This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

ObjectiveTo observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pathway and epithelial-mesenchymal transition （EMT） in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a prednisone acetate group （1.17 mg·kg^-1）， and low- and high-dose Yifei Tongluo prescription groups （10.62 and 21.24 g·kg^-1， respectively）. Administration started on the 7th day after modeling， once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin （HE） staining and Masson staining. The expression of α-smooth muscle actin （α-SMA） and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome， E-cadherin （E-cad）， and typeⅠ collagen （ColⅠ） in lung tissues was detected by immunofluorescence. The content of hydroxyproline （HYP）， tumor necrosis factor （TNF）-α， interleukin （IL）-18， and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， IL-1β， and transforming growth factor （TGF）-β₁ in rat lung tissues were determined by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NLRP3， GSDMD， ASC， and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group， the model group exhibited a significantly increased lung coefficient （P<0.01） and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition， the levels of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissues were significantly increased （P<0.01）. The levels of fibrosis- and inflammation-related factors HYP， TNF-α， IL-18， and IL-1β in serum were significantly upregulated （P<0.01）. The levels of factors related to the activation of NLRP3 inflammasome in lung tissues， including NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁， were significantly upregulated （P<0.01）. Compared with the model group， the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally， the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissue was significantly decreased （P<0.01）. The levels of HYP， TNF-α， IL-18， and IL-1β in serum were significantly reduced （P<0.01）. The expression levels of NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁ in lung tissue were also significantly decreased （P<0.01）. ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway， down-regulate release of pro-inflammatory and pro-fibrotic cytokines， alleviate NLRP3 inflammasome-mediated pyroptosis and EMT， and thereby improve pulmonary fibrosis in rats.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease mediated by T lymphocytes， and it can progress to liver cirrhosis or even liver failure without timely intervention. As a natural flavonoid compound， naringenin （NAR） shows a potential value in the prevention and treatment of AIH through multiple mechanisms such as remodeling immune homeostasis， targeted inhibition of inflammatory pathways， antioxidation， regulating hepatocyte metabolism and apoptosis， improving mitochondrial function， and regulating intestinal flora. However， the clinical translation and application of NAR is limited by issues such as low bioavailability and insufficient efficiency of liver-targeted delivery. This article systematically reviews the mechanism of action of NAR in the prevention and treatment of AIH， explores the potential signaling pathways involved in this process， and analyzes existing challenges in its translation and application and future research directions， so as to provide a reference for further research on NAR and its application in the prevention and treatment of AIH.

Diabetic microvascular complications （DMC） are major chronic complications of diabetes，primarily including diabetic kidney disease （DKD），diabetic retinopathy （DR），diabetic cardiomyopathy （DCM），and diabetic peripheral neuropathy （DPN）. These complications significantly impact patients' quality of life and prognosis. Modern medicine primarily focuses on symptomatic control in the treatment of DMC，with limited ability to reverse the disease progression. Endoplasmic reticulum stress （ERS），as a central event under hyperglycemic toxicity，is not only a key cause of pancreatic β-cell dysfunction （reduced insulin synthesis and secretion） but also a core driver of damage in various target organs of DMC. It activates three signaling pathways of the unfolded protein response （UPR）-inositol-requiring enzyme 1 （IRE1），activating transcription factor 6 （ATF6），and protein kinase R-like endoplasmic reticulum kinase （PERK），intertwining processes such as autophagy，apoptosis，oxidative stress，and calcium homeostasis imbalance. Traditional Chinese medicine （TCM） offers multi-target and multi-pathway therapeutic advantages and can curb the pathological progression of DMC by regulating ERS. This article systematically reviews the relationships of ERS with pancreatic β-cell function，insulin synthesis，and insulin secretion，and elucidates the core signaling pathways through which ERS mediates DMC. Furthermore，it categorizes and summarizes experimental evidence and mechanisms of single medicinal herbs and their extracts，TCM compound formulas，and modern TCM preparations in regulating ERS for the treatment of various DMC subtypes. Finally，this article proposes ERS as a molecular bridge for integrating traditional Chinese and Western medicine in DMC treatment. Future research should leverage emerging technologies such as network pharmacology，multi-omics analysis，and nano-formulations to establish a synergistic network combining modern hypoglycemic drugs and TCM regulation of ERS. This approach is expected to achieve dual efficacy，enhance drug targeting and bioavailability，deepen the understanding of scientific connotation of TCM，and pave new avenues for the prevention and treatment of DMC.

