The microstructures of pharmaceutical preparations play a pivotal role in determining their critical quality attributes(CQAs),such as drug release,content uniformity,and stability,which greatly impact the safety and efficacy of drugs.Unlike the inherent molecular structures of active pharmaceutical in-gredients(APIs)and excipients,the microstructures of pharmaceutical preparations are developed during the formulation process,presenting unique analytical challenges.In this review,we primarily focus on presenting the research methods used to elucidate the microstructures of pharmaceutical preparations,including X-ray imaging(XRI),scanning electron microscopy(SEM),atomic force microscopy(AFM),Raman spectroscopy,infrared(IR)spectroscopy,and rheometer technology.Subse-quently,we highlight the applications,advantages,and limitations of these methods.Finally,we discuss the current challenges and future perspectives in this field.This review aims to provide a comprehensive reference for understanding the microstructures of pharmaceutical preparations,offering new insights and potential advancements in their development.

The microstructures of pharmaceutical preparations play a pivotal role in determining their critical quality attributes (CQAs), such as drug release, content uniformity, and stability, which greatly impact the safety and efficacy of drugs. Unlike the inherent molecular structures of active pharmaceutical ingredients (APIs) and excipients, the microstructures of pharmaceutical preparations are developed during the formulation process, presenting unique analytical challenges. In this review, we primarily focus on presenting the research methods used to elucidate the microstructures of pharmaceutical preparations, including X-ray imaging (XRI), scanning electron microscopy (SEM), atomic force microscopy (AFM), Raman spectroscopy, infrared (IR) spectroscopy, and rheometer technology. Subsequently, we highlight the applications, advantages, and limitations of these methods. Finally, we discuss the current challenges and future perspectives in this field. This review aims to provide a comprehensive reference for understanding the microstructures of pharmaceutical preparations, offering new insights and potential advancements in their development.

Objective:To investigate the clinical application value of a novel filter's retraction hook capture technique of pull-assisted method for the endovascular retrieval of conical inferior vena cava (IVC) filters whose hook attached to the wall.Methods:From January 2020 to December 2024, patients with conical filters whose hook attached to the wall admitted at Beijing Jishuitan Hospital were enrolled consecutively.Results:A total of 46 patients underwent filter retrieval using filter's retraction hook capture technique of pull-assisted method. Among these patients, 39 cases (84.8%) were successful in filter retrieval, with the penetration distance of cranial anchor vertex of 3.3(2.5, 4.4) mm, and 13 (33.3%) filters were deformed. The other 7 cases were unsuccessful, with a penetration distance of cranial anchor vertex of 5.0 (4.3, 5.0) mm, and 6 (85.7%) filters were deformed. There was a statistically significant difference between the two groups ( P<0.05). One case (2.2%) had IVC injury, one case (2.2%) experienced filter fracture, and no symptomatic pulmonary embolism occurred. Logistic regression analysis showed that filter deformation was an independent dangerous factor for filter's retraction. Conclusions:Filter's retraction hook capture technique of pull-assisted method is effective in removing conical filters whose hook attached to the wall, with no symptomatic PE occurring. This method can be considered as a new adjuvant technique for filter retrieval.

Objective:To investigate the clinical application value of a novel filter's retraction hook capture technique of pull-assisted method for the endovascular retrieval of conical inferior vena cava (IVC) filters whose hook attached to the wall.Methods:From January 2020 to December 2024, patients with conical filters whose hook attached to the wall admitted at Beijing Jishuitan Hospital were enrolled consecutively.Results:A total of 46 patients underwent filter retrieval using filter's retraction hook capture technique of pull-assisted method. Among these patients, 39 cases (84.8%) were successful in filter retrieval, with the penetration distance of cranial anchor vertex of 3.3(2.5, 4.4) mm, and 13 (33.3%) filters were deformed. The other 7 cases were unsuccessful, with a penetration distance of cranial anchor vertex of 5.0 (4.3, 5.0) mm, and 6 (85.7%) filters were deformed. There was a statistically significant difference between the two groups ( P<0.05). One case (2.2%) had IVC injury, one case (2.2%) experienced filter fracture, and no symptomatic pulmonary embolism occurred. Logistic regression analysis showed that filter deformation was an independent dangerous factor for filter's retraction. Conclusions:Filter's retraction hook capture technique of pull-assisted method is effective in removing conical filters whose hook attached to the wall, with no symptomatic PE occurring. This method can be considered as a new adjuvant technique for filter retrieval.

By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.

Objective To investigate the correlation between the Controlling Nutritional Status (CONUT) score and wound repair of diabetic foot ulcer (DFU). Methods A total of 80 DFU patients treated in the Hospital from November 20, 2019 to November 20, 2022 were randomly selected as the study objects and divided into non-wound repair group (n=47) and wound repair group (n=33) based on wound repair status. Wound repair and hospital stay were recorded; clinical characteristics and the CONUT score were compared between the wound repair group and the non-wound repair group; the influencing factors of DFU wound repair were analyzed by the multivariate Logistic regression model. Results The hospital stay of patients in the non-wound repair group was 16.00 (10.50 to 24.00) days, which was significantly shorter than 44.00 (31.00 to 61.80) days of patients in the wound repair group (P < 0.05). The total cholesterol (TC), ankle-brachial index (ABI), the CONUT score, and malnutrition rate of patients in the non-wound repair group were significantly higher than those in the wound repair group (P < 0.05). The results of multivariate Logistic regression analysis showed that the CONUT score, malnutrition, TC and ABI were the independent risk factors for wound repair of DFU (P < 0.05). Conclusion Malnutrition, ABI, TC and CONUT score in DFU patients can adversely affect wound repair, and the CONUT score can accurately predict the risk of wound repair in patients, serving as a reliable reference for clinicians in early assessment of DFU.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

Although a great deal of research has been done on sepsis in children，its pathogenesis remains controversial and unresolved，one of which is immune dysfunction.Immunosuppression is the core part of immune dysfunction，and it is related to the disease progression，treatment options，and prognosis changes in patients with sepsis.Since T lymphocytes play a crucial role in immune function，they have been regarded as an important indicator for judging changes in immune function in clinical practice.This review explained the mechanism of immunosuppression caused by some T lymphocyte subsets and its clinical application value in the evaluation，prognosis and immune intervention of sepsis.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.