ObjectiveTo investigate the expression level of mammalian sterile 20-like kinase 1 （MST1） in prostate cancer （PCa） tissues， its biological functions， and its regulatory effects on androgen receptor （AR） and vascular endothelial growth factor （VEGF） expression. MethodsImmunohistochemistry was performed to detect MST1 expression in 77 prostate cancer tissues and 34 benign prostatic hyperplasia （BPH） tissues， and the relationship between MST1 expression and clinicopathological parameters was analyzed. MST1-overexpressing C4-2 and LNCaP cell lines were constructed. CCK-8 assay， Transwell migration assay， and angiogenesis assay were conducted to evaluate the effects of MST1 on cell proliferation， migration， and angiogenesis. The expression changes of AR and VEGF were detected by qRT-PCR and Western blot. ResultsMST1 expression was significantly lower in PCa tissues compared with BPH tissues （P=0.012）. Low MST1 expression was significantly associated with tumor metastasis （P=0.033）. MST1 overexpression inhibited C4-2 cell proliferation and migration， with transmembrane migrated cells reduced by 53.6% （P<0.01）. MST1 overexpression decreased the mRNA and protein expression levels of AR and VEGF （P<0.05）. Angiogenesis assay demonstrated that the length of new vessel structure was significantly reduced （P<0.05）. ConclusionMST1 shows a low expression level in PCa tissues and is associated with tumor metastasis. MST1 exerts tumor-suppressive effects in prostate cancer by inhibiting cell proliferation， migration， and angiogenesis， as well as downregulating the expression of AR and VEGF， indicating its potential as a therapeutic target for prostate cancer.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.

Objective:To explore the risk factors of intensive care unit-acquired weakness (ICU-AW) and the characteristics of Medical Research Council (MRC) score and electromyogram.Methods:A case control study was conducted. Patients with mechanical ventilation ≥ 7 days and MRC score admitted to department of respiratory and critical care medicine of China-Japan Friendship Hospital from September 2018 to January 2020 were enrolled, and they were divided into ICU-AW group (MRC score < 48) and non-ICU-AW group (MRC score ≥ 48) according to MRC score. The general situation, past medical history, related risk factors, MRC score, respiratory support mode, laboratory examination results, electromyogram examination results, ICU-AW related treatment, outcome and length of ICU stay were collected, and the differences between the two groups were compared. The risk factors of ICU-AW were analyzed by binary multivariate Logistic regression, and the characteristics of MRC score and electromyogram were analyzed.Results:A total of 60 patients were enrolled in the analysis, including 17 patients in ICU-AW group and 43 patients in non-ICU-AW group. Univariate analysis showed that there were significant differences in acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, brain natriuretic peptide (BNP), blood urea nitrogen (BUN) on the first day of ICU admission and the ratio of invasive mechanical ventilation between ICU-AW group and non-ICU-AW group [APACHEⅡ score: 21 (18, 25) vs. 18 (15, 22), SOFA score: 7 (5, 12) vs. 5 (3, 8), BNP (ng/L): 364.3 (210.1, 551.2) vs. 160.1 (66.8, 357.8), BUN (mmol/L): 9.9 (6.2, 17.0) vs. 6.0 (4.8, 9.8), invasive mechanical ventilation ratio: 88.2% vs. 46.5%, all P < 0.05]. Binary multivariate Logistic regression analysis showed no independent risk factor for ICU-AW. The average MRC score of 17 ICU-AW patients was 33±11. The limb weakness was symmetrical, and the proximal limb weakness was the main manifestation. Electromyography examination showed that the results of nerve conduction examination in ICU-AW patients mainly revealed that the amplitude of compound muscle action potential (CMAP) and sensory nerve action potentials (SNAP) were decreased, and the conduction velocity was slowed down; needle electromyography showed increased area of motor unit potential (MUP), prolonged time limit and a large number of spontaneous potentials. Prognosis evaluation showed that compared with non-ICU-AW group, patients in ICU-AW group underwent more tracheotomy (70.6% vs. 11.6%), longer length of ICU stay (days: 57±52 vs. 16±8), and more rehabilitation treatment (58.8% vs. 14.0%), and the differences were statistically significant (all P < 0.01). Conclusions:The occurrence of ICU-AW may be related to high APACHEⅡ score and SOFA score, high levels of BNP and BUN on the first day of ICU admission and the proportion of invasive mechanical ventilation, but the above factors are not independent risk factors for ICU-AW. The MRC score of ICU-AW patients was characterized by symmetrical limb weakness, mainly proximal limb weakness; in electromyography examination, the nerve conduction examination results mainly showed that CMAP and SNAP amplitude were decreased, and conduction velocity was slowed down; needle electromyography examination showed increased MUP area, prolonged duration and a large number of spontaneous potentials.

