Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

The telomere structure in the cell nucleus is crucial for maintaining the stability and functions of chromosomes.Telomerase is a ribonucleoprotein reverse transcriptase,which catalyzes the elongation of telomeres using its own RNA as a template,thereby counteracting the shortening of telomeres caused by chromosome replication and cell division.Due to its overexpression in over 85％of malignant tumor cells,telomerase has emerged as a highly promising biomarker and a novel target for cancer therapy.In recent years,given the importance of precise quantification of telomerase activity in guiding medical diagnosis and treatment strategies,researchers have developed various high-performance telomerase detection techniques.Among these,electrochemical biosensing technique has cause much attention due to its high sensitivity,operational convenience,rapid response,and ease of miniaturization.This paper focused on the latest advances in electrochemical sensing technique for detection of telomerase activity,aiming to provide inspiration for designing novel telomerase activity detection strategies by elucidating three unique properties of telomerase primer extension products.

This study aimed to address the limitations of current diagnostic methods for well leg compartment syndrome(WLCS),including invasiveness,high costs,and insufficient accuracy,by proposing a solution based on electrical impedance tomography(EIT)technology.The electrical response characteristics of the human calf muscle to changes in compartment pressure using EIT were investigated,aiming to visualize the effects of pressure variations on the electrical properties within the compartment and to provide technical support for early non-invasive detection of WLCS.EIT sensors were placed on the right calf of the experimental subjects,with pressure applied externally to the right thigh.Measurements were conducted in two phases:pre-pressure(pre)and post-pressure(post).Pre-pressure,the conductivity distribution image σpre was measured when the calf was placed horizontally.Post-pressure,the calf was raised at an angle of approximately 30°,and pressures of 0,40,80,and 120 mmHg were applied to the right thigh,and the corresponding conductivity distribution images σP=0,σP=40,σP=80,andσP=120were recorded.To quantitatively analyze the pressure effects on the compartment response,paired sample t-test was used to assess the spatial-mean conductivity((σ))from the EIT reconstructed images.Compared to the horizontal position of the right calf,raising the calf at approximately 30° resulted in a significant increase in the spatial-mean conductivity(σ)of the M1 compartment.Furthermore,when pressure was applied to the right thigh while the calf remained at a 30° angle,the spatial-mean conductivity of the M1 compartment σM1 showed an increasing trend with rising pressure.The results indicated that as compartment pressure increased,the volume of extracellular fluid and ion concentration significantly increased,leading to an increase in conductivity,which reflected ischemia and hypoxia in muscle tissue and the related pathophysiological changes.EIT,due to its high sensitivity to conductivity changes,offered a potential effective diagnostic method for non-invasively monitoring the onset and progression of muscle compartment syndrome.

