1.Mechanisms of resistance to immune checkpoint inhibitor therapy in hepatocellular carcinoma: current status and challenges
Penghui LIU ; Na LI ; Yan DONG ; Lingyun GUO ; Jie MAO
Chinese Journal of Hepatobiliary Surgery 2025;31(2):141-146
This review is based on the research progress and challenges of immune checkpoint inhibitors (ICIs) in the treatment of hepatocellular carcinoma (HCC). ICIs block the PD-1/PD-L1 and CTLA-4 pathways; thereby reactivate the body’s anti-tumor immune response, providing a new therapeutic option for patients with advanced HCC. However, the effect of ICIs is still compromised by factors such as primary and acquired resistance, immune-related adverse events and tumor microenvironment inhibition. This reveiw deeply analyzes these key mechanisms that affect the efficacy of ICIs, and proposes strategies to optimize the treatment, including combination with targeted therapy, chemotherapy and radiotherapy, modulation of tumor microenvironment, and the development of novel biomarkers. Future research should focus on personalized treatment that integrates the molecular and immunological characteristics of patients to enhance the precision and efficacy of ICIs therapy for patients with HCC.
2.Clinical features of invasive Group A Streptococcus infection in children
Bing LIU ; Gang LIU ; Suyun QIAN ; Fang DONG ; Bing HU ; Tianming CHEN ; Lingyun GUO ; Xin GUO ; Quan WANG
Chinese Journal of Applied Clinical Pediatrics 2025;40(12):927-932
Objective:To summarize the clinical characteristics of invasive Group A Streptococcus (GAS) infection in children and to provide reference for its clinical treatment and diagnosis. Methods:The medical records of inpatients whose sterile body fluids tested positive for GAS in Beijing Children′s Hospital from February 2013 to June 2024 were reviewed in this case series study.The clinical information of the patients was collected and summarized as a case report.Non-normally distributed measurement data were represented by the median ( M), and count data were represented by cases (%). Results:There were 42 cases of invasive GAS infection, with a median age of 6 years and 3 months (range: 14 days to 13 years and 7 months).Twenty-seven patients (64.3%) developed this disease in winter.In terms of susceptibility factors, there were 4 cases of trauma, 2 cases of influenza A, 1 case of neuroblastoma chemotherapy myelosuppression, 1 case of acute lymphoblastic leukemia chemotherapy myelosuppression, 1 case of varicella, and 1 case of scald among these 42 patients, there are no other obvious susceptibility factors.The types of specimens in which GAS was detected included 23 blood specimens, 9 pleural effusions, 9 sterile-site pus specimens, and 5 cerebrospinal fluids.GAS was detected in 4 children from two types of specimens simultaneously.The methods for detecting GAS included bacterial culture in 35 cases and next-generation sequencing in 9 cases.Two children tested positive for GAS by both methods.According to clinical diagnoses, there were 17 cases of pneumonia, 13 cases of streptococcus toxic shock syndrome, 10 cases of purulent meningitis, 6 cases of purulent osteomyelitis, 6 cases of purulent arthritis, 5 cases of cellulitis, 3 cases of necrotizing fasciitis, 2 cases of infectious myositis, and 2 cases of cervical abscess.Two or more clinical manifestations were detected in 26 patients.Drug sensitivity reports were available for 26 cases.All strains were sensitive to Penicillin, Vancomycin, Linezolid, Ceftriaxone and Cefepime.All except 2 were resistant to Clindamycin, and all were resistant to Erythromycin.All 42 cases were treated with intravenous antibiotics, and 21 of them also received human immunoglobulin.Three of the patients died and 39 were discharged from hospital. Conclusions:Pediatric invasive GAS infection occurs mainly in winter and manifests as pneumonia, purulent meningitis, purulent osteomyelitis, and purulent arthritis.The strains are sensitive to β-lactam antibiotics, Vancomycin and Linezolid, and most are resistant to Clindamycin and Erythromycin.