Objective : To investigate the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway molecules during the process by which kaempferol (Kae) promotes osteogenic differentiation of mouse bone marrow mesenchymal cells (BMMCs) under cyclic and uniaxial tension. Methods : BMMCs isolated and cultured in vitro were subjected to uniaxial dynamic tension with a 10% shape variable. The appropriate concentration of Kae was selected by cytotoxicity testing. The endogenous mTOR signal was inhibited by pp242. Four hours after traction, alkaline phosphatase (ALP) and osteocalcin (OCN) were detected by chemical colorimetry and ELISA, and the relative concentration of intracellular calcium was detected by flow cytometry. Phosphorylation of mTOR, 4E/BP1, and ribosomal protein S6 kinases (S6K), which are the main molecules of the endogenous mTORC1 signaling pathway, and expression of osteogenic transcription factors (Runx2 and Osterix) were detected by western blotting (WB), and mRNA expression levels of the above factors were detected by qRT-PCR. Results : The cytotoxicity test showed that 10 μmol/L Kae had little inhibitory effect on cell proliferation but had the strongest osteogenic ability. Four hours after stretching, Kae effectively promoted the osteogenic differentiation of BMMCs. The expression of ALP was （153.04 ± 18.72） U/mg, the expression of OCN was （1.64 ± 0.25） U. The mRNA and protein levels of Runx2 and Osterix were upregulated, and the intracellular calcium content was decreased. The mRNA and protein phosphorylation of mTOR and S6K was upregulated, and the opposite effect was observed with 4E/BP1. After pp242 was added to inhibit mTOR signaling, mTOR and S6K mRNA and protein phosphorylation were downregulated, but 4E/BP1 mRNA and protein phosphorylation was upregulated. The osteogenic differentiation of BMMCs was also significantly inhibited, mRNA and protein expression of Runx2 and Osterix were significantly downregulated, ALP and OCN expression were downregulated, and intracellular calcium content was increased. Conclusion Kae promotes osteogenic differentiation of mouse BMMCs under uniaxial dynamic tension through the mTORC1 signaling pathway.

Background: The gut microbial dysbiosis and gender differences in the pathogenesis of acne vulgaris have long been postulated respectively. However, there was no data about a genderrelated discrepancy in gut microbiota and microbial metabolism in acne. Objective: This study aimed at identifying the underlying gender-related difference in gut microbiota and metabolism in acne vulgaris. Methods: Fecal samples were collected from 43 acne patients and 43 age and gender-matched controls. Gut microbiota was analyzed by sequencing the V3-V4 region of 16SrDNA gene and microbial metabolites were quantitatively detected using gas chromatography time-of-flight mass spectrometry. Results: Compared with healthy controls, the men had a lower abundance of 18 microbes such as Butyricicoccus, Clostridium sensu stricto, Faecalibaculum, Bacillus, Lactococcus, Blautia, Clostridiales, Lachnospiracea incertae sedis, Ruminococcus at genus level. However, the female patients only showed increased Clostridium sensu stricto and declined Oscillibacter and Odoribacterin. Additionally, the disordered metabolism of fatty acids was identified in male patients, while the dysbiosis of amino acids metabolism in female ones. Conclusion The disorder of gut microbiota and metabolism in acne vulgaris was genderspecific, which supported the potential role of gender difference in the pathogenesis of this disease.