Objective To investigate the clinical efficacy of the Lower Limb Detumescence Formula(derived from Taohong Siwu Decoction)in treating lower limb swelling in patients with qi stagnation and blood stasis syndrome after total knee arthroplasty(TKA),and to analyze the changes in traditional Chinese medicine(TCM)syndrome types before and after surgery.Methods A total of 60 patients diagnosed with knee osteoarthritis and lower limb swelling with qi stagnation and blood stasis syndrome after TKA,hospitalized in the Department of Artificial Joints and Knee Surgery,The First Affiliated Hospital of Guangzhou University of Chinese Medicine between November 2024 and January 2025,were selected.Based on patients' preferences and postoperative medication,the patients were divided into three groups:the Chinese medicine Group(25 cases),the Lishang Group(15 cases),and the Aescuven Forte Group(20 cases).Changes in limb circumference on the affected side were used to describe knee volume changes,and were measured preoperatively and on postoperative days 1,3,and 30.Results(1)Regarding lower limb swelling,the calf and thigh circumferences of the affected side in all three groups showed a trend of early exacerbation(on postoperative days 1 and 3)followed by later relief(on postoperative day 30).Peak swelling occurred on postoperative day 3,with statistically significant differences compared to preoperative measurements(P＜0.05).Subsequently,swelling gradually alleviated,and the calf and thigh circumferences of the affected side progressively decreased,the circum ferences on postoperative day 30 differed from those on postoperative days 1 and 3(P＜0.05).However,there were no statistically significant differences in improving calf and thigh circumferences among the three groups(P＞0.05).(2)In terms of adverse reactions,the Lishang Group and the Aescuven Forte Group each reported two adverse events,including postoperative wound bleeding,subcutaneous ecchymosis,pulmonary infection,and constipation.The Chinese medicine group reported no gastrointestinal adverse events,and patient treatment compliance was better than that in the Lishang Group and the Aescuven Forte Group.(3)Regarding TCM syndrome differentiation,each patient received four assessments at different time points(preoperatively and on postoperative days 1,3,and 30),resulting in 240 valid data entries.Among these,qi stagnation and blood stasis syndrome was the most common(170 cases,70.83％),followed by liver and kidney deficiency syndrome(64 cases,26.67％),and qi and blood deficiency syndrome was the least common(6 cases,2.50％).(4)Comparison of the relationship between different groups and syndrome types revealed no significant association between group distribution and syndrome type(P＞0.05).Further generalized estimating equation analysis showed that grouping had no significant effect on TCM syndrome differentiation(P＞0.05).(5)Comparison of the relationship between different time points and syndrome types revealed that preoperative syndromes predominantly consisted of liver and kidney deficiency(96.67％),while on postoperative days 1 and 3,all cases were classified as qi stagnation and blood stasis syndrome(100.00％).On postoperative day 30,qi stagnation and blood stasis syndrome remained the most common(80.00％).There was a significant association between time points and syndrome distribution(P＜0.05).Further generalized estimating equation analysis indicated that time points significantly influenced TCM syndrome differentiation(P＜0.001).Conclusion The Lower Limb Detumescence Formula demonstrates efficacy comparable to Lishang Xiaozhong Oral Liquid and Aescuven Forte Tablets in improving lower limb swelling in patients with qi stagnation and blood stasis syndrome after TKA.By promoting blood circulation,resolving stasis,strengthening the spleen,and eliminating accumulation,this formula reduces the incidence of adverse reactions such as postoperative wound bleeding,subcutaneous ecchymosis,and constipation.It provides a new pharmacological option for treating lower limb swelling after TKA,and is particularly suitable for patients with qi stagnation and blood stasis syndrome accompanied by spleen deficiency.

OBJECTIVE: To assess the effectiveness of bone acupuncture in improving pain and function in degenerative lumbar spinal stenosis (DLSS) and compare it with Jiaji acupuncture. METHODS: From January to December 2023, 80 DLSS patients were treated with acupuncture and divided into bone acupuncture and Jiaji acupuncture groups. Among them, 40 patients in the bone acupuncture group included 15 males and 25 females, with a mean age of (60.60±6.98) years old;anthor 40 patients in the Jiaji acupuncture group included 16 males and 24 females, with a mean age of (61.48±9.55) years old. The Roland Morris disability questionnaire(RMDQ), walking distance, visual analogue scale(VAS), and the MOS item short from health survey(SF-36) of two groups at baseline, 2 weeks, 4 weeks, and 12 weeks post-treatment were compared. RESULTS: Eighty patients were followed up for 3 to 5 months with an average of (3.62±0.59) months. There was no significant differences in general data and the scores before treatment between two groups(P>0.05). The RMDQ scores in both groups decreased significantly at 2, 4 and 12 weeks after treatment compared with before treatment(P<0.05), at each time point after treatment, the decrease was more significant in the bone acupuncture group than in the Jiaji acupuncture group(P<0.05). The VAS of waist and leg in both groups was significantly lower at 2, 4 and 12 weeks after treatment that before treatment(P<0.05). At all time points after treatment, the waist VAS in the bone acupuncture group was reduced more significant than in the Jiaji acupuncture group(P<0.05);there was no significant difference in leg VAS at 2 and 12 weeks after treatment between two groups(P>0.05), the improvement was more significant in the bone acupuncture group in the 4 weeks after treatment than in the Jiaji acupuncture group. The SF-36 scores in both groups were significantly higher at 2, 4, and 12 weeks after treatment than before treatment(P<0.05);the SF-36 score raised more significant in the bone acupuncture group than in the Jiaji acupunture group(P<0.05). No significant difference in the walking distance between two groups at 2 weeks after treatment(P>0.05);the walking distance in the bone acupuncture group was significantly higher than that in the Jiaji acupuncture group at 4 and 12 weeks after treatment(P<0.05). CONCLUSION Bone-penetrating acupuncture moderately improves functional impairment, pain, and quality of life in patients with DLSS, showing better efficacy than Jiaji acupuncture.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/methods* ; Spinal Stenosis/physiopathology* ; Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management

