1.Differences in arousal threshold among obstructive sleep apnea patients of different genetic backgrounds and influencing factors
Rui ZHAO ; Ping YAO ; Zhiqiang ZHANG ; Zhiguo GUO ; Minqi XIE ; Hui DANG ; Yanrong JIA ; Jing CHENG ; Dongsheng LYU
Sichuan Mental Health 2026;39(3):240-245
BackgroundObstructive sleep apnea (OSA) represents a prevalent sleep disordered breathing condition characterized by complex pathophysiology. The arousal threshold (ArTH), a core non-anatomical contributor to OSA pathogenesis, is intimately tied to the disease severity and clinical phenotypes. To date, research regarding factors associated with ArTH has yielded inconsistent findings, and ArTH profiles and disparities across populations with different genetic backgrounds are not fully elucidated. ObjectiveTo explore the differences of ArTH in OSA patients with different genetic backgrounds and analyze the key factors affecting ArTH, thereby providing evidence for understanding OSA pathophysiology and formulating targeted treatment regimens. MethodsA total of 285 patients who met the diagnostic criteria for OSA, as defined by the Multidisciplinary Diagnosis and Treatment Guidelines for Adult Obstructive Sleep Apnea, were retrospectively enrolled in this study. All participants underwent overnight polysomnography (PSG) at the Sleep Medicine Center of Inner Mongolia Mental Health Center from December 2022 to May 2024. Based on the study design, the cohort was stratified into two distinct genetic background subgroups (group A and group B). Demographic and clinical characteristics, the Epworth Sleepiness Scale (ESS) score, and overnight PSG data were collected. The apnea hypopnea index (AHI), the lowest pulse oxygen saturation (LSpO2), and fraction of hypopneas (FHypopneas) were utilized as surrogate indicators to estimate ArTH in OSA patients. The influencing factors of low ArTH were tested by binary Logistic regression analysis. ResultsAmong the 285 OSA patients, there were 227 cases (79.65%) in group A and 58 cases (20.35%) in group B. Comparisons between the two genetic background subgroups revealed no statistically significant differences in the proportion of low ArTH, ESS score, PSG parameters, and the three markers for low ArTH (AHI<30 events/h, LSpO2>82.5%, FHypopneas>58.3%) (P>0.05). Binary Logistic regression analysis identified sex (OR=2.421, 95% CI: 1.070–5.478), BMI (OR=0.847, 95% CI: 0.770–0.932), N1 sleep duration (OR=0.974, 95% CI: 0.963–0.985), and hypertension (OR=0.348, 95% CI: 0.143–0.848) as independent factors associated with low ArTH in the total cohort. Stratified analysis by genetic backgrounds revealed that sex(OR=3.799, 95% CI: 1.389–10.392), BMI(OR=0.819, 95% CI:0.723–0.929), and N1 sleep duration(OR=0.973, 95% CI: 0.961–0.986) were independent factors of low ArTH in group A. In contrast, only N1 sleep duration (OR=0.951, 95% CI: 0.911–0.993) remained a significant factor in group B. ConclusionArthur may have conservative characteristics in patients with OSA with different genetic backgrounds, but the pathophysiological mechanism of OSA may have population heterogeneity. [Funded by Inner Mongolia Autonomous Region Natural Science Fundation Project (number, 2024QN08050); Intra-institutional Scientific Research Project of Inner Mongolia Mental Health Center (number, 2022QNWN0010)]
2.NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of Timp1 mRNA in ischemic stroke.
Li YANG ; Xiaotong LI ; Yaxuan ZHAO ; Hao CHEN ; Can WANG ; Angrong WU ; Xintong GUO ; Yue HUANG ; Qihui WANG ; Lingyun HAO ; Xiaowen LI ; Ying JI ; Jin BAN ; Guangtian WANG ; Junli CAO ; Zhiqiang PAN
Acta Pharmaceutica Sinica B 2025;15(5):2575-2592
Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.
3.Relationship between high expression of circular RNA Bardet-Biedl syndrome 9 and low expression of circRNA catenin beta 1 in peripheral blood and weaning failure of mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease.
