Objective:To explore the effect of venetoclax-based therapy on relapsed/refractory multiple myeloma (MM) patients harboring t(11;14).Methods:The data of a relapsed/refractory MM patient harboring t(11;14) treated with venetoclax-based regimen admitted to Shanghai Changzheng Hospital in June 2019 was retrospectively analyzed and the literatures were reviewed.Results:The relapsed/refractory MM patient harboring t(11;14) had progression of disease after 3 lines of therapies, and then was treated with the selective bcl-2 inhibitor venetoclax combined with daratumumab and dexamethasone. As a result, the patient achieved partial remission and better hemogram recovery. The Eastern Cooperative Oncology Group (ECOG) score of physical status decreased from 3 to 1, and the quality of life was improved significantly.Conclusions:The relapsed/refractory MM patients harboring t(11;14) could benefit from venetoclax-based therapy. In the future, the safety, sensitivity and other performances of venetoclax in the treatment of MM should be further explored.

Objective To investigate the genetic evolution of VP1 gene of pathogenic coxsackievirus A16 (CV-A16) strain isolated from clinical hand,foot,and mouth disease (HFMD) patients.Methods A total of 160 HFMD cases with CV-A16-positive results were collected from hospitals in Kunming during January 2015 to June 2017.Fecal samples were collected.Real-time polymerase chain reaction (PCR) was used to detect the CV-A16 virus nucleic acid.The VP1 genes of CV-A16-positive samples were amplified by reverse transcription-PCR.The amplified positive products were sequenced and aligned.The homologies were identified and their subgenotypes were determined.The phylogenetic tree was constructed and homology modeling was conducted.Results All the 160 CV-A16 isolates were B2 subtypes.The genetic distance between detected strains of CV-A16 and the strains in Fujian,Beijing,Nanjing was 0.76.The genetic distance to the strains in Malaysia was 0.78,and to the strains in Australia was 1.86.Homologous modeling revealed that the amino acid sequence of the VP1 gene of the strain had a G227R mutation.Conclusions There is no major genetic variation in the CV-A16 strains during 3 years.CV-A16 isolates are close to those of epidemic strains in Beijing,Fujian and Malaysia,but are far fram the strains from Australia.

Objective: To investigate the effects of sinomenine on brain edema and the expression of aquaporin 4 (AQP-4) and aquaporin 5 (AQP-5) in rats with acute brain injury. Methods: According to random number table method, rats were divided into sham operation group, model group, low-dose sinomenine group, high-dose sinomenine group, 20 in each group. In addition to the sham operation group, the rat brain injury model was established by Feeney free falling impact method. Rats in low and high dose of sinomenine group were given sinomenine 30, 60 mg/kg by intraperitoneal injection, and the sham operation group and model group were injected intraperitoneally with the same volume of normal saline, once per day for 7 days. Histopathological changes in each group were observed by HE staining and electron microscope. Western blot and RT-PCR were used to detect AQP-4 and AQP-5 protein and gene expression in brain tissue. Results: The pathological results showed that the nerve cells in the model group were loosely arranged, disordered in hierarchy, some cells appear to have degenerated. The degeneration and necrosis of nerve cells in the low and high dose sinomenine group were less than those in the model group. Compared to the model group, the expression of AQP-4 (0.74 ± 0.13, 0.49 ± 0.11 vs. 1.30 ± 0.21), AQP-5 (0.98 ± 0.07, 0.45 ± 0.10 vs. 1.47 ± 0.18) in the low dose and high dose sinomenine group significantly decreased (P<0.05). The expression of AQP-4 (1.48 ± 0.18, 1.26 ± 0.12 vs. 2.04 ± 0.14), AQP-5 (1.31 ± 0.17, 1.20 ± 0.11 vs. 1.87 ± 0.15) mRNA in the low dose and high dose sinomenine group significantly decreased (P<0.05). Conclusions Sinomenine could alleviate cerebral injury by lowering the expression of AQP-4 and AQP-5.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by a high incidence rate in middle-aged and elderly women, lymphocyte infiltration in small bile ducts, and cholestasis. Main clinical manifestations include fatigue and pruritus caused by cholestasis. Ursodeoxycholic acid and obeticholic acid are currently approved therapeutic drugs for PBC and exert a therapeutic effect by regulating bile acid metabolism and specifically and effectively improving cholestasis. This article introduces the physiological and pathological changes of bile acids in disease states and summarizes the possible ways in which bile acid metabolism is involved in the pathogenesis of diseases and the current treatment methods for bile acid metabolism. It is pointed out that the changes of bile acid metabolism in PBC are mainly associated with anion exchanger 2 deficiency, innate genetic variation and acquired adaptive changes of bile acid metabolism transporters and nuclear receptors, and changes in the structure of intestinal flora.

ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique， and then to clarify the mechanism of the two， as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group（CG）， model group（MG）， Aconiti Coreani Radix group（RA） and Typhonii Rhizoma group（RT）. Except for the CG， ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG， rats in the other groups received whole powder suspension（0.586 mg·g^-1） was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0， 3， 7 and 14. After the end of administration， the serum， brain tissue and urine of gerbils in each group were collected， and the rate of cerebral infarction was detected by 2，3，5-triphenyltetrazolium chloride（TTC）， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， malondialdehyde（MDA）， superoxide dismutase（SOD）， glutathione（GSH）， and nitric oxide（NO） in serum and brain tissue were determined by enzyme-linked immunosorbent assay（ELISA）. The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， and the data were processed by multivariate statistical analysis， and differential metabolites were screened based on value of variable importance in the projection（VIP） of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG） database and Metaboanalyst 5.0. ResultCompared with the CG， the neurological deficit score was significantly increased in the MG（P<0.05）， compared with the MG， the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d（P<0.05）. Compared with the CG， the rate of cerebral infarction was significantly increased in the MG（P<0.05）， compared with the MG， the rates of cerebral infarction in the RA and RT were significantly reduced（P<0.05）. Compared with the CG， the levels of IL-6， TNF-α， and MDA in the serum and brain tissue of gerbils from the MG were significantly increased（P<0.05）， and the levels of SOD， GSH and NO were significantly reduced（P<0.05）. Compared with the MG， Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6， TNF-α and MDA， and up-regulated the levels of SOD， GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics， of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma， and could be used as potential biomarkers for both treatments in stroke gerbils， respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism， pyrimidine metabolism， and aminoacyl-tRNA biosynthesis. In addition， Aconiti Coreani Radix could also regulate riboflavin metabolism， Typhonii Rhizoma could also regulate purine metabolism， glycine， serine and threonine metabolism， arachidonic acid metabolism， biosynthesis of pantothenate and coenzyme A， and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke， with Aconiti Coreani Radix having stronger effects. From the metabolomics results， the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism， oxidative stress and so on， while Typhonii Rhizoma mainly involve amino acid metabolism， lipid metabolism， energy metabolism， etc.