Toll-like receptor (TLR) is an important pattem recognition receptor (PRR) which partici pates in innate immunity and regulates adaptive immunity.TLR can be expressed in immune cells and malig nant tumors recognize conservative molecular structure,mediate response of inflammation,tissue injury and repair,which plays an important role in the process of tumor.Research results about some molecules and signal pathways of TLR demonstrate that it can act anti or pro-tumor dual functions,which has an extensive prospects in prevention and treatment of tumor.

Objective To evaluate the effect of penehyclidine hydrochloride on cell apoptosis during acute lung injury (ALI) induced by two-hit in rats.Methods Thirty male SPF Sprague-Dawley rats, aged 8 weeks, weighing 240-270 g, were randomly assigned into 3 groups (n =10 each) using a random number table: sham operation group (group Sham), ALI induced by blunt chest trauma and hemorrhagic shock group (group ALI), and penehyclidine hydrochloric group (group PHC).In ALI and PHC groups, the rats were subjected to the combination of chest trauma and hemorrhage (mean arterial pressure 35-40 mmHg mm Hg, lasting for 60 min) to establish a model of ALI.In group PHC, penehyclidine hydrochloric 2 mg/kg was injected intraperitoneally at 1 h before blunt chest trauma.At 8 h after successful establishment of the model, the rats were sacrificed, and lungs were removed for examination of the pathologic changes and for determination of Bax, Bcl-2 and caspase-3 expression (using Western blot), tumor necrosis factor-alpha (TNF-α) content (by enzyme-linked immunosorbent assay) , and cell apoptosis (by TUNEL).Apoptotic index was calculated.Results Compared with group Sham, the levels of Bax, caspase-3 and TNF-α and apoptotic index were significantly increased, and Bcl-2 expression was down-regulated in ALI and PHC groups.Compared with group ALI, the levels of Bax, caspase-3 and TNF-α and apoptotic index were significantly decreased, and Bcl-2 expression was up-regulated in group PHC.The pathologic changes of lungs were significantly reduced in group PHC than in group ALI.Conclusion Penehyclidine hydrochloride mitigates ALI induced by two-hit through inhibiting cell apoptosis in rats.

Objective To study the immunophenotype and chromosome karyotype of 57 adult patients with newly?diagnostic acute lymphoblastic leukemia(ALL). Methods The immunophenotype and chromosome karyotype of 57 adult patients with newly?diagnostic ALL were determined by using flow cytometer and karyotyping,and then the clinical characteristics and significance were analyzed. Results In patients with B cell acute lymphoblastic leukemia(B?ALL),the expression of CD19 and CD22 were significantly higher than CD10 and CD20(P<0.05). The expression of CD7 and CD3 were much higher in patients with T cell acute lymphoblastic leukemia(T?ALL). As for the early antigen,patients of all subtypes of ALL showed high expression rate of CD34 and CD38. In addition,the HLA?DR was only detected in B?ALL. There was no difference in comparison with clinical characteristics,total rate of CR and rate of relapse between ALL with and without myeloid antigen expression. The expression rate of CD34 and HLA?DR was higher in My+?ALL(P<0.05). The relapse rate was much higher in these patients with abnormal karyotype than other pa?tients(P<0.05). Patients with high?risk karyotype showed higher expression rates of CD20 and CD3 than those with standard?risk. Conclusion The immunophenotypes and chromosome karyotypes show obviously heterogeneous features,and the patients with abnormal karyotypes have higher relapse rate. These above mentioned methods are applicable for the diagnosis and individualized treatment of ALL patients.

Phytantriol (PT), ethanol (ET) and water were used to prepare in situ cubic liquid crystal (ISV2). The pseudo-ternary phase diagram of PT-ET-water was constructed and isotropic solution formulations were chosen for further optimization. The physicochemical properties of isotropic solution formulations were evaluated to optimize the composition of ISV2. In situ hexagonal liquid crystals (ISH2) were prepared based on the composition of ISV2 with the addition of vitamin E acetate (VitEA) and the amount of VitEA was optimized by in vitro release behavior. The phase structures of liquid crystalline gels formed by ISV2 and ISH2 in excess water were confirmed by crossed polarized light microscopy and small angle X-ray scattering, respectively. Rheological properties of ISV2 and ISH2 were studied by a DHR-2 rheometer. In vitro drug release studies were conducted by using a dialysis membrane diffusion method. Pharmacokinetics was investigated by determination of sinomenine hydrochloride (SMH) concentration in synovial membrane after intra-articular injection of SMH-loaded ISH2 in adjuvant-induced arthritis rats. The optimal ISV2 (PT/ET/water, 64 : 16 : 20, w/w/w) loaded with 6 mg x g(-1) of SMH showed a suitable pH, injectable and formed a cubic liquid crystalline gel in situ with minimum water absorption in the shortest time. The optimal ISV2 was able to sustain the drug release for 144 h. The optimal ISH2 system was prepared by addition of 5% VitEA into PT in the optimal ISV2 system. This ISH2 (PT/VitEA/ET/water, 60.8 : 3.2 : 16 : 20, w/w/w/w) was an injectable isotropic solution with suitable pH. The new ISH2 was able to sustain the drug release for more than 240 h. Local pharmacokinetics study indicated that the retention time and AUC(0-∞) of ISH2 group were increased significantly compared with that of SMH solution group and the AUC(0-∞) of ISH2 group was 6.01 times higher than that of SMH solution group. The developed ISH2 was suitable for intra-articular injection that may apply to patients in the treatment of rheumatoid arthritis.