Zhiqiang GUO ; Yunfeng LIU ; Junhui TAN ; Bowen YANG ; Jiao JIAO
Chinese Critical Care Medicine 2025;37(10):931-936
OBJECTIVE:
To investigate the relationship between peripheral blood circular RNA Bardet-Biedl syndrome 9 (circBBS9) and circRNA catenin beta 1 (circCTNNB1) and weaning failure of mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
METHODS:
A prospective, observational cohort study was conducted. The patients with AECOPD who received invasive mechanical ventilation and passed the spontaneous breathing test (SBT) admitted to the First Affiliated Hospital of Hebei North University from January 2022 to February 2024 were selected as the study subjects. According to the outcome of weaning, the patients were divided into failed weaning group and successful weaning group. At admission and before SBT, the expression levels of circBBS9 and circCTNNB1 in peripheral blood were detected by fluorescence quantitative polymerase chain reaction (PCR). General information, acute physiology and chronic health evaluation II (APACHEII) score within 24 hours of admission, vital signs before SBT and the most recent laboratory indicators before SBT of the patients were collected. The differences in circBBS9 and circCTNNB1 expression levels and clinical data between the two groups were compared. Multivariate Logistic regression was used to analyze the influencing factors of the weaning failure. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of each index on weaning failure.
RESULTS:
Ultimately, 132 patients with AECOPD who underwent invasive mechanical ventilation and passed the SBT were enrolled in the study. Among them, 82 patients were successfully weaned from mechanical ventilation, while 50 patients failed to be weaned, resulting in a weaning failure rate of 37.88%. There was no statistically significant difference in the expression levels of circBBS9 and circCTNNB1 in the peripheral blood at admission of patients between the two groups. The expression level of circBBS9 in the peripheral blood before SBT of patients in the failed weaning group was significantly higher than that in the successful weaning group (2-ΔΔCt: 131.64±30.24 vs. 100.00±21.32), and the expression level of circCTNNB1 was significantly lower than that in the successful weaning group (2-ΔΔCt: 79.90±16.82 vs. 100.00±26.43), and the differences were statistically significant (both P < 0.05). The APACHEII score within 24 hours of admission and the levels of RSBI, SCr, and PCT before SBT in the failed weaning group were significantly higher than those in the successful weaning group [APACHEII score: 22.54±4.62 vs. 16.56±4.58, RSBI: 81.90±16.56 vs. 63.25±17.00, SCr (μmol/L): 100.20±17.27 vs. 89.93±26.29, PCT (μg/L): 1.08±0.18 vs. 0.87±0.22], and the Alb level before SBT was significantly lower than that in the successful weaning group (g/L: 29.71±2.73 vs. 33.93±2.89), and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in other clinical data between the two groups. Multivariate Logistic regression analysis showed that circBBS9 [odds ratio (OR) = 1.291, 95% confidence interval (95%CI) was 1.049-1.588] and APACHEII score (OR = 2.897, 95%CI was 1.004-8.353), RSBI (OR = 1.413, 95%CI was 1.057-1.890) were independent risk factors for weaning failure (all P < 0.05), and circCTNNB1 (OR = 0.812, 95%CI was 0.688-0.959) and Alb (OR = 0.149, 95%CI was 0.036-0.614) were protective factors (both P < 0.05). ROC curve analysis showed that circBBS9, circCTNNB1, APACHEII score, RSBI, and Alb all had certain value for predicting weaning failure. The area under the ROC curve (AUC) and 95%CI were 0.820 (0.750-0.890), 0.755 (0.674-0.835), 0.827 (0.757-0.897), 0.795 (0.715-0.876), and 0.854 (0.791-0.919), respectively. Using the multivariate Logistic regression equation as the combined indicator, the AUC for predicting weaning failure reached 0.997 (95%CI was 0.993-1.000), which was significantly higher than that of the single indicators including circBBS9, circCTNNB1, APACHEII score, RSBI, and Alb (the Z value was 5.582, 6.093, 5.771, 5.932, and 5.182, respectively, all P < 0.05).
