1.Influence of antiviral treatment adjustment on the prognosis of chronic hepatitis B patients with low-level viremia
Mengwen HE ; Wucai YANG ; Chunyan WANG ; Yiming FU ; Chang GUO ; Jianjun WANG ; Dong JI
Journal of Clinical Hepatology 2025;41(6):1056-1061
ObjectiveTo investigate the incidence rate of primary liver cancer (PLC) and the progression of liver fibrosis in chronic hepatitis B (CHB) patients with low-level viremia (LLV) (HBV DNA<2 000 IU/mL but ≥20 IU/mL) after treatment adjustment, and to provide more robust evidence for clinical practice. MethodsA retrospective analysis was performed for the clinical data of LLV patients who initially received nucleos(t)ide analogue (NAs) for at least 48 weeks at the Fifth Medical Center of PLA General Hospital from August 2007 to April 2017 and subsequently underwent NAs adjustment due to LLV, and according to the virologic response after 48 weeks of treatment adjustment, the patients were divided into LLV group and complete virological response (CVR) group (HBV DNA<20 IU/mL). The patients were followed up once every 3 — 6 months till the primary endpoint event of PLC or October 2024. The incidence rate of PLC and the progression of liver fibrosis were observed, and the progression of liver fibrosis was defined as an increase of ≥1 grade in fibrosis-4 (FIB-4) index. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the cumulative incidence rate of PLC, and the Log-rank test was used for comparison between groups; the Cox regression analysis was used to investigate the risk factors for PLC, and the Logistic regression analysis was used to investigate the influencing factors for the progression of liver fibrosis. ResultsA total of 307 patients were enrolled, with a mean age of 50.0 years, and the male patients accounted for 80.5%. After 48 weeks of treatment with the adjusted NAs regimen, 254 patients (82.7%) achieved CVR, and 53 patients (17.3%) still had LLV. For the LLV group, the incidence rate of PLC was 30.2% and the rate of liver fibrosis progression was 22.6%, while for the CVR group, the incidence rate of PLC was only 13.4%, and the rate of liver fibrosis progression was 7.5%. The multivariate regression analyses showed that LLV was an independent risk factor for the onset of PLC (hazard ratio=2.623, 95% confidence interval [CI]: 1.315 — 5.234, P=0.006) and the progression of liver fibrosis (odds ratio=3.213, 95%CI: 1.385 — 7.455, P=0.007). ConclusionActive adjustment of treatment is needed immediately after the diagnosis of LLV to improve CVR, and if LLV persists after treatment adjustment, it is necessary to enhance the monitoring of liver fibrosis progression and PLC, so as to facilitate early diagnosis and treatment.
2.Mechanism of oxymatrine promoting the apoptosis of osteosarcoma MG63 cell line through mitophagy mediated by COX-2/PINK1/Parkin signaling pathway
China Pharmacy 2024;35(1):44-50
OBJECTIVE To study the mechanism of oxymatrine inducing apoptosis of osteosarcoma MG63 cell line based on mitophagy mediated by cyclooxygenase-2 (COX-2)/PTEN-induced putative kinase-1 (PINK1)/Parkinson disease protein-2 (Parkin) signaling pathway. METHODS MG63 cells were treated with 2.0, 4.0, 8.0 mg/mL oxymatrine and 6 μmol/L 5-fluorouracil, then the apoptotic rate, the expression of apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax)], the proportion of decrease in mitochondrial membrane potential, the level of mitophagy as well as the protein expressions of PINK1, Parkin, and microtubule-associated protein 1 light chain-3Ⅱ (LC3-Ⅱ) were detected. PINK1 small interfering RNA (siRNA) was adopted to intervene in the expression of PINK1, the cells were divided into control group, PINK1 siRNA group, oxymatrine group, and PINK1 siRNA+oxymatrine group; the protein expressions of PINK1, Parkin, and LC3-Ⅱ, the proportion of decrease in mitochondrial membrane potential (MMP) as well as apoptotic rate were detected. The lentivirus infection technique was used to overexpress COX-2, the cells were divided into control group, oxymatrine group, COX-2 group, and COX-2+oxymatrine group. The protein expressions of COX-2, PINK1, and Parkin, as well as the proportion of decrease in MMP were detected. RESULTS After being treated with oxymatrine, the apoptotic rate, the protein expressions of Bax, PINK1, Parkin, and LC3-Ⅱ, the level of mitophagy as well as the proportion of decrease in MMP were significantly increased (P<0.05), while the protein expression of Bcl-2 was significantly decreased (P<0.05). Compared with the oxymatrine group, the protein expressions of PINK1, Parkin, and LC3-Ⅱ, apoptotic rate and the proportion of decrease in MMP were significantly decreased in PINK1 siRNA+oxymatrine group (P<0.05). Compared with the oxymatrine group, the protein expression of COX-2 in the COX-2+oxymatrine group was increased significantly (P<0.05), while the protein expressions of PINK1 and Parkin as well as the proportion of 526087266@qq.com decrease in MMP were decreased significantly (P<0.05). CONCLUSIONS Oxymatrine can mediate the overactivity of mitophagy based on the PINK1/Parkin signaling pathway by inhibiting COX-2 expression, thus promoting the apoptosis of the MG63 osteosarcoma cell line.
