With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

This study aims to establish the S_(180) tumor-bearing mice model, and to investigate the influence of Shenqi Erpi Granules(SQEPG) on immune function, as well as the drug's tumor-suppressive effect and mechanism. SPF grade KM mice(half male and half female) were randomly divided into 6 groups: a control group, a model group, a cyclophosphamide group(50 mg·kg~(-1)), as well as SQEPG groups in low-, medium-, and high-dose(5.25, 10.5, 21 g·kg~(-1)). The control group and the model group were given distilled water, and the other 4 groups were given the corresponding drugs by gavage. The administration continued for 10 days before the mice were sacrificed. The antitumor and immune regulation effects of SQEPG were evaluated. The effect of SQEPG on delayed type hypersensitivity reaction(DTH), carbon clearance index, and serum hemolysin antibody level was observed to reflect the effect on the immune function of tumor-bearing mice. Tumor weight was recorded to calculate the tumor suppression rate and the immune organ index. Hematoxylin-eosin(HE) staining was used to detect morphological changes in tumor tissues. Flow cytometry was employed to detect the percentage of CD4~+ and CD8~+ T-cells in the spleen tissues and the tumor tissue apoptosis levels. Immunohistochemistry was conducted to detect the KI67 protein expression level of tumor tissues. ELISA resorted to the detection of the following expression levels in tumor tissues: tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), interferon-γ(IFN-γ). Western blot was performed to detect the expression levels of caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinases 4(CDK4), G_1/S-specific cyclin D1(cyclin D1), and vascular endothelial growth factor A(VEGFA). The results showed that, compared with the model group, the SQEPG could increase the swelling of the auricle of the tumor-bearing mice; significantly increase the phagocytic index of carbon granule contour(P<0.05 or P<0.01), and the middle dose of SQEPG could significantly increase the antibody level of hemolysin(P<0.05); different doses of SQEPG significantly inhibit the growth of the tumor, and decrease the mass of the tumor tissues(P<0.05 or P<0.01); the low dose of SQEPG significantly decreased spleen index(P<0.05), low and high doses of SQEPG increased thymus index, while medium doses of SQEPG decreased thymus index. High doses of SQEPG significantly elevated the levels of CD4~+ and CD8~+ T-cells in the spleens of the homozygous mice(P<0.01 or P<0.001), and increased the apoptosis rate of the cells of the tumor tissues(P<0.05); Meanwhile, high-dose SQEPG elevated the levels of immunity factors such as IL-2, IFN-γ and TNF-α in the serum of tumor-bearing mice(P<0.01); medium-and high-dose SQEPG significantly lowered the rate of positive expression of KI67 protein in tumor tissues(P<0.01). Compared with the model group, high-dose SQEPG significantly up-regulated the expression of caspase-3 and Bax proteins in tumor tissues(P<0.05), and significantly down-regulated the expression of CDK4, cyclin D1, and VEGFA proteins(P<0.05 or P<0.01). In conclusion, SQEPG has the effect of improving immune function and inhibiting tumor growth in tumor-bearing mice. Its mechanism of tumor-suppressive effects may be related to apoptosis promotion, cell cycle progression block, and tumor cell proliferation inhibition.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Apoptosis/drug effects* ; Sarcoma 180/genetics* ; Humans

OBJECTIVES: To investigate the core targets and immunomodulatory mechanisms of Huoluo Xiaoling Pellet (HLXLP) for promoting tissue repair. METHODS: Network pharmacology and protein-protein interaction network were used to screen active components in HLXLP, the disease-related targets and the core targets, followed by GO and KEGG enrichment analyses and molecular docking to predict the pharmacological mechanisms. The toxicity of HLXLP was evaluated in zebrafish, and in a tissue regeneration model established in 3 dpf zebrafish larvae by amputating 95% of the tail fin, the effects of a formulated zebrafish embryo culture medium and 10, 20, and 40 μg/mL of aqueous extract of HLXLP on tissue regeneration was evaluated; RT-qPCR was performed to detect mRNA expressions of tissue regeneration marker genes and the core target genes. Transgenic zebrafish with fluorescently labeled macrophages and neutrophils were used to observe immune cell migration during tissue regeneration, and macrophage polarization at different stages was assessed with RT-qPCR. RESULTS: We identified a total of 149 intersected targets between HLXLP active components and tissue repair and 5 core targets (AKT1, IL-6, TNF-α, EGFR and STAT3). GO and KEGG analyses suggested that the effects of HLXLP were mediated primarily through the JAK-STAT pathway, adhesion junctions and positive regulation of cell migration. HLXLP was minimally toxic below 40 μg/mL and lethal at 320 μg/mL in zebrafish, and caused renal and pericardial edema and vascular defects above 80 μg/mL. In zebrafish with tail fin amputation, HLXLP significantly promoted tissue regeneration, reduced IL-6 and TNF-α and enhanced AKT1, EGFR and STAT3 mRNA expressions, modulated neutrophil and macrophage recruitment to the injury sites, and regulated M1/M2 macrophage polarization during tissue regeneration. CONCLUSIONS HLXLP promotes zebrafish tail fin regeneration through multiple active components, targets and pathways for immunomodulation of immune cell migration and macrophage polarization to suppress inflammation and accelerate healing.
Animals ; Zebrafish/physiology* ; Animal Fins/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Regeneration/drug effects* ; Network Pharmacology ; Signal Transduction ; Macrophages

