Atopic dermatitis （AD） is a common pruritic and chronic inflammatory dermatosis in clinical practice and is one of the diseases responding specifically to traditional Chinese medicine （TCM）. With the launch of biological agents and small molecule drugs and the development and implementation of guidelines of diagnosis and treatment， clinical pathways of treatment of moderate to severe AD， and consensus on the whole-process management of AD， the clinical efficacy of moderate to severe AD has been significantly improved. However， there are still many unmet clinical needs that require more effective methods to meet. In response to the Opinions of the CPC Central Committee and the State Council on Facilitating the Inheritance， Innovation， and Development of Traditional Chinese Medicine and the spirit of the National Conference on TCM， the China Association of Chinese Medicine organized more than 20 experts in TCM dermatology， Western medicine dermatology， interdisciplinary fields， and industries to discuss the difficulties and advantages of TCM in the treatment of AD. TCM treatment for AD can not only improve rash and relieve itching but also solve many concomitant syndromes. The abundant external treatment methods of TCM have advantages for different special populations and rash characteristics. The concept of treating disease before its onset in TCM is in line with the chronic disease management mode of prevention and treatment of atopic march and prevention of recurrence. In addition， TCM therapy can reduce the use of topical glucocorticoids and has good safety. Regarding the comorbidity of AD， equal emphasis on TCM and Western medicine and multidisciplinary joint treatment should be advocated to achieve maximum benefit for patients. The exchange of TCM and Western medicine has clarified the positioning and advantages of TCM intervention in AD， providing guidance for clinical and scientific research.

By consulting relevant literature of ancient herbal books and processing specifications， this paper made a systematic research and analysis of Ostreae Concha， including the name， producing area， harvesting， quality， historical evolution of processing， relevant processing specifications， modern processing technology， and changes in chemical composition and pharmacological effects before and after processing， in order to provide documentary evidence for the research on processing technology and the establishment of quality standards. According to the textual research， it is known that Ostreae Concha has a long history of being used in medicine， and there have been many aliases and local names in each historical period. Shennong's Classic of the Materia Medica（Shennong Bencaojing） began to use Muli as the correct name， which has continued to use to today， and there were also aliases such as Muge， Zuogu Muli and Haoke. Ostreae Concha has a wide range of localities and irregular harvesting periods. The ancients believed that its left shell was of superior quality， but this has not been seen in modern. And there were many kinds of processing methods of Ostreae Concha， such as grinding， roasting， calcining， frying， simmering， quenching and so on， and the calcining was still in use. The different editions of Chinese Pharmacopoeia from 1963 to 2020 contain only calcined Ostreae Concha， and the local processing specifications mainly include three kinds of processed products（calcined products， salt-soaked products and vinegar-soaked products）. Modern processing research mainly focuses on process optimization， changes in chemical composition and pharmacological effects， and the research methods are relatively single. Overall， there are currently issues such as inconsistent processing standards， unclear process parameters and imperfect quality standards， which are not conducive to the quality control and standardized clinical use of Ostreae Concha. Therefore， it is necessary to further investigate the pharmacological substance basis of Ostreae Concha and its processed products in order to elucidate the processing mechanism， standardize the processing technology and improve the quality standard.

BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective By screening and passaging G0 generation Wistar rats,we obtained hypoxia-sensitive and hypoxia-tolerant G1 generation rats,and then the differences in hypoxia sensitivity among these rats were preliminarily explored.Methods 200 Wistar rats(half male and half female)were selected as G0 generation and placed in a controlled oxygen concentration system.The hypoxia tolerance time,which refers to the time from placement to near death,was recorded for the G0 generation rats at an oxygen volume fraction of 3％.30 rats(half male and half female)with the shortest hypoxia tolerance time were selected for mating and passage to obtain G1 generation hypoxia-sensitive rats.Similarly,30 rats(half male and half female)with the longest hypoxia tolerance time were selected for mating and passage to obtain G1 generation hypoxia-tolerant rats.An additional 24 standard Wistar rats were randomly divided into two groups:a control group and a model group,with 12 rats in each group(half male and half female).The control group was kept in a normoxic environment,while the model group,along with the G1 generation hypoxia-sensitive rats(G1 sensitive group)and G1 generation hypoxia-tolerant rats(G1 tolerant group),were placed in a hypobaric hypoxia chamber(simulating an altitude of 5 000 m).After 12 hours,various indicators,including blood gas,complete blood count,blood biochemistry,pathological sections,and hypoxia-related genes were detected or observed to compare the differences in hypoxia sensitivity among the 4 groups.Results Compared with the G0 generation standard rats,the hypoxia tolerance time of G1 generation rats was significantly prolonged(P＜0.01).Compared with the model group,the oxygen saturation(SatO2)in G1 tolerant group was significantly higher(P＜0.05).In the G1 sensitive group,the levels of white blood cell(WBC)count,neutrophil(NEUT)count,hemoglobin(HGB)concentration,hematocrit(HCT),red blood cell distribution width(RDW),platelet(PLT),and creatinine(Cr)significantly increased(P＜0.05 or P＜0.01),while actual bicarbonate(AB)content significantly decreased(P＜0.05),and the brain and lung coefficients were significantly elevated(P＜0.05).In addition,pathological section results showed that the brain and lung tissues in the model group,G1 sensitive group,and G1 tolerant group all suffered from significant damage,with no evident differences in the gene expression levels of hypoxia-inducible factor-1 α(HIF-1α)and vascular endothelial growth factor A(VEG FA)in brain tissues amongthe three groups(P＞0.05).Conclusion Compared with standard rats,G1 generation hypoxia-sensitive/tolerant rats exhibit good signs of hypoxia sensitivity/tolerance traits,but further screening and passage are still needed to purify them.

Background and objective Pembrolizumab(PEM)has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer(NSCLC),but clinical trials were based on cohorts of patients selected on specific criteria,and whether the findings are consistent with real-world patients is debatable.The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data.Methods A retro-spective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted.Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy.Results Among 450 matched patients,the incidence rates of any-grade adverse events were 79.87％in the PEM group and86.71％inthe chemotherapy group,while the incidence rates of grade＞3 adverse events were 4.03％and 7.31％,respectively.The objective response rates were 48.63％for PEM and 36.00％for chemotherapy(P=0.011).The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy(P＜0.001),and the median overall survival was not reached for PEM and 26.2 months for chemotherapy(P＜0.001).Conclusion PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Objective:To observe the long-term effect of superficial temporal fascia flap combined with severed auricle reimplantation in emergency repair of partial auricle of complete separation.Methods:The data of patients with partial auricle of complete separation admitted to Emergency Clinic of Burn and Plastic Surgery of General Hospital of Northern Theater Command from June 2014 to August 2023 were retrospectively analyzed. All of them were repaired with a superficial temporal fascia flap combined with amputating auricle reimplantation. During the operation, the superficial temporal fascia flap was harvested, and the pedicle was preserved. Then the detached auricular cartilage was removed and used as a replantation scaffold. Then the remaining skin was thinned to create a full-thickness skin graft after cartilage detachment. Referring to the position and angle of the contralateral auricle, the cartilage scaffold was sutured and fixed at the stump of the ear cartilage. The wound was covered with a superficial temporal fascia flap and a full-thickness skin graft, and then packed and sutured. The postoperative observation indicators mainly confirm whether the surgery was successful, the healing condition of the replanted ear, and whether there were problems such as skin flap necrosis, infection, hematoma, etc. The shape, color, texture and tactile recovery of the reconstructed auricle were evaluated by long-term follow-up for more than 1 year. The Vancouver scar scale (VSS) was used to assess scarring in both donor and recipient sites (total score of 0-15 points, higher scores indicated more severe scarring). The Likert 5-level scoring method was used to evaluate the patients’ satisfaction with the surgical results (total score of 30 points, ≥27 points were very satisfied, 24-26 points were somewhat satisfied, 18-23 points were indifferent, 15-17 points were somewhat dissatisfied, ≤14 points were very dissatisfied).Results:A total of 8 patients were enrolled, including 5 males and 3 females. Their ages ranged from 26 to 65 years, with an average of 41 years. All patients had unilateral ear defects, with 3 cases in the left ear and 5 cases in the right ear. The defect areas ranged from 1.5 cm × 2.5 cm to 5.0 cm × 4.0 cm. During the surgery, the harvested superficial temporoparietal fascia flaps ranged from 4.5 cm × 6.5 cm to 15.0 cm × 10.0 cm. After surgery, both the flaps and full-thickness skin graft healed satisfactorily, with primary healing observed in both the donor and recipient sites. There were no complications such as necrosis, infection, or hematoma were observed. The follow-up period ranged from 3 to 9 years, with an average of approximately 6.3 years. Except for one case that required a defatted surgery at the second stage, the reconstructed auricles of the remaining patients were basically consistent with the healthy side, with smooth contour lines, skin color and texture close to the surrounding tissues, and improved tactile sensitivity. In the final follow-up, the VSS scores for both the donor and recipient sites were ≤3 for all patients. All patients rated the surgical outcome as very satisfied.Conclusion:For the partial auricle of complete separation that has no chance of replantation, the use of superficial temporal fascia flap and detached ear composite graft to repair is a reliable and effective surgical method. Patients have good postoperative long-term effects and high levels of satisfaction.