3.Effect and mechanism of berberine-induced ferroptosis in osteosarcoma cells
China Pharmacy 2024;35(3):296-303
OBJECTIVE To investigate the effect of berberine on ferroptosis in MG63 osteosarcoma cells and its mechanism. METHODS Using cells without drug treatment as control, the cell viability, proliferation, the related indexes of ferroptosis [nuclear proliferation associated-antigen (Ki67), mitochondrial ultrastructure, ferric ion (Fe2+), reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH)], the protein expression of signal transducer and activator of transcription 3 (STAT3), tumor protein 53 (p53), and solute carrier family 7 member 11 (SLC7A11) were detected after being treated with different concentrations of berberine. Cells were transfected with p53 siRNA and then assigned to the control group, p53 siRNA group, berberine group, and p53 siRNA+berberine group to explore the role of p53 in berberine-induced ferroptosis. After 24 h incubation with 10.0 μmol/L berberine, the protein expressions of p53 and SLC7A11, the levels of mitochondrial membrane potential, GSH, and MDA content were determined. Cells were transfected with STAT3 overexpressed plasmid and then assigned to the control group, berberine group, STAT3 group, and STAT3+berberine group to explore the effect of STAT3 on the regulation of the p53/SLC7A11 pathway. After 24 h incubation with 10 μmol/L berberine, the protein expressions of p-STAT3, STAT3, p53, and SLC7A11 were detected. RESULTS Compared with the control cell, the concentrations of 2.5, 5.0 and 10.0 μmol/L berberine could reduce the cell viability and expression of Ki67, and induce the morphological changes in ferroptosis-related mitochondria, increase the levels of Fe2+, ROS and MDA, and the protein expression of p53, reduce the level of GSH, the binding activity of STAT3 with DNA, and the protein expressions of p-STAT3 and SLC7A11; the above differences were statistically significant (P< 0.05 or P<0.01). Compared with the berberine group,significantly down-regulated p53 protein expression and MDA level, up-regulated SLC7A11 protein expression, and increased mitochondrial membrane potential and GSH level were observed in the p53 siRNA+berberine group (P<0.01). Compared with the berberine group, the protein expressions of p-STAT3, STAT3, and SLC7A11 in the STAT3+berberine group were significantly increased (P<0.01), while the protein expression of p53 was significantly decreased (P<0.01). CONCLUSIONS Berberine can induce the ferroptosis of MG63 cells by mediating STAT3/p53/SLC7A11 signaling pathway.
4.Application prospect of machine learning in field of anesthesiology
Xiaoyi HU ; Di WANG ; Muhuo JI ; Jianjun YANG
The Journal of Clinical Anesthesiology 2024;40(6):634-638
Machine learning(ML)technology has been gradually applied in clinical anesthesia,and the application and research in the perioperative period are increasing.ML can warn occurrence of high-risk events,assist the diagnosis of difficult airway and ultrasound imaging in the perioperative period.Intrao-peratively,ML can predict hypotension,hypoxemia,cardiac arrest,and depth of anesthesia to help achieve precise and safe control of anesthesia.Postoperatively,ML can predict anesthesia-related adverse outcomes.This article summarizes the ML models commonly used in the field of anesthesiology,and reviews the rele-vant studies of ML application in all stages of the perioperative period.The application of ML can improve the perioperative anesthesia management,help to warn the occurrence of high-risk events and reduce anes-thesia-related risks.