OBJECTIVE: To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping. METHODS: A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety. RESULTS: All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001). CONCLUSION Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans ; Female ; Male ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae/physiopathology* ; Cupping Therapy/methods* ; Pressure ; Aged ; Treatment Outcome

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

BACKGROUND:Kaempferol has anti-osteoporotic effects,but the mechanisms by which kaempferol regulates gut microbiota and metabolites to prevent and treat osteoporosis remain unclear.OBJECTIVE:To exploring the potential mechanisms by which kaempferol inhibit osteoporosis based on gut microbiota and comprehensive targeted metabolomics.METHODS:Eighteen female Sprague-Dawley rats were randomly divided into three groups:sham operation group,model group,and kaempferol group,with 6 rats in each group.Animal models of osteoporosis were made in the latter two groups through removal of bilateral ovaries.Eight weeks after modeling,the sham operation and model groups were gavaged with distilled water,and the kaempferol group was gavaged with 40 mg/kg kaempferol.Continuous administration in each group was carried out for 12 weeks.Rat fecal samples were collected for 16S rDNA amplicon sequencing to observe changes in the gut microbiota structure.Serum samples were subjected to comprehensive targeted metabolomics analysis using ultra-high performance liquid chromatography-tandem mass spectrometry technology,along with a proprietary database and multivariate statistical analysis.RESULTS AND CONCLUSION:After 12 weeks of continuous intervention,the results of 16S rDNA amplicon sequencing showed that compared with the sham operation group,the abundance of gut microbiota increased in the model group.Compared with the model group,kaempferol group exhibited a statistically significant increase in the abundance of the genus Latilactobacillus(P=0.021),while the abundances of Pantoea(P=0.034),Enterorhabdus(P=0.000),Monoglobus(P=0.024),Butyricimonas(P=0.034),Rothia(P=0.043),and Clostridia(P=0.004)were significantly downregulated.After 12 weeks of continuous intervention,the results of the serum samples analyzed by broad-targeted metabolomics revealed that 120 and 79 metabolites were identified between the sham operation and model groups and between the model and kaempferol groups,respectively.Among the three groups,there were 17 overlapping differentially expressed metabolites,including Cis-aconitic acid,barbituric acid,L-homocitrulline,3,4,5-trimethoxycinnamic acid,L-3-phenyllactic acid,cyclo(pro-pro),L-phenylalanine-L-serine,proline-isoleucine,L-donoraminoacetic acid-L-phenylalanineacetic acid,and phenylalanine-aspartic acid.Most of them belong to amino acids and their metabolites,glycerophospholipids and fatty acyls.The Kyoto Encyclopedia of Genes and Genomes pathways involved in the differential metabolites were mainly enriched in D-amino acid metabolism,histidine metabolism,propionate metabolism,lysine degradation,fatty acid metabolism and sphingolipid metabolism.After 12 weeks of continuous intervention,combined analysis revealed that genera such as Enterorhabdus,Latilactobacillus,Rothia,and Ruminococcus were closely associated with differential serum metabolites.To conclude,kaempferol may exert its anti-osteoporotic effects by modulating the abundance,diversity,and structure of gut microbiota,thereby regulating the metabolism of amino acids,their metabolites,and fatty acids.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.