Chromosomal Abnormalities Detected by Chromosomal Microarray Analysis and Karyotype in Fetuses with Ultrasound Abnormalities.

Objective: Chromosomal microarray analysis (CMA) is a first-line test to assess the genetic etiology of fetal ultrasound abnormalities. The aim of this study was to evaluate the effectiveness of CMA in detecting chromosomal abnormalities in fetuses with ultrasound abnormalities, including structural abnormalities and non-structural abnormalities. Methods: A retrospective study was conducted on 368 fetuses with abnormal ultrasound who received interventional prenatal diagnosis at Meizhou People's Hospital from October 2022 to December 2023. Samples of villi, amniotic fluid, and umbilical cord blood were collected according to different gestational weeks, and karyotype and CMA analyses were performed. The detection rate of chromosomal abnormalities in different ultrasonic abnormalities was analyzed. Results: There were 368 fetuses with abnormal ultrasound, including 114 (31.0%) with structural abnormalities, 225 (61.1%) with non-structural abnormalities, and 29 (7.9%) with structural combined with non-structural abnormalities. The detection rate of aneuploidy and pathogenic (P)/likely pathogenic (LP) copy number variations (CNVs) of CMA in fetuses with structural abnormalities was 5.26% (6/114), the detection rate of karyotype was 2.63% (3/114), and the additional diagnosis rate of CMA was 2.63%. In the fetuses with ultrasonic non-structural abnormalities, the detection rate of karyotype was 6.22% (14/225), the detection rate of aneuploidy and P/LP CNVs in fetuses with ultrasonic structural abnormalities was 9.33% (21/225), and the additional diagnosis rate of CMA was 3.11%. There was no significant difference in chromosome abnormality detection rate of CMA among structural abnormality, non-structural abnormality, and structural abnormality combined with non-structural abnormality groups (5.3%, 9.3%, and 13.8%, p = 0.241), also among multiple ultrasonic abnormality and single ultrasonic abnormality groups (14.8%, and 7.3%, p = 0.105). Conclusion: CMA can significantly improve the detection rate of genetic abnormalities in prenatal diagnosis of ultrasonic abnormal fetuses compared with karyotype analysis. CMA is a more effective tool than karyotyping alone in detecting chromosomal abnormalities in fetuses with ultrasound abnormalities.

Factors related to the occurrence of fetal birth defects and the construction of a Nomogram model.

Objective: To explore the influencing factors of fetal birth defects (BD) and construct a nomogram model. Methods: A total of 341 newborns admitted to Meizhou people's hospital from September 2021 to September 2023 were randomly grouped into a modeling group (239 cases) and a validation group (102 cases). The modeling group fetuses were separated into BD and non-BD groups. Multivariate logistic regression analyzed risk factors for BD; R software constructed a nomogram model; Receiver operating characteristic (ROC) curve evaluated the model's discrimination for BD. Results: The top 5 types of BD were congenital heart disease, polydactyly/syndactyly, cleft lip/palate, ear malformation, and foot malformation, with incidence rates of 23.81%, 20.63%, 12.70%, 11.11%, and 7.94%, respectively. BD incidence was 26.36% (63/239). Significant differences between BD and non-BD groups were found in maternal age, gestational age, history of adverse pregnancy/childbirth, gestational hypertension, adverse emotions during pregnancy, and folic acid intake duration (P<0.05). Logistic regression showed maternal age (OR: 4.125), gestational age (OR: 3.066), adverse pregnancy history (OR: 10.628), gestational hypertension (OR: 5.658), adverse emotions (OR: 5.467), and folic acid intake duration (OR: 4.586) were risk factors for BD (P<0.05). The modeling group's ROC AUC was 0.938, calibration curve slope close to 1, H-L test =8.342, P=0.692; external validation AUC was 0.961, calibration slope close to 1, H-L test =7.634, P=0.635. Conclusion: Identified risk factors include maternal age, gestational age, adverse pregnancy history, gestational hypertension, adverse emotions, and folic acid intake duration. The nomogram model shows good discrimination and consistency for evaluating neonatal BD risk.

Chromosomal Microarray Analysis in Fetuses with Ultrasound Abnormalities.

Objective: To explore and evaluate the value of chromosomal microarray analysis (CMA) in prenatal diagnosis of fetuses with ultrasound abnormalities. Methods: A retrospective analysis was performed on 370 fetuses with ultrasound abnormalities received invasive prenatal diagnosis at Meizhou People's Hospital from October 2022 to December 2023. Fetal specimens were analyzed by CMA, and the detection rates of aneuploidy and pathogenic (P)/likely pathogenic (LP) copy number variations (CNVs) in ultrasound structural abnormalities (malformations of fetal anatomy) and non-structural abnormalities (abnormalities of fetal nonanatomical structure) were analyzed. Results: There were 114 (30.8%) cases with isolated ultrasound structural abnormalities, 226 (61.1%) cases with isolated non-structural abnormalities (182 isolated ultrasound soft markers abnormalities, 30 isolated fetal growth restriction (FGR), and 8 isolated abnormalities of amniotic fluid volume), and 30 (8.1%) cases with both structural and non-structural abnormalities. The overall detection rate of aneuploidy and P/LP CNVs in isolated ultrasonic structural abnormalities was 5.3%, among which cardiovascular system abnormalities were the highest. In addition, the largest number of fetuses with non-structural abnormalities was nuchal translucency (NT) thickening (n = 81), followed by ventriculomegaly (n = 29), and nasal bone dysplasia (n = 24). The detection rate of chromosomal abnormalities of fetuses with abnormal ultrasound soft markers was 9.9%, and the detection rate in single abnormal ultrasound soft marker, and multiple ultrasound soft markers abnormalities was 9.7% (16/165) and 11.8% (2/17), respectively. Moreover, the detection rate of chromosomal abnormalities of fetuses with FGR and structural abnormalities combined with non-structural abnormalities was 6.7% (2/30), and 13.3% (4/30), respectively. Conclusion: The incidence of chromosomal abnormalities (aneuploidy and P/LP CNVs) varies among different fetal ultrasound abnormalities.

Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies.

Triple-negative breast cancer (TNBC) poses significant challenges in oncology due to its aggressive nature, limited treatment options, and poorer prognosis compared to other breast cancer subtypes. This comprehensive review examines the therapeutic and diagnostic landscape of TNBC, highlighting current strategies, emerging therapies, and future directions. Targeted therapies, including PARP inhibitors, immune checkpoint inhibitors, and EGFR inhibitors, hold promise for personalized treatment approaches. Challenges in identifying novel targets, exploring combination therapies, and developing predictive biomarkers must be addressed to optimize targeted therapy in TNBC. Immunotherapy represents a transformative approach in TNBC treatment, yet challenges in biomarker identification, combination strategies, and overcoming resistance persist. Precision medicine approaches offer opportunities for tailored treatment based on tumor biology, but integration of multi-omics data and clinical implementation present challenges requiring innovative solutions. Despite these challenges, ongoing research efforts and collaborative initiatives offer hope for improving outcomes and advancing treatment strategies in TNBC. By addressing the complexities of TNBC biology and developing effective therapeutic approaches, personalized treatments can be realized, ultimately enhancing the lives of TNBC patients. Continued research, clinical trials, and interdisciplinary collaborations are essential for realizing this vision and making meaningful progress in TNBC management.

LncRNA OIP5-AS1 Upregulates the Cyclin D2 Levels to Promote Metastasis of Breast Cancer by Targeting miR-150-5p.

OBJECTIVE: Breast cancer (BC) is a cancer that seriously affects women's health. BC cell migration increases the mortality of BC patients. Current studies have shown that long noncoding RNAs (LncRNAs) are related to the metastasis mechanism of BC. This study aimed to explore the function and role of LncRNA OIP5-AS1 in BC. And we analyzed its regulatory mechanism and related modification process. METHODS: Our study analyzed the expression pattern of OIP5-AS1 in BC tissues and cell lines by qRT-PCR. The effects of OIP5-AS1 on the function of BC cells were detected by CCK-8 and transwell experiments. Bioinformatics analysis and double luciferase reporter gene detection were used to confirm the correlation between OIP5-AS1 and miR-150-5p and between miR-150-5p and Cyclin D2 (CCND2). The rescue test analyzed the effect of miR-150-5p regulating OIP5-AS1. In addition, the N6-methyladenosine (m6A) modification process of OIP5-AS1 was analyzed by RNA m6A dot blot, RIP assay, and double luciferase report experiment. RESULTS: OIP5-AS1 was significantly upregulated in BC tissues and cell lines. OIP5-AS1 knockdown inhibited BC cell viability, migration and invasion. OIP5-AS1 upregulated CCND2 by binding with miR-150-5p. This process affected the metastasis of BC. Higher degree of m6A methylation was confirmed in BC cell lines. There were some binding sites between methyltransferase like 3 (METTL3) and OIP5-AS1. Moreover, the silencing of METTL3 inhibited the OIP5-AS1 expression through decreasing the m6A methylation levels. CONCLUSIONS: LncRNA OIP5-AS1 promoted cell viability and metastasis of BC cells by targeting miR-150-5p/CCND2 axis. This process was modified by m6A methylation of METTL3.

