Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

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.

Objective To investigate the epidemiological characteristics and changing trend of typhus in Shaanxi Province from 2005 to 2023 to provide a scientific basis for its prevention and control. Methods Excel 2007, SPSS 25.0, Joinpoint 4.9.1.0, and Geoda 1.6 were used for data collection and statistical analysis. Super Map was used for data visualization to describe the changing characteristics of the disease. Results A total of 394 typhus cases were reported in Shaanxi Province from 2005 to 2023. The average annual incidence of typhus was 0.054/100 000, showing a dynamic fluctuation trend(AAPC=-3.3, t=-0.3, P>0.05). The cases were mainly concentrated in Baoji, Hanzhong and Xi′an, accounting for 78.68%. The incidence peak was from May to October, accounting for 64.21% of annual incidence. The epidemic season was from May to October and December. The incidence of the disease was concentrated in the 40-69 age group, accounting for 58.88%, and the sex was 1.07:1. The main occupation was farmers, accounting for 72.08%. The median time from onset to diagnosis was 7 days. Global spatial autocorrelation analysis showed that there were significant spatial autocorrelations in 11 years from 2005 to 2023(P<0.05). Local spatial autocorrelation analysis detected a total of 43“high-high”clustering areas, mainly concentrated in Baoji City. Conclusions The overall incidence of typhus in Shaanxi Province showed a dynamic fluctuation trend, with notable seasonal and regional aggregation. The incidence of typhus was higher in middle-aged and elderly people in rural areas. Surveillance should be strengthened in typhus endemic areas in summer and autumn, and health education should be conducted for key population to form good health habits and reduce the incidence of typhus.

ObjectiveTo investigate the potential mechanisms underlying the therapeutic effects of Bushen Huoxue Formulation （补肾活血方， BSHXF） in Parkinson's disease （PD） from the perspectives of synaptic vesicle cycling and intestinal barrier function. MethodsForty-eight male SD rats were randomly divided into four groups， control group， model group， Madopar group， and BSHXF group， with 12 rats in each group. Except for the control group， rats were administered rotenone by gavage once daily for 4 consecutive weeks to establish a PD rat model. After successful modeling， rats in the BSHXF group received concentrated BSHXF solution by gavage at a dose of 13.5 g/（kg·d）， while rats in the Madopar group received Madopar tablet suspension at 2 g/（kg·d）. Rats in the control group and the model group were administered distilled water by gavage at 10 ml/（kg·d）. All groups received continuous gavage treatment for 2 weeks. Motor function was evaluated using the open field test （total distance traveled， average speed， and total distance traveled in the central zone）， rotarod test （latency to fall）， and balance beam test （traversal time）. Histopathological changes in colon tissues were observed by HE staining. Western Blotting was used to detect the protein levels of α-synuclein （α-syn）， phosphorylated serine 129 α-synuclein （pSer129-α-syn）， vesicle-associated membrane protein 2 （VAMP2）， and synaptophysin （SYP） in the substantia nigra and colon tissues. The mRNA expression levels of α-syn， VAMP2， and SYP were detected by RT-PCR， and α-syn expression was examined by immunohistochemistry. Immunofluorescence staining was performed to assess the levels of tight junction protein 1 （ZO-1） and occludin in colon tissues， as well as tyrosine hydroxylase （TH） levels in substantia nigra tissues. ResultsCompared with the control group， rats in the model group showed reduced total distance traveled， average speed， and central-zone distance in the open field test， decreased latency to fall in the rotarod test， and prolonged traversal time in the balance beam test. The protein levels of pSer129-α-syn and α-syn， as well as α-syn mRNA expression were increased in the substantia nigra and colon tissues， whereas the protein and mRNA expression levels of VAMP2 and SYP were decreased. The relative integrated optical density of α-syn in the substantia nigra and colon tissues was increased， while the relative fluorescence intensities of ZO-1 and occludin in colon tissues and TH in the substantia nigra were decreased （P＜0.05）. HE staining showed focal necrosis in the mucosal layer of colon tissues， disappearance of some intestinal glands， extensive inflammatory cell infiltration， and proliferation of fibrous connective tissue in the submucosa. Compared with the model group， both the Madopar group and BSHXF group showed varying degrees of improvement in the above indicators （P＜0.05）. Pathological damage in colon tissues was also alleviated， with only mild fibrous tissue proliferation and limited diffuse inflammatory cell infiltration observed in the mucosal layer. Compared with the Madopar group， rats in the BSHXF group exhibited increased average speed， central-zone distance， and latency to fall in the rotarod test. The levels of pSer129-α-syn and α-syn proteins in the substantia nigra were decreased， while VAMP2 protein expression was increased. In colon tissues， SYP protein levels and mRNA expression were elevated. The relative fluorescence intensity of ZO-1 in colon tissues and TH in substantia nigra tissues was also increased （P＜0.05）. ConclusionBSHXF may improve motor dysfunction in PD by regulating synaptic vesicle cycling， restoring intestinal barrier integrity， and improving neuronal synaptic function through modulation of synaptic vesicle-associated protein expression in the substantia nigra and colon tissues.

