Objective To observe the expression levels of IL-8,IL-4,TNF-α of neonatal mouse with systemic inflammatory response syndrome(SIRS) treated by different doses of dexamethasone.Methods A total of 50 neonatal mice were randomly divided into five groups:blank control group,saline control group and treatment group A,B,C.The saline control group and treatment groups were established into SIRS models,treatment group A:a single high-dose of dexamethasone (2 mg/kg),subcutaneous injection (SC) ; treatment group B:two doses of dexamethasone (1 mg/kg,q1 2 h,total 2 mg/kg,SC) ; treatment group C:four doses of dexamethasone (0.5 mg/kg,q 1 2 h,total 2 mg/kg,SC) ;saline control group:saline of the same volume (0.4 ml/kg,SC).All mice were detected IL-4,IL-8,TNF-α by ELISA 72 hours after animal models being completed.Results The levels of IL-4,IL-8,TNF-α in saline control group and treatment group A,B,C were higher than those in blank control group respectively (P ＜ 0.05,respectively).The levels of IL-4,IL-8,TNF-α in treatment group A,B,C were lower compared to those of saline control group respectively (P ＜ 0.05,respectively),levels of TNF-α,IL-8 in treatment group B and C were lower than those of treatment group A(P ＜ 0.05,respectively).There were no significant differences in the level of IL-4 among treatment group A,B,and C (P ＞ 0.05).Conclusion Dexamethasone could lower the expressions of pro-inflammatory cytokines IL-8,TNF-α and anti-inflammatory factor IL-8 of neonatal mouse with SIRS,and the effect of multiple low-doses of dexamethasone on SIRS is significantly better than a single high dose.

This study aimed to investigate the therapeutic effect and possible mechanism of carboxyamidotriazole (CAI) on imiquimod (IMQ)-induced psoriasis-like mice model and M5 (IL-1α, IL-17A, IL-22, TNF-α and oncostatin M)-induced keratinocytes model of psoriasis. The severity of psoriasis-like skin lesion in mice was evaluated by psoriasis area and severity index (PASI) score. The histopathological changes of skin were examined by hematoxylin-eosin staining and Baker score was calculated. The levels of pro-inflammatory cytokines in skin were measured by enzyme-linked immunosorbent assay. Transcriptome sequencing technique was used to analyze differentially expressed genes (DEGs) and real-time quantitative PCR (qPCR) was used to detect mRNA expressions. The animal experiments conducted in this study were approved by the Institutional Animal Care Use & Welfare Committee of Institute of Basic Medical Sciences, Chinese Academy of Medical Science (grant No. ACUC-A02-2022-115). The results showed that CAI significantly improved the severity of psoriasis-like lesion, reduced PASI score, attenuated pathological changes, decreased Baker score and inhibited the levels of IL-1β, IL-6, IL-17A, IL-23 and TNF-α in skin of IMQ-induced mice. Transcriptome sequencing analysis revealed that regulating keratinocytes and their mediated keratinization might be involved in the mechanism of CAI. Further qPCR study validated that CAI down-regulated the mRNA expression of DEG S100a7. Moreover, the keratinocyte model of psoriasis was established by stimulating HaCaT cells by M5. It was shown that CAI decreased the mRNA expression levels of S100a7, Il1β, Il6, Il17, Il23 and Ccl20, which were up-regulated by M5 stimulation. In conclusion, CAI might have a good therapeutic efficacy on psoriasis, and its mechanism was related to regulate the function of keratinocytes and downregulate cytokines and S100a7.

