1.Skeleton Binding Protein 1 of Plasmodium berghei Influences Deformability and Cytoskeletal Ultrastructure of Infected Erythrocyte
Xin-Yue GUO ; Huan-Qi ZHAO ; Yan-Xuan ZHONG ; Ru-Meng JIANG ; Yao-Xian LI ; Lei-Ting PAN ; Qian WANG ; Xiao-Yu SHI
Progress in Biochemistry and Biophysics 2026;53(4):1015-1027
ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.
2.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
3.Shenshuai Guanchang Prescription Treats Non-dialysis Patients with Chronic Kidney Disease Stage 4-5 of Spleen and Kidney Deficiency,Blood Stasis and Dampness Turbidity: A Randomized Controlled Trial
Xiangyu LI ; Ning ZHANG ; Tongxia LI ; Pu YAN ; Qian ZHANG ; Fanyu HOU ; Zhiquan ZHAO ; Xinrong FAN ; Kaifeng SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(22):198-208
ObjectiveTo observe the clinical efficacy and safety of Shenshuai Guanchang prescription in improving the intestinal barrier function,reducing non-indole uremic toxins,ameliorating micro-inflammatory state,and delaying renal function progression in non-dialysis patients with chronic kidney disease (CKD) stage 4-5. MethodsA total of 80 patients with CKD stage 4-5 who did not receive dialysis replacement therapy and were diagnosed with the syndrome of spleen and kidney deficiency,blood stasis and dampness turbidity were randomly assigned into a control group and a treatment group,with 40 patients in each group. The control group received conventional basic treatment and Western medicine symptomatic treatment,while the treatment group received combined intervention with Shenshuai Guanchang prescription through retention enema in addition to the treatment of the control group. Both groups had a treatment course of 4 weeks. The two groups were compared regarding the changes in urine toxin indicators [p-cresyl sulfate (PCS) and trimethylamine oxide (TMAO)],intestinal barrier indicators [D-lactic acid (D-LA),lipopolysaccharide (LPS),and intestinal fatty acid-binding protein (I-FABP)],renal function indicators [serum creatinine (SCr),blood urea nitrogen (BUN),and estimated glomerular filtration rate (eGFR)],and micro-inflammatory state indicators [interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),and neutrophil-to-lymphocyte ratio (NLR)] before and after treatment. The therapeutic effects were evaluated from three aspects:The efficacy regarding traditional Chinese medicine (TCM) symptom scores,the efficacy regarding laboratory indicators,and comprehensive efficacy. The safety of the clinical research drugs used by both groups of patients was also observed. ResultsA total of 37 cases in the treatment group and 38 cases in the control group completed the observation. After treatment,the treatment group showed declined levels of PCS,TMAO,D-LA,SCr,TNF-α,and NLR,spleen and kidney deficiency symptom score,blood stasis and dampness symptom score,and total symptom score (P<0.05),and increased eGFR (P<0.05). Moreover,the treatment group had lower levels of PCS,TMAO,D-LA,I-FABP,IL-6,and TNF-α,spleen and kidney deficiency symptom score,blood stasis and dampness symptom score,and total symptom score (P<0.05),higher response rate regarding TCM symptoms (χ2=6.68,P<0.05),and higher comprehensive efficacy (χ2=4.08,P<0.05) than the control group. No significant abnormalities were observed in the safety indicators of the two groups of patients. During the treatment period,adverse reactions were reduced after symptomatic treatment,and no serious adverse reactions occurred. ConclusionShenshuai Guanchang prescription can alleviate the clinical symptoms,improve the intestinal barrier function,reduce non-indole-type uremic toxins,alleviate the micro-inflammatory state,and has good clinical application safety of non-dialysis patients with CKD stage 4-5.