MiR-760 exerts a critical regulatory role in glioma proliferation, migration, and invasion by modulating MMP2 expression.

Background: Glioma represents the predominant subtype of brain tumor, characterized by an unfavorable prognosis. Current evidence indicates the involvement of microRNAs (miRNAs) in the initiation and progression of glioma malignancies. While miR-760 has been recognized in the context of tumorigenesis, its precise role in gliomas remains insufficiently explored. Methods: In this investigation, we harnessed the GSE25631 database to scrutinize the aberrant expression profiles of microRNAs, whereby the diminished expression of miR-760 in glioblastoma was validated. Our aim was to delineate the expression patterns of microRNA-760 (miR-760) and probe its prognostic significance within the realm of glioma. Employing quantitative real-time polymerase chain reaction, we ascertained the relative expression levels of miR-760 and MMP2 in glioma cell lines. The impact of miR-760 on cell proliferation, migration, and invasion was assessed through Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assays. Bioinformatics analysis corroborated the downstream target gene of miR-760. Furthermore, a luciferase reporter experiment was conducted to pinpoint MMP2 as the direct target gene of miR-760. The assessment of MMP2 protein levels was accomplished through Western blotting and immunofluorescence techniques. Result: Our data unequivocally revealed a substantial reduction in miR-760 expression within glioma tissues and cell lines. Heightened miR-760 levels exerted a restraining influence on the proliferation, migration, and invasion capabilities of glioma cell lines. The outcomes of our bioinformatics analysis unveiled the ability of miR-760 to engage with and curtail MMP2 expression. Collectively, these findings posit that miR-760 exerts a restraining influence on glioma growth by orchestrating the upregulation of miR-760 along the miR-760/MMP2 axis. Conclusion: The delineation of the miR-760/MMP2 axis promises to broaden our comprehension of the intricate molecular mechanisms underpinning glioma proliferation and may unveil prospective therapeutic avenues for the management of glioma.

Clinical features of adult patients with allergic parotitis.

Background: Allergic parotitis (AP), due to its non-specific symptoms, frequently poses a diagnostic challenge, leading to cases being overlooked or misdiagnosed by clinicians. Objective: This study aimed to elucidate detailed clinical characteristics and common diagnostic indicators of AP. Methods: A comprehensive review and analysis of medical records was conducted from patients diagnosed with AP, encompassing demographic, clinical, and laboratory data, at the Affiliated Stomatological Hospital of Nanjing Medical University between January 2019 and March 2022. Results: The study enrolled 17 patients, evidenced by an average age of 36.00 ± 12.95 years. Common presentations of AP among the patients included notable symptoms such as parotid gland swelling, associated pain, and xerostomia. Ten patients had other atopic diseases. Palpation revealed the affected parotid glands to be soft and nodular, with an elevated local skin temperature. The unstimulated whole saliva flow rate was decreased. Ultrasonography demonstrated increased volume, reduced echo heterogeneity, and lymph node enlargement in the affected parotid glands. All cases observed increased serum salivary amylase and total IgE levels. Investigation of food allergens and inhaled allergen-specific IgE showed that all patients had suspected food allergies. Food provocation tests (FPT) induced AP in 13 cases, confirming the role of food allergens. Conclusion: Food allergens are involved in the etiology of AP, underscoring the importance of comprehensive clinical evaluation, including symptoms, signs, and confirmatory auxiliary tests, such as FPT, for accurate diagnosis and differentiation from other salivary gland pathologies.

BRCA1 and BRCA2 germline mutations in Chinese Hakka breast cancer patients.