Objective:To observe the long-term effect of superficial temporal fascia flap combined with severed auricle reimplantation in emergency repair of partial auricle of complete separation.Methods:The data of patients with partial auricle of complete separation admitted to Emergency Clinic of Burn and Plastic Surgery of General Hospital of Northern Theater Command from June 2014 to August 2023 were retrospectively analyzed. All of them were repaired with a superficial temporal fascia flap combined with amputating auricle reimplantation. During the operation, the superficial temporal fascia flap was harvested, and the pedicle was preserved. Then the detached auricular cartilage was removed and used as a replantation scaffold. Then the remaining skin was thinned to create a full-thickness skin graft after cartilage detachment. Referring to the position and angle of the contralateral auricle, the cartilage scaffold was sutured and fixed at the stump of the ear cartilage. The wound was covered with a superficial temporal fascia flap and a full-thickness skin graft, and then packed and sutured. The postoperative observation indicators mainly confirm whether the surgery was successful, the healing condition of the replanted ear, and whether there were problems such as skin flap necrosis, infection, hematoma, etc. The shape, color, texture and tactile recovery of the reconstructed auricle were evaluated by long-term follow-up for more than 1 year. The Vancouver scar scale (VSS) was used to assess scarring in both donor and recipient sites (total score of 0-15 points, higher scores indicated more severe scarring). The Likert 5-level scoring method was used to evaluate the patients’ satisfaction with the surgical results (total score of 30 points, ≥27 points were very satisfied, 24-26 points were somewhat satisfied, 18-23 points were indifferent, 15-17 points were somewhat dissatisfied, ≤14 points were very dissatisfied).Results:A total of 8 patients were enrolled, including 5 males and 3 females. Their ages ranged from 26 to 65 years, with an average of 41 years. All patients had unilateral ear defects, with 3 cases in the left ear and 5 cases in the right ear. The defect areas ranged from 1.5 cm × 2.5 cm to 5.0 cm × 4.0 cm. During the surgery, the harvested superficial temporoparietal fascia flaps ranged from 4.5 cm × 6.5 cm to 15.0 cm × 10.0 cm. After surgery, both the flaps and full-thickness skin graft healed satisfactorily, with primary healing observed in both the donor and recipient sites. There were no complications such as necrosis, infection, or hematoma were observed. The follow-up period ranged from 3 to 9 years, with an average of approximately 6.3 years. Except for one case that required a defatted surgery at the second stage, the reconstructed auricles of the remaining patients were basically consistent with the healthy side, with smooth contour lines, skin color and texture close to the surrounding tissues, and improved tactile sensitivity. In the final follow-up, the VSS scores for both the donor and recipient sites were ≤3 for all patients. All patients rated the surgical outcome as very satisfied.Conclusion:For the partial auricle of complete separation that has no chance of replantation, the use of superficial temporal fascia flap and detached ear composite graft to repair is a reliable and effective surgical method. Patients have good postoperative long-term effects and high levels of satisfaction.