3.Clinical features of invasive Group A Streptococcus infection in children
Bing LIU ; Gang LIU ; Suyun QIAN ; Fang DONG ; Bing HU ; Tianming CHEN ; Lingyun GUO ; Xin GUO ; Quan WANG
Chinese Journal of Applied Clinical Pediatrics 2025;40(12):927-932
Objective:To summarize the clinical characteristics of invasive Group A Streptococcus (GAS) infection in children and to provide reference for its clinical treatment and diagnosis. Methods:The medical records of inpatients whose sterile body fluids tested positive for GAS in Beijing Children′s Hospital from February 2013 to June 2024 were reviewed in this case series study.The clinical information of the patients was collected and summarized as a case report.Non-normally distributed measurement data were represented by the median ( M), and count data were represented by cases (%). Results:There were 42 cases of invasive GAS infection, with a median age of 6 years and 3 months (range: 14 days to 13 years and 7 months).Twenty-seven patients (64.3%) developed this disease in winter.In terms of susceptibility factors, there were 4 cases of trauma, 2 cases of influenza A, 1 case of neuroblastoma chemotherapy myelosuppression, 1 case of acute lymphoblastic leukemia chemotherapy myelosuppression, 1 case of varicella, and 1 case of scald among these 42 patients, there are no other obvious susceptibility factors.The types of specimens in which GAS was detected included 23 blood specimens, 9 pleural effusions, 9 sterile-site pus specimens, and 5 cerebrospinal fluids.GAS was detected in 4 children from two types of specimens simultaneously.The methods for detecting GAS included bacterial culture in 35 cases and next-generation sequencing in 9 cases.Two children tested positive for GAS by both methods.According to clinical diagnoses, there were 17 cases of pneumonia, 13 cases of streptococcus toxic shock syndrome, 10 cases of purulent meningitis, 6 cases of purulent osteomyelitis, 6 cases of purulent arthritis, 5 cases of cellulitis, 3 cases of necrotizing fasciitis, 2 cases of infectious myositis, and 2 cases of cervical abscess.Two or more clinical manifestations were detected in 26 patients.Drug sensitivity reports were available for 26 cases.All strains were sensitive to Penicillin, Vancomycin, Linezolid, Ceftriaxone and Cefepime.All except 2 were resistant to Clindamycin, and all were resistant to Erythromycin.All 42 cases were treated with intravenous antibiotics, and 21 of them also received human immunoglobulin.Three of the patients died and 39 were discharged from hospital. Conclusions:Pediatric invasive GAS infection occurs mainly in winter and manifests as pneumonia, purulent meningitis, purulent osteomyelitis, and purulent arthritis.The strains are sensitive to β-lactam antibiotics, Vancomycin and Linezolid, and most are resistant to Clindamycin and Erythromycin.
4.Mechanisms of resistance to immune checkpoint inhibitor therapy in hepatocellular carcinoma: current status and challenges
Penghui LIU ; Na LI ; Yan DONG ; Lingyun GUO ; Jie MAO
Chinese Journal of Hepatobiliary Surgery 2025;31(2):141-146
This review is based on the research progress and challenges of immune checkpoint inhibitors (ICIs) in the treatment of hepatocellular carcinoma (HCC). ICIs block the PD-1/PD-L1 and CTLA-4 pathways; thereby reactivate the body’s anti-tumor immune response, providing a new therapeutic option for patients with advanced HCC. However, the effect of ICIs is still compromised by factors such as primary and acquired resistance, immune-related adverse events and tumor microenvironment inhibition. This reveiw deeply analyzes these key mechanisms that affect the efficacy of ICIs, and proposes strategies to optimize the treatment, including combination with targeted therapy, chemotherapy and radiotherapy, modulation of tumor microenvironment, and the development of novel biomarkers. Future research should focus on personalized treatment that integrates the molecular and immunological characteristics of patients to enhance the precision and efficacy of ICIs therapy for patients with HCC.
