[Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache].

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

Observational Insights into Isoprene Secondary Organic Aerosol Formation through the Epoxide Pathway at Three Urban Sites from Northern to Southern China.

Isoprene is the most abundant precursor of global secondary organic aerosol (SOA). The epoxide pathway plays a critical role in isoprene SOA (iSOA) formation, in which isoprene epoxydiols (IEPOX) and/or hydroxymethyl-methyl-α-lactone (HMML) can react with nucleophilic sulfate and water producing isoprene-derived organosulfates (iOSs) and oxygen-containing tracers (iOTs), respectively. This process is complicated and highly influenced by anthropogenic emissions, especially in the polluted urban atmospheres. In this study, we took a 1-year measurement of the paired iOSs and iOTs formed through the IEPOX and HMML pathways at the three urban sites from northern to southern China. The annual average concentrations of iSOA products at the three sites ranged from 14.6 to 36.5 ng m-3. We found that the nucleophilic-addition reaction of isoprene epoxides with water dominated over that with sulfate in the polluted urban air. A simple set of reaction rate constant could not fully describe iOS and iOT formation everywhere. We also found that the IEPOX pathway was dominant over the HMML pathway over urban regions. Using the kinetic data of IEPOX to estimate the reaction parameters of HMML will cause significant underestimation in the importance of HMML pathway. All these findings provide insights into iSOA formation over polluted areas.

[Strategies for efficacy and function positioning of new resources of Chinese materia medica].

Chinese materia medica( CMM) serves as an important cornerstone for the development of traditional Chinese medicine( TCM) culture and industry due to its unique ecological,medical,economic,scientific and technological,and cultural values. The supply shortage and unstable quality of some CMM resources have hindered the development of TCM. Ensuring the sustainable use of CMM resources has become essential for the development of TCM in China. Enriching CMM resources is the key to ensuring the sustainable utilization of TCM resources in China,which can be achieved via expanding the medicinal parts,developing the substitutes,seeking for analogues,exploring the ethnic and folk medicines,or introducing foreign medicinal materials. CMM efficacy or function positioning plays a very important role in the transformation of new CMM resources. The strategies and methods for efficacy or function positioning of new CMM resources,including analogy,plant genetic relationship exploration,medicinal property deduction,ethnobotanical investigation,text mining,network pharmacology,and structure-activity relationship exploration,were systematically proposed in this study based on CMM theory,textual research,and modern methodologies. This paper is expected to provide a theoretical reference for the continuous enrichment and development of CMM resources and the high-quality development of TCM culture and industry.

Significant Increase of Aromatics-Derived Secondary Organic Aerosol during Fall to Winter in China.

Human activities release large amounts of anthropogenic pollutants into the air, and thereby produce substantial secondary organic aerosol (SOA). Aromatic hydrocarbons (AHs) that mainly emitted from coal combustion, transportation, solvent use and biofuel/biomass burning, are a major class of anthropogenic SOA precursors. At present, there are few field studies focusing on AH-derived SOA (SOAA) on a continental scale, especially in polluted regions of the world. In this study, a one-year concurrent observation of the SOAA tracer, 2,3-dihydroxy-4-oxopentanoic acid (C5H8O5, DHOPA) was carried out at 12 sites across six regions of China for the first time. The annual averages of DHOPA among the 12 sites ranged from 1.23 to 8.83 ng m-3 with a mean of 3.48 ± 1.96 ng m-3. At all observation sites, the concentrations of DHOPA from fall to spring were significantly higher than those in summertime, and positive correlations were observed between DHOPA and the biomass burning tracer (levoglucosan). This indicated that such a nationwide increase of SOAA during the cold period was highly associated with the enhancement of biomass burning emission. In the northern China, the highest levels of DHOPA were observed in the coldest months during winter, probably due to the enhancement of biofuel and coal consumption for household heating. In the southern China, the highest levels of DHOPA were mostly observed in fall and spring, which were associated with the enhancement of open biomass burning. The apparent increases of DHOPA and levoglucosan levels during the cold period and the negative correlations of visibility with DHOPA and levoglucosan imply that the reduction of SOAA amount and biomass burning emission is an efficient way to reduce haze pollution during fall to winter in China.

Characterization of biomass burning tracers in particulate matter at 12 sites in China: Significant increase of coal combustion emitted levoglucosan in northern China during winter.