5.Perioperative anesthetic management for patients with multimorbidity:challenges and opportunities
Muhuo JI ; Xiaoyi HU ; Jianjun YANG
The Journal of Clinical Anesthesiology 2024;40(11):1125-1129
The intensifying aging of the population has led to a growing severity of multimorbidity,significantly impacting patients'quality of life.Current anesthetic management approaches primarily target individual diseases,which struggle to effectively address the complexity of multimorbidity.This article re-views the concept and research status of multimorbidity,analyzes the interconnections among aging,multi-morbidity,and frailty,and discusses the influence of multimorbidity on perioperative risks.For patients with multimorbidity,the article proposes perioperative management strategies encompassing preoperative assess-ment,multidisciplinary collaboration,personalized anesthesia plans,intraoperative monitoring,and postop-erative care.Furthermore,the article underscores the shift from single-disease assessments to comprehensive multimorbidity assessment frameworks,and explores novel management models utilizing big data and artificial intelligence to enhance surgical safety and improve patient prognosis.
6.Short-term results of a multicenter study based on a modified N7 induction regimen combined with arsenic trioxide in the treatment of children with high-risk neuroblastoma
Shu YANG ; Kailan CHEN ; Yunyan HE ; Xiaomin PENG ; Hao XIONG ; Wenguang JIA ; Sha WU ; Xunqi JI ; Yuwen CHEN ; Chuan TIAN ; Zhonglü YE ; Zhen YANG ; Jianjun ZHU ; Aiguo LIU ; Xiaohua TIAN ; Fengjuan PAN ; Ke HUANG ; Dunhua ZHOU ; Jianpei FANG ; Yang LI
Chinese Journal of Pediatrics 2024;62(10):949-955
Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.
7.Risk factors for in-hospital mortality in patients with severe trauma and their predictive value
Lin YANG ; Chen YANG ; Cen CHEN ; Yan WU ; Junchi YANG ; Xiaolong CHENG ; Haifei WU ; Jianjun ZHU ; Bing JI
Chinese Journal of Trauma 2024;40(10):903-909
Objective:To explore the risk factors for in-hospital mortality in patients with severe trauma and their predictive predictive value.Methods:A retrospective case-control study was used to analyze the data of 509 patients with severe trauma in the trauma database of the Trauma Center of the Second Affiliated Hospital of Soochow University from January 2017 to December 2021, including 377 males and 132 females, aged 18-94 years [53(42, 65)years]. Injury severity score (ISS) was 16-75 points [22(18, 29)points]. Injured parts included the head and neck in 409 patients (80.35%), the chest in 328(64.44%), the abdomen in 193(37.91%), the pelvis in 142(27.90%), the spine in 79(15.52%), and the limb in 247(48.53%). According to the clinical outcome during the hospital stay, the patients were divided into survival group ( n=390) and non-survival group ( n=119). Baseline and clinical data of the two groups were compared, including gender, age, cause of injury (traffic injury, fall from height, sharp instrument injury, etc.), injury site (head and neck, chest, abdomen, pelvis, spine, limb), vital signs on admission (temperature, systolic blood pressure, heart rate, respiratory rate), blood tests on admission [hemoglobin, platelets, prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen (FIB)], Glasgow coma scale (GCS) upon admission to the emergency room, revised trauma score (RTS) upon admission to the emergency room, ISS after whole-body CT examination, quick sequential organ failure assessment (qSOFA) score upon admission to the emergency room, and INR combined with qSOFA score. The baseline and clinical data of the survival group and the non-survival group were first compared with univariate analysis. Then, the independent risk factors of in-hospital mortality in patients with severe trauma were determined by multivariate Logistic stepwise regression (forward and backward). Based on the above data, receiver operating characteristic (ROC) curves were generated with Medcalc statistical software to analyze the efficacy of each risk factor in assessing in-hospital mortality in patients with severe trauma. Results:Univariate analysis showed that there were significant differences in age, injury site, temperature, systolic blood pressure, hemoglobin, platelet, PT, APTT, INR, FIB, GCS, RTS, ISS, qSOFA score, and INR combined with qSOFA score between the two groups ( P<0.05 or 0.01), while there were no significant differences in gender, cause of injury, heart rate, and respiratory rate between the two groups ( P>0.05). Multivariate Logistic stepwise regression analysis showed that age, systolic blood pressure, APTT, ISS, and INR combined with qSOFA score were significantly correlated with in-hospital mortality in patients with severe trauma ( P<0.01). ROC curve analysis results showed that the area under the curve (AUC) of in-hospital mortality in patients with severe trauma predicted by age, systolic blood pressure, APTT, ISS, and INR combined with qSOFA score were 0.63(95% CI 0.59, 0.68) and 0.60(95% CI 0.55, 0.64), 0.66(95% CI 0.62, 0.70), 0.73(95% CI 0.69, 0.77), and 0.75(95% CI 0.72, 0.80), respectively. Conclusions:Age, systolic blood pressure, APTT, ISS, and INR combined with qSOFA score are the independent risk factors for in-hospital mortality in patients with severe trauma. ISS and INR combined qSOFA score can better predict in-hospital mortality of patients with severe trauma than age, systolic blood pressure and APTT.