5.Association between plasma-glycosylated hemoglobin A 1c/high-density lipoprotein cholesterol ratio and urinary albumin-creatinine ratio in Chinese adults
Wenjing DONG ; Ping PANG ; Lingyun SONG ; Di SUN ; Shiju YAN ; Guoqing YANG ; Yiming MU ; Weijun GU
Chinese Journal of Internal Medicine 2024;63(12):1228-1237
Objective:To explore the relationship between glycosylated hemoglobin A 1c/high-density lipoprotein cholesterol ratio (HbA 1c/HDL-C) and urinary albumin-creatinine ratio (UACR) in Chinese adults. Methods:In this cross-sectional study, the clinical data of 43 820 community residents (age>40 years) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals (REACTION study; March-December 2012) across eight centers (Liaoning, Guangdong, Shanghai, Gansu, Guangxi, Henan, Hubei, and Sichuan) in China were collected and analyzed. Participants were divided into three groups based on UACR levels:<10 mg/g, 10-30 mg/g, and >30 mg/g. The HbA 1c/HDL-C ratio was divided into four groups according to quartile division of the subjects: 1st quartile (Q1<3.79), 2nd quartile (3.79≤Q2<4.59), 3rd quartile (4.59≤Q3≤5.66), and 4th quartile (Q4>5.66). Multivariate ordinal logistic regression model was used to analyze the relationship between HbA 1c/HDL-C and UACR. Receiver operating characteristic (ROC) analysis was used to explore the predictive value of HbA 1c/HDL-C to UACR. Results:The 43 820 subjects included 13 452 (30.70%) male and 30 378 (69.30%) female patients, with an average age of (58.00±0.05) years. According to results of one-way analysis of variance analysis, the HbA 1c/HDL-C ratio was significantly associated with the risk of increased UACR ( F=495.73, P<0.001). After adjusting for clinically relevant confounding variables in logistic regression model, compared with participants with the lowest HbA 1c/HDL-C ratio (Q1), women with the highest HbA 1c/HDL-C ratio (Q4) had a 1.483-fold (95% CI 1.376-1.598, P<0.001) and men had a 1.161-fold (95% CI 1.019-1.323, P<0.001) increased risk of UACR. The ROC curve analysis showed that the area under the curve of HbA 1c/HDL-C for predicting increased UACR was 0.623 (95% CI 0.597-0.606), with a sensitivity of 60.18% and a specificity of 54.91%. The HbA 1c/HDL-C ratio showed the highest predictive value of all glycemic and lipidemic parameters. In individuals with well-controlled blood glucose (HbA 1c<6.5%) or lipid levels (HDL-C≥1.0 mmol/L), the HbA 1c/HDL-C ratio was still independently associated with the risk of increased UACR after adjusting for confounding variables [ OR(95% CI) of quartile 4: 1.563 (1.210-2.019, P=0.001) in participants with HbA 1c<6.5% and 1.822 (1.687-1.968, P<0.001) in participants with HDL-C≥1.0 mmol/L]. Conclusion:As a novel compound indicator for evaluating glucose homeostasis and dyslipidemia, the HbA 1c/HDL-C ratio was independently associated with increased UACR in the general population aged>40 years in China, which was superior to both glycemic and lipid parameters alone.
6.Current situation and influencing factors of intrinsic capacity of elderly people in the community
Xue LIU ; Shuqin XIAO ; Lingyun WANG ; Huimin WEN ; Xian MA ; Hongsai ZHANG ; Luqi DONG
Chinese Journal of Modern Nursing 2024;30(7):885-892
Objective:To explore the current situation of the intrinsic capacity of elderly people in the community and analyze its influencing factors.Methods:From September 2022 to March 2023, convenience sampling was used to select 360 elderly community residents from Xicheng District, Beijing, and Xingtai City, Hebei Province, as the research subjects. The subjects were surveyed using the Intrinsic Capacity Assessment Questionnaire, Intrinsic Capacity Influencing Factors Questionnaire, Barthel Index, and Lawton Instrumental Activities of Daily Living Scale.Results:A total of 360 questionnaires were distributed, and 360 valid questionnaires were collected, with an effective response rate of 100.0% (360/360). The overall impairment rate of intrinsic capacity among 360 elderly people in the community was 90.3% (325/360), and the impairment rates in various fields from high to low were sensation, psychology, vitality, cognition, and exercise. Multiple linear regression analysis showed that age, gender, residential pattern, education level, work status, grip strength, number of geriatric syndrome, self-rated health status, adverse life events, number of social activities, transportation conditions, and social security were the influencing factors of the intrinsic capacity of elderly people in the community, and the difference was statistically significant ( P<0.05) . Conclusions:The impairment rate of intrinsic capacity among elderly people in the community is relatively high. Grassroots medical and nursing staff should assess the intrinsic capacity of elderly people in the community in health promotion work, identify elderly people with decreased intrinsic capacity early and carry out effective interventions to prevent elderly people from becoming disabled and dependent on care.
