1.Safety and efficacy of argon-helium cryoablation combined with targeted therapy and anti-programmed death-1 monoclonal antibody in treatment of patients with unresectable hepatocellular carcinoma aged 60 years or older
Shujuan GONG ; Xiujuan CHANG ; Yan LIU ; Dong JI ; Yan CHEN ; Quanwei HE ; Yongping YANG
Journal of Clinical Hepatology 2026;42(3):629-638
ObjectiveTo investigate whether anti-programmed death-1 (PD-1) monoclonal antibody can enhance the efficacy and safety of argon-helium cryoablation combined with targeted therapy in patients with unresectable hepatocellular carcinoma (uHCC) aged 60 years or older. MethodsA retrospective analysis was performed for the clinical data of 124 patients with advanced uHCC aged 60 years or older who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to September 2024. After propensity score matching, 57 patients received cryoablation combined with targeted therapy (double combination group), while 57 received cryoablation combined with targeted therapy and anti-PD-1 monoclonal antibody (triple combination group). The indicators for efficacy assessment included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the incidence rate of adverse events. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison between groups. A Cox proportional-hazards regression model analysis was used to investigate the influencing factors for survival prognosis. ResultsThe triple combination group had a significantly higher ORR than the double combination group (59.6% vs 29.8%, χ2=9.083, P=0.003), while there was no significant difference in DCR between the two groups (87.7% vs 77.2%, χ2=1.516, P=0.218), and compared with the double combination group, the triple combination group had significantly longer median PFS (9.1 months vs 4.8 months, χ2=7.813, P=0.005) and median OS (26.1 months vs 13.6 months, χ2=14.199, P<0.001). The multivariate Cox proportional-hazards regression model analysis showed that triple combination treatment was an independent influencing factor for PFS (hazard ratio [HR]=0.52, 95% confidence interval [CI]: 0.35 — 0.78, P=0.001) and OS (HR=0.32, 95%CI: 0.20 — 0.51, P<0.001). There was no significant difference in the incidence rate of adverse events between the two groups (P>0.05). ConclusionTriple combination treatment with argon-helium cryoablation, targeted therapy, and anti-PD-1 monoclonal antibody can significantly improve survival benefits in uHCC patients aged 60 years or older, with a controllable safety profile.
2.Fluid Suppression Techniques Combined With Amide Proton Transfer-Weighted Imaging for the Evaluation of Adult-Type Diffuse Gliomas
Hongquan ZHU ; Yuanhao LI ; Yujie DING ; Yufei LIU ; Nanxi SHEN ; Yan XIE ; Su YAN ; Dong LIU ; Xiaoxiao ZHANG ; Li LI ; Wenzhen ZHU
Korean Journal of Radiology 2026;27(3):252-263
Objective:
To evaluate the diagnostic potential of fluid suppression (FS) techniques combined with amide proton transferweighted imaging (APTw) for assessment of isocitrate dehydrogenase (IDH) mutation status, glioma subtypes, and tumor proliferation.
Materials and Methods:
This retrospective study included 117 patients with adult-type diffuse gliomas. Conventional APTw, FSAPTw, and spillover-corrected FS-APTw (SCFS-APTw) metrics were calculated from 3T MRI data in tumor parenchyma, necrotic or cystic regions, and contralateral normal-appearing white matter. APTw signals were compared across the three techniques within each region, between IDH-mutant and IDH-wildtype gliomas, and among astrocytoma, oligodendroglioma, and glioblastoma subtypes. Diagnostic performance for distinguishing IDH mutation status and glioma subtypes was assessed using receiver operating characteristic (ROC) analysis. Correlations between APTw metrics and Ki-67 expression were also analyzed.
Results:
Both FS-APTw and SCFS-APTw significantly reduced signal intensity in tumor parenchyma and necrotic or cystic regions, with SCFS-APTw demonstrating a stronger suppression effect. IDH-wildtype gliomas showed significantly higher APTw metrics than IDH-mutant gliomas (all P < 0.001). Glioblastomas exhibited significantly higher metrics than oligodendrogliomas (all corrected P ≤ 0.015) and astrocytomas (all corrected P < 0.001). SCFS-APTw achieved the highest area under the ROC curve (AUC) of 0.846 for identification of IDH mutation status. For differentiation between astrocytomas and glioblastomas, the 90th percentile of APTw yielded the highest AUC (0.860), followed by SCFS-APTw (0.849). For discrimination between oligodendrogliomas and glioblastomas, the highest AUC (0.832) was obtained using the 90th percentile of SCFS-APTw. None of these metrics successfully differentiated oligodendrogliomas from astrocytomas. SCFS-APTw demonstrated the strongest correlation with Ki-67 expression (r = 0.451).
