This study was performed to explore the differential genes and functions of double-negative T cells in peripheral blood of patients with colorectal cancer.Two colorectal cancer patients and two healthy physical examiners were selected,and peripheral blood double-negative T cells were firstly sorted by flow cytometry,and then sequencing data were obtained using single cell full-length transcriptome(SMART-seq2)sequencing technology to screen differentially expressed genes.The screened differentially expressed genes were subjected to Gene Ontology Enrichment(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.The STRING database was used to construct the protein interaction network and identify key genes by Cytoscape software;RT-qPCR was used to verify the differential expression genes in DNT cells.Compared with healthy subjects,there were 1 276 peripheral blood double-negative T-cell differential genes in colorectal cancer patients,including 141 up-regulated genes and 1 135 down-regulated genes.GO analysis showed that the differential genes were mainly involved in biological functions such as methylation,metabolic processes and transferase activity;KEGG pathway analysis showed that the differential genes were mainly involved in signaling pathways such as autophagy,P53 signaling pathway and phosphatidylinositol metabolism.The protein interaction network contains 1 154 nodes and 1 022 edges,in addition,10 hub genes were identified:PIK3C3,WIPI1,ATG101,PIK3R4,DDX10,RBM28,SDAD1,ATG16L1,UVRAG,ATG7.RT-qPCR validated 10 differentially expressed genes,of which 7 differentially expressed genes showed trends consistent with sequencing results,and 3 genes showed expression inconsistent with sequencing results.DNT cells may be involved in the development of colorectal cancer through methylation,P53 signaling pathway and autophagy,and at the same time,DNT cells may inhibit the development of colorectal cancer through the regulation of genes.This study provides a theoretical basis for further investigation of the function of DNT cells in malignant tumors.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

The blood-brain barrier (BBB) constitutes a major obstacle to effective delivery of drugs to the brain. Recent technological advances have led to improvements in brain-targeted drug delivery. In this review, we summarize existing technologies for efficient drug delivery across the BBB. We discuss the mecha-nisms of current BBB-based drug delivery strategies and introduce prospects for application in brain-targeted delivery of traditional Chinese medicine. We highlight the use of physical techniques for brain-targeted drug delivery, including electroporation, ultrasound, magnetophoresis, microneedles, microwaves, and laser. The characteristics of these techniques and relevant studies employing these approaches are discussed. In general, microneedles, lasers, ultrasound, electroporation, magnetophoresis, and microwaves are effective for drug delivery across the BBB. Notably, the synergistic effects of multiple approaches are superior to the additive effects of each technique in isolation. Our review provides guidance for the practical application of brain-targeted drug delivery techniques in an efficient and safe manner.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2016 to December 2017. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI) 2019. WHONET 5.6 was used to analyze data.Results:During the study period, 8 154 bacterial strains were collected from 33 hospitals, of which 2 325 (28.5%) were Gram-positive bacteria and 5 829 (71.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (34.7%), Klebsiella pneumoniae (15.8%), Staphylococcus aureus (11.3%), coagulase-negative Staphylococci (7.4%), Acinetobacter baumannii (4.6%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.8%), Streptococci (2.9%), Enterobacter cloacae (2.7%) and Enterococcus faecalis (2.5%). Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCNS) accounted for 34.2%(315/922) and 77.7%(470/605), respectively. No vancomycin-resistant Staphylococcus was detected. The resistance rate of Enterococcus faecium to vancomycin was 0.6%(2/312), and no vancomycin-resistant Enterococcus faecium was detected. The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus were 55.7%(1 576/2 831), 29.9%(386/1 289) and 38.5%(15/39), respectively. The incidences of carbapenem-resistance in Escherichia coli, Klebsiella pneumoniae were 1.2%(33/2 831), 17.5%(226/1 289), respectively. The resistance rates of Acinetobacter baumannii to polymyxin and tigecycline were 14.8%(55/372) and 5.9%(22/372) respectively, and those of Pseudomonas aeruginosa to polymyxin and carbapenem were 1.3%(4/315) and 18.7%(59/315), respectively. Conclusion:The surveillance results from 2016 to 2017 showed that the main pathogens of blood stream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen; the MRSA incidence was lower than other surveillance data in the same period in China; carbapenem-resistant Escherichia coli was at a low level during this surveillance, while carbapenem-resistant Klebsiella pneumoniae is on the rise.