7.A randomized controlled trial on effects of brief mindfulness meditation training on negative emotions in patients with coronary heart disease after percutaneous coronary intervention
Xia YAN ; Xiaofen DONG ; Wei TAN ; Lingyun WANG ; Lihua HE ; Laimei LUO ; Yi CHENG
Chinese Mental Health Journal 2024;38(10):867-872
Objective:Evaluate the effects of brief mindfulness meditation training on improving negative e-motions,mindfulness attention awareness,and sleep quality in patients after percutaneous coronary intervention(PCI)for coronary heart disease.Methods:Eighty-four patients with coronary heart disease after PCI admitted to the cardiology department were selected.According to the principle of simple randomization,they were divided into an intervention group of 42 cases and a control group of 42 cases.The Self Rating Anxiety Scale/Self Rating De-pression Scale,Mindfulness Attention Awareness Scale,and Pittsburgh Sleep Quality Index Scale were used as eval-uation indicators before and after intervention.Results:The difference in total scores of anxiety,depression,and mindfulness attention awareness before and after intervention in the intervention group was higher than that in the control group(P<0.05).The difference in total sleep score,sleep quality,time to fall asleep,sleep duration,use of hypnotic drugs,daytime dysfunction,and total sleep score before and after intervention was higher than that of the control group(P<0.05).Conclusion:It suggests that brief mindfulness meditation training could alleviate negative emotions in patients with coronary heart disease after PCI,improve mindfulness awareness,and improve sleep quali-ty.
8.Application of image recognition in automatic review scheme of coagulation test
Zhenghua DONG ; Yuqin ZUO ; Xiaoming ZHAO ; Lingyun JI ; Ji YANG
International Journal of Laboratory Medicine 2024;45(11):1368-1374
Objective To establish an automatic review plan for coagulation tests with image recognition function,and evaluate the correctness and effectiveness of the plan.Methods Artificial intelligence software and hardware were combined to establish an image recognition system that could automatically determine the characteristics of specimens,blood volume and hematocrit.The correctness of the determination results of specimen character was compared with the visual method,the correctness of the determination results of blood volume was compared with the manual measurement method,and the correctness of hematocrit was compared with the hematology analyzer.According to the flow chart,reference interval,medical decision level,critical value range,relevant literature,work experience and historical data,the autoverification rules of coagulation tests were formulated.The autoverification rules were manually verified,and the autoverification pass rate,true positive rate,true negative rate,false positive rate,and false negative rate were calculated.The change of turnaround time in the laboratory after the implementation of the autoverification scheme was evaluated.Re-sults The accuracy rate of sample trait determination in the image recognition system was 96.72%,and the false negative rate of judging hemolytic,jaundice,and lipoid blood samples as normal samples was 0.04%.The image recognition system was compared with the blood volume data of two groups of specimens measured manually,P=0.4881.The image recognition method was not inferior to the manual measurement method.Comparing the two sets of hematocrit data from the image recognition system and the blood cell analyzer,P=0.1130,the image recognition system was not inferior to the blood cell analyzer.A total of 61 automatic re-view rules for coagulation tests had been established,including numerical abnormalities,logical abnormalities,Delta Check,sample quality abnormalities,reaction curve abnormalities,etc.The automatic review pass rate was 76.19%,true positive rate was 23.77%,true negative rate was 76.19%,false positive rate was 0.04%,and false negative rate was 0.00%.After implementing the automatic audit plan,the turnaround time of sam-ples in each quantile was shortened,with an average shortening time of 13.66 min.Conclusion The applica-tion of image recognition technology in the automatic review of coagulation tests makes the automatic review function more automated and scientific,standardizes specimen quality judgment,improves the accuracy of test results,effectively improves work efficiency and saves manpower.
