Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

Objective Exploring genetic differences among geographic strains of Anopheles sinensis in China. Methods Based on the mitochondrial cytochrome oxidase subunit I(COⅠ )and ribosomal the second internal transcribed spacer(ITS2), genetic distance analyses were conducted on An. sinensis samples collected nationwide. Results Genetic differentiation was observed within An. sinensis geographic strains, primarily reflected in the genetic distances of COⅠ sequences, with some distances between samples exceeding those between closely related species. However, ITS2 sequences showed relatively low levels of differentiation within geographic strains. No significant separation was observed, and gene exchange exhibited a random pattern among geographic strains. Conclusions Significant differences in genetic distance were observed among An. sinensis samples, along with evidence of interspecific continuity among sibling species. For the identification of closely related species using wild-collected Anopheles mosquitoes samples, reliance solely on commonly used barcodes such as COⅠ and ITS2 may be insufficient. Additional molecular markers, including COⅡ and D3 gene fragments, should also be considered. Caution should be exercised when using COⅠ genes to identify cryptic species, especially within Anopheles mosquitoes.

Objective:To investigate the molecular mechanisms of bexarotene in treating double hit lymphoma(DHL)based on Weighted Gene Co-expression Network Analysis(WGCNA),thereby providing potential targets and experimental evidence for DHL treatment.Methods:The gene expression datasets GSE44164 and GSE43677 were downloaded from the Gene Expression Omnibus(GEO)database,and differentially expressed genes(DEGs)were identified.WGCNA was employed to identify gene modules associated with DHL.A protein-protein interaction(PPI)network was constructed to screen for key hub genes.Drug-gene association analysis was conducted using the EpiMed platform to identify potential targeted drugs for DHL.The effects of bexarotene on DHL cell proliferation and key protein expression were evaluated using the CCK-8 assay and Western blotting(WB),and its effects on cell apoptosis was evaluated using flow cytometry.Results:WGCNA identified a turquoise module highly associated with DHL,and 10 hub genes(COL1A2,COL3A1,MMP2,COL5A2,DCN,BGN,FN1,MMP9,FBN1,and LUM)were screened from the PPI network.Drug association analysis nominated bexarotene as a potential therapeutic agent.In vitro validation demonstrated that bexarotene significantly inhibited U2932 cell viability(P<0.05),promoted cell apoptosis(P<0.001),and downregulated c-Myc and COL1A2 expression(P<0.05).Conclusion:Bexarotene may exert anti-DHL effects by suppressing the c-Myc signaling pathway and modulating extracellular matrix-related genes.Further studies are warranted to validate its in vivo efficacy and potential for combination therapy.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.

Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.

Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.