CONCLUSIONS
High expression of circBBS9 and low expression of circCTNNB1 in the peripheral blood of AECOPD patients receiving invasive mechanical ventilation before SBT are associated with weaning failure. circBBS9, circCTNNB1 combined with APACHEII score, RSBI and Alb are helpful for predicting the failure of weaning in these patients.
Humans
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Pulmonary Disease, Chronic Obstructive/blood*
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Prospective Studies
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Ventilator Weaning
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RNA, Circular/blood*
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Respiration, Artificial
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Male
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Female
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Aged
4.A thyroid nodule ultrasound image segmentation method based on a feature-adaptive extraction and gated fusion mechanisms net
Chengzi YAO ; Han GUO ; Zhiqiang JIA
International Journal of Biomedical Engineering 2025;48(4):357-364
Objective:To propose a thyroid nodule ultrasound image segmentation method based on a feature-adaptive extraction and gated fusion mechanisms net (FAGF-Net).Methods:The FAGF-Net was constructed by designing a feature coupling encoder (FC-Encoder), which integrated a convolutional neural network and a Transformer to extract both local and global features. The perception of multi-scale geometric characteristics of nodules was enhanced by developing a multi-scale feature space coupling module (MFSC-Module), and a context-gated feature attention module (CGFA-Module) was introduced to filter redundant information and suppress noise interference. A retrospective analysis was conducted on 3 493 physician-annotated two-dimensional thyroid nodule ultrasound images obtained from the publicly available TN3K medical imaging dataset. The dataset was divided into training and validation sets at a ratio of 8∶2, resulting in 2 794 training images and 699 validation images. FAGF-Net was compared with several mainstream semantic segmentation models, including UNet, Deeplabv3, HRNet, PSPNet, and SegFormer using UNet as the baseline model. Additionally, module ablation experiments were performed to evaluate the effectiveness of each core module within the FAGF-Net. Visual comparisons were also conducted between the original ultrasound images, the annotated nodule regions, and the segmentation results produced by the different models.Results:The accuracy, intersection over union and Dice coefficient of the FAGF-Net method were 95.59%, 83.53% and 90.60%, respectively. These values were 3.77%, 2.29% and 3.55% higher than those of the UNet method (91.82%, 81.24% and 87.05%). Additionally, the FAGF-Net method achieved a frame rate of 19.8, meeting the requirements for image segmentation in medical environment scenarios. The module ablation experiments showed that compared with the UNet, the accuracy (92.85%), intersection over union (81.76%) and Dice coefficient (88.45%) of the FC-Encoder model were increased by 1.03%, 0.52% and 1.40%, respectively. The accuracy (93.13%), intersection over union (81.91%) and Dice coefficient (88.76%) of the CGFA-Module model were introduced separately, which were 1.31%, 0.67% and 1.71% higher than those of UNet, respectively. Compared with the FC-Encoder model alone, the accuracy (94.61%), intersection over union (82.45%) and Dice coefficient (89.54%) of the MFSC-Module increased by 1.76%, 0.69% and 1.09%, respectively when FC-Encoder was used as the feature double branch extraction encoder. Compared with the FC-Encoder model alone, the accuracy (94.39%), intersection over union (82.33%) and Dice coefficient (89.46%) of the CGFA-Module were increased by 1.54%, 0.57% and 1.01%, respectively, when FC-Encoder was used as the feature double branch extraction encoder. Visualization results showed that the FAGF-Net method produced smoother and more complete in boundary fitting and was more accurate at identifying small and low-contrast lesions.Conclusions:A thyroid nodule ultrasound image segmentation method based on FAGF-Net was proposed, which effectively improves the segmentation accuracy of thyroid nodule ultrasound image segmentation.
5.Three-dimensional human-robot mechanics modeling for dual-arm nursing-care robot transfer based on individualized musculoskeletal multibody dynamics.