OBJECTIVE: To investigate the prevalence of BRCA1/2 gene variants and evaluate the clinical and pathological characteristics associated with these variants in Chinese Hakka breast cancer patients. METHODS: A total of 409 breast cancer patients were analyzed based on next-generation sequencing results, with 337 categorized as non-carriers and 72 as carriers of BRCA1/2 variants. Data on the patients' BRCA1/2 gene mutation status, clinical and pathological characteristics, as well as menstrual and reproductive information, were collected, analyzed, compared, and tabulated. Logistic regression analysis was performed to explore the relationship between clinical characteristics and pathogenic variants. RESULTS: Among the patients, 72 were identified as carriers of pathogenic or likely pathogenic variants in BRCA1/2, while 337 had likely benign or benign mutations. The BRCA1 c.2635G > T (p. Glu879*) variant was detected at a high frequency, accounting for 12.5% (4/32) of the BRCA1 mutations, while the c.5164_5165del (p.Ser1722Tyrfs*4) variant was common among the BRCA2 mutations, accounting for 17.5% (7/40). It was observed that a higher proportion of BRCA1 carriers had the triple-negative breast cancer subtype, whereas more BRCA2 carriers exhibited estrogen receptor (ER) + and progesterone receptor (PR) + subtypes. Multivariate logistic regression analysis revealed that a family history of cancer (OR = 2.36, 95% CI = 1.00-5.54), bilateral cancer (OR = 4.78, 95% CI 1.61-14.20), human epidermal growth factor receptor 2 (HER2)- (OR = 8.23, 95% CI 3.25-20.84), and Ki67 ≥ 15% (OR = 3.88, 95% CI 1.41-10.65) were associated with BRCA1/2 mutations, with the age at diagnosis, age at menarche, and premenopausal status serving as covariates. CONCLUSIONS: The most common pathogenic variant of the BRCA1 and BRCA2 in breast cancer patients was c.2635G > T and c.5164_5165del, respectively. Additionally, a family history of cancer, bilateral cancer, HER2-, and Ki67 ≥ 15% were identified as independent predictors of BRCA1/2 pathogenic variants.

An Integrative Bioorthogonal Nanoengineering Strategy for Dynamically Constructing Heterogenous Tumor Spheroids.

Although tumor models have revolutionized perspectives on cancer aetiology and treatment, current cell culture methods remain challenges in constructing organotypic tumor with in vivo-like complexity, especially native characteristics, leading to unpredictable results for in vivo responses. Herein, the bioorthogonal nanoengineering strategy (BONE) for building photothermal dynamic tumor spheroids is developed. In this process, biosynthetic machinery incorporated bioorthogonal azide reporters into cell surface glycoconjugates, followed by reacting with multivalent click ligand (ClickRod) that is composed of hyaluronic acid-functionalized gold nanorod carrying dibenzocyclooctyne moieties, resulting in rapid construction of tumor spheroids. BONE can effectively assemble different cancer cells and immune cells together to construct heterogenous tumor spheroids is identified. Particularly, ClickRod exhibited favorable photothermal activity, which precisely promoted cell activity and shaped physiological microenvironment, leading to formation of dynamic features of original tumor, such as heterogeneous cell population and pluripotency, different maturation levels, and physiological gradients. Importantly, BONE not only offered a promising platform for investigating tumorigenesis and therapeutic response, but also improved establishment of subcutaneous xenograft model under mild photo-stimulation, thereby significantly advancing cancer research. Therefore, the first bioorthogonal nanoengineering strategy for developing dynamic tumor models, which have the potential for bridging gaps between in vitro and in vivo research is presented.

KRAS/NRAS Mutations Associated with Distant Metastasis and BRAF/PIK3CA Mutations Associated with Poor Tumor Differentiation in Colorectal Cancer.

