The multimorbidity of rheumatoid arthritis （RA） and periodontitis （PD） has drawn increasing attention， as both conditions are characterized by chronic inflammation， immune dysregulation， and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development， and their coexistence mutually exacerbates disease progression. However， traditional Chinese medicine （TCM） currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study， based on the TCM theory of abnormal collateral， thoroughly examines the intrinsic connection between RA and PD multimorbidity， proposing "abnormal collateral as the pivot， with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral"， where its pathogens act as toxic factors that invade the joints through collaterals， triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows： the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation， leading to collateral malnutrition； heat-toxins traversing collaterals induce collateral hyperactivity， resulting in pathological angiogenesis； ultimately， toxin accumulation at the pivotal abnormal collateral site erodes bone， activating the receptor activator of nuclear factor kappa-B ligand （RANKL）-receptor activator of nuclear factor kappa-B （RANK） signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology， immune-inflammation， and bone metabolism， offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity， the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs"， along with TCM therapeutic principles such as "unblocking， clearing， and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration， thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.

The multimorbidity of rheumatoid arthritis （RA） and periodontitis （PD） has drawn increasing attention， as both conditions are characterized by chronic inflammation， immune dysregulation， and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development， and their coexistence mutually exacerbates disease progression. However， traditional Chinese medicine （TCM） currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study， based on the TCM theory of abnormal collateral， thoroughly examines the intrinsic connection between RA and PD multimorbidity， proposing "abnormal collateral as the pivot， with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral"， where its pathogens act as toxic factors that invade the joints through collaterals， triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows： the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation， leading to collateral malnutrition； heat-toxins traversing collaterals induce collateral hyperactivity， resulting in pathological angiogenesis； ultimately， toxin accumulation at the pivotal abnormal collateral site erodes bone， activating the receptor activator of nuclear factor kappa-B ligand （RANKL）-receptor activator of nuclear factor kappa-B （RANK） signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology， immune-inflammation， and bone metabolism， offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity， the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs"， along with TCM therapeutic principles such as "unblocking， clearing， and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration， thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.

Objective To analyze survival outcomes and influencing factors among patients with colorectal cancer in Yunnan Province. Methods Clinical data were retrospectively collected from 4 892 patients with colorectal cancer. Survival data were obtained through follow-up. Overall survival (OS) was calculated by using the Kaplan-Meier method. Univariate analysis was performed by applying the log-rank test. Meanwhile, multivariate analysis employed the Cox proportional hazards regression model. Results The 1-, 3-, 5-, and 10-year OS rates for the entire cohort were 91.90%, 74.40%, 64.40%, and 28.70%, respectively. Univariate analysis revealed that age, ethnicity, region, differentiation grade, TNM stage, clinical stage, metastatic status, histological type, and treatment modality (chemotherapy, radiotherapy, and surgery) were associated with patient prognosis (all P<0.05). Multivariate analysis identified age (HR=1.250), region (HR=1.262), differentiation grade (HR=0.761), clinical stage (HR=3.128), and treatment modality (chemotherapy, HR=0.644; radiotherapy, HR=1.605; surgery, HR=0.384) as independent factors affecting survival prognosis in patients with colorectal cancer (all P<0.001). Conclusion Age, region, clinical stage, and treatment modality are independent factors influencing survival among patients with colorectal cancer in Yunnan Province. In clinical practice, these factors should be integrated to develop individualized prevention and treatment strategies, thereby improving patient outcomes.

The therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with intestinal probiotics on the wound healing of diabetic mice and its potential mechanism were explored. A diabetic wound mouse model was established, and 25 male C57BL/6J mice were randomly divided into five groups: blank control group, model group, hUCMSCs treatment group, probiotics treatment group, and hUCMSCs combined with probiotics treatment group. The wound healing conditions were photographed and recorded on days 0, 3, 6, 9, and 12 after modeling, and the differences in wound healing rates among the groups were analyzed. HE and Masson staining were used to observe the histopathological changes and collagen deposition. CD31 immunofluorescence was used to detect angiogenesis. Collagen I immunohistochemistry was used to evaluate the formation of type I collagen. ELISA was used to detect the expression levels of anti-inflammatory factors (Arg1) and pro-inflammatory factors (IL-6, IL-1β, TNF-α) in wounded skin tissue and serum. The results showed that on day 12 after modeling, compared with the other groups, the combined treatment group had the most significant wound contraction and the fastest healing rate. HE and Masson staining showed that the combined treatment group had the fastest epithelialization and the most collagen deposition. Immunofluorescence and immunohistochemistry showed that the combined treatment group had the highest expression levels of CD31 and Collagen I. ELISA results indicated that the combined treatment group had higher expression levels of Arg1 in wound skin tissue and serum than the other groups, while the expression levels of IL-6, IL-1β, and TNF-α were significantly lower. These results suggest that the combined treatment of hUCMSCs and intestinal probiotics can accelerate wound healing in diabetic mice through mechanisms such as promoting angiogenesis, enhancing collagen deposition, and regulating the inflammatory microenvironment. The therapeutic effect was significantly better than that of single treatment, providing a new potential strategy for the clinical treatment of diabetic foot.

