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.

ObjectiveTo systematically identify the main chemical components of Linggui Zhugan granules （LGZGG）， and to explore the pharmacodynamic substance basis for the treatment of metabolic dysfunction-associated steatohepatitis （MASH）. MethodsThe chemical components of LGZGG were systematically analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. The protein-protein interaction （PPI） network and "compound prescription-disease-component-target" network were constructed by network target analysis to predict the potential pharmacodynamic substances and core targets of LGZGG in the treatment of MASH. The potential pharmacodynamic substances were enriched by macroporous adsorption resin， and the chemical composition of the LGZGG-50% ethanol elution fraction （LGZGG-50） was analyzed by UPLC-Q-TOF-MS/MS. The mouse model of MASH was established by feeding a high-fat， high-cholesterol， and high-fructose diet for 12 weeks. Mice were randomly allocated into normal， model， positive drug （MGL-3196， 1 mg·kg^-1）， LGZGG （crude drug， 34 g·kg^-1·d^-1）， LGZGG-50 （crude drug， 34 g·kg^-1·d^-1） groups. The levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in the serum were measured， and the pathological changes in the liver tissue were observed by hematoxylin-eosin （HE） and Sirius red staining. The in vivo efficacy of LGZGG and LGZGG-50 in the treatment of MASH was evaluated on the basis of the findings. The expression levels of adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， silent information regulator 2-related enzyme 1 （SIRT1）， peroxisome proliferator-activated receptor α （PPARα）， and carnitine palmitoyltransferase 1A （CPT1A） in the liver tissue were determined by Western blot to verify the regulatory effects of core targets. ResultsA total of 83 chemical components were identified from LGZGG， including 20 flavonoids， 13 terpenoids， 17 organic acids， 7 amino acids， 11 glycosides， 3 nucleosides， 3 aromatics， 3 alkaloids， 2 phenylpropanoids， 2 sugars， 1 nucleic acid， and 1 steroid. A total of 134 common targets were obtained by network target analysis. The core targets included SIRT1， PPARα， nuclear factor-kappa B subunit 1 （NF-κB1）， and interleukin-6 （IL-6）. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis revealed that the targets were mainly enriched in the AMPK， PPAR and other signaling pathways. The topological analysis of the "compound prescription-disease-component-target" network showed that the potential pharmacodynamic substances of LGZGG against MASH were flavonoids and terpenoids. The relative content of flavonoids and terpenes in LGZGG-50 were 74.00% and 62.41% in positive and negative ion modes， respectively， indicating that LGZGG-50 effectively enriched total flavonoids and total terpenoids. The results of in vivo efficacy showed that compared with the model group， LGZGG and LGZGG-50 reducef the body weight， liver weight， serum TG， GLU， and ALT levels of MASH mice （P<0.05，P<0.01）， and LGZGG additionally increased the HDL-C level （P<0.01）. Both groups alleviated the pathological damage in the liver tissue. The results of Western blot showed that compared with the model group， the protein levels of p-AMPK/AMPK， SIRT1， PPARα， and CPT1A were up-regulated in the LGZGG group （P<0.05，P<0.01）， and those of p-AMPK/AMPK and CPT1A were up-regulated in the LGZGG-50 group （P<0.01）. ConclusionLGZGG ameliorates MASH， with the main pharmacodynamic substances being flavonoids and terpenoids. The mechanism may be related to the regulation of AMPK/SIRT1/PPARα signaling pathway， improvement of lipid metabolism， and alleviation of pathological damage in the liver tissue.

To address the scarcity of annotated data for pediatric abdominal CT imaging and the insufficient generalization capability of existing models, we constructed a self-supervised pretraining architecture tailored for pediatric CT domain adaptation based on the visual foundation model DINOv3, and validated its performance in the task of pediatric abdominal multi-organ segmentation.