ObjectiveTo investigate the potential mechanisms underlying the therapeutic effects of Bushen Huoxue Formulation （补肾活血方， BSHXF） in Parkinson's disease （PD） from the perspectives of synaptic vesicle cycling and intestinal barrier function. MethodsForty-eight male SD rats were randomly divided into four groups， control group， model group， Madopar group， and BSHXF group， with 12 rats in each group. Except for the control group， rats were administered rotenone by gavage once daily for 4 consecutive weeks to establish a PD rat model. After successful modeling， rats in the BSHXF group received concentrated BSHXF solution by gavage at a dose of 13.5 g/（kg·d）， while rats in the Madopar group received Madopar tablet suspension at 2 g/（kg·d）. Rats in the control group and the model group were administered distilled water by gavage at 10 ml/（kg·d）. All groups received continuous gavage treatment for 2 weeks. Motor function was evaluated using the open field test （total distance traveled， average speed， and total distance traveled in the central zone）， rotarod test （latency to fall）， and balance beam test （traversal time）. Histopathological changes in colon tissues were observed by HE staining. Western Blotting was used to detect the protein levels of α-synuclein （α-syn）， phosphorylated serine 129 α-synuclein （pSer129-α-syn）， vesicle-associated membrane protein 2 （VAMP2）， and synaptophysin （SYP） in the substantia nigra and colon tissues. The mRNA expression levels of α-syn， VAMP2， and SYP were detected by RT-PCR， and α-syn expression was examined by immunohistochemistry. Immunofluorescence staining was performed to assess the levels of tight junction protein 1 （ZO-1） and occludin in colon tissues， as well as tyrosine hydroxylase （TH） levels in substantia nigra tissues. ResultsCompared with the control group， rats in the model group showed reduced total distance traveled， average speed， and central-zone distance in the open field test， decreased latency to fall in the rotarod test， and prolonged traversal time in the balance beam test. The protein levels of pSer129-α-syn and α-syn， as well as α-syn mRNA expression were increased in the substantia nigra and colon tissues， whereas the protein and mRNA expression levels of VAMP2 and SYP were decreased. The relative integrated optical density of α-syn in the substantia nigra and colon tissues was increased， while the relative fluorescence intensities of ZO-1 and occludin in colon tissues and TH in the substantia nigra were decreased （P＜0.05）. HE staining showed focal necrosis in the mucosal layer of colon tissues， disappearance of some intestinal glands， extensive inflammatory cell infiltration， and proliferation of fibrous connective tissue in the submucosa. Compared with the model group， both the Madopar group and BSHXF group showed varying degrees of improvement in the above indicators （P＜0.05）. Pathological damage in colon tissues was also alleviated， with only mild fibrous tissue proliferation and limited diffuse inflammatory cell infiltration observed in the mucosal layer. Compared with the Madopar group， rats in the BSHXF group exhibited increased average speed， central-zone distance， and latency to fall in the rotarod test. The levels of pSer129-α-syn and α-syn proteins in the substantia nigra were decreased， while VAMP2 protein expression was increased. In colon tissues， SYP protein levels and mRNA expression were elevated. The relative fluorescence intensity of ZO-1 in colon tissues and TH in substantia nigra tissues was also increased （P＜0.05）. ConclusionBSHXF may improve motor dysfunction in PD by regulating synaptic vesicle cycling， restoring intestinal barrier integrity， and improving neuronal synaptic function through modulation of synaptic vesicle-associated protein expression in the substantia nigra and colon tissues.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， with a complex pathogenesis. Mitochondria play a pivotal role in this disease process， and studies have confirmed that mitochondrial dysfunction can exacerbate metabolic disorders and induce innate immune imbalance， while mitochondrial DNA （mtDNA） is the core molecule mediating these two pathological effects. After the abnormal release of mtDNA， it can be recognized by intracellular pattern recognition receptors， which in turn triggers innate immune responses and causes tissue damage， forming a pathological pathway of “mtDNA release-immune activation-tissue damage”. Currently， there is a lack of systematic reviews summarizing the mechanism of action of this pathway in different stages of MAFLD and the intervention strategies targeting this pathway. This article systematically reviews the core molecular mechanism of this pathway， its pathological role in the development and progression of MAFLD， and the current intervention strategies targeting this mechanism， in order to provide a theoretical basis for analyzing the pathogenesis of MAFLD and developing novel therapeutic strategies.

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans ; Computational Biology ; Diabetic Nephropathies/physiopathology* ; Protein Interaction Maps ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Phagocytosis/genetics* ; Efferocytosis