Condusion The algorithm proposed has high accuracy for heart rate prediction,and can be invovled in cell phones for daily heart rate monitoring.[Chinese Medical Equipment Journal,2024,45(8):16-20]

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson’s disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann–Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.