Objective To evaluate the value of single leaflet replacement of bovine pericardium in the treatment of aortic valve insufficiency using transthoracic echocardiography(TTE) and transesophageal echocardiography(TEE).Methods TTE and TEE examination were performed for 25 cases pre-operation,postpump intraoperative and 3-6 months after the operation,to judge the structure and the regurgitation of the aortic valve.And the inside diameter of left atrium(LA)and left ventricle(LV)in the same plane and the same phase were also been measured.Results The degree of aortic regurgitation(AR)before operation were significantly different with that postpump intraoperative(P＜0.001)evaluated by TEE.There was no difference in the degree of AR by postpump intraoperative TEE and those of AR by TTE 3-6 months after surgery(P＞0.1).The inside diameter of LA[(3.80±1.37)em]and LV[(5.75±1.32)cm]before repair were larger than those 3～6 months after surgery[LA(3.19±0.90)cm,LV(4.72±1.19)cm,P＜0.001].Conclusions The replacement of single aortic valve with bovine pericardium to treat aortic valve insufficiency is a good alternative for patients with satisfactory short-term results,but long-term results are not clear.

Objective To analyze mutations in the ATP2A2 gene in a Kazakh family with Darier's disease.Methods Clinical data were collected from 49 members from a family with Darier's disease,and peripheral blood samples were obtained from 44 family members and 100 unrelated healthy people.Genomic DNA was extracted from these blood samples.PCR and DNA sequencing were performed to detect mutations in the ATP2A2 gene.Results Darier's disease was inherited in an autosomal dominant manner in this family.A G→A heterozygous mutation (1288-1G→A) was identified at position 1288-1 at the splice site in exon 12 of the ATP2A2 gene in 11 patients in this family,but not in 33 healthy members or 100 healthy controls.Conclusion Darier's disease in this family may be caused by the heterozygous mutation (1288-1G→A)at the splice site in exon 12 of the ATP2A2 gene.

Objective:To explore the clinical characteristics and treatment of a family with inherited generalized epilepsy with febrile seizures plus (GEFS + ) caused by the KCNT2 gene mutation and review the literature. Methods:Clinical data of a child with GEFS + and his family members who visited Department of Pediatric Neurology, Guangzhou Women and Children′s Medical Center in May 2019 were collected.DNA samples were collected from the peripheral blood of the proband, his parents, his elder brother, and his maternal grandparents, and genetic analysis and verification were performed using the next-generation sequencing technique.Using " KCNT2" as the key word, literature was retrieved from PubMed, China National Knowledge Infrastructure and Wanfang databases (up to August 2019). Results:The proband was a 3-year-old boy who was admitted to Guangzhou Women and Children′s Medical Center because of frequent epileptic seizures in the past 5 months.He presented with a binocular gaze and experienced 3 to 8 times of extremities myoclonic-spastic epileptic attacks every day.He had a history of 3 times of febrile seizures at the age of 2 years old.His seizures were refractory to Sodium valproate, Topiramate, Nitrazepam and Levetiracetam.His elder brother and mother had a history of childhood febrile seizures.Other members in the family had no history of convulsion.Ictal electroencephalogram showed general 1 Hz high voltage spike-slow waves.A heterozygous nonsense mutation of KCNT2 gene c. 574C>T(p.Q192X) that was never reported previously was detected in the proband, his brother, mother and maternal grandmother.Furthermore, no other family members carried the mutation at the c. 574 locus of the KCNT2 gene.No article in Chinese was found, and 2 articles in a language other than Chinese provided the complete data of 3 sporadic cases.Together with 4 cases in the family studied in this article, there were 7 cases and 4 mutation sites in KCNT2 gene.Of these mutations, there were 3 missense mutations and 1 nonsense mutation.Three sporadic patients presented with early infantile epileptic encephalopathy.The family of this study was characterized with febrile seizures and febrile seizures plus. Conclusions:A de novo mutation and phenotype of the KCNT2 gene is found in a family with GEFS + .It would expand the gene mutation spectrum and provide basis for family genetic counseling. KCNT2 mutation induced GEFS + is refractory to antiepileptic drugs.