9.Short-term clinical and echocardiographic outcomes of the novel domestic transcatheter edge-to-edge repair Neonova? system in patients with mitral regurgitation
Yun YANG ; He LI ; Wenqian WU ; Xiaoke SHANG ; Shu CHEN ; Yucheng ZHONG ; Manwei LIU ; Lin HE ; Zhenxing SUN ; Ziming ZHANG ; Yi ZHOU ; Xin ZHANG ; Nianguo DONG ; Lingyun FANG ; Mingxing XIE
Chinese Journal of Ultrasonography 2023;32(1):51-59
Objective:To investigate short-term safety, efficacy and the learning curve of this self-developed novel transcatheter valve repair system (Neonova?) in patients with mitral regurgitation, and explore the role of perioperative echocardiography.Methods:Ten patients who visited the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from June 2021 to March 2022 and met the inclusive criteria were prospectively enrolled. All the patients were at high risk of surgery with moderate to severe or severe mitral regurgitation (MR). Clamps of Neonova? were implanted under guidance of transesophageal echocardiography and digital subtraction angiography. Clinical outcomes, echocardiography indexes and learning curves of this technique were evaluated immediately after intervention, 7 d, 1 month and 3 months post-intervention.Results:The technical success rate was 100% with MR relieved in all patients immediately after intervention. The device and procedural success rates were both 90.0% with 1 patient received surgical replacement at 37 days post-intervention while the others′ reduced to mild (8/9) and moderate (1/9) MR. New York Heart Association class and the Kansas City Cardiomyopathy Questionnaire improved significantly (all P<0.001). Mean mitral valve pressure gradient didn′t increase significantly after intervention when compared with that before intervention( P=0.324), and no mitral stenosis was observed. Left ventricular end-diastolic diameter decreased significantly ( P=0.008) during follow up.Procedure duration ranged from 60 to 300 (175.8±75.2)minutes. The simple linear regression model between procedure volume and duration showed that procedure duration decreased significantly with the increase of procedure volume ( F=15.857, P=0.004). Conclusions:Neonova? implantation can improve MR severity and clinical symptoms safely and effectively. Transthoracic echocardiography and transesophageal echocardiography are essential for perioperative management of transcatheter mitral valve repair.
10.Correlation of Th1/Th2 and Th17/Treg with treatment efficacy of PD-1 inhibitor in advanced non-small cell lung cancer patients complicated with chronic obstructive pulmonary disease
Weizhen SONG ; Jiangnan ZHENG ; Xiaoting ZHOU ; Lingyun DONG
Cancer Research and Clinic 2023;35(9):675-679
Objective:To investigate the relationship between peripheral blood helper T cell 1/helper T cell 2 (Th1/Th2), helper T cell 17/regulatory T cell (Th17/Treg) and efficacy of programmed death receptor 1 (PD-1) inhibitor in patients with advanced non-small cell lung cancer (NSCLC) combined with chronic obstructive pulmonary disease (COPD).Methods:The clinical data of 107 patients with advanced NSCLC combined with COPD who were admitted to Suzhou Ninth Hospital Affiliated to Soochow University from April 2021 to September 2022 were retrospectively analyzed. The patients were treated with PD-1 inhibitor, and they were categorized into the disease control group (82 cases) and the disease progression group (25 cases) according to the clinical efficacy. Th1/Th2, Th17/Treg and clinical data of patients before treatment were compared between the two groups, and logistic regression was used to analyze the independent influencing factors of patients' PD-1 inhibitor efficacy.Results:Th1/Th2 and Th17/Treg before treatment in the disease control group were higher than those in the disease progression group (12.49±1.14 vs. 7.04±1.06, t = 21.26, P < 0.001; 0.14±0.03 vs. 0.09±0.04, t = 6.72, P < 0.001). The proportions of patients with TNM stage Ⅳ, lymph node metastasis and brain metastasis in the disease progression group were higher than those in the disease control group (all P < 0.01). The results of multivariate logistic regression analysis showed that pre-treatment Th1/Th2 ( OR = 0.744, 95% CI 0.685-0.799, P < 0.001), pre-treatment Th17/Treg ( OR = 0.514, 95% CI 0.465-0.552, P < 0.001), TNM stage ( OR = 1.258, 95% CI 1.049-1.656, P = 0.048), lymph node metastasis ( OR = 1.790, 95% CI 1.223-2.734, P = 0.005), and brain metastasis ( OR = 1.640, 95% CI 1.184-2.348, P = 0.005) were independent influencing factors of PD-1 inhibitor efficacy in patients with advanced NSCLC combined with COPD. Conclusions:Patients with advanced NSCLC combined with COPD who have high Th1/Th2 and Th17/Treg before treatment have good outcomes with PD-1 inhibitor therapy.

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