Zhiqiang YANG ; Funing HOU ; Qiang LIN ; Jiexin XIE ; Hao LU ; Shijie GUO
Journal of Biomedical Engineering 2025;42(1):96-104
During transfer tasks, the dual-arm nursing-care robot require a human-robot mechanics model to determine the balance region to support the patient safely and stably. Previous studies utilized human-robot two-dimensional static equilibrium models, ignoring the human body volume and muscle torques, which decreased model accuracy and confined the robot ability to adjust the patient's posture in three-dimensional spatial. Therefore, this study proposes a three-dimensional spatial mechanics modeling method based on individualized human musculoskeletal multibody dynamics. Firstly, based on the mechanical features of dual-arm support, this study constructed a foundational three-dimensional human-robot mechanics model including body posture, contact position and body force. With the computed tomography data from subjects, a three-dimensional femur-pelvis-sacrum model was reconstructed, and the individualized musculoskeletal dynamics was analyzed using the ergonomics software, which derived the human joint forces and completed the mechanic model. Then, this study established a dual-arm robot transfer platform to conduct subject transfer experiments, showing that the constructed mechanics model possessed higher accuracy than previous methods. In summary, this study provides a three-dimensional human-robot mechanics model adapting to individual transfers, which has potential application in various scenarios such as nursing-care and rehabilitating robots.
Humans
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Robotics
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Biomechanical Phenomena
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Posture
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Imaging, Three-Dimensional
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Nursing Care
6.Clinical efficacy and safety of a domestic calcipotriol/betamethasone dipropionate ointment in the treatment of stable plaque psoriasis: a multicenter, randomized, double-blind, controlled study
Lixin XIA ; Guang XIANG ; Qingchun DIAO ; Kun HUANG ; Shoumin ZHANG ; Shanshan LI ; Yumei LI ; Zhiqiang SONG ; Qing SUN ; Xiumin YANG ; Meng PAN ; Yuling SHI ; Shuping GUO ; Huiping WANG ; Tiechi LEI ; Xiaoyong ZHOU ; Songmei GENG ; Suchun HOU ; Juan SU ; Yong CUI ; Rixin CHEN ; Yanyan FENG ; Hongxia FENG ; Rushan XIA ; Zudong MENG ; Fang YIN ; Jingjing WANG ; Xinghua GAO
Chinese Journal of Dermatology 2025;58(11):1020-1026
Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.
7.Estimation of 131I internal exposure of thyroid and dose to nuclear medicine staff in Zhejiang province
Zhiqiang XUAN ; Xiaoji HAO ; Shunfei YU ; Zhongjun LAI ; Jiadi GUO ; Yiyao CAO ; Donghang WANG ; Guijia HU
Chinese Journal of Radiological Medicine and Protection 2025;45(6):531-536
Objective:To investigate the current situation of nuclear medicine practices, determine the number of nuclear medicine staff, conduct internal exposure monitoring and dose estimation for nuclear mecidine staff engaged in 131I treatment in Zhejiang province. Methods:A survey was conducted over all the 22 hospitals involved in 131I treatment in the province. The 131I activity in thyroid of 96 stafff in 131I treatment workplaces were measured by means of direct method. At the same time, the effective doses from internal exposure were estimated and the influencing factors were analyzed. Results:131I activity in thyroids was found to be above the detection limit for 49 staff (51.04%) in nineteen hospitals. The maximum value of 131I activity was 629.18 Bq. There was no statistically significant difference in 131I detection rate in thyroid of 131I treatment staff between different positions, different genders and different levels of hospitals ( P>0.05). Comparisons of 131I activity of thyroid of nuclear medicine staff for theatment of thyroid cancers had shown that the highest was for nurses, followed by technicians and doctors, and the lowest was for cleaning staff ( H=6.39, P<0.05). The estimated committed effective dose to the nuclear medicine staff ranged from 0.05 to 2.37 mSv, with those below 1 mSv accounting for 93.88% of the total. Logistic regression analysis showed that nursing position was the risk factor contributing to the committed effective dose ( OR=2.805, 95% CI 1.076-7.314). Conclusions:In Zhejiang province, the committed effective dose to thyroid of nuclear medicine staff from 131I internal exposure was not in excess of the dose limit. However, the staff performing iodine therapy still need to strengthen protection against internal exposure and take scientific and effective protective measures to reduce the risk of health hazards from internal exposure.
