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.

AIM: To investigate the guiding role of individualized medication adjustment based on CYP2C19 metabolic typing in the treatment of ischemic stroke with clopidogrel, and to provide reference for clinical individualized medication. METHODS: The total of 80 patients with ischemic stroke were divided into the individualized drug instruction group with gene detection (n=40) and the control group without gene detection (n=40) according to whether they received CYP2C19 gene detection. According to the metabolism of CYP2C19, the individualized medication instruction group was divided into slow metabolic type, intermediate metabolic type, fast metabolic type and ultra-fast metabolic type. Patients with fast and ultra-fast metabolites were given clopidogrel dose of 75 mg once a day. Patients with intermediate metabolic type were given double clopidogrel dose of 150 mg once a day. Patients with slow metabolism were given tigrillo dose of 90 mg twice a day or aspirin dose of 100 mg once a day. The control group received 75 mg clopidogrel once a day. All patients enrolled in the groups were followed up for 3 months by outpatients or telephone. The incidence of vascular events and mRS scale scores were compared between the two groups. RESULTS: The incidence of vascular events in the individualized drug instruction group was significantly lower than that in the control group, and the incidence of mRS score(0-1) was significantly higher than that in the control group, with statistically significant differences (P<0.05). CONCLUSION: The individualized medication for patients with ischemic stroke by CYP2C19 gene detection can significantly reduce the incidence of adverse vascular events and improve the prognosis and living ability of patients.

Clostridia inhabiting in jiupei and pit mud plays key roles in the formation of flavour during the fermentation process of Luzhou-flavour baijiu. However, the differences of Clostridial communities between jiupei and pit mud remains unclear. Here, the species assembly, succession, and metabolic capacity of Clostridial communities between jiupei and pit mud were analysed by high-throughput sequencing and pure culture approaches. The ratio of Clostridial biomass to bacterial biomass in the pit mud was relatively stable (71.5%-91.2%) throughout the fermentation process. However, it varied widely in jiupei (0.9%-36.5%). The dominant Clostridial bacteria in jiupei were Clostridium (19.9%), Sedimentibacter (8.8%), and Hydrogenispora (7.2%), while Hydrogenispora (57.2%), Sedimentibacter (5.4%), and Caproiciproducens (4.9%) dominated in the Clostridial communities in pit mud. The structures of Clostridial community in pit mud and jiupei were significantly different (P=0.001) throughout fermentation. Isolated Clostridial strains showed different metabolic capacities of volatile fatty acids in pure culture. Spatial and temporal heterogeneity of Clostridial communities existed in the baijiu fermentation pit, which was closely related to the main flavour components of Luzhou-flavour baijiu.
Alcoholic Beverages ; microbiology ; Bacteria ; classification ; metabolism ; Clostridium ; physiology ; Fatty Acids, Volatile ; metabolism ; Fermentation ; Food Microbiology

Radiation pneumonitis is a common complication in the radiotherapy for thoracic malignant tumors. And the resulting respiratory failure is one of the most serious side effects. The occurrence and severity of radiation pneumonitis depend on many factors such as age, performance status scores, smoking status, lung condition, tumor sizes, tumor location, chemoradiotherapy related factors, inflammatory factors and single-nucleotide polymorphism, et al. Some imaging examinations, for example single-photon emission computed tomography and PET-CT, have been used to predict radiation pneumonitis, while its usefulness remains to be strengthened. Further researches are still needed to find the gold standard in the prediction of radiation pneumonitis.

Objective:To study the expression of Resistin protein in breast cancer and to evaluate its significance to clinicopathology.Methods:The immunohistochemical technique, EnVision method, was used to evaluate the expression of Resistinin in 42 cases of normal breast tissues and 145 cases of breast cancer, and to analyze the relationship between Resistin protein expression and clinicopathological characteristics and molecular typing of invasive breast cancer patients.Results:The positive rate and strong positive rate of Resistin protein in normal breast tissue were 23.8% (10/42) and 0.0% (0/42) , respectively, while the positive rate and strong positive rate in invasive breast cancer were 88.3% (128/145) and 24.8% (36/145) . The positive rate and strong positive rate of Resistin protein in invasive breast cancer tissues were significantly higher than those in normal breast tissues (both P=0.000) . The positive rate of Resistin protein in invasive breast cancer was significantly higher in estrogen receptor (ER) -negative patients than in ER-positive patients ( P=0.006) , and it was higher in histological grade III and progesterone receptor (PR) -negative subjects than that of I-II and PR-positive, but the difference was not statistically significant ( P=0.053 and P=0.058, respectively) . The strong positive rate of Resistin protein in histological grade III, ER negative, PR negative and human epidermal growth factor receptor 2 (HER2) positive was significantly higher than that in histological grade I-II, ER positive, PR positive and HER2 negative ( P=0.001, P=0.001, P=0.001, and P=0.015, respectively) .The positive rate and strong positive rate of Resistin protein in triple negative breast cancer (TNBC) were significantly higher than those in other breast cancer subtypes ( P=0.048 and P=0.003, respectively) . Conclusion:Resistin plays an important role in the development of breast cancer and is expected to be a potential anti-cancer therapy biologic marker.