This study aims to investigate the therapeutic effects of the Coptidis Rhizoma-Scutellariae Radix on cytokine storm secondary lung injury(CSSLI) induced by CpG1826 in mice, and to elucidate the potential molecular mechanisms by which its major active components, i.e., coptisine and wogonin, alleviate CSSLI by inhibiting the mitochondrial permeability transition pore(mPTP)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome pyroptosis pathway. In vivo, a mouse model of CSSLI was established by CpG1826 induction. Pulmonary edema was assessed by lung wet-to-dry weight ratio(W/D), lung injury was evaluated by hematoxylin-eosin(HE) staining, and ultrastructural changes in lung tissue were observed by transmission electron microscopy(TEM). The levels of interleukin(IL)-1β, high mobility group box 1 protein(HMGB1), IL-18, and IL-1α in bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that the decoction of the Coptidis Rhizoma-Scutellariae Radix significantly reduced pulmonary edema, alleviated lung injury, and decreased the concentrations of related cytokines in BALF more effectively than either single herb alone, thereby improving CSSLI. In vitro, a CpG1826-induced CSSLI model was established in mouse alveolar macrophage MH-S cells. Calcein-AM quenching was used to screen for the most effective monomer components from the herb pair in inhibiting mPTP opening. Coptisine(5, 10, 20 μmol·L~(-1)) and wogonin(10, 20, 40 μmol·L~(-1)) markedly inhibited mPTP opening, with optimal effects and a clear dose-dependent pattern. These components suppressed mPTP opening, thereby reducing the release of mitochondrial DNA(mtDNA) and the accumulation of reactive oxygen species(ROS), effectively reversing the CpG1826-induced decrease in mitochondrial membrane potential(MMP). Further studies revealed that both coptisine and wogonin inhibited pyroptosis and downregulated the expression of key proteins in the NLRP3/Caspase-1/gasdermin D(GSDMD) pathway. In conclusion, the Coptidis Rhizoma-Scutellariae Radix improves CpG1826-induced CSSLI in mice, and this effect is associated with the inhibition of the mPTP/NLRP3 pyroptosis pathway, providing scientific evidence for its clinical application and further development.
Animals ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Male ; Lung Injury/immunology* ; Cytokines/immunology* ; Scutellaria baicalensis/chemistry* ; Oligodeoxyribonucleotides/adverse effects* ; Mice, Inbred C57BL ; Coptis chinensis

Stress is a critical inducer in the onset and progression of many chronic diseases. Prolonged or intense stress can disrupt the overall balance between the nervous, immune, and endocrine systems. The resulting biological signals may act on corresponding receptors in the cervical spine region, leading to adverse pathological changes. The vertebral artery and the surrounding muscular and connective tissues are influenced by biomechanical abnormalities and inflammatory cascades associated with cervical spondylosis of vertebral artery type (CSA), which promotes the release of various hormones. These hormones, through the neuroendocrine-immune system, affect the central nervous system, inducing or exacerbating negative emotional feedback and thereby establishing a "central-local-central" vicious cycle. This article explores the mechanisms underlying the impact of stress on the key CSA symptoms through the neuroendocrine-immune network (NEI) theory, providing a more comprehensive framework for targeted therapeutic interventions in CSA.
Humans ; Neurosecretory Systems/immunology* ; Spondylosis/etiology* ; Vertebral Artery/immunology* ; Stress, Psychological/complications* ; Chronic Disease

Objective:To investigate the clinical efficacy of robotic surgery via the bilateral axillo-breast approach（BABA） in lateral lymph node dissection for papillary thyroid carcinoma（PTC）. Methods:Clinicopathological records of 324 PTC patients receiving unilateral neck dissection in Tianjin Medical University Cancer Institute and Hospital from December 2020 to November 2024 were retrospectively analyzed. Of these patients, 108 underwent robotic surgery via BABA（robotic group）, while the remaining patients underwent conventional open surgery（open group）. The extent of lateral neck lymph node dissection included level Ⅱ, Ⅲ and Ⅳ. The differences in surgical indexes, postoperative complication rates and cosmetic outcomes of incisions were compared between two groups. Results:All study subjects completed the operation successfully, and there was no conversion in the robotic group. The average age of patients in the robotic group was lower than that in the open group, and the proportion of female patients was higher in the robotic group compared to the open group（P<0.05）. Patients in the robotic group had a greater number of dissected lymph nodes in level ⅡB and higher cosmetic scores（P<0.05）. There were no statistically significant differences between the two groups in the average dissection time of lateral cervical lymph nodes, the number of dissected lymph nodes and metastatic lymph nodes in level ⅡA, Ⅲ, and Ⅳ, average postoperative drainage volume, average postoperative hospital stay, and postoperative complication rates（P>0.05）. Conclusion:The application of robotic surgical system via BABA in lateral neck lymph node dissection for PTC is safe and feasible, with superior advantages in level ⅡB dissection and better postoperative cosmetic outcomes.
Humans ; Thyroid Neoplasms/surgery* ; Robotic Surgical Procedures/methods* ; Female ; Retrospective Studies ; Neck Dissection/methods* ; Lymph Node Excision/methods* ; Male ; Thyroid Cancer, Papillary ; Axilla/surgery* ; Thyroidectomy/methods* ; Breast/surgery* ; Middle Aged ; Adult ; Lymph Nodes/surgery* ; Treatment Outcome