Objective:To investigate the effect of concentrated growth factor (CGF) on the biological performance of human dental pulp stem cells (hDPSCs) under oxidative stress status induced by hydrogen peroxide (H 2O 2). Methods:The hDPSCs were isolated by using tissue block separation method from healthy permanent teeth extracted for orthodontic reason. hDPSCs surface markers CD34, CD45, CD90 and CD105 were detected by flow cytometry. Alkaline phosphatase (ALP), alizarin red S (ARS), oil red O staining and colony formation assay were used to identify hDPSCs. After the cell counting kit-8 (CCK-8) detection, the optimal H 2O 2 concentration was used to construct the hDPSCs oxidative stress model. CGF conditioned medium was prepared by repeated freeze-thaw methods. After CCK-8 detection, the optimum CGF concentration was chosen for the subsequent experiments. The hDPSCs were divided into control group, H 2O 2 (only H 2O 2 processing), H 2O 2+CGF group (H 2O 2 processing in combination with the CGF) and CGF group (only CGF processing). Subsequent experiments were performed according to these groups. The oxidative stress model was verified by reactive oxygen species, β-galactosidase staining and Western blotting. The effects of CGF on the proliferation and migration of hDPSCs under oxidative stress status were detected by CCK-8 and cell scratch assay, respectively. ALP activity and ARS staining were used to detect the effect of CGF on the osteogenic differentiation of hDPSCs under oxidative stress status. The mRNA expression levels of odontogenesis related genes were detected by real-time fluorescence quantitative PCR (RT-qPCR), and the expression levels of odontogenesis and osteogenesis related proteins were detected by Western blotting. Results:Isolated hDPSCs showed positive expression of mesenchymal stem cells surface markers of CD90, CD105, and negative expression of hematopoietic stem cells surface markers CD34, CD45. The hDPSCs were proved to have the capacity of osteogenic, adipogenic differentiation and clone formation. The optimal concentration to construct the oxidative stress model was 200 μmol/L H 2O 2. Twenty percent CGF was the optimal concentration for subsequent experiments. Compared with the control group, the expression of aging protein p53 was significantly up-regulated from (0.82±0.12) to (1.19±0.14) in H 2O 2 group ( P<0.05), with deepened β-galactosidase staining and increased fluorescence intensity of reactive oxygen species. The proliferative capacity of cells in H 2O 2+CGF group on day 1, 3, 5 and 7 (0.23±0.01, 0.50±0.02, 1.60±0.07, 1.80±0.21) were all higher than in H 2O 2 group (0.15±0.01, 0.14±0.02, 0.50±0.03, 0.90±0.09) ( P<0.05). Cell healing capacity of cells in H 2O 2+CGF group at 12 h and 24 h [(47±7)%, (58±44)%] also increased compared with the H 2O 2 group [(36±2)%, (44±2)%] ( P<0.05), and similar results in the activity of ALP and the formation of mineralized nodules. On day 28, the mRNA expressions of dentin sialophosphoprotein (0.52±0.16) and dental matrix protein 1 (DMP-1) (0.39±0.13) in H 2O 2 group were all significantly lower than those in H 2O 2+CGF group (0.96±0.24, 0.83±0.30, respectively) and CGF group (1.12±0.18, 1.23±0.19, respectively) ( P<0.05). On day 28, the expressions of odontogenesis related protein DMP-1 (0.27±0.04) and osteogenesis related protein Runt-related transcription factor-2 (0.42±0.15) in H 2O 2 group were all significantly lower than those in H 2O 2+CGF group (0.66±0.18, 0.68±0.04) and CGF group (1.15±0.13, 1.06±0.19, respectively) ( P<0.05). Conclusions:H 2O 2 can induce oxidative stress in hDPSCs, while CGF can promote proliferation, migration, odontogenic and osteogenic differentiation of hDPSCs under oxidative stress status.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To explore the characteristics of serum galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1/IgA ratio in normal children.Methods:The children from a kindergarten and 3 primary or secondary schools in Baoding (Hebei Province) from March to August 2023 were included in the cross-sectional study.According to their age, the children were divided into the 3-6-year-old group, >6-11-year-old group, and >11-16-year-old group.Besides, some adults were also included as the control group.The immunoturbidimetric assay was used to detect serum IgA levels, and the enzyme-linked immunosorbent assay (ELISA) was employed to detect Gd-IgA1 and Gd-IgA1/IgA levels.The above indicators were subject to normal distribution tests and analysis of variance (ANOVA)or rank sum test.Results:A total of 136 normal subjects were included for analysis.Among these subjects, there were 64 males and 72 females.There were 13 children in the 3-6-year-old group, 51 children in the >6-11-year-old group, and 56 children in the >11-16-year-old group.Besides, 16 normal adults (28-45 years old) from the physical examination center were also included as the control group.The serum IgA levels of the 3-6-year-old group, >6-11-year-old group, >11-16-year-old group, and adult group were (0.88±0.35) g/L, (1.38±0.65) g/L, (1.78±0.61) g/L, and (2.49±0.94) g/L, respectively.Except for no statistically significant difference between the 3-6-year-old group and the >6-11-year-old group, as well as between the >11-16-year-old group and the adult group, all other age groups showed statistically significant differences in serum IgA levels (all P<0.05).The serum Gd-IgA1 levels of the 3-6-year-old group, >6-11-year-old group, >11-16-year-old group, and adult group were 7.77(5.77, 16.51) μg/L, 7.12(5.29, 9.82) μg/L, 8.96(6.21, 14.30) μg/L, and 9.39(6.63, 40.00) μg/L, respectively, with statistically significant differences ( H=9.22, P=0.027).There was no significant difference in the Gd-IgA1/IgA ratio among different groups ( P=0.130).The correlation analysis suggested that Gd-IgA1/IgA1 did not correlate with age ( r=0.134, P=1.200).The Gd-IgA1 level was positively correlated with the IgA level ( r=0.204, P=0.017).There was no significant difference in serum IgA, Gd-IgA1, and Gd-IgA1/IgA levels between different gender groups. Conclusions:There are differences in Gd-IgA1 levels among different age groups among these children, but Gd-IgA1/IgA is not correlated with age.As a diagnostic biomarker, Gd-IgA1 should be emphasized from the different levels among different age groups, while Gd-IgA1/IgA seems to be more convenient for clinical research and application.

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin