Stereoselective Construction of Halogenated Quaternary Carbon Centers by Brønsted Base Catalyzed [4+2] Cycloaddition of α-Haloaldehydes.

Asymmetric construction of halogenated quaternary carbon centers under mild reaction conditions remains challenging. Reported here is an unprecedented and highly stereoselective Brønsted base catalyzed [4+2] cycloaddition between either α-chloro- or α-bromoaldehydes and cyclic enones. The key intermediate, an α-halogenated enolate, is susceptible to dehalogenation and can be stabilized and stereochemically controlled using bifunctional tertiary amines. This method provides facile access to a collection of optically pure bicyclic dihydropyrans having three contiguous stereocenters, including a halogen-bearing quaternary carbon center. Of note, the product can be transformed in situ into densely functionalized spirocyclopropanes in a highly efficient and stereoselective manner.

Diastereoselective Synthesis of Spirocyclopropanes under Mild Conditions via Formal [2 + 1] Cycloadditions Using 2,3-Dioxo-4-benzylidene-pyrrolidines.

A highly diastereoselective cyclopropanation of cyclic enones with sulfur ylides was developed under catalyst-free conditions, producing multifunctional spirocyclopropanes in generally excellent yields (up to 99% yield and >99:1 d.r.). The asymmetric version of this method was realized by using an easily available chiral sulfur ylide, affording products with moderate to good stereoselectivity.

Circulating levels of adipocytokine omentin-1 in patients with renal cell cancer.

Renal cell carcinoma (RCC) is the fifth most common cancer worldwide, and becomes one of the leading causes of genitourinary cancer-related death in both males and females. Genetic alternations, alcohol consumption, occupationally harmful exposure and even obesity are well-established risk factors of RCC. Omentin-1 is a plasma adipokine synthesized in visceral adipose tissue, and its circulating serum concentration alters not only in conditions associated with insulin resistance such as Polycystic Ovary Syndrome (PCOS), but also in colorectal cancer and prostate cancer. To our best knowledge, the relationship between omentin-1 and RCC has not been clarified previously. Thus, we evaluated serum omentin-1 levels in RCC patients in the current matched case-control study. Forty-one patients newly diagnosed with RCC and forty-two healthy controls confirmed by the comprehensive medical examination were assessed. The omentin-1 concentrations were determined via utilizing enzyme-linked immunosorbent assays (ELISA) in the paired groups, in which the patients and healthy controls had no statistically significant differences in gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist-hip ratio (WHR), estimate glomerular filtration rate (eGFR), body-mass index (BMI) and biochemical parameters. The omentin-1 levels in healthy people were 9.86±1.44ng/mL and the circulating omentin-1 levels were dramatically decreased to 3.62±0.76ng/mL in RCC patients (p<0.001). Besides, we revealed a negative correlation between omentin-1 with WHR (r=-0.261, p=0.017) and BMI (r=-0.310, p=0.004), further indicating BMI was the main influential factor on omentin-1 levels (p=0.0091). Follow-up studies would be conducted to establish the concrete mechanisms underlying the altered circulating levels of omentin-1 and elucidate the interaction between "RCC complex system" and adipose tissues, which may together provide promising and novel pharmacological insights for RCC theragnosis in the near future.

Catheterization Before Transperineal Ultrasound-guided Prostate Biopsy and the Risk of Urethrorrhagia.

OBJECTIVE: To investigate the efficacy of catheterization before transperineal ultrasound-guided prostate biopsy in reducing risk of urethrorrhagia. Currently, transperineal ultrasound-guided prostate biopsy (TPPB) is one of the most commonly used measures to help diagnose prostate cancer. However, whether the retention of catheterization before transperineal ultrasound-guided prostate biopsy is associated with the reduced risk of urethrorrhagia remains uncertain. METHODS: A cohort study was conducted in our hospital from January 2021 to September 2021. This study included 93 patients who participated in transperineal ultrasound-guided prostate biopsy. We compared the risk of urethrorrhagia in patients who underwent indwelling catheterization before biopsy and those who did that after biopsy, and performed an unadjusted analysis. We also analyzed the use of related confounding factors to limit the cohort of men, and applied propensity-score adjustment to control potential confounders. Analyses that restricted the cohort men with the related confounding factors and that used propensity-score adjustment to control for potential confounders. RESULTS: A total of 93 men were recruited in the cohort study, and the numbers of patients in group 1 and group 2 were 64 and 29, respectively. There were 34 patients (53.1%) of urethrorrhagia in group 1, and 22 patients (75.8%) of urethrorrhagia in group 2. This was a significant difference between the 2 groups (P = .008). After adjusting for correlative factors, the preoperative catheterization is still a protective factor for postoperative urethrorrhagia through multivariate multiple piecewise linear regression analysis. CONCLUSION: The result of this cohort study suggested that preoperative catheterization can significantly reduce the risk of urethrorrhagia.

Gene variation profile and it's potential correlation with clinical characteristics in HBV-associated HCC patients of Sichuan Han nationality in China.