Conclusion
FS techniques effectively reduce elevated APTw signals originating from fluid compartments. Their combination with APTw imaging enables evaluation of IDH mutation status, glioma subtypes, and tumor proliferative activity in adulttype diffuse gliomas.
3.Acetyl-coenzyme A synthetase 2-mediated acetyl-coenzyme A accumulation promotes mitophagy and tumor growth via increased H3K27ac in hepatitis B virus-related hepatocellular carcinoma
Shan LI ; Jie HU ; Yihan YAN ; Xinrui LIU ; Xiao DONG ; Huijun LIANG ; Xin TANG ; Junji TAO ; Rong ZHANG ; Yuan HU ; Ailong HUANG ; Kai WANG ; Ni TANG
Clinical and Molecular Hepatology 2026;32(2):661-682
Background/Aims:
Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial.
Methods:
A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining.
Results:
Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth.
Conclusions
These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.
4.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
5.The first record of Anopheles messeae (Diptera: Culicidae) parasitized by water mites in China
Xue-ru CHEN ; Wen-zhen YAO ; Yu-hao LI ; Gui-chang LI ; Tao MENG ; Qun-ling FENG ; Xin-hui LIU ; Li-hong QIAO ; Xiang-ting WU ; Xue-feng ZHANG ; Cheng-lin LI ; Xue-cheng DONG ; Da-wei WANG ; Xiao-yan SI ; Yu-hong GUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):53-57
Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.
6.Annual review of basic research on lung transplantation worldwide in 2025
Jier MA ; Kemeng SUN ; Xiaohan JIN ; Jiaqi LI ; Xinyue ZHANG ; Chama LOUJAINE ; Junmin ZHU ; Hengtao LIN ; Xiangyun ZHENG ; Junjie WANG ; Zengwei YU ; Yaling LIU ; Haoji YAN ; Dong TIAN
Organ Transplantation 2026;17(4):582-593
Lung transplantation is a definitive treatment for end-stage lung disease and can significantly improve patient prognosis. However, postoperative complications such as infection, rejection, ischemia-reperfusion injury and chronic lung allograft dysfunction intertwine to form a complex pathological network, posing persistent challenges to long-term patient survival. In 2025, research teams worldwide have made systematic progress in the field of basic lung transplantation research. By integrating cutting-edge technologies including single-cell multi-omics, spatial transcriptomics and novel animal models, significant breakthroughs have been achieved in the evolutionary dynamics of drug-resistant infections, molecular mechanisms of immune regulation, programmed cell death, optimization of donor lung protection strategies and early warning of chronic lung allograft dysfunction. This article systematically reviews the representative advances in basic lung transplantation research worldwide in 2025, and deeply analyzes the implications of mechanistic breakthroughs for optimizing diagnosis and treatment strategies, aiming to anchor the direction for innovative breakthroughs and clinical translation in basic lung transplantation research.
7.Comparison of multiple machine learning models for predicting the survival of recipients after lung transplantation
Lingzhi SHI ; Yaling LIU ; Haoji YAN ; Zengwei YU ; Senlin HOU ; Mingzhao LIU ; Hang YANG ; Bo WU ; Dong TIAN ; Jingyu CHEN
Organ Transplantation 2025;16(2):264-271
Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC 6 months 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC 1 year 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.