Objective To investigate the effect of serum-deprivation on the changes of [ Ca2+ ] i and the protein release of S100A13 and fibroblast growth factor 1 ( FGF-1 ) in thyroid cancer TT cell,and to reveal the role of Ca2+in the protein release of S100Al3 and FGF-1.Methods The protein expressions of FGF-1 and S100A13 in TT cells under serum-deprivation were detected by Western blot.The released FGF-1 protein from TT cells in the supernatant fluid was detected by ELISA.Realtime dynamic examinations on the change of 1 h [ Ca2+ ] i in TT cells under serum-deprivation were detected by confocal laser scanning microscopy.Then,the effect of EGTA( 2.5 mmol/ L),BAPTA-AM (2.5 μmol/L)on distributions of the fluorescence of S100AI 3 and FGF-1 in TT cells under serumdeprivation for6 h were detected by indirect immunofluorescence.Results The expressions of FGF-1 and S100A13 in TT cells after serum-deprivation for4 h and 6 h were reduced( P＜0.05 or P＜0.01 ),but the released FGF-1 protein from TT cells in the supernatant fluid was elevated ( P＜0.05 or P＜0.01).Confocal laser scanning of Ca2+ imaging indicated that [ Ca2+ ] i of serum-deprivation TT cells maintained the relative stabilization within 23 win,but the rapid rise of [ Ca2+ ] i achieved peak value 1.6 μmol/L after 30 min,and remained stable for about 17 win,and thereafter 40 win slowly dropped to a low level From 40 win to 60 win the [ Ca2+ ] i was about 0.3-0.6 μ mol/L.The average [ Ca2+ ] i was higher than that in normal group,EGTA group,and BAPTA-AM group within 1 h.The protein expressions of S100A13 and FGF-1 did not drop obviously in EGTA group and BAPTA-AM group.Conlusion The release of S100A13 and FGF-1 from TT cell under serum-deprivation is possibly related with the change of [ Ca2+ ]i.Both Ca2+-chelating agents EGTA and BA PTA-AM are able to inhibit the rise of [ Ca2+ ] i and release of S100A 13 and FGF-1 from TT cells under serum-deprivation.

Aim The effect and mechanism of human placental extract(HPE) on the lipoprotein-cholesterol metabolism, peroxidation and the function of platelet aggregation in hyperlipaemia rats were abserved.Methods Wistar rat with hyperlipaemia models were given each HPE 0.4 ml (100 g)-1?d-1 through lavage for 12 days.The serum levels of TG,TC,LDL-C,HDL-C and HDL2-C in its subgroup were measured.The activies of LPO and SOD in both blood and liver tissue were determined .The effect of HPE on lipidosis of liver were abserved by fat dyeing.The levels of 6-keto-PGF1?,TXB2 in plasma and maximum platelet aggregation rate were measured by ELASA. Result The levels of HDL-C and HDL2-C were increased (P

Clostridium difficile is a gram-positive,anaerobic spore-forming bacillus commonly found in the environment and human gut.Excessive use of antibiotics,immunosuppressive agents and chemotherapy drugs may lead to overgrowth of the toxic strain of Clostridium difficile with high resistance,which are supposed to be the major contributing factors leading to Clostridium difficile associated diarrhea(CDAD).The globally increasing incidence of CDAD,especially the outbreak of nosocomial infection caused by the hypervirulent strain in North America,arouse worldwide attention.For providing new ideas to the early diagnosis and treatment of CDAD,this review summarize the latest development on pathogenesis and rapid laboratory diagnosis of Clostridium difficile.

Effect and safety of repeated embryo aspiration for reduction of muhifetal cervical pregnancy Was retrospectively evaluated.Three women with muhifetal cervical pregnancy successfully received conservative treatment of repeated embryo aspiration under the guidance of transvaginal ultrasound,and the gestational sac contents were aspirated completely.Local(2.5～5.0 mg injectable methotrexate,MTX) or systemic medication was used.Our findings showed that repeated embryo aspiration for reduction of cervical multifetal pregnancy could improve the coupe of disease,decrease systemic medication of MTX,and discontinue a cervical pregnancy within 8 weeks effectively and safely.However,the mminimum therapeutic dose of MTX remained to be explored.