4.Distribution of traditional Chinese medicine syndromes and related influencing factors in colorectal cancer comorbid with metabolic dysfunction-associated fatty liver disease
Zhiyao SHI ; Zhiyang ZHAO ; Ruofei YAN ; Yu GAO ; Xixing WANG
Journal of Clinical Hepatology 2026;42(9):2106-2115
ObjectiveTo investigate the distribution and characteristics of traditional Chinese medicine (TCM) syndromes in patients with colorectal cancer and metabolic dysfunction-associated fatty liver disease (CRC-MAFLD), to explore the correlation between influencing factors and syndrome distribution, and to provide a reference for clinical syndrome differentiation. MethodsA total of 319 patients who were admitted to Shanxi Provincial Institute of Traditional Chinese Medicine and The Affiliated Hospital of Shanxi University of Chinese Medicine from January 2021 to December 2025 and were diagnosed with CRC-MAFLD based on pathology and radiological examination were enrolled as subjects, and TCM syndrome differentiation was performed for all subjects. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between multiple groups. The indicators with statistical significance in the univariate analysis were incorporated into the unordered multinomial Logistic regression model, and the syndrome of liver depression and spleen deficiency was set as the reference group to identify the independent influencing factors for each TCM syndrome. ResultsThe main clinical symptoms of CRC-MAFLD included fatigue (78.06%), abdominal distension (64.26%), poor appetite (61.13%), loose stool (57.05%), and costal pain (52.04%). The syndrome of liver depression and spleen deficiency showed the highest distribution frequency, followed by intermingled phlegm and blood stasis, internal retention of dampness turbidity, damp-heat accumulation, deficiency of liver and kidney, and deficiency of spleen and kidney. Comparison between groups with different TCM syndromes showed significant differences in the distribution of body mass index (χ2=42.216, P<0.001), the clinical stage of colorectal cancer (χ2=11.666, P=0.040), liver metastasis (χ2=19.279, P=0.002), degree of hepatic steatosis (χ2=71.085, P<0.001), diabetes (χ2=12.486, P=0.029), chemotherapy (χ2=21.920, P<0.001), fasting plasma glucose (FPG) (F=10.367, P<0.001), glycosylated hemoglobin (HbA1c) (F=3.696, P=0.003), albumin (Alb) (F=3.302, P=0.006), alkaline phosphatase (ALP) (H=34.350, P<0.001), gamma-glutamyl transferase (GGT) (H=41.679, P<0.001), and triglyceride (TG) (H=28.826, P<0.001). An unordered multinomial Logistic regression model was constructed with the syndrome of liver depression and spleen deficiency as the reference, and the results showed that overweight/obesity was a common independent risk factor for intermingled phlegm and blood stasis (odds ratio [OR]=4.468, P=0.002), internal retention of dampness turbidity (OR=2.944, P=0.024), and damp-heat accumulation (OR=5.651, P=0.001); clinical stage Ⅳ was an independent risk factor for deficiency of liver and kidney (OR=6.746, P=0.003) and deficiency of spleen and kidney (OR=10.074, P=0.001); presence of liver metastasis was an independent risk factor for intermingled phlegm and blood stasis (OR=5.145, P=0.001); severe fatty liver disease was an independent risk factor for intermingled phlegm and blood stasis (OR=5.201, P=0.007) and internal retention of dampness turbidity (OR=7.412, P=0.001), and moderate fatty liver disease was an independent risk factor for intermingled phlegm and blood stasis (OR=2.643, P=0.045), internal retention of dampness turbidity (OR=3.182, P=0.029), and damp-heat accumulation (OR=3.073, P=0.036); diabetes was an independent risk factor for internal retention of dampness turbidity (OR=5.133, P=0.003) and damp-heat accumulation (OR=3.716, P=0.031). As for continuous variables, elevated FPG was an independent risk factor for internal retention of dampness turbidity (OR=2.375, P=0.003) and damp-heat accumulation (OR=2.701, P=0.005); elevated HbA1c was an independent risk factor for intermingled phlegm and blood stasis (OR=2.029, P=0.032) and deficiency of liver and kidney (OR=3.308, P=0.010); elevated ALP was an independent risk factor for damp-heat accumulation (OR=1.053, P=0.019); elevated GGT was an independent risk factor for intermingled phlegm and blood stasis (OR=1.029, P=0.026) and damp-heat accumulation (OR=1.030, P=0.047); elevated TG was an independent risk factor for intermingled phlegm and blood stasis (OR=2.931, P=0.006) and internal retention of dampness turbidity (OR=2.449, P=0.019); elevated Alb was a protective factor against deficiency of spleen and kidney (OR=0.756, P=0.005). ConclusionBody mass index, the clinical stage of colorectal cancer, liver metastasis, degree of hepatic steatosis, diabetes, chemotherapy, FPG, HbA1c, Alb, ALP, GGT, and TG are the main influencing factors for TCM syndromes in CRC-MAFLD.
5.Chinese expert consensus on the clinical application of recombinant human thyroid-stimulating hormone (2025 edition)
Chentian SHEN ; Yushen GU ; Hui TAN ; Anren KUANG ; Sijin LI ; Yaming LI ; Jing WANG ; Ningyi JIANG ; Jian TAN ; Zhuoying WANG ; Shaoyan LIU ; Xiaoyi LI ; Jugao FANG ; Dingcun LUO ; Youben FAN ; Hui WANG ; Yuetao WANG ; Xuemei WANG ; Feng WANG ; Wei FU ; Feng SHI ; Xuegong LIU ; Zhongwei LÜ ; Yan XING ; Lin LI ; Hui YANG ; Jun XIN ; Yifan ZHANG ; Yue CHEN ; Yansong LIN ; Wei OUYANG ; Shuzhan YAO ; Changjiu ZHAO ; Xinming ZHAO ; Zairong GAO ; Dingde HUANG ; Qiang WEN ; Xingmin HAN ; Cen LOU ; Weibing MIAO ; Wei FAN ; Quanyong LUO ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2026;33(5):932-944
The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before 131I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.
6.Bibliographical cataloging for ancient TCM books
Hongtao LI ; Weina ZHANG ; Lin TONG ; Jingpeng DENG ; Qian ZHAO ; Honglei WANG ; Naiying LIU ; Mei SHI ; Qiang LIU ; Ying LIN ; Xiaohong ZHANG ; Lili FENG ; Mingrui ZHANG ; Yanqiu LUO ; Guangkun CHEN ; Yan DONG ; Bin LI ; Sihong LIU ; Bing LI ; Chen LI ; Meng LI ; Rui WANG ; He LU
International Journal of Traditional Chinese Medicine 2025;47(6):729-740
With reference to the Information and Documentation-Resource Description (GB/T 3792-2021) and Bibliographical Description for Ancient Chinese Books (GB/T 3792.7-2008) and other cataloging standards and rules, drawing on the practical experience of cataloging ancient TCM books, Bibliographical Cataloging for Ancient TCM Books was formulated. This standard specifies the entry items and their order of ancient TCM books, cataloging identifier, cataloging text, cataloging information source, and cataloging item details. The standard can provide standardized and unified guiding principles and methods for the work of ancient TCM books, and promote the sharing and utilization of ancient TCM books.
7.Research on objective evaluation of pilot ground simulation ejection training based on pressure detection
Yanpeng ZHAO ; Weiping BU ; Shu ZHANG ; Fei SHI ; Heqing LIU ; Yan JIANG ; Yining ZHANG ; Xinpo SONG ; Lei WANG
Space Medicine & Medical Engineering 2025;36(3):236-240
Objective In response to the practical issues of pilot ground simulation ejection training relying on subjective evaluation,which requires high professionalism and lacks objectivity and systematicity,an objective evaluation system and method for ejection training based on pressure detection has been designed.Methods According to the rules of ejection training about posture,maneuver and time,and utilizing technologies such as pressure detection,infrared detection,and time-triggered detection,this paper designed separate modules for ejection posture detection,ejection timing detection,and comprehensive analysis and evaluation.These modules are closely integrated with the ejection training process,achieving objective evaluation of the ejection training.Results This system and method can provide a scientific and real-time objective evaluation of the posture,movements,and time in ejection training without affecting the normal organization and process.Conclusion The objective evaluation system can provide a new approach that is highly objective and easy to operate for comprehensively evaluating and enhancing the effectiveness of ejection training,as well as for scientifically conducting ejection training and assessment.
8.Discovery of E0199:A novel compound targeting both peripheral Nav and Kv7 channels to alleviate neuropathic pain
Boxuan ZHANG ; Xiaoxing SHI ; Xingang LIU ; Yan LIU ; Xuedong LI ; Qi WANG ; Dongyang HUANG ; Weidong ZHAO ; Junru CUI ; Yawen CAO ; Xu CHAI ; Jiahao WANG ; Yang ZHANG ; Xiangyu WANG ; Qingzhong JIA
Journal of Pharmaceutical Analysis 2025;15(1):244-261
This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.