Biomass burning (BB) is the largest contributor to carbonaceous aerosols globally. Specific organic tracers can track BB particles and identify BB types. At present, there is limited information on the composition of BB tracers on a continental scale. In this study, we conducted year-round sampling of particulate matter (PM) at 12 sites in China. Nine BB tracers were measured in PM with aerodynamic diameters <1.1 µm (PM<1.1), in the range of 1.1-3.3 µm (PM1.1-3.3), and > 3.3 µm (PM>3.3). The annual average concentration of these nine BB tracers (∑9 BB tracers) in the total PM was 366 ng m-3 with the majority of levoglucosan (66 %). The concentration of ∑9 BB tracers was higher in northern China than in southern China, especially in winter. ∑9 BB tracers were most enriched in PM<1.1 (50-61 % in mass), followed by PM1.1-3.3 and PM>3.3. The highest concentrations of ∑9 BB tracers were observed in winter, while satellite-recorded fire spots were intensive in autumn and spring. The mismatch of seasonal trends between them indicated that the high levels of BB tracers in winter was not due to open BB. The composition of 4-hydroxybenzoic acid, syringic acid and vanillic acid suggested that the burning of crop residues and softwoods were the major BB types in China. The ratio of levoglucosan to mannosan could neither identify the major BB types in China nor distinguish between BB and coal combustion. Correlation analysis and the PMF model demonstrated that non-BB sources contributed 7 %-58 % to levoglucosan at the 12 sites, with coal combustion being the predominant non-BB source in China, especially in northern urban sites during winter. Our findings suggest that caution should be taken in application of these organic tracers to identify BB types and estimate BB aerosols.

Pseudolaric acid B induces apoptosis associated with the mitochondrial and PI3K/AKT/mTOR pathways in triple­negative breast cancer.

Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi, has been shown to exert strong antitumor properties. The aim of the present study was to investigate the mechanisms underlying the proposed antitumor properties of PAB in the triple­negative breast cancer cells, MDA­MB­231. The cell processes evaluated included cell proliferation by Cell Counting Kit­8 assay, colony formation and EdU assay, apoptosis by Annexin V­FITC/PI apoptosis assay, cell migration by Transwell migration assay and invasion by Transwell invasion assay. PAB significantly inhibited the proliferation of MDA­MB­231 cells through a mechanism that was considered to be associated with cell cycle arrest at the G2/M phase. There was decreased protein expression levels of CDK1 and cyclin B1 and increased protein expression levels of p53 and p21. However, there were no well­defined inhibitory effects on the normal breast cell line MCF10A. PAB also triggered apoptosis in a concentration­dependent manner through the mitochondrial apoptosis pathway. It caused collapse of mitochondrial membrane potential, accumulation of reactive oxygen species and release of cytochrome c, as well as upregulation of cleaved caspase­3, cleaved caspase­9, cleaved PARP and Bax, and downregulation of Bcl­2 and Bcl­xl. The migration and invasion ability of MDA­MB­231 cells were inhibited by decreasing the expression levels of the epithelial­mesenchymal transition­related markers N­cadherin and vimentin and increasing the expression of E­cadherin. Moreover, the expression levels of PI3K (p110ß), phosphorylated (p)­AKT (ser473) and p­mTOR (ser2448) were downregulated and LY294002, a PI3K inhibitor, could interact additively with PAB to induce apoptosis of MDA­MB­231 cells. Overall, the present results demonstrated that PAB induced apoptosis via mitochondrial apoptosis and the PI3K/AKT/mTOR pathway in triple­negative breast cancer. It also inhibited cellular proliferation, migration and invasion, suggesting that PAB may be a useful phytomedicine for the treatment of triple­negative breast cancer.

Clinical and molecular characterization of 10 Chinese children with congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency.

BACKGROUND: The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of non-classical 21-hydroxylase deficiency. For this study, we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature, which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal hyperplasia. METHODS: Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed. We examined the effects of gene mutations on protease activity and constructed three-dimensional structure prediction models of proteins. RESULTS: We describe 10 patients with 11beta-hydroxylase gene mutations (n = 5, 46,XY; n = 5, 46,XX), with 10 novel mutations were reported. Female patients received treatment at an early stage, with an average age of 2.08 ± 1.66 years, whereas male patients received treatment significantly later, at an average age of 9.77 ± 3.62 years. The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C > T. All mutations lead to spatial conformational changes that affect protein stability. CONCLUSIONS: Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations. Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations. The correlation between genotype and phenotype needs further study. Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.

Ureteroscopic Lithotripsy in Reverse Trendelenburg Position and Intraoperative Furosemide.