Diabetic microvascular complications （DMC） are major chronic complications of diabetes，primarily including diabetic kidney disease （DKD），diabetic retinopathy （DR），diabetic cardiomyopathy （DCM），and diabetic peripheral neuropathy （DPN）. These complications significantly impact patients' quality of life and prognosis. Modern medicine primarily focuses on symptomatic control in the treatment of DMC，with limited ability to reverse the disease progression. Endoplasmic reticulum stress （ERS），as a central event under hyperglycemic toxicity，is not only a key cause of pancreatic β-cell dysfunction （reduced insulin synthesis and secretion） but also a core driver of damage in various target organs of DMC. It activates three signaling pathways of the unfolded protein response （UPR）-inositol-requiring enzyme 1 （IRE1），activating transcription factor 6 （ATF6），and protein kinase R-like endoplasmic reticulum kinase （PERK），intertwining processes such as autophagy，apoptosis，oxidative stress，and calcium homeostasis imbalance. Traditional Chinese medicine （TCM） offers multi-target and multi-pathway therapeutic advantages and can curb the pathological progression of DMC by regulating ERS. This article systematically reviews the relationships of ERS with pancreatic β-cell function，insulin synthesis，and insulin secretion，and elucidates the core signaling pathways through which ERS mediates DMC. Furthermore，it categorizes and summarizes experimental evidence and mechanisms of single medicinal herbs and their extracts，TCM compound formulas，and modern TCM preparations in regulating ERS for the treatment of various DMC subtypes. Finally，this article proposes ERS as a molecular bridge for integrating traditional Chinese and Western medicine in DMC treatment. Future research should leverage emerging technologies such as network pharmacology，multi-omics analysis，and nano-formulations to establish a synergistic network combining modern hypoglycemic drugs and TCM regulation of ERS. This approach is expected to achieve dual efficacy，enhance drug targeting and bioavailability，deepen the understanding of scientific connotation of TCM，and pave new avenues for the prevention and treatment of DMC.

Curcumin (Cur), a natural polyphenolic compound extracted from the rhizomes of plants belonging to the Zingiberaceae and Araceae families, has attracted considerable interest for its remarkable antioxidant, anti-inflammatory, antibacterial, and anticancer activities. Extensive studies have focused on its potential in treating various diseases, including cancers, neurodegenerative diseases, inflammation, and autoimmune disorders. However, its clinical application has been hampered by inherent physicochemical challenges, such as poor aqueous solubility, short half-life, and low bioavailability. To address these challenges, nanodrug delivery systems have been developed to improve the pharmacokinetic and pharmacodynamic profiles of curcumin, thereby enhancing its therapeutic efficacy. This review summarizes the pharmacological activities and underlying mechanisms of curcumin, encompassing its antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial effects. Furthermore, it highlights the significant advancements achieved through the development of curcumin-based nanomedicines. By synthesizing current findings, this review aims to provide insights that may inspire innovative strategies for the future design and broader applications of curcumin nanomedicines.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective:To explore the intervention effects of the skill training for parents with autism child (STPAC) on toddlers with autism spectrum disorder (ASD).Methods:A multicenter non-randomized concurrent controlled study design was conducted. Thirty children with ASD aged 15-30 months, first diagnosed at the Children′s Hospital of Fudan University, the First Hospital of Jilin University, and Chengdu Women′s and Children′s Central Hospital from 2019 to 2020, were enrolled in the STPAC group. Thirty children with ASD who visited the same hospitals during the same period but refused the STPAC intervention were selected as the control group. The STPAC group received an 8-week intervention (3 h/week) followed by quarterly follow-ups for 1 year, while the control group voluntarily chose community-based routine interventions. The Griffiths development scales-Chinese (GDS-C) was used to assess the developmental levels, and the communication and symbolic behavior scales developmental profile infant-toddler checklist (CSBS-DP-ITC) was completed by the primary caregivers to evaluate social, language and symbolic behavior. The independent samples t-tests or Mann-Whitney U tests, etc.was used for inter-group comparison. The paired t-tests or Wilcoxon signed-rank tests, etc. was used for inter-group pre-post intervention comparison. Results:The STPAC group included 30 children (22 males and 8 females, aged (23.9±2.2) months), and the control group included 30 children (20 males and 10 females, aged (24.2±2.6) months). Before the intervention, there were no statistically differences in GDS-C development quotient (DQ) and CSBS-DP-ITC scores between groups (all P>0.05). After 1-year intervention, GDS-C DQ in personal-social, hearing-language, hand-eye coordination, performance domains of STPAC group and GDS-C DQ in personal-social, hearing-language domains of control group were all increased (all P<0.01). After 1-year intervention, CSBS-DP-ITC scores of both groups were all improved in socia, language, symbolic behavior, and total scores (all P<0.001). GDS-C DQ changes before and after 1 year of intervention in hearing-language, hand-eye coordination, performance domains of the STPAC group were all higher the those of control group (34(15, 48 vs. 10(-4, 39), 11±20 vs. -1±19, 23±25 vs. 8±22, all P<0.05). CSBS-DP-ITC scores changes before and after 1 year of intervention in social and total scores of the STPAC group were both higher the those of control group (10(5, 30) vs. 3(1, 7), 26±17 vs. 11±8, both P<0.001). Conclusion:Compared with the community routine interventions, the STPAC better improves the language, hand-eye coordination, visual-spatial, social communication, and play skills in ASD toddlers.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.