Objective To investigate the molecular mechanism by which STAT1 regulates the expression of APOL6 in order to mediate lipid deposition in tumor-associated macrophages(TAM)in laryngeal cancer tissues.Methods Real-time polymerase chain reaction,Western blotting,immunohistochemistry,and enzyme-linked immunosorbent assays were used to detect the expression levels of STAT1 and APOL6 in laryngeal cancer tissues,as well as the regulatory effect of STAT1 on APOL6 expression.Chromatin immunoprecipitation was used to elucidate the molecular mechanisms underlying APOL6 regulation by ST AT1.Oil Red O staining was used to evaluate the lipid deposition in TAM.Results The expression levels of STAT1 and APOL6 in laryngeal cancer tissues were significantly higher than those in the adjacent normal tissues(P＜0.01).STAT1 transcriptionally activated APOL6 gene expression.STAT1 overexpression sig-nificantly promoted the expression and secretion of APOL6 in laryngeal cancer cells and induced lipid deposition in TAM.Conclusion STAT1 is a novel transcription factor for the APOL6 gene.STAT1 promotes lipid deposition in the TAM of laryngeal cancer tissues by regu-lating APOL6 expression,thereby reshaping the lipid metabolism of TAM.

Central venous access device associated skin impairment is a common complication of indwelling central venous catheters in cancer patients. To further enhance the standardization of nursing staff's practice of central venous access device associated skin impairment, a clinical nursing practice guideline for central venous access device associated skin impairment in cancer patients was developed through the Delphi expert consultation and expert meeting methods in accordance with the methodology for developing evidence-based nursing practice guidelines. Recommendations cover four aspects of management requirements, assessment, prevention, and management of central venous access device associated skin impairment, providing a practical basis for clinical healthcare professionals to make scientific decisions on central venous access device associated skin impairment.

Objective To investigate the molecular mechanism by which STAT1 regulates the expression of APOL6 in order to mediate lipid deposition in tumor-associated macrophages(TAM)in laryngeal cancer tissues.Methods Real-time polymerase chain reaction,Western blotting,immunohistochemistry,and enzyme-linked immunosorbent assays were used to detect the expression levels of STAT1 and APOL6 in laryngeal cancer tissues,as well as the regulatory effect of STAT1 on APOL6 expression.Chromatin immunoprecipitation was used to elucidate the molecular mechanisms underlying APOL6 regulation by ST AT1.Oil Red O staining was used to evaluate the lipid deposition in TAM.Results The expression levels of STAT1 and APOL6 in laryngeal cancer tissues were significantly higher than those in the adjacent normal tissues(P＜0.01).STAT1 transcriptionally activated APOL6 gene expression.STAT1 overexpression sig-nificantly promoted the expression and secretion of APOL6 in laryngeal cancer cells and induced lipid deposition in TAM.Conclusion STAT1 is a novel transcription factor for the APOL6 gene.STAT1 promotes lipid deposition in the TAM of laryngeal cancer tissues by regu-lating APOL6 expression,thereby reshaping the lipid metabolism of TAM.

Central venous access device associated skin impairment is a common complication of indwelling central venous catheters in cancer patients. To further enhance the standardization of nursing staff's practice of central venous access device associated skin impairment, a clinical nursing practice guideline for central venous access device associated skin impairment in cancer patients was developed through the Delphi expert consultation and expert meeting methods in accordance with the methodology for developing evidence-based nursing practice guidelines. Recommendations cover four aspects of management requirements, assessment, prevention, and management of central venous access device associated skin impairment, providing a practical basis for clinical healthcare professionals to make scientific decisions on central venous access device associated skin impairment.

Brain computer interface(BCI)is a rapidly developing rehabilitation technology in recent years, which has been gradually used for cognitive rehabilitation of stroke patients.BCI can activate brain regions related to cognition to a greater extent through motor imagery and neural feedback technology, promote functional connectivity between brain regions, and ameliorate cognitive impairment after stroke.This paper summarized the mechanisms involved in BCI promoting cognitive rehabilitation and current applications of BCI in post-stroke cognitive impairment, and identifies the shortcomings of BCI in the treatment of post-stroke cognitive impairment, in order to provide insight for the research and clinical practice of BCI in post-stroke cognitive rehabilitation.