Objective To analyze the distribution and antimicrobial resistance profile of clinical bacterial strains isolated from blood culture in China.Methods Clinical bacterial strains isolated from blood culture from participating hospitals of Blood Bacterial Resistance Investigation Collaborative System (BRICS) during January 2014 to December 2015 were collected.Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods as recommended by US Clinical and Laboratory Standards Institute(CLSI)2018.The data were analyzed with Whonet 5.6 software.Results During the study period,4 801 clinical bacterial isolates were collected from 26 hospitals,of which 1 798 (37.5％) were Gram-positive bacteria and 3 003 (62.5％) were gram-negative bacteria.The top 10 isolates were Escherichia coli (33.8％),coagulase-negative Staphylococcus (19.0％),Klebsiella pneumoniae (11.9％),Staphylococcus aureus (10.1％),Acinetobacter baumannii (4.0％),Pseudomonas aeruginosa (3.8％),Streptococcus (3.0％),Enterobacter sulcus (2.9％),Enterococcus faecium (2.8％) and Enterococcus faecalis (1.8％).Methicillin-resistant Staphylococcus aureus (MRSA) and methicillinresistant coagulase-negative Staphylococcus (MRCNS) accounted for 33.9％ (165/487) and 56.9％ (520/913) of Staphylococcus aureus and coagulase-negative Staphylococcus respectively.No vancomycinresistant Staphylococcus was detected.The resistance rate of Enterococcus faecium to vancomycin was 0.7％ (1/135),and no vancomycin-resistant Enterococcus faecaliss was detected.The positive rates of extendedspectrum β-1actamases(ESBLs)-producing Escherichia coli,Klebsiella pneumoniae and Proteus were 56.9％ (923/1 621),30.1％ (172/572) and 29.2％ (7/24),respectively.The positive rates of carbapenemresistant Escherichia coli,Klebsiella pneumoniae,Enterobacter,Salmonella and Citrobacter were 1.2％ (20/1 621),7.2％ (41/572),4.3％ (6/141),1.5％ (1/67) and 2.9％ (1/34),respectively.The resistance rates of Acinetobacter baumannii to polymyxin and tegacycline were 2.6％ (5/190) and 8.9％ (17/190)respectively,and that of Pseudomonas aeruginosa to polymyxin and fosfomycin were 1.1％ (2/183)and 0.6％ (1/183),respectively.Conclusions The surveillance results from 2014 to 2015 show that the main pathogens of blood stream infection in China are Gram-negative bacteria,while Escherichia coli is the most common pathogen,the detection rate of MRSA is lower than other surveillance data in the same period in China;carbapenem-resistant Klebsiella pneumoniae and Escherichia coli are at a low level as shown in this surveillance.

Objective To investigate the value of continuous renal replacement therapy (CRRT) coupled with minimally invasive ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) for the treatment of severe acute biliary pancreatitis.Methods Hospitalized patients with severe acute biliary pancreatitis were recruited from the intensive care unit (ICU) of the Mfiliated Hospital of Qingdao University from June 2010 to June 2015,and divided into conventional CRRT alone group (n =30) and CRRT + PTGD group (n =30).Comparisons of postoperatively symptoms (time required for abdominal pain relief,time consumed for,gastrointestinal decompression),laboratory findings (WBC,PLT,PCT,CRP,AMS,TBIL,ALT,ALB,Lac) and acute physiology and chronic health evaluation score (APACHE Ⅱ,Balthazar CT,MODS) were carried out between two groups.The occurrence of complications (ARDS,abdominal infection,bile leakage,abdominal hemorrhage,intestinal injury,catheter translocation,catheter dislocation) was observed.The differences in duration of ventilator support,the length of stay in ICU,and fatality rate were compared between the two groups.Results Compared with the conventional CRRT alone group,the postoperative symptoms were significantly relieved,and time required for abdominal pain relief and time consumed for gastrointestinal decompression were evidently shortened in the CRRT + PTGD group (P ＜ 0.05).There were statistically significant differences in laboratory findings (WBC,PLT,PCT,CRP,AMS,TBIL,ALT) between two groups (P ＜ 0.05).The differences in APACHE Ⅱ,Balthazar CT and MODS score between the two groups also presented statistical significance (P ＜ 0.05).The comparisons of the duration of ventilator support [(6.1 ± 1.3) d vs.(9.5 ± 1.4) d] andthe length of stay [(15.7 ± 1.1) dvs.(21.1 ± 2.5) d] between thetwo groups revealed statistical significance (P ＜ 0.05).Conclusions CRRT coupled with PTGD for the treatment of severe acute biliary pancreatitis can effectively eliminate the inflammatory mediators and toxins from patients.On this basis,the coupled therapy with gallbladder puncture and drainage is capable of decompressing the biliary tract,improving liver function,effectively relieving clinical symptoms,minimizing the changes of laboratory findings an,d APACHE Ⅱ score,and thereby optimizing the prognosis of patients.