According to the existing Provisions for Drug Registration (SFDA Order No. 28), applications for new drugs of traditional Chinese medicine are divided into two parts: the applications for drug clinical trial and for drug production (including new drug certificate). It will last for about 10 years from the application for drug clinical trial to get approving, and it also remains many problems and the low probability to succeed. From the sight of pharmaceutical review, there are mainly two aspects of regulatory compliance and technical issues, mainly for changes without approval of the competent authorities of the country. For example, sample preparation and approval of clinical trial process are significant changes. Technical problems are reporting incomplete data or information submitted does not comply with the technical requirements for review, such as: production process validation does not provide information, the preparation of samples for clinical trials and field inspection, production information, or the information provided does not meet the technical requirements. This paper summarizes the frequently asked questions and to make recommendations to advise applicants concerned, timely detection of problems, avoid risk, improving the quality and efficiency of the application for registration.
China ; Drug Approval ; legislation & jurisprudence ; Drug Evaluation ; legislation & jurisprudence ; Humans ; Legislation, Drug ; Medicine, Chinese Traditional

Small molecule covalent inhibitors, or called as irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity. Nevertheless, these agents may also exhibit larger toxicity once off-target effects arise. This "double-edged swords" property often leads drug researchers to avoid attaching them. In recent years, some problems such as drug resistance are difficult to be solved with reversible inhibitors leading researchers to pay more attention on the covalent inhibitors. In this review, we shall make a short summary to the recent research progress of covalent inhibitors and the interaction modes between covalent inhibitors and their target protein residues.
Amino Acids ; chemistry ; Antineoplastic Agents ; chemical synthesis ; chemistry ; therapeutic use ; Antiviral Agents ; chemical synthesis ; chemistry ; therapeutic use ; Drug Discovery ; Drug Resistance ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Hepatitis C ; drug therapy ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; Protein Binding ; Protein Kinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Serine Proteinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use

Inflammation is a defensive reaction and the most common pathological manifestation of dry eye.In addition,excessive inflammatory response is considered to be the most common pathogenic factor and main cause of dry eye.Currently,the active mechanism of anti-inflammatory drugs has been well-known,and topical antiinflammatory therapy for dry eye is exerting a role at certain extend.However,some adverse responses of these drugs are emerging during the treating procedure.Therefore,it is emphasized that a large sample size of and multicenter randomized-controlled clinical trial is needed to identify the different effects of various anti-inflammatory drugs for different types of dry eye diseases,which will offer a basis for standardized anti-inflammatory treatment for dry eye.

Objective To apply fluorescence-activated cell sorting (FACS) and magnetic activated cell sorting (MACS) in sorting natural killer (NK) cells from human peripheral blood. The efficiency of these two methods were compared so that the basic conditions for the further study on the lower proportion of peripheral blood cells could be created. Methods Twenty cases of normal peripheral blood and 3 cases of post-hematopoietic stem cell transplantation (post-HSCT) were collected and NK cell were sorted by FACS and MACS. Results Before sorting the normal peripheral blood, the proportion of the NK cell in the leukocyte was (12.86±3.62) %, the purity of NK cell was up to (96.15±2.03) % and the recovery was (95.08±2.16) %after sorting by FACS, the purity was up to (93.35±3.61) % and the recovery was (94.11±3.01) % by MACS.And before sorting the post-HSCT peripheral blood, the proportion of the NK cell in the leukocyte was (11.01±2.08) %, the purity of NK cell was up to (96.22±2.16) % and the recovery was (95.27±1.18) % after sorting by FACS. The purity was up to (90.98±1.94) % and the recovery was (94.54±3.52) % by MACS. Thereis difference in purity of NK cell (t = 5.925, P ＜0.05), while no difference in rate of recovery between 2methods (t = 0.789, P ＞0.05). Conclusion FACS is more efficient, rapidly and easily than MACS in sorting NK cell, especially for post-HSCT cases.