Objective: To investigate the association of the joint effect of body fat levels and dyslipidemia with cardiovascular structural abnormalities in children, so as to provide a scientific reference for the early prevention of cardiovascular damage. Methods: Based on the data from the second follow up (October 2021 to January 2022) of the Huantai Children Cardiovascular Health Follow up Cohort, 1 308 children with complete data were included. The fat mass percentage (FMP), fat mass index (FMI), subcutaneous fat mass (SFM) and visceral fat mass (VFM), left ventricular mass index (LVMI), relative wall thickness (RWT), thickening of carotid intima-media thickening (cIMT) , left ventricular hypertrophy (LVH) and left ventricular geometric remodeling (LVG), triglyceride (TG), total cholesterol (TC) ,high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were obtained. Multivariable Logistic regression model was used to analyze the associations of FMP, FMI, SFM and VFM with thickening of cIMT, LVH and LVG. The joint effects of these body fat indicators and dyslipidemia on the aforementioned cardiovascular outcomes were further explored. Restricted cubic spline model was used to examine the dose response relationships between body fat levels and cardiovascular structural abnormalities. Results: Elevated body fat levels were significantly associated with an increased risk of cardiovascular structural abnormalities, exhibiting J shaped dose response relationships (all P <0.05). Compared with the group with normal body fat and normolipidemia, the risks of thickening of cIMT, LVH, and LVG in the group with elevated FMP combined with dyslipidemia were higher[ OR (95% CI )=11.70 (6.49-21.27), 5.53 (2.97-10.17), 2.33 (1.30-4.05)]; in the group with elevated FMI combined with dyslipidemia, the corresponding risks were higher[ OR (95% CI )= 11.68 (6.43-21.38), 6.98 (3.73-12.92), 2.65 (1.50-4.61)]; in the group with elevated SFM combined with dyslipidemia, the corresponding risks were higher[ OR (95% CI )=10.55 (5.83-19.24), 5.11 (2.71-9.45), 1.99 (1.11- 3.46 )]; and in the group with elevated VFM combined with dyslipidemia, the corresponding risks were higher[ OR (95% CI )=12.44 (6.76-23.14), 6.17 ( 3.31 -11.38), 2.30 (1.30-3.99)] (all P <0.05). Sex stratified analyses showed that the risk of thickening of cIMT in the combined exposure group of all four body fat indicators and dyslipidemia was significantly higher in girls than in boys (all P <0.01). Conclusions Elevated body fat levels and dyslipidemia have a combined effect in children, collectively increasing the risk of cardiovascular structural abnormalities. Prevention of cardiovascular damage in children should focus on both adiposity management and blood lipid regulation.

ObjectiveTo investigate the incidence and influencing factors of posttraumatic stress disorder （PTSD） three months after a traffic accident， and to explore the role of social support and coping strategies. MethodsA total of 117 individuals exposed to trauma following road traffic accidents were recruited. General demographic and clinical information was collected within one week， and the hamilton anxiety rating scale （HAMA）， the hamilton depression rating scale-24 （HAMD-24）， the social support rating scale （SSRS）， and the simplified coping style questionnaire （SCSQ） were administered. A 3-month follow-up was subsequently conducted， during which PTSD symptoms were assessed using the post-traumatic stress disorder checklist for DSM-5 （PCL-5）. Participants were divided into a PTSD group and a non-PTSD group according to whether PTSD occurred. Between-group comparisons were performed using the Mann-Whitney U non-parametric test or the χ² test， as appropriate. Spearman correlation analysis was used to examine the associations between general characteristics and PCL-5 scores. Binary Logistic regression was applied to identify factors influencing PTSD， and receiver operating characteristic （ROC） curve analysis was conducted to evaluate the diagnostic value of the SCSQ and SSRS. ResultsDuring the 3-month follow-up of the 117 trauma-exposed individuals， 17 cases developed PTSD， with a higher proportion of females （70.59%）. Between-group comparisons showed that， compared with the PTSD group， the non-PTSD group had higher scores for positive coping， objective support， and subjective support （P<0.05）， and lower scores for negative coping， HAMA， HAMD， and PCL-5 （P<0.05）. Correlation analysis indicated that female gender， negative coping， and higher HAMA and HAMD scores were associated with greater PTSD severity. Logistic regression analysis demonstrated that educational level （OR=1.715， 95% CI： 1.020-2.883， P=0.042） and negative coping （OR=1.590， 95% CI： 1.003-2.522， P=0.048） were risk factors for PTSD， whereas objective support （OR=0.646， 95% CI： 0.451-0.925， P=0.017） was a protective factor. The ROC analysis showed that the total SCSQ score and its negative and positive coping dimensions， the total SSRS score and its subjective and objective support dimensions， as well as their combined use， all demonstrated good discriminative ability in distinguishing between the PTSD and non-PTSD groups. ConclusionThe results suggest that individuals who are female， with higher HAMA and HAMD scores after a motor vehicle accident， and those with lower social support and negative coping strategies， should be given particular attention. Early interventions for these individuals may reduce the incidence of PTSD.

The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP₆), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP₆-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.

Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.

Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.