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

Sesquiterpenes are natural terpenoids with 15 carbon atoms in the basic skeleton, which mainly exist in plant volatile oil and have important physiological and medicinal value. Cytochrome P450 (CYP450) is a kind of monooxygenase encoded by supergene family, which is one of the largest gene families in plants. It is involved in the synthesis and metabolism of terpenoids, alkaloids and other secondary metabolites. In the process of terpene biosynthesis, CYP450 participates in the post-modification stage of terpenes by introducing functional groups such as hydroxyl, carboxyl and carbonyl, which plays an important role in enriching the diversity of terpenes. The CYP450 enzymes involved in sesquiterpene synthesis and their substrate catalytic specificity mechanisms have been partially investigated. In this paper, the biosynthetic pathway of plant sesquiterpenes, the structure and classification of CYP450 enzymes were briefly introduced, and the CYP450 enzymes involved in sesquiterpene biosynthesis were summarized, in order to provide a reference for intensive study of the role of CYP450 enzymes in the synthesis of sesquiterpenoids.

Objective:To develop a grading system for necrosis of pedicled flaps in reconstruction of foot and ankle, and to verify its effectiveness and repeatability.Methods:A retrospective observational study was conducted. A total of 40 necroses of foot and ankle pedicled flaps were selected by 2 senior surgeons based on the flap surgery performed by the same surgical group in Department of Orthopaedic Surgery, the 920 Hospital of Joint Logistic Support Force of PLA from January 2010 to January 2022. A grading system for pedicled flap necrosis was proposed by a working group and the 40 necrotic flaps were graded. The coincidence rate was calculated to evaluate the effectiveness of the grading system through correlation studies between grading and clinical treatment. One photo of a typical postoperative necrotic flap was collected from each of the 40 flaps. Then 5 extramural surgeons were asked to grade the necroses shown on the photos according to the proposed grading system. Moreover, weighted Kappa analysis was performed on the results of proposed grading system and also on the standard grading currently in use, to evaluate the repeatability of the proposed grading system. Evaluated data were expressed by Mean±SD, and the coincidence rate was expressed by percentage. The reproducibility was studied by weighted Kappa analysis.Results:Of the 40 necrotic flaps, 7 flaps were classified in Grade I, 16 in Grade Ⅱ, 12 in Grade Ⅲ and 5 in Grade IV. In comparison with the actual treatment methods, the overall coincidence rate of the grading system was 92.5%. It indicated that the proposed grading system could effectively guide the selection of a treatment procedure. The average weighted Kappa coefficient of surgeons was at 0.628 with a 95% confidence interval (95%CI) between 0.460-0.796, which was strongly consistent with the standard of the grading system currently in use.Conclusion:The grading system for necrosis of pedicled flap in reconstruction of foot and ankle proposed in this study is simple and clear. It is able to effectively guide the treatment of flap necrosis. The preliminary validation shows that the classification system has good repeatability.

