Aim To investigate the effect of salvianolic acid B (Sal B)on c-Jun N-terminal kinase (JNK)ac-tivation and apoptosis of INS-1 cells induced by inter-mittent high glucose.Methods INS-1 cells were pre-incubated with Sal B for 24 h,followed by exposure to intermittent high glucose (IHG,11.1 mmol·L-1 12 h,33. 3 mmol·L-1 12 h)for 72 h.Cell viability was assessed by MTT assay and cell apoptosis was evalua-ted by flow cytometry.Glucose induced insulin secre-tion capacity and intracellular reactive oxygen species (ROS)contents were measured by enzyme linked im-munosorbent assay (ELISA)and a fluorescent probe DCFH-DA,respectively.Levels of JNK activation and PDX-1 protein expression were determined by Western blot analysis.Results Sal B significantly alleviated IHG-induced cell injury and apoptosis,with glucose induced insulin secretion capacity improved evidently (P<0.05 or P<0.01).Preincubation with Sal B no-tably decreased intracellular ROS and JNK activation in INS-1 cells,while the level of PDX-1 protein was in-creased markedly (P<0.05 or P<0.01 ).Conclu-sion Sal B is capable of ameliorating IHG-induced cell injury and apoptosis in INS-1 cells,which might be derived from suppression of JNK activation and up-regulation of PDX-1 protein expression.

OBJECTIVE:To study and evaluate the efficacy and safety of homemade sterilized powder for injection of rifampicin(weifunin) in the treatment of pulmonary tuberculosis(PT) and to compared with same import preparation . METHODS:Divide the 121 of bacteriological positive PT patients in the proportion of 1 to 1 with computer automatically into the trial group and the control group used with homemade rifampicin (weifuxin) and import rifampicin(nifu)respectively,the others regimens was same in 2 groups,to evaluate the sputum culture negative conversion rates,X-ray results and adverse drug event etc.after treatment 1 and 2 months . RESULTS: 116 cases were finished ,at the end of 2 month the sputum smear negative conversion rates were 86.21 % and 91.38% (X2=0.780,P=0.377), the sputum culture negative conversion rates were 91.38% and 93.10%(X2=0.120,P=0.729)in the trial group and the control group respectively .The X-ray remarkable effective rates of 2 groups were 82.76% amd 70.69%(X2=2.365,P=0.124)respectively, and the effective rates of the 2 groups were both be 96.55% .The adverse drug event rates were 8.20% and 11.67% respectively, there was on sighificant difference in each indexes .CONCLUSIONS:2 preparation were similar in efficacy ,safety and tolerance.

Quantitative proteomics is a mass spectrometry-based toolkit used to analyze and quantify entire proteins contained in whole cells, tissues or organisms. It has become an increasingly important element in exploring the mechanism of various biological processes such as discovering novel biomarkers and unknown drug targets. Emerging advances in biological mass spectrometry instrumentation and data acquisition methodologies have provided a state-of-the-art platform for protein quantification, prompting the research of proteomics evolving from the simple qualitative to the accurate quantitative approach. This review aims to introduce the most recent advancements in mass spectrometry instrumentation and methodologies of data acquisition, focusing on their characteristics and applying fields. It also highlights several significant applications of biological mass spectrometry in pharmaceutical research such as quantifitation of drug transporters and metabolizing enzymes, and pharmacokinetic study of therapeutic peptides and proteins.

Objective To investigate the clinical,biochemical and genetic findings in patients with isolated methylmalonic aciduria. Methods From January 2001 to December 2014,a total of 126 patients with isolated methyl-malonic aciduria from Peking University First Hospital were enrolled in this study. In 60 patients,gene analysis was per-formed. The clinical characteristics,laboratory findings,treatment and outcomes were retrospectively analyzed. Results Among the 126 patients,only 3 cases(2. 4% )were detected through newborn screening and treated with dietary in-tervention,cobalamin and L - camitine. The age at onset of 123 cases(97. 6% )varied from a few hours after birth to 7 years and 11 months old. The common presentations were recurrent vomiting,mental retardation,poor feeding,lethargy, respiratory distress,coma,seizures,cutaneous lesion and jaundice with 11 patients(8. 73% )dead. Abnormal family his-tory was found in 27(21. 4% )patients. Metabolic acidosis and anemia were frequent laboratory findings. Basal ganglia damage and white matter changes were observed in most patients. Sixty patients got genetic analysis,and 58 cases of them had MUT gene mutations. One case had MMAA defect. One case had MMAB defect. In MUT gene,12 novel muta-tions were identified. After treatment,mild to severe psychomotor retardation was observed in 112 patients with isolated methylmalonic aciduria. Conclusions The clinical manifestation of patients with isolated methylmalonic aciduria is complex,and prone to appear metabolic crisis. MUT defect is the main cause. Early metabolic investigation is very im-portant to reach diagnosis. Newborn screening,early diagnosis and adequate therapy are key points to reduce the morta-lity and handicap.

Objective To explore the clinical, therapeutic and genetic features of IVD gene in late-onset non-classical isovaleric aciduria. Methods One boy and two girls presented with intractable vomiting were admitted. Urine organic acids and blood acylcarnitines proifles were analyzed. Isovaleric aciduria was diagnosed and conifrmed by IVD gene analysis. The patients were treated with leucine-restricted diet and the supplements of L-carnitine and glycine. Results Three patients had recurrent vomiting, drowsiness, odor of sweaty feet and metabolic acidosis from the age of 1 to 2 years. All of them had normal intelligence and leukopenia. One had oligocythemia. The blood isovalerylcarnitines (4.6 to 8.2μmol/L) and urine isovalerylglycines (36.1 to 1783.56 mmol/mmol creatinine) were elevated. Six mutations were found in their IVD gene. Four mutations (c.157C>T, c.214G>A, c.1183C>G and c.1208A>G) were reported. Two (c.1039G>A and c.1076A>G) were novel. The patients completely recovered after treatment with protein-restricted diet and the supplements of L-carnitine and glycine. Currently, they were aged 19 months to 14 years with normal physical and psychomotor development. Conclusions The clinical features of late-onset non-classical isovaleric aciduria are complex. It is onset in infants and young children and characteristic of recurrent vomiting and metabolic acidosis, which can be diagnosed by the blood acylcarnitine spectrum, urine organic acid analysis, and conifrmed by genetic analysis. L-carnitine supplement and diet intervention has signiifcant effects.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.