Background: The occurrence, progression, and prognosis of colorectal cancer (CRC) are regulated by EGFR-mediated signaling pathways. However, the relationship between the core genes (KRAS/NRAS/BRAF/PIK3CA) status in the signaling pathways and clinicopathological characteristics of CRC patients in Hakka population remains controversial. Methods: Patients were genotyped for KRAS (codons 12, 13, 61, 117, and 146), NRAS (codons 12, 61, 117, and 146), BRAF (codons 600), and PIK3CA (codons 542, 545 and 1047) mutations. Clinical records were collected, and clinicopathological characteristic associations were analyzed together with mutations of studied genes. Results: Four hundred and eight patients (256 men and 152 women) were included in the analysis. At least one mutation in the four genes was detected in 216 (52.9%) patients, while none was detected in 192 (47.1%) patients. KRAS, NRAS, BRAF, and PIK3CA mutation status were detected in 190 (46.6%), 11 (2.7%), 10 (2.5%), 34 (8.3%) samples, respectively. KRAS exon 2 had the highest proportion (62.5%). Age, tumor site, tumor size, lymphovascular invasion, and perineural invasion were not associated with gene mutations. KRAS mutations (adjusted OR 1.675, 95% CI 1.017-2.760, P=0.043) and NRAS mutations (adjusted OR 5.183, 95% CI 1.239-21.687, P=0.024) appeared more frequently in patients with distant metastasis. BRAF mutations (adjusted OR 7.224, 95% CI 1.356-38.488, P=0.021) and PIK3CA mutations (adjusted OR 3.811, 95% CI 1.268-11.455, P=0.017) associated with poorly differentiated tumor. Conclusion: KRAS/NRAS mutations are associated with distant metastasis and BRAF/PIK3CA mutations are associated with poor tumor differentiation in CRC. And the results provided a better understanding between clinicopathological characteristics and gene mutations in CRC patients.

Differences in the Proportion of CYP2C19 Loss-of-Function Between Cerebral Infarction and Coronary Artery Disease Patients.

Background: Cytochrome P450 2C19 (CYP2C19) genotypes and metabolic phenotypes (extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM)) are related to the metabolism of therapeutic drugs for cardiovascular and cerebrovascular diseases. This study aimed to investigate the differences of CYP2C19 gene polymorphism distribution between coronary artery disease (CAD) patients and cerebral infarction (CI) patients. Methods: We identified 413 CI patients, 509 CAD patients, and 241 CI+CAD patients from 2016 to 2020 and studied genotypes of CYP2C19 rs4986893 (636G>A) and rs4244285 (681G>A) polymorphisms using PCR-gene chip detection method. Differences in CYP2C19 genotypes and metabolic phenotypes between the groups were compared. To analyze the efficacy of CYP2C19 metabolic phenotypes in discriminating between cerebral infarction and coronary artery disease, multiple logistic regression analysis was conducted after adjusting for gender, age, smoking history, drinking history, hypertension, and diabetes. Results: There were significant differences in the distribution of CYP2C19 genotypes and metabolic phenotypes between CI and CAD patients. The results of multivariate logistic regression (adjusted for sex, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 IM phenotype (IM vs EM: OR 1.443, 95% CI: 1.086-1.918, P=0.011) and CYP2C19 IM+PM phenotype (IM or PM vs EM: OR 1.440, 95% CI: 1.100-1.885, P=0.008) may be indicators of CI from CAD. Conclusion: CYP2C19 EM metabolic phenotype was dominant in CAD patients, and CYP2C19 IM metabolic phenotype was dominant in CI patients. After adjusting for other confounding factors, patients with the CYP2C19 IM metabolic phenotype were more likely to develop CI than CAD.

[Evaluation of the effect of cattle calcined bone grafting material to repair alveolar bone defect after tooth extraction].

PURPOSE: To verify the efficacy and safety of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction. METHODS: A randomized, bind, parallel, positive-control multicenter clinical trial was conducted. A total of 280 subjects were randomly assigned to either the experimental group (calcined cattle bone group) or control group (Bio-Oss group) equally. The main efficacy indicator was the imaging changes 24 weeks after material implantation. Secondary efficacy indicators were wound healing, rejection, bone metabolism, post-filling symptoms and signs of bone infection. The safety of material was assessed by the incidence of adverse events and serious adverse events. SAS 8.2 software package was used for statistical analysis. RESULTS: A total of 280 cases were included, of them 267 cases completed the study while 13 cases fell off. The effective rate of FAS(PPS) was 90.58%(97.46%) in the experimental group and 87.05% (95.04%) in the control group. The difference of effective rate between the experimental group and control group (95%CI) was 3.53% (-3.88%, 10.94%) of FAS, 2.42% (-2.38%, 7.22%) of PPS, and there was no significant difference between the two groups. The incision healing of the two groups was good, and the incidence of rejection, bone infection signs, post-filling symptoms and bone metabolic changes was very low. The incidence of adverse events was similar in the two groups, and no serious adverse events related to the study materials occurred. CONCLUSIONS: The efficacy of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction is not inferior to that of Bio-Oss, and it is safe and effective for alveolar bone defect repair.

