1.From Metabolic Reprogramming to Lactylation: Targeting Dilemmas and Breakthrough Directions in Colorectal Cancer
Xin ZHANG ; Zhao-Huan LI ; Jing-Wen ZHAO ; Jie DU ; Feng GAO
Progress in Biochemistry and Biophysics 2026;53(8):2123-2146
Colorectal cancer (CRC) is characterized by persistently high incidence and mortality. Current therapies are limited by drug resistance and modest patient benefit, underscoring the urgent need for new perspectives rooted in tumor biology. The unique metabolic landscape of CRC makes it an ideal model in which to dissect the pathological roles of lactylation regulatory networks: microsatellite-stable (MSS) CRC, which accounts for approximately 85% of cases, concurrently upregulates glycolysis and oxidative phosphorylation, engaging in intense metabolic competition with immune cells; the intratumoral lactate pool exhibits a distinctive “dual-source supply” feature—in addition to tumor-intrinsic glycolysis, substantial exogenous lactate is provided by gut microbiota dysbiosis and by colonizing bacteria within liver metastases; high-frequency oncogenic mutations and lactylation modifications establish a feed-forward circuit of “oncogene-driven lactate accumulation-lactylation-facilitated tumor progression”. Moreover, MSS CRC displays near-complete unresponsiveness to immune checkpoint inhibitors, a phenomenon underpinned by multiple immune evasion mechanisms mediated by lactate and lactylation. Lactate metabolism is a hallmark of metabolic reprogramming in cancer. Lactate homeostasis provides tumor cells with metabolic substrates, modulates redox status, and regulates fatty acid metabolism to promote malignant progression. Notably, lactate can drive lactylation—an emerging post-translational modification (PTM) in which lactyl groups are attached to lysine residues, dynamically governing gene transcription and protein function and thereby establishing a bridge between metabolism and epigenetics. Lactate and lactylation form a multidimensional, coordinated network: lactylation of key metabolic enzymes such as LDHA reinforces a positive feedback loop that sustains lactate production; lactylation of upstream transcription factors such as HIF-1α drives metabolic reprogramming; furthermore, lactylation engages in crosstalk with m6A and m5C RNA modifications as well as with other PTMs such as acetylation, profoundly reshaping cellular behavior. In CRC, histone lactylation drives malignant phenotypes by activating immunosuppressive programs, inhibiting ferroptosis, and promoting invasion and migration; non-histone lactylation accelerates translation elongation, stabilizes β‑catenin, maintains redox homeostasis, and prevents PD-L1 degradation, thereby facilitating tumor progression. Lactylation-related gene signatures have demonstrated potential for prognostic stratification. Therapeutic strategies targeting the lactylation network range from upstream metabolic intervention to modulation of the modifying enzymes and direct blockade of lactylation modifications, forming a hierarchical interventional framework. However, current evidence derives predominantly from cell lines and xenograft models, and a causal relationship between lactylation and malignant progression in CRC has yet to be rigorously established. Whether inhibition of lactylation can alter CRC phenotypes independently of metabolic alterations and acetylation fluctuations remains a central unanswered question in the field. This review systematically examines the research progress and translational challenges surrounding lactylation regulatory networks, aiming to provide a circumspect assessment to inform the development of novel therapeutic strategies for CRC.
2.Proteomic Profiling of Qi-blood Deficiency vs Damp-heat Syndrome in Colorectal Cancer: Therapeutic Targeting by Astragaloside IV-berberine
Zhao-Huan LI ; Jing-Wen ZHAO ; Xin ZHANG ; Jian-Jin GUO ; Jie XU ; Zeng-Qiang YANG ; Hao TU ; Min ZOU ; Ming-Bin GUI ; Feng GAO
Progress in Biochemistry and Biophysics 2026;53(9):2462-2479
ObjectiveColorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a “syndrome-differential protein-herbal component” network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. MethodsTumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the anti-proliferative activities of these compounds in vitro. ResultsA total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF‑κB signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than -5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC50 value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. ConclusionCRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.
3.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.
4.Identification of core genes of osteoarthritis by bioinformatics
Xuekun ZHU ; Heng LIU ; Hui FENG ; Yunlong GAO ; Lei WEN ; Xiaosong CAI ; Ben ZHAO ; Min ZHONG
Chinese Journal of Tissue Engineering Research 2025;29(3):637-644
BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.
