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.

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.

ObjectiveTo analyze the epidemiological trends and characteristics of brucellosis in humans (hereinafter referred to as brucellosis) in Tangshan City, Hebei Province from 2016 to 2023, and to provide a scientific basis for formulating brucellosis prevention and control strategies in the region. MethodsThe incidence data of human brucellosis in Tangshan City from 2016 to 2023 were collected from the China Disease Prevention and Control Information System. The diagnosis time, infection route, and clinical characteristics of the cases were obtained from the case investigation reports. Descriptive epidemiological methods were used to analyze the temporal, spatial, demographic distributions, and clinical characteristics of human brucellosis. Brucella species were identified using agglutination tests with bacterial suspension and A/M antigen-positive serum. ResultsA total of 2 193 cases of human brucellosis were confirmed and clinically diagnosed in Tangshan City from 2016 to 2023, with the peak incidence occured from March to August, and which exhibited distinct geographic distribution patterns. The highest incidence rate was found in people aged 60‒<70 years. The occupation of cases were primarily farmers. The incidence rate in males (528/100 000) was higher than that in females (184/100 000). All cases had confirmed exposure to infected animals or contaminated animal products. ConclusionThe epidemic of human brucellosis in Tangshan exhibited an overall steady downward trend from 2016 to 2023, except for a slight increase in 2016 and 2021, with the incidence rate controlled at 289/100 000‒335/100 000. The prevention and control situation of human brucellosis still remains severe, with the highest incidence rate in the eastern region of Tangshan, which are characterized by the breeding, slaughtering, and processing of cattle and sheep. Therefore, it it is necessary to enhance the prevention and control of human brucellosis among the personnel engaged in these industries in the eastern areas.

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Objective:To investigate the value of elevated preoperative troponin T (TnT) in predicting perioperative adverse cardiac events in geriatric hip fracture patients.Methods:A total of 273 elderly patients undergoing surgical treatment for hip fracture at Department of Cardiology, Tianjin Hospital between January 2024 and December 2024 were enrolled. Basic demographic information was recorded, and preoperative TnT levels were measured. Patients with elevated preoperative TnT ( n=114) were enrolled into the elevated group, while those with normal TnT ( n=159) were enrolled into the normal group. Fracture types included femoral neck fracture ( n=141) and intertrochanteric fracture ( n=132). The impact of elevated preoperative TnT on perioperative major adverse cardiovascular events (MACEs), as well as the influence of different fracture types on MACEs, were analyzed. Normally distributed continuous data were expressed as Mean±SD and compared by independent samples t-test. Categorical data were expressed as case(%) and compared by χ2 test. Multivariate binary logistic regression analysis was performed. The predictive value of TnT for MACEs was assessed by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results:The incidence of perioperative MACEs was significantly higher in the elevated TnT group (21.9%, 25/114) compared to the normal TnT group (3.1%, 5/159), with a statistically significant difference ( χ2=23.95, P<0.001). The comparison of postoperative MACEs incidence between different fracture types showed no statistically significant difference [12.1% (17/141) vs. 9.8% (13/132)] ( χ2=0.34, P=0.560). Multivariate binary logistic regression analysis indicated that elevated TnT level ( OR=8.633, 95% CI: 3.117-23.911, P<0.001) was an independent risk factor for perioperative major adverse cardiovascular events (MACEs), increasing the risk by 7.633 times compared to patients with normal TnT. A TnT threshold of ≥0.028 μg/L predicted MACEs with a sensitivity of 0.600 and specificity of 0.954 (AUC=0.839, 95% CI: 0.751-0.926, P<0.05). Conclusion:Troponin T can serve as an independent predictor of perioperative adverse cardiovascular events in elderly patients undergoing surgery for hip fracture and plays a crucial role in the perioperative cardiovascular risk assessment of these patients.

Paclitaxel(PTX)is a first-line chemotherapy drug for breast cancer,but its resistance issues significantly impact clinical treatment efficacy.Fucosylation,especially core fucosylation,is closely related to tumor chemoresistance,resulting in poor chemotherapy responses and poor prognosis in patients.In this study,we investigated the effect and mechanism of the fucosylation inhibitor 2-fluorofucose(2-F-Fuc)on the chemosensitivity of paclitaxel-resistant breast cancer MCF-7/PTX cells.The drug resistanceindex(RI)of MCF-7/PTX cells was 8.49 by MTT assays.Western blotting,real-time PCR,enzyme-linked immu-nosorbent assay(ELISA)and Lens Culinaris Agglutinin(LCA)lectin imprinting showed that compared with MCF-7 cells,the expression of FUT8,MDR1and core fucosylation in MCF-7/PTX cells was high.Western blotting showed that 2-F-Fuc had a significant inhibitory effect on the growth of MCF-7/PTX cells,and the expression levels of FUT8 and MDR1 were significantly down-regulated after 2-F-Fuc treatment,and the down-regulation was more pronounced in the PTX and 2-F-Fuc combination group(P＜0.05).Compared to the control,expression of PCNA in MCF-7/PTX cells in the PTX and the 2-F-Fuc group were down-regulated,and the apoptosis-related proteins,such as cleaved caspase-3 and Bax/Bcl-2 were in-creased.The level of p-PI3K and p-AKT were down-regulated,and the changes in the combination of 2-F-Fuc and PTX were more robust(P＜0.05).The above results showed that the core fucosylation level of MCF-7/PTX cells was significantly increased,and 2-F-Fuc could reduce the core fucosylation level of MCF-7/PTX cells by inhibiting the expression of FUT8,and enhance the sensitivity of drug-resistant cells to PTX,which may correlate with the downregulation of PI3K/AKT signaling pathway proteins.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.