PURPOSE: Upward stone migration is a significant problem during ureteroscopic lithotripsy (URSL) for upper ureteral stone, especially in absence of a ureteral occlusion device. In this study, we evaluated the novel strategy of reverse Trendelenburg position (RTP) and intraoperative diuresis for URSL without ureteral occlusion devices to avoid upward migration. MATERIALS AND METHODS: From March 2018 to May 2020, a total of 119 URSLs were performed for upper ureteral stone (6-15 mm) with 67 procedures in RTP and 52 procedures in conventional lithotomy position (CLP). 20 mg of intravenous furosemide was administered prior to stone fragmentation with holmium laser only in RTP group. Patient demographics, stone side, stone size and operative characteristics were recorded and compared between the two groups. RESULTS: Patient data, stone side and size were similar in the two groups. All procedures were complete without conversion to open surgery and major complications. There was no significant difference in the mean operative time (47.9 ± 7.7 min vs 45.3 ± 7.0 min, P = .062) and mean hospital stay (3.9 ± 0.9 d vs 4.0 ± 1.0 d, P = .336) between the RTP and CLP group. Stone upward migration was significantly less in RTP group (3.0%, 2/67) than in CLP group (19.2%, 10/52) (P = .005). Stone-free rate at one month after initial treatment was 92.5% in RTP group and 73.1% in CLP group (P = .004). CONCLUSION: The strategy of placing the patient in RTP and intraoperative administration of intravenous furosemide is simple, feasible and cost-effective in preventing stone upward migration during URSL with holmium laser in absence of a ureteral occlusion device for upper ureteral stone.

Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes.

Introduction: The frequency of celiac disease autoantibody (CDAb) positivity in type 1 diabetes (T1D) has increased due to unclear mechanisms, including autoimmune injury. Circular ribonucleic acids (circRNAs) participate in autoimmune diseases, but the roles of circRNAs in T1D with CDAbs are currently unknown. This study aimed to determine the frequency of CDAbs in Chinese children with T1D and describe the relationship between CDAbs and circRNAs. Materials and methods: Eighty patients diagnosed with T1D were screened for CDAbs and CD-predisposing genes, and circRNAs in peripheral blood mononuclear cells (PBMCs) were collected from 47 patients. The Gene Expression Omnibus (GEO) database was searched for candidate circRNAs in related studies on T1D PBMCs. Data on clinical characteristics (i.e., blood glucose control, residual islet function, and daily insulin dosage) and immunophenotypes (i.e., islet autoantibodies and immune cell subsets) were collected. Results: In total, 35.0% of patients were positive for CDAbs. CD-predisposing genes accounted for 52.5% of the genes, and no significant difference in frequency was found between the CDAb-positive (CDAb+) and CDAb-negative (CDAb-) groups. In addition, among the differentially expressed circRNAs from the GEO database, five highly conserved circRNAs homologous to humans and mice were screened, and only the expression of hsa_circ_0004564 in the CDAb+ group significantly decreased (CDAb+ vs. CDAb-:1.72 ± 1.92 vs. 11.12 ± 8.59, p = 6.0 × 10-6), while the expression of hsa_circ_0004564 was upregulated in the general T1D population. Moreover, its parental gene RAPH1 was significantly upregulated (CDAb+ vs. CDAb-:1.26 ± 0.99 vs. 0.61 ± 0.46, p = 0.011). Importantly, the positive correlation between hsa_circ_0004564 and CD3+ cells was validated in children with T1D after adjustments for CDAbs (p = 0.029), while there were no correlations between hsa_circ_0004564 and clinical characteristics or other immune cell subsets (i.e., CD4+ T cells, CD8+ T cells, and natural killer cells). Conclusion: This study highlights the importance of screening for CD in Chinese children with T1D, considering the high prevalence of CDAb positivity and CD-predisposing genes. The profile of candidate circRNAs in children with T1D with CDAbs was different from that in previous reports on general T1D patients from the GEO database. Moreover, hsa_circ_0004564 and its parental gene RAPH1 may be new targets for studying immune mechanisms in children with T1D and CD.

Alström syndrome with a novel mutation of ALMS1 and Graves' hyperthyroidism: A case report and review of the literature.

BACKGROUND: Alström syndrome (AS, OMIM ID 203800) is a rare disease involving multiple organs in children and is mostly reported in non-Chinese patients. In the Chinese population, there are few reports on the clinical manifestations and pathogenesis of AS. This is the first report on the association between AS and Graves' hyperthyroidism. CASE SUMMARY: An 8-year-old Chinese girl was diagnosed with AS. Two years later, Graves' hyperthyroidism developed with progressive liver dysfunction. The patient's clinical data were collected; DNA from peripheral blood of the proband, parents and sibling was collected for gene mutation detection using the second-generation sequencing method and gene panel for diabetes. The association between the patient's genotype and clinical phenotype was analyzed. She carried the pathogenic compound heterozygous mutation of ALMS1 (c.2296_2299del4 and c.11460C>A). These stop-gain mutations likely caused truncation of the ALMS1 protein. CONCLUSION: The manifestation of hyperthyroidism may suggest rapid progression of AS.

