Tissue repair requires the reconstruction of functional vascular networks to restore oxygen and nutrient delivery, eliminate metabolic waste, and maintain tissue homeostasis. Although biochemical factors such as growth factors and cytokines have been extensively studied in vascular regeneration, increasing evidence indicates that mechanical signals from the extracellular matrix (ECM) are equally important regulators of angiogenesis. Matrix stiffness, as a major biomechanical property of the tissue microenvironment, provides critical information that influences endothelial cell (EC) behavior and vascular remodeling through mechanotransduction. However, the biological effects of matrix stiffness are not universally defined as either pro- or anti-angiogenic, but are highly dependent on tissue context, cellular composition, disease progression, and the dynamic changes occurring during tissue repair. Therefore, understanding how matrix stiffness regulates vascular regeneration is essential for developing more precise strategies for tissue engineering and regenerative medicine. In this review, we summarize recent advances in the regulation of angiogenesis by matrix stiffness during tissue repair from multiple perspectives. First, we discuss the direct effects of matrix stiffness on EC behaviors, including differentiation, morphological remodeling, migration, proliferation, barrier maintenance, and vascular network formation. ECs sense mechanical alterations in the surrounding matrix through various mechanosensitive structures, including integrins, focal adhesion complexes, and mechanosensitive ion channels such as Piezo1 and TRPV proteins. These mechanical signals are subsequently transmitted through intracellular pathways involving FAK, RhoA/ROCK, MAPK, and Hippo-YAP/TAZ signaling, leading to cytoskeletal reorganization and transcriptional regulation. Through these mechanisms, matrix stiffness regulates endothelial functional states and determines the balance between regenerative vascular formation and pathological vascular remodeling. Beyond the direct regulation of ECs, we further highlight the importance of stiffness-mediated intercellular communication within the regenerative microenvironment. Matrix stiffness can regulate the behavior and secretory profiles of vascular-associated cells, including mesenchymal stem cells and macrophages, thereby indirectly affecting endothelial function through paracrine mechanisms. Changes in matrix mechanics influence the secretion of angiogenic factors, inflammatory cytokines, and extracellular vesicles from these cells, creating a mechanical regulation network that coordinates vascular regeneration. This perspective extends the traditional concept of matrix stiffness from a physical support structure to an active regulatory signal that integrates multiple cellular responses during tissue repair. Furthermore, we discuss the tissue-specific effects of matrix stiffness in vascular regeneration across different organs, including the aorta, lung, liver, and heart. Although excessive matrix stiffening is frequently associated with fibrosis and vascular dysfunction, the consequences of mechanical changes vary considerably among tissues. Moderate stiffness alterations may support endothelial activation and vascular stabilization in certain regenerative contexts, whereas persistent pathological stiffening can promote inflammation, endothelial dysfunction, and impaired vascular repair. These findings emphasize that the biological meaning of “soft” and “stiff” microenvironments should be interpreted according to specific tissue and experimental conditions rather than as universal mechanical classifications. Finally, we summarize current challenges and future perspectives in this field. A major limitation is the lack of standardized mechanical characterization among different studies, as stiffness measurements are influenced by material properties, testing methods, and experimental conditions, limiting direct comparison across research systems. Moreover, most existing models fail to fully reproduce the dynamic and viscoelastic properties of native ECM during tissue regeneration. Future studies should combine advanced biomaterials with standardized mechanical analysis, organoid models, and multi-omics approaches to establish more accurate mechanical regulatory maps. Overall, this review proposes that matrix stiffness is not merely a structural feature of tissues, but an active biological signal that regulates vascular regeneration through coordinated mechanotransduction and multicellular interactions. A deeper understanding of stiffness-mediated vascular regulation will provide new theoretical insights and therapeutic opportunities for improving tissue repair outcomes.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective To clarify the understanding of types of laboratories and manufacturers for GB 9706.1-2020 Medical electrical equipment-Part 1:General requirements for basic safety and essential performance by laboratory proficiency testing for creepage distance and electrical clearance test.Methods An operation guide was formed according to the testing program in GB 9706.1-2020,and the homogeneity and stability of the samples were evaluated according to CNAS-GL003:2018 Guidance on Evaluating the Homogenneity and Stability of Samples Used for Proficiency Testing.Robust statistic methods were used to assess the quantitative parameters of the test results of the participating laboratories according to the requirements in GB/T 28043-2019 Statistical methods for use in proficiency testing by interlaboratory comparison;the results reported by the expert laboratories were used as the specified values of the qualitative parameters.SPSS 25.0 statistical software was used for data analysis.Results All the results of the crreepage distance and electrical clearance tests met the requirements for homogeneity and stability.Of the 46 laboratories involved in,37 ones did have comprehensive satisfactory determinations while the remained 9 ones not.Conclusion Some laboratories don't behave well in understanding the standard,which have to be reformed accordingly to enhance their proficiencies.[Chinese Medical Equipment Journal,2024,45(10):54-59]