8.Diagnostic efficacy of artificial intelligence model based on yolox framework integrating left ventricular segmentation and key point detection to automatically measure left ventricular ejection function in patients with chronic renal failure
Hanxiao LI ; Qiang JI ; Yang ZHAO ; Chuang JIA ; Shujiao JI ; Jianjun YUAN ; Yu XING ; Tian ZENG ; Haohui ZHU
Chinese Journal of Ultrasonography 2024;33(5):407-414
Objective:To evaluate the detection performance of left ventricular ejection fraction (LVEF) in patients with chronic renal failure (CRF) by an artificial intelligence (AI) model based on yolox framework integrating left ventricular segmentation and critical point detection.Methods:From January 2019 to June 2023, a total of 4 284 echocardiographic images of 2 000 adults aged 18-80 years without segmental wall motion abnormalities, structural heart disease, cardiac surgery or cardiomyopathy were collected in Henan Provincial People′s Hospital to delineate the endocardial membrane, as a training set, an AI model based on yolox framework integrating left ventricular segmentation and critical point detection was established. The images were divided into the training set( n=1 675) and the test set( n=325) in a ratio of about 5∶1. All 228 echocardiographic images of 100 normal adult volunteers who were treated in Henan Provincial Chest Hospital from May 2020 to May 2021 were collected as external test set validation. All 792 echocardiographic images of 204 patients treated in Henan Provincial People′s Hospital from April 2019 to June 2023 were continuously enrolled to evaluate the measurement efficiency of AI model. Spearman correlation statistical method was used to analyze the consistency of AI model measurement with manual measurement and TomTec software measurement methods of 3 senior echocardiographic professionals. Subjects were divided into clear image group, unclear image group, normal LVEF group and reduced LVEF group, the differences of general data between the two groups were compared. The correlation coefficient(ICC) within the group was calculated to analyze the consistency, so as to evaluate the model performance. Results:LVEF measured by AI model was significantly correlated with both manual measurement and TomTec model measurement ( rs=0.834, 0.826; all P<0.01). ICC values of the clear image group and the unclear image group were 0.96 and 0.97, respectively. ICC values for all subjects, normal LVEF group and reduced LVEF group were 0.96, 0.90 and 0.96, respectively. Conclusions:The AI model based on yolox framework integrating left ventricular segmentation and critical point detection has good diagnostic performance in the automatic measurement of LVEF in patients with CRF.