Sinomenine Protects against Early Brain Injury by Inhibiting Microglial Inflammatory Response via Nrf2-Dependent Pathway after Subarachnoid Hemorrhage.

Microglial activation and sustained inflammation plays an important role in the processes of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Sinomenine (SIN) has been demonstrated to have neuroprotective effects in the traumatic brain injury (TBI) model. However, the role of SIN in SAH-induced EBI and its latent mechanisms remain unclear. This study was carried out to explore the role of SIN on SAH-induced EBI and its effects on the microglial inflammatory response following SAH. In this study, a model of SAH in rats was established. Modified neurological severity scores (mNSS), encephaledema, and Nissl staining were employed to determine the effects of SIN. Western blot and immunofluorescence analysis were performed to evaluate nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Nrf2-related downstream proteins, including heme oxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO-1), were detected with immunohistochemistry analyses and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Microglia activation and associated inflammatory factors, factor-kappa B (NF-κB), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), were assessed after SAH. The results showed that SIN administration improved neurobehavior function, and attenuated neural apoptosis and brain edema after SAH. In addition, SIN inhibited microglial action and the subsequent inflammatory response after SAH through the upregulated expression of HO-1 and NQO-1 via activation of the Nrf2 pathway. These results demonstrated that SIN supplementation provided protection against SAH-induced neuronal apoptosis by microglial inflammatory response regulation and possible involvement of the Nrf2 pathway.

Rabies virus glycoprotein 29 (RVG29) promotes CAR-T immunotherapy for glioma.

Chimeric antigen receptor T cell (CAR-T) therapy has limited efficacy for treating glioma because of the infiltrative nature of the blood-brain barrier (BBB) and T cell exhaustion. Conjugation with rabies virus glycoprotein (RVG) 29 enhances the brain-related efficacy of various agents. Here we assess whether RVG enhances the ability of CAR-T cells to cross the BBB and improves their immunotherapy. We generated 70R CAR-T cells (anti-CD70 CAR-T modified with RVG29) and validated their tumor-killing efficacy in vitro and in vivo. We validated their effects on tumor regression in a human glioma mouse orthotopic xenograft model as well as in patient-derived orthotopic xenograft (PDOX) models. The signaling pathways activated in 70R CAR-T cells were revealed by RNA sequencing. The 70R CAR-T cells we generated showed effective antitumor function against CD70+ glioma cells both in vitro and in vivo. 70R CAR-T cells were better able to cross the BBB into the brain than CD70 CAR-T cells under the same treatment conditions. Moreover, 70R CAR-T cells significantly promote the regression of glioma xenografts and improve the physical characteristics of mice without causing overt adverse effects. RVG modification enables CAR-T cells to cross the BBB, and stimulation with glioma cells induces 70R CAR-T cells to expand in a resting state. The modification of RVG29 has a positive impact on CAR-T therapy for brain tumors and may have potential in CAR-T therapy for glioma.

Periostin Protects Against Alcohol-related Liver Disease by Activating Autophagy by Interacting With Protein Disulfide Isomerase.

BACKGROUND & AIMS: The matricellular protein periostin plays a critical role in liver inflammation, fibrosis, and even carcinoma. Here, the biological function of periostin in alcohol-related liver disease (ALD) was investigated. METHODS: We used wild-type (WT), Postn-null (Postn-/-) mice and Postn-/- mice with periostin recovery to investigate the biological function of periostin in ALD. Proximity-dependent biotin identification analysis identified the protein that interacted with periostin, and coimmunoprecipitation analysis validated the interaction between protein disulfide isomerase (PDI) and periostin. Pharmacological intervention and genetic knockdown of PDI were used to investigate the functional correlation between periostin and PDI in ALD development. RESULTS: Periostin was markedly upregulated in the livers of mice that were fed ethanol. Interestingly, periostin deficiency severely aggravated ALD in mice, whereas the recovery of periostin in the livers of Postn-/- mice significantly ameliorated ALD. Mechanistic studies showed that the upregulation of periostin alleviated ALD by activating autophagy through inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which was verified in murine models treated with the mTOR inhibitor rapamycin and the autophagy inhibitor MHY1485. Furthermore, a protein interaction map of periostin was generated by proximity-dependent biotin identification analysis. Interaction profile analysis identified PDI as a key protein that interacted with periostin. Intriguingly, periostin-mediated enhancement of autophagy by inhibiting the mTORC1 pathway in ALD depended on its interaction with PDI. Moreover, alcohol-induced periostin overexpression was regulated by transcription factor EB. CONCLUSIONS: Collectively, these findings clarify a novel biological function and mechanism of periostin in ALD and the periostin-PDI-mTORC1 axis is a critical determinant of ALD.