ObjectiveTo explore the listed varieties and prescription characteristics of Chinese patent medicines for stroke in China， explore the medication rules of Chinese medicine for stroke， and provide guidance for further clinical research and development of Chinese patent medicines. MethodsExcel 2021 and the Ancient and Modern Medical Record Cloud Platform （V2.3.5） were used to systematically mine and analyze the varieties and prescriptions of Chinese patent medicines for stroke in China. ResultsA total of 244 Chinese patent medicines （two for different dosage forms of the same prescription）， 1 736 approval documents for Chinese patent medicines， 792 manufacturers， and 83 varieties of protected Chinese patent medicines were finally included in the database. The top three dosage forms were capsules （75）， pills （53）， and tablets （42）. There were 28 Chinese patent medicines for stroke in the National Essential Drug Catalogue （2018）， 129 in the National Essential Medical Insurance， Industrial Injury Insurance and Maternity Insurance Drug Catalogue （2023）， and 4 in the National Non-prescription Drug Catalogue. Among the 138 prescriptions screened out， Chinese patent medicines mainly treated stroke patients with the syndrome of Qi deficiency and blood stasis. The top three most frequent medicinal herbs were Chuanxiong Rhizoma （63）， Pheretima （47）， and Salviae Miltiorrhizae Radix et Rhizoma （47）. The medicinal herbs used were mainly warm， pungent， with the meridian tropism to the liver meridian. The correlation analysis showed that the herb pair with the highest support was Astragali Radix-Chuanxiong Rhizoma， and that with the highest confidence was Carthami Flos-Chuanxiong Rhizoma. Five herb combinations were identified based on the cluster analysis. ConclusionThe Chinese patent medicines for stroke mainly treat patients with the syndrome of Qi deficiency and blood stasis. The medicinal herbs used in the prescriptions mainly have the functions of activating blood and resolving stasis， extinguishing wind and stopping convulsions. Drug compatibility usually focuses on activating blood and resolving stasis， as well as expelling phlegm and opening orifices. This review of the varieties and prescription characteristics of Chinese patent medicines for stroke helps optimize clinical decision-making， guide drug research and development， promote medical research and scientific progress， and provide more effective support and guarantee for the treatment of stroke patients.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Intervertebral disc degeneration(IDD)is a prevalent clinical degenerative disease that currently can only be treated through conservative and surgical treatments,which only alleviate symptoms and are not significantly effective.In recent years,nanoparticles have been widely studied in the biomedical field due to their biodegradability,biocompatibility,extended body circulation,sustained and controlled release,and precise drug targeting.Nanoparticle drug delivery systems have the potential to deliver a range of therapeutic agents including proteins,drugs,genes,and cells,thereby promoting tissue and cell repair and regeneration,which offers hope for IDD treatment.However,there are still challenges in translating experimental data into practical therapies applicable to humans.This review summarizes recent research progress on drug delivery systems for IDD treatment based on nanoparticles and provides insights and prospects for the challenges faced by nanoparticles,aiming to provide a reference for the clinical translation of nanoparticle-based treatment for IDD.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To determine the prevalence of GJB2 gene c. 109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. Methods:One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c. 109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c. 109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children′s Hospital of Ningbo University (Ethics No.: EC2023-009). Results:For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c. 109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c. 109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined ( n=53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined ( n=24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls ( P=0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1±12.0 dB nHL, P=0.005). Conclusion:Infants harboring the GJB2 c. 109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c. 109G>A variant can confer a more severe hearing loss.

This study aimed to investigate the effects of acupuncture on dynamic changes in Ca²⁺, Na⁺, and H₂O₂ flux following eccentric exercise-induced muscle injury. The total of 324 healthy male Wistar rats were randomly divided into 6 groups: control group (C), eccentric exercise group (E), eccentric exercise with acupuncture group (EA), EA with TRP channel blocker group (EAT), EA with NOX2 blocker group (EAN) and EA with placebo group (EAP). Gastrocnemius muscles were subject to lengthening contractions with percutaneous electrical stimulation, followed by immediate pretreatment with blocking agents. After 30 min, acupuncture needling was administered to the gastrocnemius muscle, and real-time dynamic changes of Ca²⁺, Na⁺ and H₂O₂ flux were measured with non-invasive micro-test technique during the needle retention period, immediately, 3 h, 6 h, and 24 h post-extraction respectively. Results showed that compared with the E group, acupuncture significantly increased net Ca²⁺ efflux (P < 0.05), extended the period of net Na⁺ influx, and significantly decreased net H₂O₂ efflux (P < 0.05). However, these effects were significantly attenuated in the EAT and EAN groups, where excessive net H₂O₂ efflux was observed (P < 0.001). These findings indicate that acupuncture regulates the dynamic changes of Ca²⁺, Na⁺ and H₂O₂ flux by activating the TRP channels and interacting with NOX2 activity following eccentric exercise-induced skeletal muscle injury.
Animals ; Muscle, Skeletal/metabolism* ; Rats, Wistar ; Rats ; Male ; Calcium/metabolism* ; Hydrogen Peroxide/metabolism* ; Physical Conditioning, Animal ; Sodium/metabolism* ; Acupuncture Therapy ; NADPH Oxidase 2

With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO_4·2H_2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO_4·2H_2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO_4·2H_2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO_4·2H_2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO_4·2H_2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO_4·2H_2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO_4·2H_2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO_4·2H_2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO_4·2H_2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO_4·2H_2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.
Drugs, Chinese Herbal/chemistry* ; Calcium Sulfate/chemistry* ; Glycyrrhiza/chemistry* ; Crystallization ; Particle Size ; Medicine, Chinese Traditional ; Rhizome/chemistry*