Objective: To select the preferred flaps for the reconstruction of different maxillary defects and to propose a new classification of maxillary defects. Methods: A total of 219 patients (136 males and 83 females) underwent the simultaneous reconstruction of maxillary defects in the Beijing Tongren Hospital, Capital Medical University, between January 2005 and December 2018 were reviewed. Age ranged from 16 to 78 years. Based on the proposed new classification of the maxillary defects, 22 patients with class Ⅰ defects (inferior maxillectomy), 44 patients with class Ⅱ defects (supperior maxillectomy), 132 patients with class Ⅲ defects (total maxillectomy) and 21 patients with class Ⅳ defects (extensive maxillectomy) were enrolled. Survival rate, functional and aesthetic outcomes of flaps were evaluated. Survival analysis was performed in 169 patients with malignant tumor, Kaplan-Meier method was used to calculate the survival rate, and Log-rank method was used to compare the difference of survival rate in each group. Results: A total of 234 repairs for maxillary defects were performed in 219 patients. Fibula flaps were used in 4/13 of class Ⅰ defects; temporal muscle flaps (11/24, 45.8%) and anterolateral thigh flaps (6/24, 25.0%) used in class Ⅱ defects; temporal muscle flaps (71/128, 55.5%), anterolateral thigh flaps (6/24, 25.0%) and fibula flaps (12/128, 9.4%) used in class Ⅲ defects; and anterolateral thigh flaps (8/20, 40.0%) and rectus abdominis flaps (8/20, 40.0%) used in class Ⅳ defects. The success rate of local pedicled flaps was 95.6% (109/114) and that of free flaps was 95.8% (115/120). Thrombosis(10/234,4.3%) was a main reason for repair failure. Among the followed-up 88 patients, swallowing and speech functions recovered, 82 (93.2%) of them were satisfied with appearance, and 75 (85.2%) were satisfied with visual field. The 3-year and 5-year overall survival rates were 66.5% and 63.6%, and the 3-year and 5-year disease-free survival rates were 57.1% and 46.2%, respectively, in the 169 patients with malignant tumors. Conclusion: A new classification of maxillary defects is proposed, on which suitable flaps are selected to offer patients good functional and aesthetic outcomes and high quality of life.
Adolescent ; Adult ; Aged ; Female ; Free Tissue Flaps ; Humans ; Male ; Maxilla/surgery* ; Middle Aged ; Quality of Life ; Reconstructive Surgical Procedures ; Young Adult

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

The effects of alcohol extracts from roots, stems, leaves, and flowers of Scutellaria Baicalensis Georgi (SBG) on endogenous metabolism in D-gal-induced aging-model rats were investigated by ¹H NMR metabolomics. Results showed that 32 endogenous metabolites were identified in the urine. Combined with the VIP value and t-test, 14 different metabolites were found by multivariate statistical analysis of the spectrum. Compared with the control group, the content of α-ketoglutaric acid, hippuric acid and 3-hydroxybutyrate in the urine of rats in the model group was significantly decreased (P<0.05) and the content of trimethylamine oxide, glycine, alanine, lactic acid, dimethylglycine, acetate, pyruvate, taurine, allantoin, betaine, N-acetylated glycoprotein was significantly increased (P<0.05). The metabolites were mainly derived from taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; pyruvate metabolism; glycolysis/gluconeogenesis; glyoxylic acid and dicarboxylic acid metabolism; and the tricarboxylic acid cycle. The content of differential metabolites in urine samples was altered by the alcohol extracts from the different parts of SBG. Leaves extracts of SBG had the greatest effect on urine metabolites, and mainly affected taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; and pyruvate metabolism. This study provides a reliable experimental basis for the future development of SBG. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036).