Tropism and transduction of oncolytic adenovirus vectors in prostate cancer therapy.

Oncolytic adenovirus has been applied in cancer therapy because of several advantages such as cost-effective production, high transduction efficiency and low toxicity. Recent efforts have been focused on the modification of oncolytic adenovirus by encoding transgenes within the viral genome to efficiently and selectively replicate within cancer cells, destroy cancerous cells, induce tumor cell apoptosis, and stimulate the recruitment of immune cells to the tumor site. Nevertheless, there are still big challenges for translational research of oncolytic virotherapy in clinical cancer management. Therefore, here we summarize current status on the design and application of oncolytic adenovirus vectors for prostate cancer therapy. In particular, we describe the main receptors associated with the tropism and transduction of oncolytic adenovirus vectors, and propose new directions in future studies for prostate cancer virotherapy.

[Construction of an oncolytic adenovirus expressing small hairpin RNA and targeting the SATB1 gene].

OBJECTIVE: To construct an oncolytic adenovirus with the DD3 promoter regulation, expressing small hairpin RNA and targeting the SATB1 gene (SATBI-shRNA), and to evaluate its potential for inhibiting the growth of human prostatic carcinoma cells (LNCaP) in vitro. METHODS: SATB1-shRNA expression cassettes containing the H1 promoter were produced by PCR from pSilencer3. 1-SATB1 and inserted into the pZD55 vector, and the recombinant plasmid pZD55-SATB1-shRNA was constructed, pZD55SATB1-shRNA and pZXC2-DD3-E1A were digested with EcoRV and Xba I , and the obtained expression cassettes linked each other to construct the recombinant plasmid pDD3-ZD55-SATB1, which was cotransfected with the pBHGE3 packaging plasmids mixture into 293 cells by Effectence. The recombined adenoviruses DD3-ZD55-SATB1 were identified by PCR. Viruses were propagated on HEK293 cells and purified by standard techniques, and the functional PFU titers determined by plaque assay on 293 cells. The antitumor potential of DD3-ZD55-SATB1 to LNCaP was evaluated by the crystal violet dye method. The expression level of the E1A gene was detected by Western blot, and that of the SATB1 gene in the adenovirus-infected LNCaP cells by both Western blot and RT-PCR. RESULTS: An oncolytic adenovirus expressing SATB1-shRNA with the DD3 promoter regulation, DD3-ZD55-SATB1, was constructed successfully, whose functional PFU titer was 1.2 x 10(10) PFU/ml. DD3-ZD55-SATB1 showed an obvious cytopathic effect and a selective expression of E1A in the adenovirus-infected LNCaP cells; it exhibited a high LNCaP-targetability and specific SATB1-silencing effect. CONCLUSION: The successful construction of the oncolytic adenovirus DD3-ZD55-SATB1 offers a new tool for researches on the gene therapy for human prostate cancer.

[Skip metastasis of prostate cancer: diagnosis and treatment].

OBJECTIVE: To improve the diagnosis and treatment of far advanced prostate cancer without clinically detectable bone metastasis. METHODS: Cancer metastatic lesions were found in the liver and lungs respectively of two patients on routine medical examination, and only an abnormally elevated level of the serum prostate specific antigen (PSA) was observed in the following system examinations. The patients were diagnosed as having prostate cancer by prostate biopsy. MRI showed a discontinued prostate capsule, and ECT revealed no bone metastasis. Diagnostic treatment was conducted by giving LHRHa combined with antiandrogens. One of the patients underwent surgical castration at 12 months, and both received intensity modulated radiation therapy (80 Gy) at 15 and 18 months, respectively. RESULTS: The metastatic lesions in the liver and lungs of the patients were either absent or significantly reduced after treated by maximal androgen blockade for 3 months, and all disappeared after 6 months'treatment, with the PSA level stabilized at less than 0.02 microg/L in one patient, and around 0.5 microg/L in the other. Antiandrogen treatment was suspended after radiotherapy. The results of liver, lung and bone scanning were normal during the 12-month follow-up, and the PSA level was below 1.0 microg/L. CONCLUSION: Remote metastasis of prostate cancer may occur in ectosteal organs first, which deserves special attention. A combination of different treatment methods promises satisfactory results.