9.Influence of patelloplasty combined with cartilage surface resection on early function and anterior knee pain during total knee arthroplasty
Ran BO ; Bin DENG ; Dong WANG ; Jianjun JI ; Shicheng XIE
International Journal of Surgery 2023;50(11):737-743
Objective:To investigate the effects of patelloplasty combined with cartilage surface resection on early function and anterior knee pain during total knee arthroplasty(TKA).Methods:This is a prospective controlled study, 100 patients with knee osteoarthritis(KOA) who received TKA treatment in Zoucheng People′s Hospital of Shandong Province from February 2021 to April 2022 were selected and divided into the combined group and the control group using the random number table method, 50 cases in each group. The combined group received patelloplasty combined with cartilage surface resection during TKA, while the control group only received patelloplasty. Preoperative osteoarthritis Kellgren-Lawrance (K-L) grade, joint motion (ROM), the operation time and the decrease of hemoglobin in two groups were recorded.Knee function was evaluated by Hospital for Special Surgery(HSS) knee score at 1, 3, 6, and 12 months after surgery. Anterior knee pain during stair climbing was evaluated by visual analogue scale(VAS), and recovery of patellofemoral joint was evaluated by Feller score system. The measurement data were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data between groups was conducted by Chi-square test. Results:There was no significant difference in preoperative K-L grading and ROM between the two groups ( P> 0.05). The operation time of the combined group was longer than that of the control group[(71.49±9.34) min vs (66.27±8.22) min], the difference was statistically significant ( P <0.05), and there was no statistical significance in the decrease of hemoglobin between the two groups ( P>0.05). At 3, 6 and 12 months after treatment, the HSS scores of the combined group were higher than those of the control group [3 months: (76.93±8.26) vs (71.74±7.84), 6 months: (85.72±6.27) vs (81.47±6.19), 12 months: (88.64±5.27) vs (85.72±4.85)], the difference were statistically significant ( P <0.05). At 1, 3, 6 and 12 months after treatment, the VAS scores of anterior knee pain in combined group were lower than those in control group [1 months: (2.54±0.48) vs (2.77±0.63), 3 months: (2.02±0.53) vs (2.58±0.45), 6 months: (1.32±0.35) vs (1.97±0.38), 12 months: (1.14±0.33) vs (1.75±0.35)], the difference were statistically significant ( P <0.05). The incidence of anterior knee pain at 3, 6 and 12 months after operation in combined group was lower than that in control group [3 months: 20.0% vs 38.0%, 6 months: 14.0% vs 32.0%, 12 months: 10.0% vs 28.0%], the difference were statistically significant ( P <0.05). At 3, 6 and 12 months after treatment, the patellar Feller score in the combined group was higher than that in the control group[3 months: (18.63±3.52) vs (15.36±3.28), 6 months: (22.27±3.18) vs (19.63±3.48), 12 months: (25.82±3.27) vs (22.47±3.47)], the difference were statistically significant ( P <0.05). Conclusion:Patelloplasty combined with cartilage surface resection during TKA can effectively prevent the occurrence of postoperative anterior knee pain and improve the therapeutic effect.
10.Effect of different anesthesia onset time on postoperative circadian rhythm in patients undergoing robot-assisted radical prostatectomy
Jin GUO ; Huijie SHANG ; Muhuo JI ; Jianjun YANG
The Journal of Clinical Anesthesiology 2023;39(11):1147-1151
Objective To analyze the effect of different anesthesia induction time on postoperative circadian rhythm in patients undergoing robot-assisted radical prostatectomy.Methods A total of 103 pa-tients,aged 50-85 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ,undergoing robot-assisted radi-cal prostatectomy from January 2022 to October 2022 were recruited.The patients were grouped according to the induction time:the morning 8:00-11:59 group(group M,n=53)and the afternoon 12:00-18:00 group(group A,n=50).D'Amico risk grade,duration of anesthesia,number of effective com-pressions of analgesic pump(D1)and actual compressions(D2)were recorded,D1/D2 were calculated.HR,MAP,SpO2 were recorded at 5 minutes after entrying the operation room(T0),5 minutes after anes-thesia induction(T,),5 minutes after the surgery start(T2),60 minutes after the surgery start(T3),at the end of surgery(T4)and 5 minutes after extubation(T5).BIS at T1-T4 were recorded.Sleeping status was assessed by the Athens insomnia scale(AIS)1 day before surgery,1 day and 3 days after surgery,and pain level was assessed 1 and 3 days after surgery using the digital rating scale(NRS).According to the re-sults of the morningness-eveningness questionnaire of sleep-wake assessment(MEQ-SA)1 day before surgery and 3 days after surgery,the patients'circadian rhythm was determined.Results There were no statistically significant differences in D'Amico risk grade,duration of anesthesia,D1/D2,HR,MAP,SpO2 and BIS at different time point,AIS scores 1 day before surgery,1 day and 3 days after surgery,and NRS scores 1 day and 3 days after surgery between the two groups.In group M,there were 11 cases(21%)of circadian rhythm changes,of which 5 people's circadian rhythm changed to"later"and 6 people's circadian rhythm changed to"earlier".In group A,there were 3 cases(6%)of circadian rhythm changes,of which 1 person's circadian rhythm changed to"later"and 2 people's circadian rhythm changed to"earlier".The rate of circadian rhythm change in group M was significantly higher than that in group A(P<0.05).Conclusion The incidence of perioperative circadian rhythm alteration is significantly higher in patients undergoing robot-assisted radical prostatectomy who starts anesthesia in the morning than those in the after-noon.

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