Preliminary Study on Human Adipose Stem Cells Promoting Skin Wound Healing through Notch Signaling Pathway.

BACKGROUND: Mesenchymal stem cells (MSCs) have been documented as possible candidates for wound healing treatment because their use could reinforce the regenerative capacity of many tissues. Human adipose stem cells (hADSCs) have the advantages of easy access, large quantity and easy operation. They can be fully applied in the treatment of skin wounds. OBJECTIVE: In this study, we aim to explore the roles and potential mechanisms of hADSCs in cutaneous wound healing. METHODS: hADSCs were obtained from human subcutaneous fat. Adipocytes and osteocytes differentiated from hADSCs were determined by staining with Oil Red O and alkaline phosphatase (ALP), respectively. We assessed the effects of hADSCs and hADSC conditional medium (CM) on wound healing in an injury model of mice. Then, we investigated the biological effects of hADSCs on human keratinocytes HaCAT cells in vitro. RESULTS: The results showed that hADSCs could be successfully differentiated into osteogenic and lipogenic cells. hADSCs and hADSCs-CM significantly promote skin wound healing in vivo. hADSCs significantly promoted HaCAT cell proliferation and migration by activating the Notch signaling pathway and activated the AKT signaling pathway by Rps6kb1 kinase in HaCAT cells. In addition, we found that hADSCs-mediated activation of Rps6kb1/AKT signaling was dependent on the Notch signaling pathway. CONCLUSION: We demonstrated that hADSCs can promote skin cell-HaCAT cell proliferation and migration via the Notch pathway, suggesting that hADSCs may provide an alternative therapeutic approach for the treatment of skin injury.

A Smart "Energy NanoLock" Selectively Blocks Oral Cancer Energy Metabolism through Synergistic Inhibition of Exogenous Nutrient Supply and Endogenous Energy Production.

The major challenge in oral cancer is the lack of state-of-the-art treatment modality that effectively cures cancer while preserving oral functions. Recent insights into tumor metabolic dependency provide a therapeutic opportunity for exploring optimal treatment approaches. Herein, a smart responsive "Energy NanoLock" is developed to improve cancer metabolic intervention by simultaneously inhibiting nutrient supply and energy production. NanoLock is a pomegranate-like nanocomplex of cyclicRGD-modified carboxymethyl chitosan (CyclicRC, pI = 6.7) encapsulating indocyanine green and apoptotic peptides functionalized gold nanoparticles (IK-AuNPs), which together form a dual pH- and photoresponsive therapeutic platform. NanoLock exhibits good stability under physiological conditions, but releases small-size CyclicRC and IK-AuNPs in response to the tumor acidic microenvironment, leading to deep tumor penetration. CyclicRC targets integrins to inhibit tumor angiogenesis, and consequently blocks tumor nutrient supply. Meanwhile, IK-AuNPs specifically induce apoptotic peptides and photothermally mediated mitochondrial collapse, and consequently inhibits endogenous energy production, thereby facilitating cell death. Importantly, in both xenograft and orthotopic oral cancer models, NanoLock selectively eliminates tumors with little cross-reactivity with normal tissues, especially oral functions, resulting in prolonged survival of mice. Therefore, NanoLock provides a novel metabolic therapy to exploit synergistic inhibition of exogenous nutrient supply and endogenous energy production, which potentially advances oral cancer treatment.

Preliminary clinical application of multimodal imaging combined with frameless robotic stereotactic biopsy in the diagnosis of primary central nervous system lymphoma.

Objective: To evaluate the clinical application of multimodal imaging combined with frameless robotic stereotactic biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL). Methods: We retrospectively reviewed the clinical data of 8 patients who were considered suspected cases of PCNSL by multimodal imaging techniques. The final pathologic diagnosis were determined by the frameless robotic stereotactic biopsy. The postoperative related complications and pathological results were analyzed. Results: All patients underwent biopsies under general anesthesia with an average surgery time of 29.5 ± 4.5 min. The final pathological diagnostic accordant rate with the preoperative ones was 100%, and the pathologic examination of our patients showed features of diffuse large B-cell lymphoma. During the surgery, one patient suffered intratumoral hemorrhage without leading to serious cerebral edema, and conservative treatment was given. There was no death occurring during the study, and there were no significant differences in the Karnofsky Performance Scale Scores of all patients before and after surgery. Finally, they were transferred to the hematology department for standardized chemoradiotherapy according to the pathological results of PCNSL. Conclusion: This study shows that it may play a vital role in the early diagnosis of PCNSL with the technique of multimodal imaging. The technique of frameless robotic stereotactic biopsy for obtaining the pathology outcomes in suspected PCNSL patients has the advantages of safety, efficiency, and minimally invasiveness.