Development and Preliminary Clinical Application of Circulating Tumor Cell Detection System for Prostate Cancer.

Real-time detection of circulating tumor cell (CTC) markers that are constantly changing and renewing during disease progression is of great significance for the timely regimen switch or individualized target therapy. The abnormally expressed special AT-rich sequence binding protein 1 (SATB1), a nuclear matrix attachment region binding protein, in various tumors, promotes the growth and metastasis of tumor cells by regulating gene expression. In this paper, a CTC detection system for prostate cancer (PCa) was developed on the basis of epithelial cell adhesion molecule (EpCAM)-targeted immunomagnetic separation and CK-FITC and SATB-1-APC immunofluorescence assay, and the recovery rate of tumor cells in PBS and simulated whole blood by this system was detected. Subsequently, we isolated, identified, and counted SATB-1 ositive CTCs in the peripheral blood and urine samples of 60 tumor-bearing nude mice, 5 healthy volunteers and 13 PCa patients. Combined with the clinicopathological factors, the clinical value of the system was analyzed, and the possibility of SATB-1-positive CTCs in the diagnosis of PCa was evaluated. The results showed that the CTC sorting and identification system for prostate cancer constructed in this study had a recovery rate of more than 85% for CTC in PBS, urine and blood simulation samples. The expression level of SATB-1 was different in different PCa cell lines, which was relatively high in the highly invasive PCa DU-145 cell line. The expression of SATB-1 in CTCs in the blood samples of PCa patients with different clinical characteristics and in the urine samples of a few PCa patients with bone metastases were different, and the detection sensitivity of peripheral blood was higher than that of urine. This study has important clinical reference value for the early diagnosis of PCa and the evaluation of bone metastasis based on the CTC counting and the SATB-1 expression in CTCs.

Phosphoric acid-catalyzed atroposelective construction of axially chiral arylpyrroles.

Axially chiral arylpyrroles are key components of pharmaceuticals and natural products as well as chiral catalysts and ligands for asymmetric transformations. However, the catalytic enantioselective construction of optically active arylpyrroles remains a formidable challenge. Here we disclose a highly efficient strategy to access enantioenriched axially chiral arylpyrroles by means of organocatalytic atroposelective desymmetrization and kinetic resolution. Depending on the remote control of chiral catalyst, the arylpyrroles were obtained in high yields and excellent enantioselectivities under mild reaction conditions. This strategy tolerates a wide range of functional groups, providing a facile avenue to approach axially chiral arylpyrroles from simple and readily available starting materials. Selected arylpyrrole products proved to be efficient chiral ligands in asymmetric catalysis and also important precursors for further synthetic transformations into highly functionalized pyrroles with potential bioactivity, especially the axially chiral fully substituted arylpyrroles.

Publisher Correction: Phosphoric acid-catalyzed atroposelective construction of axially chiral arylpyrroles.

The original PDF version of this Article contained an error in Table 3, in which all chemical structures were omitted and only the numerical data was shown. This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.

Organocatalytic atroposelective construction of axially chiral arylquinones.

Atropisomeric biaryl motifs are ubiquitous in chiral catalysts and ligands. Numerous efficient strategies have been developed for the synthesis of axially chiral biaryls. In contrast, the asymmetric construction of o-quinone-aryl atropisomers has yet to be realized. Inspired by the rapid progress of the chemistry of biaryls, here we present our initial investigations about the atroposelective construction of axially chiral arylquinones by a bifunctional chiral phosphoric acid-catalyzed asymmetric conjugate addition and central-to-axial chirality conversion. With o-naphthoquinone as both the electrophile and the oxidant, three types of arylation counterparts, namely 2-naphthylamines, 2-naphthols and indoles, are utilized to assemble a series of atropisomeric scaffolds in good yields and excellent enantioselectivities. This approach not only expands the axially chiral library but also offers a route to a class of potential, chiral biomimetic catalysts.

Copper-catalyzed cyclization of 2-cyanobenzaldehydes and 2-isocyanoacetates: an efficient strategy for the synthesis of substituted 1-aminoisoquinolines.

A Cu(acac)2-catalyzed cyclization reaction of 2-cyanobenzaldehydes with 2-isocyanoacetates has been successfully developed providing an efficient strategy for the synthesis of substituted 1-aminoisoquinolines. The reaction proceeds smoothly under mild conditions with high efficiency, and might provide an alternative strategy for the synthesis of 1-aminoisoquinoline containing molecules.