8.Xiaozhong Zhitong Mixture(消肿止痛合剂)Combined with Antibiotic Bone Cement in the Treatment of Diabetic Foot Ulcers with Damp-Heat Obstructing Syndrome:A Randomized Controlled Trial of 35 Patients
Xiaotao WEI ; Zhijun HE ; Tao LIU ; Zhenxing JIANG ; Fei LI ; Yan LI ; Jinpeng LI ; Wen CHEN ; Bihui BAI ; Xuan DONG ; Bo SUN
Journal of Traditional Chinese Medicine 2025;66(7):704-709
ObjectiveTo observe the clinical effectiveness and safety of Xiaozhong Zhitong Mixture (消肿止痛合剂) combined with antibiotic bone cement in the treatment of diabetic foot ulcer (DFU) with damp-heat obstructing syndrome. MethodsA total of 72 DFU patients with damp-heat obstructing syndrome were randomly assigned to treatment group (36 cases) and the control group (36 cases). Both groups received standard treatment and topical antibiotic bone cement for ulcer wounds, while the treatment group received oral Xiaozhong Zhitong Mixture (50 ml per time, three times daily) in additionally. Both groups underwent daily wound dressing changes for 21 consecutive days. Ulcer healing rate, serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), malondialdehyde (MDA), superoxide dismutase (SOD), C-reactive protein (CRP), and white blood cell (WBC) count were observed before and after treatment, and visual analog scale (VAS) scores for wound pain, traditional Chinese medicine (TCM) syndrome scores, and the DFU Healing Scale (DMIST scale) were also compared. Liver and kidney function were evaluated before and after treatment, and adverse events such as allergic reactions, worsening ulcer pain were recorded. ResultsTotally 35 patients in the treatment group and 33 in the control group were included in the final analysis. The ulcer healing rate in the treatment group was (87.93±9.34)%, significantly higher than (81.82±12.02)% in the control group (P = 0.035). Compared to pre-treatment levels, both groups showed significant reductions in serum CRP, WBC, MDA, IL-1β, and TNF-α levels, with an increase in SOD level (P<0.05). TCM syndrome scores, VAS, and DMIST scores also significantly decreased in both groups (P<0.05), with greater improvements in the treatment group (P<0.05). No significant adverse reactions were observed in either group during treatment. ConclusionXiaozhong Zhitong Mixture combined with antibiotic bone cement has significant advantages in promoting DFU healing, reducing inflammatory response, and alleviating oxidative stress in DFU patients with damp-heat obstructing syndrome, with good safety for DFU patients with damp-heat obstructing syndrome.
9.Research Progress on the Correlation Between Mitophagy and Vascular Cognitive Impairment
Yan LIU ; Xingang DONG ; Xiaoyuan WANG ; Gege QI ; Yiqin REN ; Lianpeng ZHOU ; Hui LI ; Suqing ZHANG ; Weifeng LI
Medical Journal of Peking Union Medical College Hospital 2025;16(2):338-349
Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.
10.Influence evaluation of pharmaceutical quality control on medication therapy management services by the ECHO model
Kun LIU ; Huanhuan JIANG ; Yushuang LI ; Yan HUANG ; Qianying ZHANG ; Dong CHEN ; Xiulin GU ; Jinhui FENG ; Zijian WANG ; Yunfei CHEN ; Yajuan QI ; Yanlei GE ; Aishuang FU
China Pharmacy 2025;36(9):1123-1128
OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management (MTM) services for patients with coronary heart disease by using Economic, Clinical and Humanistic Outcomes (ECHO) model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 (pre-quality control implementation group, n=96) and June-August 2023 (post-quality control implementation group, n=164). Using propensity score matching analysis, 80 patients were selected from each group. The study subsequently compared the economic, clinical, and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching (P>0.05). Compared with pre-quality control implementation group, the daily treatment cost (16.26 yuan vs. 24.40 yuan, P<0.001), cost-effectiveness ratio [23.12 yuan/quality-adjusted life year (QALY) vs. 32.32 yuan/QALY, P<0.001], and the incidence of general adverse drug reactions (2.50% vs. 10.00%, P=0.049) of post-quality control implementation group were decreased significantly; the utility value of the EuroQol Five-Dimensional Questionnaire (0.74± 0.06 vs. 0.71±0.07, P=0.003), the reduction in the number of medication related problems (1.0 vs. 0.5, P<0.001), the medication adherence score ([ 6.32±0.48) points vs. (6.10±0.37) points, P=0.001], and the satisfaction score ([ 92.56±1.52) points vs. (91.95±1.56) points, P=0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups (1.25% vs. 3.75%, P=0.310). CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care, and the ECHO model can quantitatively evaluate the effect of MTM services, making pharmaceutical care better priced and more adaptable to social needs, thus being worthy of promotion.


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