Background and purpose: Gemcitabine (GEM) is a first-line chemotherapy drug for pancreatic cancer. With the emergence of clinical drug resistance, the efficacy of chemotherapy has been greatly reduced, while the expression of secretory clusterin (sCLU) was closely related to chemotherapy resistance in multiple tumors. This study aimed to explore the effects of secretory clusterin on oxidative damage in MIA PaCa-2 cells treated by GEM and preliminary mechanism of resistance to GEM. Methods: MIA PaCa-2 was exposed to GEM and sCLU intervened groups with different concentrations (0, 0.63, 1.25, 2.50, 5.00 and 10.0 μg/mL) for 24 hours. The intervened concentration of GEM was 5.4 μmol/L. The inhibition rates of cell proliferation were determined by CCK-8. Cell reactive oxygen species (ROS) was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) method. Superoxide dismutase (SOD) activity and catalase (CAT) activity were measured by their corresponding assay kits respectively. Results: Compared with the negative control group (0 μg/mL), the inhibition rates of the GEM groups and sCLU intervened groups were significantly increased (P＜0.05) in a distinct dose-effect manner. At a low concentration of 0.63 μg/mL, the inhibition rates of the GEM groups were higher than those of the sCLU intervened groups, while the trend was reversed in high concentration range. Compared with the negative control group (0 μg/mL), the intracellular ROS levels, SOD and CAT activity of the GEM and sCLU intervened groups significantly increased (P＜0.05). ROS levels presented a distinct dose-effect relationship while the SOD and CAT activities increased first and then decreased along with the increase of GEM concentrations. The ROS levels of the GEM group were lower than those of the sCLU intervened group at the same dose (P＜0.05). The SOD activities of the GEM group were higher than those of the sCLU intervened group, while the CAT activities were opposite at the concentrations of 5.00 and 10.00 μg/mL (P＜0.05). Conclusion: GEM exposure can inhibit the growth of MIA PaCa-2 cells. After GEM exposure, the ROS levels, SOD and CAT activity of MIA PaCa-2 cells can be changed by sCLU intervention. GEM resistance could be regulated by sCLU through oxidative damage effect.

Spliceosomal dysfunction plays a major role in pathogenesis of myelodysplastic syndrome (MDS). Splicing factor somatic mutations, including SF3B1, U2AF1 (U2AF35), SRSF2, ZRSR2, PRPF40B, SF1, SF3A1, and U2AF2, comprise a common (45%–85%) class of mutated genes in MDS. These genes exist in a mutually exclusive manner at the 3'splice site of mRNA processing and are predomi-nantly heterozygous and missense. RNA splicing might have therapeutic and prognosis values in MDS. This review mainly describes the pathogenesis of common splicing factor gene mutations in MDS and discusses possible therapeutic implications, clinical analysis, and prognosis.