8.Simultaneous Use of Three Endoscopes Combined With Holmium Laser in the Treatment of Gallstones Complicated With Common Bile Duct Stones:a Prospective Randomized Controlled Study
Junkai YANG ; Zedong HAO ; Wenliang GUO ; Zhiqiang WANG ; Biao WU
Chinese Journal of Minimally Invasive Surgery 2025;25(7):398-404
Objective To investigate the clinical effect of simultaneous use of three endoscopes(laparoscope,choledochoscope,and duodenoscope)combined with holmium laser in the treatment of gallstones complicated with common bile duct stones.Methods A prospective randomized controlled study was carried out.A total of 80 patients with cholecystolithiasis combined with choledocholithiasis in our hospital from August 2022 to January 2024 were selected and divided into three-endoscope group(n=40)and two-endoscope group(n=40)according to random number table method.Patients in the three-endoscope group underwent laparoscopic cholecystectomy(LC)and laparoscopic common bile duct exploration(LCBDE)combined with holmium laser lithotripsy,primary closure of the common bile duct,endoscopic retrograde cholangiopancreatography(ERCP),and endoscopic nasobiliary drainage(ENBD),while the two-endoscope group underwent LC+LCBDE+T-tube drainage.The intraoperative bleeding volume,operation time,hospitalization time,hospitalization costs,and postoperative complications between the two groups were observed and analyzed.Results There was no significant difference in intraoperative bleeding volume between the two groups[(55.6±14.3)ml vs.(53.2±16.3)ml,t=0.703,P=0.484].The operation time of the three-endoscope group was significantly longer than that in the two-endoscope group[214.5(171.5,246.8)min vs.178.0(151.0,227.8)min,Z=-2.069,P=0.039].The length of hospital stay in the three-endoscope group was significantly shorter than that in the two-endoscope group[(13.2±3.3)d vs.(16.2±3.7)d,t=3.864,P=0.001].The hospitalization costs were significantly higher in the three-endoscope group than those in the two-endoscope group[39 316.0(32 338.5,43 421.0)yuan vs.33 717.0(30 873.3,37 813.3)yuan,Z=-3.272,P=0.001].There were no significant differences in the incidence of postoperative pancreatitis[2.5%(1/40)vs.2.5%(1/40),χ2=0.000,P=1.000],the incidence of bile leakage[7.5%(3/40)vs.2.5%(1/40),χ2=0.263,P=0.615],and residual stone rate[7.5%(3/40)vs.0.0%(0/40),P=0.241]between the two groups.Forty cases in the three-endoscope group were followed up for 2-20 months,with a median of 13 months.One case of stone recurrence occurred at 8 months after surgery.Forty patients in the two-endoscope group were followed up for 1-21 months,with a median of 15 months.There was 1 case of stone recurrence at 6 and 10 months postoperatively,respectively.There was no statistically significant difference in stone recurrence rate between the two groups[2.5%(1/40)vs.5.0%(2/40),χ2=0.000,P=1.000].Conclusions LC+LCBDE combined with holmium laser lithotripsy,primary closure of the common bile duct,ERCP,and ENBD in the treatment of cholecystolithiasis and choledocholithiasis can shorten the hospitalization time.The replacement of T-tube with nasobiliary duct protects the function of the Oddi sphincter,which is more in line with the concept of minimally invasive surgery and worthy of clinical application.
9.Shikonin attenuates blood–brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/ Nrf2/HO-1 signaling
Guanghu LI ; Yang'e YI ; Sheng QIAN ; Xianping XU ; Hao MIN ; Jianpeng WANG ; Pan GUO ; Tingting YU ; Zhiqiang ZHANG
The Korean Journal of Physiology and Pharmacology 2025;29(3):283-291
Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.
10.Shikonin attenuates blood–brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/ Nrf2/HO-1 signaling
Guanghu LI ; Yang'e YI ; Sheng QIAN ; Xianping XU ; Hao MIN ; Jianpeng WANG ; Pan GUO ; Tingting YU ; Zhiqiang ZHANG
The Korean Journal of Physiology and Pharmacology 2025;29(3):283-291
Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

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