Characteristics of serum lipid levels in patients with hypertension: a hospital-based retrospective descriptive study.

BACKGROUND: Dyslipidaemia is different among patients with hypertension in different populations. The serum lipid profiles among Hakka patients with hypertension in southern China are still unclear. METHODS: 35 448 patients with hypertension were enrolled in this study from January 2016 to October 2020, and their serum lipids were analysed. RESULTS: Low high-density lipoprotein-cholesterol (HDL-C) (29.9%) accounted for the highest proportion in dyslipidaemia, followed by high triglyceride (TG) (20.7%), high total cholesterol (TC) (14.0%) and high low-density lipoprotein-cholesterol (LDL-C) (7.9%) in all subjects. The largest proportion of dyslipidaemia types was independent low HDL-C (12.7%). The proportion of low HDL-C was 15.5% in non-elderly men, 6.4% in non-elderly women, 16.7% in elderly men and 8.5% in elderly women, respectively. The largest proportion of dyslipidaemia types was independent high TG in non-elderly female patients (13.7%) and elderly patients (8.9%). The results showed that higher LDL-C, TC and TG levels in non-elderly patients than elderly patients. TG, TC and LDL-C levels decreasing with the increasing age, the differences were statistically significant. The levels of TG, TC, HDL-C and LDL-C in women were higher than in men among various age groups. Homocysteine level was increasing with increasing age. CONCLUSIONS: Serum lipid levels varied in different groups according to age and sex in patients with hypertension. Dyslipidaemia is more common in non-elderly patients than elderly. TG, TC and LDL-C levels were higher in female patients than male.

A randomized controlled trial to verify the irrigation of salivary glands in relieving xerostomia in patients with Sjögren's syndrome.

Objective: To verify the effect of triamcinolone acetonide (TA) and major salivary glands saline irrigation on relieving xerostomia in Sjögren's syndrome (SS) patients. Methods: The enrolled 49 SS patients were randomly assigned to the control group (no irrigation, n=16), saline group (irrigation with saline, n=17) and TA group (irrigation with TA, n=16). Fourteen cases of each group were treated differently but received the same examinations. The examinations include unstimulated whole saliva flow (UWS), chewing-stimulated whole saliva flow (SWS), citric acid-stimulated parotid flow (SPF), Clinical Oral Dryness Score (CODS), Xerostomia Inventory (XI) and EULAR SS Patient Reported Index (ESSPRI) of 1 week before irrigation (T0) and 1 week(T1), 8 weeks (T8), 16 weeks (T16) and 24 weeks (T24) after major salivary irrigation. Results: Each group had 14 cases with completed follow-ups. Both TA and saline irrigation of major salivary glands resulted in higher SWS and SPF of T8, T16 and than those at T0. ESSPRI (oral dryness domain) of T8, T16 and T24 were significantly lower than that at T0, respectively (P < 0.05). SWS and SPF of T8, T16 and T24 in the saline group were significantly higher than in the control group (P< 0.05). XI and ESSPRI (oral dress domain) of T8, T16 and T24 in the saline group were significantly lower than those in the control group, respectively (P< 0.05). SWS and SPF of T16 and T24 in the TA group were significantly higher than in the control group (P< 0.05). All cases with completed follow-up in TA and saline groups were divided into responders and non-responders. Compared with responders, the UWS, SWS, SPF and CODS of T0 in non-responders were significantly increased (P<0.05). Compared with responders, the XI and ESSPRI of T0 in non-responders were significantly decreased (P<0.05). Conclusion: The irrigation of major salivary glands by TA and saline relieve xerostomia in SS patients. Patients with non-severe xerostomia (responders) have better relief after irrigation than patients with severe xerostomia (non-responders). Clinical Trial Registration: www.chictr.org.cn, identifier (ChiCTR210052314).