5.Influencing factors of overactive bladder in college freshmen and the impacts on anxiety,quality of life,and social interaction
Guowei SI ; Ce GAO ; Sida SHAO ; Feng SI ; Yakai LIU ; Songyang WANG ; Maochuan FAN ; Huiqing ZHANG ; Qifeng DOU ; Jianguo WEN
Journal of Modern Urology 2025;30(6):513-519
Objective: To investigate the influencing factors of overactive bladder (OAB) in college freshmen and the impacts of OAB on their mental health, quality of life and social interaction. Methods: An epidemiological questionnaire survey was conducted in an anonymous manner on the prevalence of OAB among 5300 freshmen aged 17 to 22 years enrolled in the 2023—2024 academic year in Xinxiang Medical University and Sanquan College of Xinxiang Medical University.The questionnaire included questions on basic information, history of urinary tract infection, constipation, smoking, history of alcohol consumption, history of coffee/strong tea drinking, history of carbonated beverage drinking, redundant prepuce, phimosis, holding urine, chronic insomnia, self-rating anxiety scale (SAS), quality of life score (QoL), and social avoidance and distress scale (SADS).The influencing factors of OAB were analyzed with multivariate logistic regression analysis.The subjects were grouped according to whether they had OAB, and the differences in SAS, QoL and SADS between the OAB group and non-OAB group were compared.The impacts of OAB on the anxiety level, quality of life, and social interaction were analyzed with multiple linear regression analysis. Results: The overall prevalence rate of OAB was 4.9% (244/5018).Multivariate logistic regression analysis showed that the history of urinary tract infection (OR=0.177), constipation (OR=0.636), smoking (OR=0.582), alcohol consumption (OR=0.685), coffee/strong tea drinking (OR=0.387), carbonated beverage drinking (OR=0.631), redundant prepuce (OR=0.673), phimosis (OR=0.311), urine holding (OR=0.593), and chronic insomnia (OR=0.256) were influencing factors for the occurrence of OAB (P<0.05).The OAB group had higher SAS score [(41.18±6.54) vs. (38.61±6.36)], QoL score [(3.65±1.20) vs. (2.79±0.95)], social avoidance score [(6.25±1.86) vs. (5.86±1.51)], social distress score [(6.27±1.59) vs. (5.97±1.32)], and total SADS score [(12.51±2.35) vs. (11.84±2.01)] than the non-OAB group (P<0.05).The results of multiple linear regression analysis showed that OAB could independently affect the scores of QoL, SAS, and SADS.The OAB group had higher scores of QoL, SAS, and SADS compared with the non-OAB group (P<0.001). Conclusion: History of urinary tract infection, constipation, smoking, alcohol consumption, coffee/strong tea drinking, carbonated beverage drinking, redundant prepuce, phimosis, urine holding, and chronic insomnia are influencing factors for the occurrence of OAB in male college students.Moreover, OAB has negative impacts on their mental health, quality of life, and social interaction.
6.Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough: a randomized controlled trial.
Mingjie TANG ; Wen LU ; Xiaoni ZHANG ; Jiawei GAO ; Xinchang WEI ; Jin LU ; Jia ZHU ; Yulu FENG ; Lejing JIAO ; Xiaofang XIA ; Zhi ZHOU ; Zhaoming CHEN
Chinese Acupuncture & Moxibustion 2025;45(8):1047-1052
OBJECTIVE:
To observe the clinical efficacy of acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough (GERC).
METHODS:
A total of 120 GERC patients were randomly assigned to an observation group (60 cases, 1 case dropped out) and a control group (60 cases, 1 case was eliminated). The observation group received acupoint thread-embedding treatment at positive response points of governor vessel. If no such points were detected, the following acupoints were used: Dazhui (GV14), Fenghu (Extra), Shendao (GV11), Lingtai (GV10), and Zhiyang (GV9). Treatment was administered once every two weeks. The control group received oral rabeprazole enteric capsules at 20 mg twice daily. All the treatment was given for 6 weeks. Clinical outcomes were assessed using cough symptom score, reflux disease questionnaire (RDQ) score, and Leicester cough questionnaire (LCQ) score before and after treatment in the two groups. Clinical efficacy was also compared between the two groups.
RESULTS:
After treatment, both groups showed decreased cough symptom scores and the each item scores and total scores of RDQ (P<0.001), and increased LCQ scores (P<0.001) compare with those before treatment. The observation group exhibited lower cough symptom score and chest pain, reflux and total score of RDQ, and higher LCQ score compared to those in the control group (P<0.05). The total effective rate in the observation group was 94.9% (56/59), which was higher than 84.7% (50/59) in the control group (P<0.05).
CONCLUSION
Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux could effectively alleviate cough and reflux symptoms in patients with GERC and improve their quality of life.
Humans
;
Acupuncture Points
;
Gastroesophageal Reflux/physiopathology*
;
Male
;
Female
;
Cough/physiopathology*
;
Middle Aged
;
Aged
;
Acupuncture Therapy
;
Adult
;
Treatment Outcome
;
Lung/physiopathology*
;
Meridians
7.Research progress of the dopamine system in neurological diseases.
Yu-Qi NIU ; Jin-Jin WANG ; Wen-Fei CUI ; Peng QIN ; Jian-Feng GAO
Acta Physiologica Sinica 2025;77(2):309-317
The etiology of nervous system diseases is complicated, posing significant harm to patients and often resulting in poor prognoses. In recent years, the role of dopaminergic system in nervous system diseases has attracted much attention, and its complex regulatory mechanism and therapeutic potential have been gradually revealed. This paper reviews the role of dopaminergic neurons, the neurotransmitter dopamine, dopamine receptors and dopamine transporters in neurological diseases (including Alzheimer's disease, Parkinson's disease and schizophrenia), with a view to further elucidating the disease mechanism and providing new insights and strategies for the treatment of neurological diseases.
Humans
;
Dopamine/metabolism*
;
Nervous System Diseases/physiopathology*
;
Parkinson Disease/physiopathology*
;
Receptors, Dopamine/metabolism*
;
Dopaminergic Neurons/physiology*
;
Dopamine Plasma Membrane Transport Proteins/metabolism*
;
Alzheimer Disease/physiopathology*
;
Schizophrenia/physiopathology*
;
Animals
8.Health Risks from Exposure to PM 2.5-bound Polycyclic Aromatic Hydrocarbons in Fumes Emitted from Various Cooking Styles and Their Respiratory Deposition in a City Population Stratified by Age and Sex.
Jun Feng ZHANG ; Xi CHEN ; Ke GAO ; Shui Yuan CHENG ; Wen Jiao DUAN ; Li Ying FU ; Jian Jia LI ; Shu Shu LAN ; Cui Lan FANG
Biomedical and Environmental Sciences 2025;38(10):1230-1245
OBJECTIVES:
To characterize fine particulate matter (PM 2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups.
METHODS:
Sixteen PM 2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM 2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions.
RESULTS:
The total concentrations of PM 2.5-bound PAHs ranged from 61.10 to 403.80 ng/m 3. Regardless of cooking styles, the ILCR total values for adults (1.23 × 10 -6 to 3.70 × 10 -6) and older adults (1.28 × 10 -6 to 3.88 × 10 -6) exceeded the acceptable limit of 1.00 × 10 -6. With increasing age, the ILCR total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children.
CONCLUSION
ILCR total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans
;
Polycyclic Aromatic Hydrocarbons/analysis*
;
Cooking/methods*
;
Male
;
Female
;
Particulate Matter/analysis*
;
Adult
;
Child
;
Middle Aged
;
Air Pollutants/analysis*
;
Adolescent
;
Air Pollution, Indoor/analysis*
;
Young Adult
;
Child, Preschool
;
Aged
;
China
;
Inhalation Exposure
;
Age Factors
;
Sex Factors
;
Cities
;
Infant
9.Research Progress in the Impact of Accelerated Rehabilitation on Bone Tunnel Enlargement After Anterior Cruciate Ligament Reconstruction.
Wen-Bo TANG ; Feng GAO ; Xiao-Han ZHANG ; Bing-Ying ZHANG ; Hao DUAN ; Jing-Bin ZHOU
Acta Academiae Medicinae Sinicae 2025;47(4):634-643
This paper explores the impacts of accelerated rehabilitation protocols following anterior cruciate ligament reconstruction(ACLR)on bone tunnel enlargement(BTE).While accelerated rehabilitation can shorten the recovery time and improve the knee function,it may increase the risk of BTE.In the early rehabilitation phase after ACLR,excessive early weight-bearing and rapid progression of knee flexion angles should be avoided,along with the proper use of braces.Continuous passive motion is not recommended in the early phase post-ACLR to prevent potential effects on BTE.Further research is needed to investigate the mechanisms of BTE and develop more effective rehabilitation strategies.This will help to select appropriate rehabilitation protocols for patients and balance functional recovery with the risk of BTE,thereby reducing the revision rate and improving postoperative outcomes.
Humans
;
Anterior Cruciate Ligament Reconstruction/rehabilitation*
10.Simultaneous content determination of sixteen constituents in Jiawei Huoxiang Zhengqi Soft Capsules by UPLC-MS/MS
Qian WANG ; Xia GAO ; Jian FENG ; Bin JIN ; Xia-lin CHEN ; Liang CAO ; Ji-feng LI ; Yong-wen ZHANG ; Zhen-zhong WANG
Chinese Traditional Patent Medicine 2025;47(5):1431-1436
AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin,liquiritin apioside,verbascoside,narirutin,isoacteoside,apigetrin,hesperidin,isoliquiritin,ononin,liquiritigenin,glycyrrhizic acid,isoliquiritigenin,honokiol,obovatol,pogostone and magnolol in Jiawei Huoxiang Zhengqi Soft Capsules.METHODS The analysis was performed on a 40 ℃ thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r>0.990 0),whose average recoveries were 83.74%-105.12%with the RSDs of 1.10%-4.8%.CONCLUSION This accurate,sensitive,stable and reproducible method can provide a reference for the overall quality control of Jiawei Huoxiang Zhengqi Soft Capsules.

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