Objective:To investigate the effect of alteplase on the expressions of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells after thrombolysis in the rats with acute cerebral infarction and its mechanism,and to provide experimental evidence for its clinical application. Methods: The models of acute thrombosis of middle cerebral artery of the rats were established.Fifty-four SD rats were randomly divided into sham operation group,model group and alteplase group (n= 18).The ultrastructure of brain endothelial cells of the rats was observed under transmission electron microscope.The expression levels of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats were detected by immunoflurorescence and Western blotting methods.Results:The transmission electron microscope results showed that the brain volume in the ischemic area of the rats in model group was significantly increased and the endothelial cells were swollen,some of the cortical and surrounding brain tissues had obvious boundaries,and the thickness of the basement membrane was uniform and the tightly connected structure was very loose and disappeared;the swelling condition of the capillary endothelial cells in infarcted area of the rats in alteplase group was significantly reduced and the thickness of the basement membrane was improved,and most of the tightly connected structures between the brain capillary endothelial cells and the endothelial cells were loose and the fracture was lost and the structure disappeared.The immunofluorescence results showed that the expressions of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats in alteplase group were significantly improved compared with model group. The Western blotting results showed the expression levels of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats in model group were significantly decreased compared with sham operation group (P < 0.01 ); compared with model group, the expression levels of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats in alteplase group at different time points were increased (P < 0.01 ). Conclusion: Alteplase can improve the structure of brain endothelial cells in the rats with acute cerebral infarction,and the mechanism may be related to decreasing the expressions of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats induced by alteplase.

OBJECTIVE:To systematically review the efficacy and safety of the Bushen huoxue lishi category TCM compound in the treatment of chronic prostatitis,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from VIP Database,Wanfang Database,CJFD and CBM,randomized controlled trials(RCT)about Bushen huoxue lishi category TCM com-pound preparation (test group) versus conventional Western medicine (control group) in the treatment of chronic prostatitis were collected. Meta-analysis was performed by Rev Man 5.3 software after data extraction and quality evaluation. RESULTS:Totally 22 RCTs were enrolled,involving 1 863 patients. Results of Meta-analysis showed the total effective rate [OR=4.46,95%CI(3.40, 5.84),P<0.001],total scores of chronic prostatitis symptoms[MD=-3.62,95%CI(-5.21,-2.04),P<0.001] and lecithin count [MD=7.58,95%CI(2.15,13.01),P=0.006] in test group were significantly higher than control group,prostatic fluid white blood cell count [MD=-1.68,95%CI(-3.26,-0.10),P=0.04] was significantly lower than control group,with significant differenc-es. CONCLUSIONS:Bushen huoxue lishi category TCM compound has good efficacy in the treatment of chronic prostatitis.

OBJECTIVEIo compare the difference on the clinical efficacy in treatment of chronic nephritis albuminuria between acupuncture and moxibustion at "Xiasanhuang", DONG's extra points and benazepril hydrochloride so as to provide the effective therapeutic method for the treatment of chronic nephritis albuminuria. Methods One hundred and six cases of nephritis albuminuria were randomized into an acupuncture and moxibustion group and a western medication group, 53 cases in each one. In the acupuncture and moxibustion group, acupuncture and moxibustion were applied to "Xiasanhuang" (Tianhuang fuxue namely "shenguan", "Dihuang", "Renhuang"), once a day, the interval of 2 days once every 10 treatments. In the western medication group, benazepril hydrochloride was prescribed for oral administration, 5 to 10 mg each time, once a day. The treatment of 2 months made, one session in the two groups. After 1 session treatment, the clinical efficacy, red blood cell count (RBC) of urinary sediment, 24 h urine protein quantitation and creatinine clearance rate (Ccr) before and after treatment were observed in the two groups.

RESULTSThe total effective rate was 84. 9% (45/53) in the acupuncture and moxibustion group, superior to 52. 8% (28/53) in the western medication group (P<0. 01). After treatment, RBC of urinary sediment and 24 h urine protein quantitation were reduced as compared with those before treatment (P< 0. 01, P<0. 05), and the results in the acupuncture and moxibustion group were lower than those in the western medication group (P<0. 05, P<0. 01). After treatment, Ccr in the acupuncture and moxibustion group was higher than that before treatment (P<0. 05) and higher than that in the western medication group (P<0. 05). Ccr was not different significantly before and after treatment in the western medication group (P>0. 05).

CONCLUSIONAcupuncture and moxibustion at DONG's extra points (Xiasanhuang) reduce proteinuria and improve kidney, function in patients of chronic nephritis and the efficacy is better than that with benazepril hydrochloride.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Albuminuria ; therapy ; Chronic Disease ; therapy ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Nephritis ; therapy ; Treatment Outcome ; Young Adult