Diabetic cardiomyopathy （DCM） is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM， the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion， and divides the pathological process into three phases： Gaozhuo invasion， turbid heat damage to the channels， and turbid blood stasis and heat junction. Among them， the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors， and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress， it eventually develops into a depletion of the heart Yang， leading to the ultimate regression of heart failure. According to the theory of Gaozhuo， traditional Chinese medicine （TCM） should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause， and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat， strengthening the spleen and tonifying the kidney， and clearing heat and resolving turbidity should be the therapy. If the turbidity， stasis， and heat are knotted in the heart and collaterals， strengthening the spleen and tonifying the kidney， and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity， benefiting Qi and clearing heat to resolve turbidity， and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors， improve the inflammatory damage to myocardium and blood vessels， myocardial fibrosis， and cardiac systole and diastole， and thus slow down the onset and progression of DCM.

Non-alcoholic fatty liver disease （NAFLD） is one of the most common complications of type 2 diabetes mellitus （T2DM）， and hepatic stellate cell （HSC） activation is the key link in the progression of NAFLD to liver fibrosis. According to the theory of "Gaozhuo"， spleen deficiency and Qi stagnation， along with Gaozhuo invasion， are the causes of NAFLD progression to liver fibrosis， which reveals the pathogenesis essence of HSC activation in traditional Chinese medicine （TCM）. Among them， spleen deficiency and Qi stagnation are the root causes of the endogenous formation of Gaozhuo. Spleen deficiency indicates the insulin sensitivity decrease and glucose metabolism disorders， and Qi stagnation means the dysregulation of hepatic glucose and lipid metabolism， which creates the preconditions for HSC activation. Gaozhuo invasion is the direct cause of HSC activation， including three stages： Internal retention of Gaozhuo， turbidity and stasis stagnation， and toxic stasis and consolidation. Internal retention of Gaozhuo refers to the abnormal metabolism and deposition of hepatic lipids， as well as the microcirculatory disorders. Turbidity and stasis stagnation is the process by which lipotoxicity stimulates the transformation of HSC into myofibroblast （MFB）， and toxic stasis and consolidation represent the secretion of a large amount of extracellular matrix （ECM） by MFB to promote the fibrosis. According to the theory of Gaozhuo and the activation process of HSC， syndromes for T2DM combined with NAFLD can be classified into spleen deficiency and Qi stagnation with internal retention of Gaozhuo， spleen Qi deficiency with turbidity and stasis stagnation， and spleen Qi deficiency with toxic stasis and consolidation. Clinically， the treatment principle is to strengthen the spleen and promote Qi， resolve turbidity， and eliminate blood stasis. Both TCM compounds and monomers can effectively inhibit the HSC activation. TCM compounds can be classified into categories for regulating spleen and harmonizing liver， resolving turbidity and removing stasis， and detoxifying and removing stasis. They mainly work by improving lipid metabolism， reducing lipid accumulation in the liver， alleviating inflammatory and oxidative stress responses， inhibiting the activation and proliferation of HSC， and reducing ECM deposition， thereby delaying the progression of liver fibrosis.

Objective: To explore the cross sectional and longitudinal associations between 24 hour movement behaviors and physical fitness in preschool children, and to adopt the method of equal time substitution analysis to evaluate the impact of time redistribution of different activity behaviors on physical fitness scores,so as to provide a scientific basis for promoting the health of preschool children. Methods: A total of 193 preschool children aged 3-6 years were selected from three Shanghai districts (Jing an, Baoshan, Jiading) from October to December 2023 by the stratified cluster random sampling method. The 24 hour movement behaviors were monitored via 7 day accelerometry, and physical fitness was measured according to the National Physical Fitness Measurement Standards (Revised 2023, preschool section). From October to December 2024, the follow up of physical fitness among preschool children used the same testing method. The comparison between groups was conducted by t-test. Compositional regression analyses evaluated the relationship of 24 hour movement behaviors and physical fitness among preschool children. Results: At baseline, moderate to vigorous physical activity (MVPA) time was significantly higher in boys [(84.10±25.78)min/d] than in girls [( 70.44± 25.98)min/d]; the composite physical fitness score was significantly higher in boys (71.65±8.69) than in girls (68.84±9.89), and the differences were statistically significant ( t =3.65, 2.10, both P <0.01). After adjusting for gender, age and body mass index, the results of component multiple linear regression analysis showed that MVPA time proportion was positively correlated with the composite physical fitness score at baseline among preschool children ( β =6.61), but was negatively correlated with two legged continuous hopping time at 1 year ( β =-1.12) (both P <0.05). Light physical activity (LPA) time proportion was negatively correlated with walking on the balance beam time at 1 year ( β =-4.44), and sedentary behavior (SB) time proportion was negatively correlated with the composite score of physical fitness at baseline ( β =-6.55) (both P <0.05). Isotemporal substitution analysis revealed that replacing 10 minutes of sleep (SP), SB, and LPA with MVPA increased the baseline physical fitness composite score by 0.750, 0.689 and 0.575 units, respectively; at 1 year follow up, the composite score increased by 1.440, 1.419 and 1.430 units, respectively (all P <0.05). Conversely, replacing MVPA with 10 minutes of SP, SB, and LPA,resulted in decreases in baseline physical fitness composite scores of 0.836, 0.777 and 0.669 units, and reductions of 1.613, 1.592 and 1.598 units at 1 year follow up (all P < 0.05 ). Conclusions Preschool children s 24 hour movement behaviors, especially MVPA, are closely related to physical health. Implementing appropriate strategies to increase physical activity and reduce sedentary time may improve the physical fitness of preschoolers.

Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging. However, investigations into the microstructural pathology of brain white matter (WM) associated with these deficits remain limited. This study aimed to examine the microstructural characteristics of WM in the non-demented population with abnormal color discrimination, utilizing Neurite Orientation Dispersion and Density Imaging (NODDI), and to explore their correlations with cognitive functions and cognition-related plasma biomarkers. The tract-based spatial statistic analysis revealed significant differences in specific brain regions between the abnormal color discrimination group and the healthy controls, characterized by increased isotropic volume fraction and decreased neurite density index and orientation dispersion index. Further analysis of region-of-interest parameters revealed that the isotropic volume fraction in the bilateral anterior thalamic radiation, superior longitudinal fasciculus, cingulum, and forceps minor was significantly correlated with poorer performance on neuropsychological assessments and to varying degrees various cognition-related plasma biomarkers. These findings provide neuroimaging evidence that WM microstructural abnormalities in non-demented individuals with abnormal color discrimination are associated with cognitive dysfunction, potentially serving as early markers for cognitive decline.
Humans ; White Matter/pathology* ; Male ; Female ; Cognitive Dysfunction/physiopathology* ; Middle Aged ; Aged ; Color Perception/physiology* ; Brain/pathology* ; Neuropsychological Tests ; Diffusion Tensor Imaging

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Objective:To investigate the killing effect of the oncolytic virus Rigvir on six different colorectal cancer cell lines in vitro and differences in the sensitivity of different cell lines to Rigvir,to analyze the differentially expressed genes and signaling pathways be-tween sensitive and insensitive cells and the reasons for such differences,to explore the killing mechanism of the oncolytic virus Rigvir on colorectal cancer cells based on experimental results,and to lay a theoretical foundation for the use of the oncolytic virus Rigvir as a novel immunotherapeutic drug for the treatment of colorectal can-cer.Methods:Cell Counting Kit-8(CCK-8)assay was used for quantitative assessment of the inhibition rate of Rigvir on cells,and the Annexin V-FITC\PI method was used to measure the apoptosis rate of sensitive cell lines and preliminarily analyze its killing mechanism.Bioinformatics techniques were used to investigate the differentially expressed genes and signaling pathways between sensitive and insensitive cells,and Western blot experiments were used for validation and detecting the expression of apoptosis factors.High expression of upstream factors in differential signaling pathways,and application of real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and WB to detect the effect of Rigvir on the expression levels of target genes and proteins in overexpressing sensitive cell lines.Results:SW480 and HT29 were sensitive to the oncolytic virus Rigvir,others had relatively insensi-tive(P<0.001).However,the inhibitory effect of Rigvir with two concentration gradients on HT29 was more significant(P<0.001).After 48 hours of infection,the cell inhibition rate of SW480 cells no longer increased with the prolongation of infection time(F=52.010,P=0.147),but it was more sensitive to changes in virus concentration(F=13.490,P<0.001).On the contrary,changes in virus concentration had no significant effect on the inhibition rate of HT29 cells(F=8.450,P=0.281),but the inhibition rate continued to in-crease after 48 hours with the prolongation of infection time(F=24.380,P<0.001).The apoptosis rate of sensitive group cells gradually increased with the prolongation of infection time(P<0.001),which mainly characterized by late stage apoptosis and necrotic cells.Through bioinformatics techniques,significant differences were observed in the classic PI3K/Akt/mTOR signaling pathway between the sensitive and insensitive groups.Western blot experiments showed that after the application of Rigvir,the upstream protein expression of PI3K/Akt/mTOR in the sensitive cell group was significantly reduced(P<0.001).The expression levels of apoptosis factors caspase-3 and caspase-8 increased,while the Bcl-2/Bax ratio decreased(P<0.001).The results of RT-qPCR and Western blot showed that after Rigvir was applied to the sensitive cell line HT29 overexpression type,the expression levels of PI3K/Akt/mTOR upstream and downstream signaling molecules(Akt,4EBP1,and p70S6K)were significantly reduced compared to the control group(P<0.05).Conclusion:Rigvir can effectively kill some colorectal cancer cell lines(SW480,HT29)in vitro,its mechanism of action is partially in-duced by the PI3K/Akt/mTOR classical signaling pathway to induce cell apoptosis.