BACKGROUND: Long non-coding RNAs (lncRNAs) play key roles in human cancers. In our previous study, we demonstrated that lncRNA FKBP prolyl isomerase 9 pseudogene 1 (FKBP9P1) was highly expressed in head and neck squamous cell cancer (HNSCC) tissues. However, its functional significance remains poorly understood. In the present study, we identify the role and potential molecular biologic mechanisms of FKBP9P1 in HNSCC. METHODS: Quantitative real-time polymerase chain reaction was used to detect the expression of FKBP9P1 in HNSCC tissues, matched adjacent normal tissues, human HNSCC cells (FaDu, Cal-27, SCC4, and SCC9), and human immortalized keratinocytes cell HaCaT (normal control). Cal-27 and SCC9 cells were transfected with sh-FKBP9P1-1, sh-FKBP9P1-2, and normal control (sh-NC) lentivirus. Cell counting kit-8 assay, colony formation assay, wound healing assay, and trans-well assay were used to explore the biologic function of FKBP9P1 in HNSCC cells. Furthermore, western blotting was used to determine the mechanism of FKBP9P1 in HNSCC progression. Chi-squared test was performed to assess the clinical significance among FKBP9P1 high-expression and low-expression groups. Survival analyses were performed using the Kaplan-Meier method and assessed using the log-rank test. The comparison between two groups was analyzed by Student t test, and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test. RESULTS: FKBP9P1 expression was significantly up-regulated in HNSCC tissues (tumor vs. normal, 1.914 vs. 0.957, t = 7.746, P < 0.001) and cell lines (P < 0.01 in all HNSCC cell lines). Besides, the median FKBP9P1 expression of HNSCC tissues (1.677) was considered as the threshold. High FKBP9P1 level was correlated with advanced T stage (P = 0.022), advanced N stage (P = 0.036), advanced clinical stage (P = 0.018), and poor prognosis of HNSCC patients (overall survival, P = 0.002 and disease-free survival, P < 0.001). Knockdown of FKBP9P1 led to marked repression in proliferation, migration, and invasion of HNSCC cells in vitro (P all < 0.01). Mechanistically, silencing FKBP9P1 was observed to restrain the PI3K/AKT signaling pathway. CONCLUSIONS Silencing lncRNA FKBP9P1 represses HNSCC progression and inhibits PI3K/AKT (phosphatidylinositol 3 kinase/AKT Serine/Threonine Kinase) signaling in vitro. Therefore, FKBP9P1 could be a potential new target for the diagnosis and treatment of HNSCC patients.

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

OBJECTIVETo observe the effect of puerarin on methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) in the hippocampus of a rat model of vascular dementia (VD).

METHODSThirty-six healthy Sprague-Dawley rats were randomly assigned to the sham-operated group, dementia group and puerarintreated group using a random number table (n=12 per group). The modifified permanent bilateral common carotid artery occlusion method was used to establish the VD model. The sham-operated and dementia groups were given 2 mL/d of saline, while the puerarin-treated group was given 100 mg/(kg•d) of puerarin for 17 days. The learning and memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin staining, immunohistochemical (IHC) staining and Western blot analysis were carried out to observe changes in neuron morphology and in level of pMeCP2 in the hippocampus, respectively.

RESULTSThe morphologies of rat hippocampal neurons in the puerarintreated group were markedly improved compared with the dementia group. The escape latency of the dementia group was significantly longer than the sham-operated group (P<0.05), while the puerarin-treated group was obviously shorter than the dementia group (P<0.05). Cross-platform times of the dementia group were signifificantly decreased compared with the sham-operated group (P<0.05), while the puerarin-treated group was obviously increased compared with the dementia group (P<0.05). IHC staining showed no significant difference in the number of MeCP2 positive cells among 3 groups (P>0.05). The number of pMeCP2 positive cells in the CA1 region of hippocampus in the dementia group was signifificantly increased compared with the sham-operated group, and the puerarin-treated group was signifificantly increased compared with the dementia group (both P<0.05). Western blot analysis showed no signifificant difference of MeCP2 expression among 3 groups (P>0.05). The expression of pMeCP2 in the dementia group was signifificantly increased compared with the sham-operated group, while it in the puerarin-treated group was signifificantly increased compared with the dementia group (P<0.05).

CONCLUSIONPuerarin could play a role in the protection of nerve cells through up-regulating pMeCP2 in the hippocampus, improving neuron morphologies, and enhancing learning and memory ablities in a rat model of VD.

Animals ; Dementia, Vascular ; drug therapy ; genetics ; physiopathology ; Hippocampus ; pathology ; Isoflavones ; chemistry ; pharmacology ; therapeutic use ; Memory ; drug effects ; Methyl-CpG-Binding Protein 2 ; metabolism ; Phosphorylation ; drug effects ; Rats, Sprague-Dawley ; Up-Regulation ; drug effects

BACKGROUNDWith the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.

METHODSAll infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.

RESULTSA total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.

CONCLUSIONSOur study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

China ; Female ; Humans ; Infant ; Infant Mortality ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; statistics & numerical data ; Male ; Morbidity ; Respiratory Distress Syndrome, Newborn ; mortality ; Retrospective Studies ; Surveys and Questionnaires