9.Microbial community mediated by microbial agents improves the quality of Epimedium pubescens Maxim.
Kunyang LAI ; Xiufu WAN ; Jiancai XIAO ; Hongyang WANG ; Shangxuan SHI ; Binbin YAN ; Chaogeng LYU ; Chengcai ZHANG ; Yufei ZHANG ; Feng YUAN ; Zhe ZHAO ; Shoudong ZHU ; Chuanzhi KANG ; Yan ZHANG
Science of Traditional Chinese Medicine 2025;3(3):270-281
Background: Optimizing cultivation techniques for traditional Chinese medicine has become a crucial means to improve the quality of medicinal materials. Microbial agents, as environmentally friendly and efficient plant growth promoters and soil conditioners, have increasingly attracted attention in eco-agriculture research. Objective: Our understanding remains limited regarding how the application of microbial agents, alone or in combination, affects changes in the rhizosphere microbiome and its association with the bioactive components of medicinal materials. Methods: In this study, Epimedium pubescens Maxim. was employed as a model plant to examine the effects of 2 microbial agents(Paenibacillus mucilaginosus and Bacillus subtilis) applied individually and in combination on plant growth and the accumulation of bioactive components. Additionally, this study explored the relationship between the rhizosphere microbiome and plant development. Results: The application of microbial agents increased the yield of E. pubescens leaves by 20.30% to 33.66% and enhanced the total flavonol glycosides content by 11.40% to 29.94%. Meanwhile, microbial treatments reshaped the rhizosphere microbiome, promoted the enrichment of beneficial microorganisms (e.g., Frankia and Paenibacillus), suppressed phytopathogenic fungi such as Didymella and Scytalidium, and enhanced the stability of the soil microbial co-occurrence network. The partial least squares path model suggested that microbial agents not only directly impact the quality of medicinal herbs but also indirectly alter the accumulation of bioactive components by modulating the soil microbiome. Conclusion: These findings deepen our understanding of the relationship between medicinal plant quality and rhizosphere microbiomes as mediated by microbial agents. They also provide a basis for designing and manipulating synthetic microbial communities to promote sustainable development in eco-agriculture.
10.Extraction of the ear canal centerline and rapid measurement of its length and curvature based on 3D reconstruction
Dashan CAO ; Yan YAN ; Miao ZHANG ; Yan SHI ; Jing MA ; Chenchen WANG ; Riyuan LIU ; Zibo LI ; Qiaohui LU ; Hui ZHAO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(11):1431-1438
Objective:To measure the length and curvature of the external auditory canal (EAC) centerline using a three-dimensional (3D) measurement method based on high-resolution computed tomography (HRCT).Methods:A retrospective analysis was conducted on HRCT images of healthy EAC from 49 patients (64 ears) examined at the Sixth Medical Center of the PLA General Hospital from June to October 2024. The cohort included 25 males (28 ears) and 24 females (36 ears), aged 22-78 years (mean age 47.3 years), categorized into age groups: 18-30 years (20 ears), 31-60 years (22 ears), and 61-80 years (22 ears). The EAC comprised 29 left and 35 right ears. 3D reconstruction of the EAC was performed using medical software (3D Slicer), and the central curve of the EAC was extracted using an improved measurement method to determine its length and curvature. Statistical analysis was performed using Origin Pro 2023 software to compare differences across genders, sides, and age groups.Results:The measurements of EAC length and curvature revealed that the EAC was significantly longer in males than in females (27.46 mm vs. 25.44 mm, P=0.014) and longer on the right side than on the left (27.99 mm vs. 25.87 mm, P=0.031). No statistically significant difference in EAC length was observed among the different age groups ( P>0.05). Furthermore, no statistically significant differences in EAC curvature were found regarding gender, side, or age group (all P>0.05). Conclusion:The HRCT-based 3D reconstruction technique enables the establishment of a rapid and effective automated workflow for extracting the central curve of the EAC and systematically measuring its length and curvature. The data obtained provide a reference and methodological support for further research on anatomical variations of the human EAC and its potential clinical applications, such as the design of otological instruments or surgical planning.

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