Objective To investigate the changes in the tumor microenvironment of pancreatic cancer(PDAC)complicated with diabetes mellitus(DM)in a mouse model of hyperglycemia and orthotopic pancreatic cancer by analyzing transcriptome and single-cell transcriptome data in order to identify potential therapeutic targets.Method By integrating single-cell transcriptome and bulk transcriptome data,bioinformatics analysis was conducted to compare the characteristics of tumor cells and tumor immune microenvironment between PDAC patients with DM(DM group)and those without DM(non-DM group).Twenty male C57BL/6 mice(6 weeks old,weighing 18～20 g)were randomly divided into a hyperglycemic group[STZ group,continuous intraperitoneal injection of 50 mg/kg streptozocin(STZ)(final concentration of 1％)dissolved in citrate buffer],and a control group(Control group,an equivalent volume of citrate buffer without STZ at the same time points),with 10 mice in each group.Tail-tip blood glucose level was measured to monitor glycemic status.After orthotopic inoculation of pancreatic cancer cells in both Control and STZ groups,tumor-infiltrating immune cells were harvested.Flow cytometry was employed to determine the effects of hyperglycemia on:total CD8+T cell and Treg cell populations;CD8+T cell subsets expressing Ki67,TNF-α,granzyme B(GZMB)and IFN-γ;surface expression of PD-1,lymphocyte activation gene-3(LAG-3)and T cell immunoglobulin and mucin domain-3(Tim-3)on CD8+T cells;programmed death-ligand 1(PD-L1)expression on tumor cells;and tumor-associated macrophage surface expression of major histocompatibility complex classⅠ(MHC-Ⅰ)and cluster of differentiation 206(CD206).Results Bioinformatics analysis revealed that,compared to the non-DM group,the genes significantly up-regulated in the DM group were associated with poor prognosis(P＜0.001).The proportion of type 2 ductal cells was increased in the DM group,exhibiting higher levels of copy number variation(P＜0.001).In the tumor immune microenvironment of the DM group,there was an increase in the proportion of Treg cells(P＜0.05)and an elevated exhaustion score for CD8+T cells(P＜0.001),accompanied by down-regulated expression of effector molecules,up-regulated expression of inhibitory checkpoints,and a significant increase in the M2 score of M2-like macrophages(P＜0.001).Animal experiments and flow cytometry found that,compared to the Control group,the STZ group had a shorter survival time(P＜0.001),with decreased proportions of total CD8+T cells(P＜0.01)and CD8+T cells expressing Ki67,TNF-α,GZMB and IFN-γ(P＜0.01),increased proportion of Treg cells(P＜0.001),up-regulated expression of PD-1,LAG-3 and Tim-3 on the surface of CD8+T cells(P＜0.001),and up-regulation of PD-L1 on tumor cell surface(P＜0.001)and enhanced expression of CD206 on the surface of tumor-associated macrophages,while down-regulated expression of MHC-Ⅰ(P＜0.001).Conclusion High glucose promotes the formation of an immunosuppressive microenvironment in PDAC,and targeting type 2 ductal cells and immunosuppressive cells in the tumor microenvironment,combined with dual immune checkpoint antibody therapy,may improve patient prognosis.

Objective To integrate multi-source heterogeneous literature data from China Na-tional Knowledge Infrastructure(CNKI),Wanfang,VIP,and Web of Science(WoS)databases u-sing bibliometric methods,and to comparatively analyze the differences in knowledge structure charac-teristics and evolutionary pathways of organoid research between China and foreign countries.Meth-ods CiteSpace software was employed to conduct a visual atlas analysis of the publication volume,countries,institutions,authors,and keywords of 1,118 Chinese literatures and 10,871 English lit-eratures.Results China ranked the second globally in terms of publication volume(accounting for 22.09％),but exhibited low centrality in international collaboration networks.The density of the do-mestic institutional collaboration network was 0.003,indicating a relatively loose structure,with Fudan University leading domestic output with 15 Chinese papers.Keyword emergence analysis revealed that"organ-on-a-chip"and"biomechanics"have emerged as new hotspots since 2024.Conclusion It is recommended to establish an interdisciplinary collaborative innovation alliance to focus on break-throughs in the translational directions of organ-on-a-chip and biomechanics,thereby addressing the imbalance between"scale and quality"in China's organoid research.

Oncomelania hupensis snail control by chemical treatment is an important approach for control and elimination of snails, and an appropriate apparatus for spraying chemicals is an important support to molluscicidal effects. Nevertheless, the research and evaluation of molluscicidal apparatuses have not been paid high attention in the schistosomiasis control programme for a long period of time. Currently, agricultural plant-protective apparatuses have been widely used for chemical treatment. This comment provides a short overview of the application of drones in O. hupensis snail control by chemical treatment, and proposes suggestions for solving the problems of use of drones in O. hupensis snail control by chemical treatment in China.

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.