OBJECTIVES: This study aims to evaluate the changes in the mandibular canal following the treatment of large odontogenic keratocysts through decompression and curettage, providing a theoretical basis for sequential treatment. METHODS: Twenty patients were selected for each decompression and curettage treatment of large odontogenic keratocysts in the mandible. Postoperative follow-up with was conducted every three months, during which cone beam computed tomography (CBCT) scans were performed. Then, the data were imported into MIMICS software to observe 3D changes in the position and structure of the mandibular nerve canal, followed by a comparative analysis. RESULTS: The total displacement of the mandibular canal was (1.89±0.21) mm on the decompression side and (0.80±0.19) mm on the curettage side. Vertically, the displacement range of the mandibular canal on the decompression side (M=1.03, SD=0.17) was larger than on the curettage side (M=0.52, SD=0.010) within nine months post-operation. In the buccal-lingual direction, the ratio of the thickness of the buccal plate to the lingual plate gradually increased with time. The amount of bone reconstruction at the part of the mandibular nerve canal closest to the cyst was (1.75±0.15) mm on the decompression side and (1.45±0.09) mm on the curettage side after nine months. CONCLUSIONS The mandibular nerve canal showed varying degrees of recovery and "relocation" after two surgical procedures. Osteogenesis around the mandibular nerve canal was more remarkable after decompression than after curettage. Therefore, for large odontogenic keratocyst, decompression is recommended as the initial treatment, followed by secondary curettage nine months later.
Humans ; Odontogenic Cysts/diagnostic imaging* ; Retrospective Studies ; Cone-Beam Computed Tomography ; Decompression, Surgical/methods* ; Mandibular Nerve/surgery* ; Mandible/innervation* ; Curettage ; Male ; Female ; Adult ; Middle Aged

Objective To explore the role of resveratrol in the immune response and proliferation of macrophages induced by homocysteine(Hcy).Methods ANA-1 cells were divided into control group(conventional culture),model group(100 μmol·L-1 Hcy),experimental-L,-M,-H groups(adding 25,50 and 100 μmol·L-1 resveratrol to model group,respectively),Hcy+Ad-SIRT1 group(100 μmol·L-1 Hcy+Ad-SIRT1),Hcy+si-FOXO1 group(100 μmol·L-1 Hcy+si-FOXO1),Hcy+Res-L+Ad-SIRT1+si-FOXO1 group(100 μmol·L-1 Hcy+25 μmol·L-1 Resveratrol transfected with Ad-SIRT1+si-FOXO1).The cell proliferation was detected by methyl thiazolyl tetrazolium(MTT),and the concentration of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the supernatant of cell culture medium was detected by enzyme-linked immunosorbent assay.The gene and protein expression of silencing information regulator 1(SIRT1)and forkhead protein 01(FOXO1)were detected by Western blot.Results The optical density of 450 nm in control group,model group and experimental-L,-M,-H groups were 0.25±0.02,0.36±0.02,0.33±0.01,0.30±0.02 and 0.29±0.01,respectively.Compared with the control group,the cell proliferation in the model group was significantly increased(P＜0.05).Cell proliferation in experimental-L,-M,-H groups was significantly decreased compared with model group(all P＜0.05).IL-6 in the supernatant of cell culture medium of control group,model group and experimental-L group were(394.04±20.06),(614.23±21.09)and(501.53±16.52)pg·mL-1,respectively;TNF-α were(516.54±18.96),(717.22±24.81)and(632.74±19.11)pg·mL-1,respectively;SIRT1 relative protein expression were(1.00±0.05),(0.57±0.05)and(0.77±0.04),respectively;the relative protein expression of FOXO1 were 1.00±0.05,2.31±0.18 and 1.58±0.11,respectively.Compared with the control group,the above indexes in the experimental-L group had statistical significance(all P＜0.05).The contents of IL-6 and TNF-α in cell culture fluid supernatant in model group,experimental-L group,Hcy+Ad-SIRT1 group and Hcy+si-FOXO1 group were significantly lower than those in model group,with statistical significance(all P＜0.05).After co-transfection with Ad-SIRT1 and si-FOXO1,the contents of IL-6 and TNF-α in cell culture medium superserum of experimental-L group were significantly lower than those of Ad-SIRT1 group and si-FOXO1 group(all P＜0.05).Conclusion Resveratrol can attenuate the immune response and proliferation of macrophages induced by Hcy,which may be related to the alteration of SIRT1/FOXO1 pathway.