OBJECTIVE: To explore the correlation between hepatocellular carcinoma (HCC) gene variation profile and clinical characteristics in Han nationality with HBV infection in Sichuan province. METHODS: The clinical data and HCC tissues were obtained from the enrolled patients. Whole exome sequencing and bioinformatics analysis were performed on formalin-fixed and paraffin-embedded samples from HCC. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. RESULTS: Sixteen high-frequency mutated genes with differential expressions were identified by WES. SMG1 gene variation could be positively correlated with satellite lesions. AMY2B and RGPD4 gene mutation seemed to have a greater chance of vascular invasion. The patients with TATDN1 variation have bigger diameters and greater chances of vascular and microvascular invasion (all P < 0.05). Univariate analysis indicated patients with gene TATDN1 variation had worse prognoses both in disease free survival (DFS) and overall survival (OS). In addition, the enrichment analysis showed many pathways, including the cell cycle pathway, viral oncogene pathway, MAPK pathway, PI3K-AKT pathway, etc., may be associated with HCC. CONCLUSION: This study explores the gene variation profile of HCC patients with HBV infection in Han nationality of Sichuan Province for the first time, which confirmed the existence of some high-frequency mutated genes and the possibility that the gene variations are involved in the tumorigenesis of HCC through multiple signal pathways. Also, patients with TATDN1 wild type showed a trend of better prognosis both in DFS and OS.

Diagnostic features and therapeutic strategies for malignant paraganglioma in a patient: A case report.

BACKGROUND: Paragangliomas and extra-adrenal pheochromocytomas are uncommon neuroendocrine tumors with ubiquitous distribution. Malignant paraganglioma is a relatively rare entity. We report the treatment and pathological characteristics of a patient with malignant paraganglioma, and summarize the latest advances in the treatment of malignant paraganglioma based on a literature review. CASE SUMMARY: A 45-year-old Chinese woman presented to the hospital due to pain in the waist (right side) and right buttock, and was diagnosed as malignant paraganglioma after the placement of ureteral stent, implantation of ileus catheter, and transvaginal removal of the vaginal mass. After relief of intestinal obstruction, the patient received intravenous chemotherapy and peritoneal perfusion chemotherapy. Although her pelvic mass disease was stable, she developed multiple liver metastases and bone metastases. Due to the development of spinal cord compression, she underwent orthopedic surgery, followed by radiotherapy, and molecular targeted therapy with apatinib, but with poor disease control. CONCLUSION: Clinical management of paraganglioma is challenging for endocrinologists and oncologists. Prospective studies are required to develop standardized therapeutic strategies for malignant paragangliomas.

Progress in the Clinical Assessment and Treatment of Myocardial Depression in Critically Ill Patient with Sepsis.

Myocardial inhibition is the main cause of death in patients with sepsis.In recent years, methodological differences in the diagnosis, assessment, and treatment of septic myocardial depression have been observed, and how to objectively and accurately evaluate the degree of myocardial depression and the timing of treatment strategies have generally been the focus of this area of research. Based on the relevant research at home and abroad, the current review summarizes the clinical characteristics, methodological diagnosis, and symptomatic treatment of septic myocardial depression. The aim of doing so is to provide a reference for the early identification and treatment of patients with sepsis and myocardial depression.

Direct Sulfide-Catalyzed Enantioselective Cyclopropanations of Electron-Deficient Dienes and Bromides.

A catalytic highly regioselective, diastereoselective, and enantioselective cyclopropanation of electron-deficient dienes and bromides via direct sulfide organocatalysis is reported. A variety of vinylcyclopropanes featuring a quaternary chiral center were synthesized in up to 99% yield and up to 98:2 enantiomeric ratio (er). These products could be facilely transformed to various interesting molecules with great structural diversity.

Highly enantioselective synthesis of fused bicyclic dihydropyranones via low-loading N-heterocyclic carbene organocatalysis.

Highly diastereo and enantioselective [4+2] cycloadditions have been achieved between pyrrolidone-derived cyclic enones and α-haloaldehydes under mild conditions. Relying on extremely reactive in-situ generated chiral N-heterocyclic carbenes, this stereoselective annulation proceeds efficiently even on the gram scale with the catalyst loading as low as 0.025 mol% (250 ppm). A variety of cis-substituted bicyclic dihydropyranones can be produced in up to 96% yield with up to >99% ee. In addition, simple, inexpensive linear aldehydes such as n-propanal can be used directly in asymmetric cycloadditions via oxidative N-heterocyclic carbene organocatalysis with low catalyst loading. This method may provide an economical and practical approach for the asymmetric synthesis of medicinally relevant molecules.

Structural characterization and radioprotection of bone marrow hematopoiesis of two novel polysaccharides from the root of Angelica sinensis (Oliv.) Diels.

Two novel homogeneous polysaccharides, APS-1a and APS-3a were successfully isolated from the root of Angelica sinensis. APS-1a was composed of galactose, arabinose and glucose in a relatively molar percentage of 57.34%, 27.67% and 14.98%, and had a molecular weight of 49.0kDa, whereas APS-3a was composed of galactose, arabinose and glucose in a relatively molar percentage of 84.54%, 6.50%, and 8.96%, and had a molecular weight of 65.4kDa. APS-1a and APS-3a mainly consisted of 1,4-linked galactose, 1,3,6-linked galactose, T-galactose and T-arabinose, and the molar ratio of each linkage was different between APS-1a and APS-3a. The bioactivity analysis showed that APS-1a and APS-3a increased the thymus and spleen index, the number of red blood cell (RBC) and white blood cell (WBC) in peripheral blood and the cellularity of bone marrow cell numbers in irradiated mice, protected mice against radiation-induced micronucleus formation in bone marrow, suggesting that polysaccharides could be used as radioprotective agents, especially for promoting bone marrow hematopoiesis.