ABSTRACT:Objective To investigate the effect and mechanism of anthocyanin on hepatic ischemia reperfusion injury in rats .Methods Totally 30 SD rats were randomly divided into sham group ,model group and anthocyanin group (n=10 in each) .Hepatic ischemia was constructed in model group and anthocyanin group by ligating left middle lobe of liver vascular branches for 90 min . Anthocyanin was administered at 90 min before ischemia by intraperitoneal injection at the concentration of 100 mg/kg for rats in anthocyanin group .Rats in model group and sham group were injected with the same dosage of normal saline at the same time .Serum and liver tissues were collected at 4 h after reperfusion by putting the rats to death .The expressions of ALT ,AST ,IL‐6 ,IL‐1βand TNF‐αin the serum were examined by ELISA .The pathological changes of liver tissue were evaluated by HE .The mRNA levels of IL‐6 ,IL‐1βand TNF‐αwere measured by RT‐PCR .The content of MDA was examined by TBA . The activities of CAT ,GPx and SOD were evaluated by xanthine oxidase method and the expression of p‐JAK2 ,p‐STAT3 ,JAK2 ,STAT3 and P53 were measured by Western blot .Results Compared with those in the sham group ,the activities of ALT and AST ,the expressions of p‐JAK2 ,p‐STAT3 ,P53 ,IL‐6 ,IL‐1β,TNF‐α and the content of MDA as well as the pathological changes of the liver in model group were significantly increased . However ,the activities of CAT ,GPx and SOD in model group were decreased and the expressions of JAK2 and STAT3 between the two groups did not differ .Compared with those in model group ,the activities of ALT and AST ,the expressions of p‐JAK2 ,p‐STAT3 ,P53 ,IL‐6 ,IL‐1β,TNF‐α,the content of MDA and the pathological changes of the liver in anthocyanin group were significantly decreased . But the activities of CAT , GPx and SOD in anthocyanin group were increased and the expressions of JAK 2 and STAT3 between the two groups did not differ , either .Conclusion Anthocyanin pretreatment can significantly decrease hepatic ischemia/reperfusion injury by suppressing oxidative stress and inflammation ,and the mechanism may be associated with reducing JAK2/STAT3/P53 signaling activation .

Objective To observe the clinical therapeutic effect of oral solution of Huaixue Shenshu for treatment of patients with IgA nephropathy and explore its mechanism. Methods A prospective study was conducted. Forty patients with IgA nephropathy diagnosed by pathology were selected, and they were randomly divided into treatment group and control group, 20 cases in each group. The two groups were subjected to the routine treatment, and on this base, the control group also received cozaar 50-100 mg, while the treatment group additionally received oral solution of Huaixue Shenshu decoction (drug composition:Centellae herba 15 g, Sophorae Flos 20 g, Ecliptae Herba 20 g, Ligustri Lucidi Fructus 15 g, Cicadae Periostracum 15 g, Pyrolae Herba 20 g, Saposhnikoviae Radix 10 g, Astragali Radix 15 g, the above ingredients were immersed in water and boiled to form 200 mL decoction, as a dose, and then divided into two parts to take orally one of them each time, twice a day). Both groups took two therapeutic courses in total, 3 months constituting one course. After treatment, the integral changes of clinical symptoms and clinical efficacy were observed, and before treatment and 3 months and 6 months after treatment, the 24-hour urine protein, serum creatinine (SCr), and albumin (Alb) were measured in the two groups. Results Before treatment, there was no significant difference in integral of clinical symptoms between treatment group and control group (score: 18.42±5.41 vs. 19.95±6.25, P>0.05);after treatment, the integrals of two groups were significantly lower than those before treatment, and the degree of decrease in treatment group was more obvious (score: 6.35±2.11 vs. 9.45±3.55, P < 0.05). After treatment the total effective rate in treatment group was significantly higher than that in control group [75.0% (15/20) vs. 40.0% (8/20), P<0.05]. Before treatment, the differences in 24-hour urinary protein, SCr and Alb were not significant between the two groups (all P > 0.05); with the prolongation of treatment, the 24-hour urinary protein was decreased gradually, and Alb was increased gradually, reaching its peak after 6 months of treatment, and the changes were more obvious in treatment group [24-hour urinary protein (g):0.71±0.58 vs. 1.31±0.55, Alb (g/L):37.8±6.1 vs. 35.5±5.2, both P<0.01]. No significant difference in SCr was found before and after treatment between the two groups (both P > 0.05). Conclusion The effect of oral solution of Huaixue Shenshu in treatment of IgA nephropathy is good.