Objective:To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma.Methods:This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis.Results:A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups ( P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group ( P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ 2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ 2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death ( P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion:The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Traumatic fractures and stress fractures are common orthopedic diseases,and there is great potential in researching bone turnover,repair,and promotion of fracture healing.Basic medical experiments often use animal models of long bone fractures in limbs to study the mechanisms of various interventions on fracture healing.Fracture healing is a complex process influenced by multiple factors and involves multiple molecules and pathways.Therefore,to explore the mechanisms more deeply,accelerate the translation of results,and improve the clinical efficacy,it is particularly important to choose the appropriate animal fracture modeling methods in experimental research.Based on this,this paper conducts a literature review of animal species and modeling methods commonly used for long bone fracture models in experimental research.It summarizes five methods:bone defect method,physical impact method,mechanical bending method,open osteotomy method,and drilling method.A side-by-side comparison of their advantages,disadvantages,and scope of application is made,aiming to provide suitable fracture models for studyingthe mechanisms of fracture healing interventions.

Objective This study analyzes the omics data resources in human-infecting coronavirus animal models collected from various public databases,focusing on data distribution,dataset quantity,data types,species,strains,and research content.It aims to enhance our understanding of biological characteristics and pathogenic mechanisms of coronaviruses,thereby providing a solid foundation for devising effective therapeutic strategies and preventive measures.Methods Query strategies,including specific virus names,time ranges,and inclusion and exclusion criteria,were defined to retrieve data from major public omics databases such as GEO and ArrayExpress.Secondary filtering was performed based on different field types to obtain a more accurate data list.An omics data text database was established for bibliometric analysis.Co-occurrence networks were constructed for the analysis of the correlation strengths between different research themes,technical methods,and involved species.The cell types,organs,and biological pathways involved in studies were examined to further elucidate the pathogenic interplay between pathogens and hosts.Results About twenty public databases containing coronavirus-related omics data were identified,with a primary focus on novel coronavirus infection.Commonly used species include humans,mice,hamsters,and monkeys,while the commonly used virus strains are Wuhan-Hu-1 and USA-WA1/2020.Lung tissues are primarily used in animal models such as mice,macaques,and ferrets,while airway epithelial cells and Calu-3 cells are predominantly employed in human-related studies.Expression profiling data indicate that gene pathways involved in inflammation,cytokine response,complement pathway,cell damage,proliferation,and differentiation are significantly upregulated after infection.Proteomics studies reveal significant changes in phosphoproteome,ubiquitinome,and total proteome of patient samples at different infection stages.Specific protein categories,including viral receptors and proteases,transcription factors,cytokines,proteins associated with coagulation system,angiogenesis-related proteins,and fibrosis markers,show alterations after coronavirus infection.In addition,metabolomics data suggest that phosphocholine,phosphoethanolamine,arachidonic acid,and oleic acid could serve as potential metabolic markers.Epigenomics research indicates m6A methylation plays a role in SARS-CoV-2 replication,infection,and transmission,affecting host cell-virus interactions.Among these,N,S,and non-structural proteins 2 and 3 exhibit the most significant ubiquitination.Trends in microbiomics research suggest that microbial communities in the gut and wastewater are emerging as new research focuses.Conclusion The data types of coronavirus omics are diverse,with a wide variety of models and cell types used.The selection of species and technical methods for modelling varies based on the characteristics of different viruses.Multi-omics data from animal models of coronavirus infection can reveal key interactions between hosts and pathogens,identifying biomarkers and potential therapeutic targets,and provide valuable information for a deeper understanding of biological characteristics and infection mechanisms of coronaviruses.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.