BACKGROUND:Nanostructure modification of pure titanium surface is a hot research field of titanium implant surface treatment. OBJECTIVE:To evaluate the effect of nano-modified titanium surface treated with alkali heat treatment on early adhesion and growth of osteoblasts. METHODS:Four-grade pure titanium sheets with a diameter of 15 mm and a thickness of 1.5 mm were taken and processed in three groups:the smooth treatment group was polished step by step with 250 mesh,800 mesh,and 1 500 mesh silicon carbide sandpaper.In the sandblasting group,the smoothed titanium sheet was sandblasted with 100 μm Al2O3 particles at 0.45 MPa pressure,and then the acid etching was carried out.In the alkali heat treatment group,the smoothed titanium sheet was placed in the reactor,immersed in 10 mol/L NaOH solution,and heated in the oven at 100 ℃for 12 hours.The surface morphology,roughness,and hydrophilicity of three groups of titanium sheets were measured.MG63 osteoblasts were inoculated on the surface of three groups of titanium tablets,and the adhesion of the cells was observed by immunofluorescence staining. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of titanium sheets in the smooth treatment group had uniform scratches;the surface of titanium sheets in the sandblasting group was uneven,and the surface of titanium sheets in the alkali heat treatment group had uniform nanoscale three-dimensional pore morphology.The roughness value of the titanium sheets in sandblasting and alkali heat treatment groups was higher than that in the smooth treatment group(P<0.05),and the water contact angle was lower than that in the smooth treatment group(P<0.05).(2)Immunofluorescence staining after 3 and 6 hours of inoculation of MG63 cells showed that the number of adhesion cells on the surface of the titanium sheet in the sandblasting group and alkali heat treatment group was higher than that in the smooth treatment group(P<0.05).Immunofluorescence staining 12 hours after inoculation showed that compared with the smooth treatment group,the actin skeleton of cells on the surface of titanium sheets in the sandblasting group and alkali heat treatment group was more extended,and most cells extended stronger pseudopodia,which was conducive to subsequent intercellular signal transduction and intercellular interaction.(3)The results showed that the nanostructures with certain biological activity could be prepared on the surface of a titanium sheet by alkali heat treatment,which was conducive to the early adhesion of osteoblasts.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective:To investigate the prevalence and risk factors of sarcopenia in patients following radical gastrectomy with the aim of guiding clinical decisions.Methods:This was a retrospective observational study of data of patients who had undergone radical gastrectomy between June 2021 and June 2022 at the Department of General Surgery, First Medical Center of Chinese PLA General Hospital. Participants were reviewed 9-12 months after surgery. Inclusion criteria were as follows: (1) radical gastrectomy with a postoperative pathological diagnosis of primary gastric cancer; (2) no invasion of neighboring organs, peritoneal dissemination, or distant metastasis confirmed intra- or postoperatively; (3) availability of complete clinical data, including abdominal enhanced computed tomography and pertinent blood laboratory tests 9-12 after surgery. Exclusion criteria were as follows: (1) age <18 years; (2) presence of gastric stump cancer or previous gastrectomy; (3) history of or current other primary tumors within the past 5 years; (4) preoperative diagnosis of sarcopenia (skeletal muscle index [SMI) ≤52.4 cm2/m2 for men, SMI ≤38.5 cm2/m2 for women). The primary focus of the study was to investigate development of postoperative sarcopenia in the study cohort. Univariate and multivariate logistic regression were used to identify the factors associated with development of sarcopenia after radical gastrectomy.Results:The study cohort comprised 373 patients of average age of 57.1±12.3 years, comprising 292 (78.3%) men and 81 (21.7%) women. Postoperative sarcopenia was detected in 81 (21.7%) patients in the entire cohort. The SMI for the entire group was (41.79±7.70) cm 2/m 2: (46.40±5.03) cm 2/m 2 for men and (33.52±3.63) cm 2/m 2 for women. According to multivariate logistic regression analysis, age ≥60 years (OR=2.170, 95%CI: 1.175-4.007, P=0.013), high literacy (OR=2.512, 95%CI: 1.238-5.093, P=0.011), poor exercise habits (OR=3.263, 95%CI: 1.648-6.458, P=0.001), development of hypoproteinemia (OR=2.312, 95%CI: 1.088–4.913, P=0.029), development of hypertension (OR=2.169, 95%CI: 1.180-3.984, P=0.013), and total gastrectomy (OR=2.444, 95%CI:1.214-4.013, P=0.012) were independent risk factors for postoperative sarcopenia in post-gastrectomy patients who had had gastric cancer ( P<0.05). Conclusion:Development of sarcopenia following radical gastrectomy demands attention. Older age, higher education, poor exercise habits, hypoproteinemia, hypertension, and total gastrectomy are risk factors for its development post-radical gastrectomy.