Objective To investigate the relationship between genetic polymorphisms in nucleotide excision repair gene excision repair cross complementing group 6(ERCC6),xeroderma pigmentosum group A(XPA) and coal-burning-borne-arsenism in Guizhou Province.Method ERCC6 A3368G,ERCC6 C-6530G and XPA A23G gene polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism technique(PCR-RFLP) of 205 cases which were chosen as patients with arsenism and 187 residents as control group.Results The distributions of ERCC6 A3368G,ERCC6 C-6530G and XPA A23G in the case group were not statistically significant compared with those of the control group(x2 =3.209,2.963,3.335,all P ＞ 0.05); individuals carrying G allelomorphic gene(AG + GG) had a lower risk than individuals carring A allelomorphic gene(ORadj =0.282,95％CI:0.126-0.628,P =0.002); relationship was not found between single genetic polymorphisms of ERCC6 C-6530G,XPA A23G and coal-burning-borne-arsenism; the risk of arsenism was decreased for individuals carrying the following five genotypes combination:ERCC6 A3368G(AG + GG) genotype and ERCC6 C-6530G CC genotype(ORadj =0.287,95％CI:0.087-0.946,P=0.040); ERCC6 A3368G(AG + GG) genotype and ERCC6 C-6530G(CG + GG) genotype (ORadj =0.226,95％CI:0.077-0.661,P =0.007); ERCC6 A3368G(AG + GG) genotype and XPA A23G AA genotype (ORadj =0.150,95％CI:0.038-0.596,P =0.007); ERCC6 A3368G (AG + GG) genotype and XPA A23G(AG + GG) genotype(ORadj =0.325,95％CI:0.118-0.897,P =0.030) ; ERCC6 C6530G (CG + GG) genotype and XPA A23G AA genotype (ORadj =0.397,95％CI:0.162-0.975,P=0.036).Conclusions Individuals carring ERCC6 A3368G (AG + GG) genotype have a low risk of arsenism.There are five genotypes combination of three gene polymorphisms in two genes,ERCC6 and XPA,which may reduce the risk of coal-burning-borne-arsenism.

Objective To determine the normal range of minimal erythema dose (MED) for ultraviolet A (UVA) and B (UVB) in volunteers from Urumqi region.Methods One hundred and twenty-seven volunteers including healthy subjects and patients with noninflammatory skin disorders were enrolled in this study.SUV-1000 type UV simulator was used as the light source to determine MED of UVA and UVB in these subjects.Results These subjects included 48 persons with Fitzpatrick skin type Ⅲ,79 with Fitzpatrick skin type Ⅳ,51 males and 76 females.The median MED value for UVA and UVB was 38.1 J/cm2 and 31.8 mJ/cm2 respectively in subjects with skin type Ⅲ,59.16 J/cm2 and 48.00 mJ/cm2 respectively in subjects with skin type Ⅳ.Significantly lower median MED values of UVA (both P ＜ 0.01) and UVB (both P ＜ 0.05) were observed in the male and female subjects with skin type Ⅲ compared with those with skin type Ⅳ.The male subjects showed a significantly higher median UVA-MED value (59.16 J/cm2 vs.41.10 J/cm2,P ＜ 0.05),but a similar UVB-MED value (39.60 mJ/cm2 vs.35.55 mJ/cm2,P ＞ 0.05) compared with the female subjects.No significant difference was observed in the median value of UVA-or UVB-MED in subjects with skin type Ⅲ or Ⅳ between Han and Uygur nationality (all P ＞ 0.05).Also,no correlation was found in the median value of UVA-or UVB-MED with age or duration of outdoor exposure in the male or female subjects (all P ＞ 0.05).The lower reference limit was 33.38 J/cm2 for UVA-MED and 27.90 mJ/cm2 for UVB-MED in the population in Urumqi region.Conclusion Skin phototype may be an important determinant of MED.

Objective The aim of this study was to generate human cholesteryl ester transfer protein ( CETP) transgenic rabbits and analyze their biological properties.Methods We generated human CETP transgenic rabbits by DNA microinjection, and detected the expression of human CETP by real-time PCR and Western blot assay.The activity of CETP was measured using an activity assay kit.Results Human CETP transgenic rabbits were successfully generated by DNA microinjection.Compared with wide type rabbits, the expression of human CETP was dramatically increased in the liver of the human CETP transgenic rabbits.The plasma CETP activity was also much higher in the liver of human CETP transgenic rabbits than that of control rabbits.Conclusions The model of human CETP transgenic rabbits is successfully established by DNA microinjection.It will provide a useful tool for the studies of CETP biological function and its involvement in the mechanisms of cardiovascular diseases.