Objective:To explore the clinical characteristics of 1q21.1 microdeletion by using single nucleotide polymorphism microarrays (SNP array).Methods:Eighteen cases of 1q21.1 microdeletion syndrome diagnosed at the Longgang District Maternal and Child Health Care Hospital of Shenzhen City from June 2017 to December 2022 were selected as the study subjects. Clinical data of the patients were collected. Results of chromosomal karyotyping and SNP assay were retrospectively analyzed.Results:Among the 18 cases with 1q21.1 microdeletions, 13 had a deletion between BP3 and BP4, 4 had a deletion between BP1/BP2 and BP4, whilst 1 had a proximal 1q21.1 deletion (between BP2 and BP3) involving the Thrombocytopenia-absent radius (TAR) region. The deletions had spanned from 360 kb to 3.9 Mb, which encompassed the GJA5, GJA8, CHD1L, RBM8AB and other morbid genes. In three families, the proband child has inherited the same 1q21.1 microdeletion from their parents, whose clinical phenotype was normal or slightly abnormal. The clinical phenotypes of 1q21.1 microdeletion had included cognitive or behavioral deficits in 9 cases (9/18, 50.0%), growth retardation in 8 cases (8/18, 44.4%), craniofacial deformities in 7 cases (7/18, 38.8%), cardiovascular malformations in 5 cases (5/18, 27.8%), and microcephaly in 3 cases (3/18, 16.7%). Conclusion:1q21.1 microdeletion syndrome has incomplete penetrance and varied expression such as intellectual impairment, growth and development delay, and microcephaly, with a wide range of non-specific phenotypes.

Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To investigate the differences in the expression levels of miR-196a-5p and miR-105-5p in serum of patients with benign and malignant pulmonary nodules and their diagnostic value of malignant pulmonary nodules.Methods:The expression levels of miRNAs in cancer tissues of lung adenocarcinoma and lung squamous cell carcinoma and paracancerous tissues in The Cancer Genome Atlas (TCGA) database were analyzed, and the miRNAs with significantly different expression levels in cancer tissues and paracancerous tissues were selected as target miRNAs. A total of 72 patients with pulmonary nodules admitted to Weifang People′s Hospital of Shandong Province from June 2019 to July 2020 were selected. The expression levels of target miRNAs in serum of patients with pulmonary nodules were detected by qRT-PCR. Receiver operating characteristic (ROC) curve was used to compare the diagnostic value of target miRNAs with tumor markers Cyfra21-1, NSE and CEA in malignant pulmonary nodules.Results:After screening, the target miRNAs were identified as miR-196a-5p and miR-105-5p. Twenty-six patients in the benign pulmonary nodules group and 46 patients in the malignant pulmonary nodules group were included. The levels of serum miR-196a-5p [ M ( P25, P75)] in the benign and malignant nodules group were 0.63 (0.09, 2.15) and 1.93(0.93, 4.97) respectively, and the levels of miR-105-5p in the two groups were 2.03 (0.54, 7.95) and 10.65 (5.94, 18.39) respectively. Compared with the benign pulmonary nodules group, the levels of serum miR-196a-5p and miR-105-5p in the malignant pulmonary nodules group were increased, and there were statistically significant differences ( Z=-3.083, P=0.002; Z=-4.092, P<0.001). The levels of serum Cyfra21-1 in the benign and malignant pulmonary nodules group were 2.48 (1.84, 3.78) and 2.20 (1.47, 3.32) μg/L respectively, the levels of serum NSE in the two groups were 15.58 (12.45, 18.95) and 14.43 (12.07, 17.87) μg/L respectively, and the levels of serum CEA in the two groups were 1.16 (0.55, 2.11) and 1.17 (0.61, 1.68) μg/L respectively. There were no significant differences in serum Cyfra21-1, NSE and CEA between the benign and malignant pulmonary nodules group ( Z=-1.161, P=0.246; Z=-0.305, P=0.761; Z=-0.271, P=0.786). The area under the curve (AUC) of the combination of miR-196a-5p and miR-105-5p for the diagnosis of malignant pulmonary nodules was 0.762 (sensitivity 89.1%, specificity 61.5%), which was higher than the value of the combination of Cyfra21-1, NSE and CEA for the diagnosis of malignant pulmonary nodules (AUC=0.591, sensitivity 58.7%, specificity 64.5%). Conclusion:The combination of serum miR-196a-5p and miR-105-5p can assist in the diagnosis of malignant pulmonary nodules and has higher diagnostic value.

In order to evaluate the consistency of the release behavior between the self-made saxagliptin and metformin hydrochloride sustained-release tablets and the reference preparations in vitro, the similarity of the dissolution curves between the self-made preparations and the reference preparations in four dissolution mediums: HCl (pH 1.0), acetate buffer saline (pH 4.5), phosphate buffer saline (pH 6.8) and pure water, and the gel morphology and strength of the self-made preparations and the reference preparations in the HCl (pH 1.0) solution medium were compared.Results showed that in four dissolution mediums, the dissolution rates of saxagliptin in the self-made preparations and the reference preparations at 15 min were greater than 85%, and the ?2 similarity factors of metformin hydrochloride were 89, 83, 80, 86, all greater than 50, so the dissolution of the self-made preparations was consistent with those of the reference preparations.The volume expansion rate, water absorption rate and erosion rate were consistent with those of the reference preparations, and the gel strength of the self-made preparations was the same as that of the reference preparations.The in vitro release behaviors of the self-made preparations and the reference preparations are consistent, which provide a good guarantee for bioequivalence.