Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective:To analyze the genotype of hereditary eye diseases with early-onset high myopia (eoHM) and its relationship with phenotype.Methods:The families with eoHM were collected in Ningxia Eye Hospital from January 2019 to June 2020.The medical records of the probands and their family members were inquired and recorded in detail, and the relevant ocular examinations were performed.Peripheral venous blood samples were collected from patients and their family members, and whole-genome DNA was extracted.Sequence capture sequencing technology was applied to screen for disease-causing gene mutations in probands.The detected suspected pathogenic variants were verified by Sanger sequencing and were analyzed by family cosegregation analysis.According to ACMG guidelines, the pathogenicity of novel variants was evaluated.The original literature about hereditary eye diseases with eoHM was searched to analyze the relationship between mutated genes and clinical phenotype.This study protocol adhered to the Declaration of Helsinki.All subjects or their guardians were informed of the purpose and procedure of the study and signed the informed consent form.The study protocol was approved by the Ethics Committee of the People's Hospital of Ningxia Hui Autonomous Region (No.2016018).Results:A total of 20 eoHM families were collected, among which pathogenic variants associated with inherited eye diseases were detected in 8 families.Of the 8 probands, two were diagnosed with familial exudative vitreoretinopathy, one with X-linked retinitis pigmentosa, one with congenital stationary nightblindness, one with Stickler syndrome, one with achromatopsia, one with Leber congenital amaurosis, and one with gyrate atrophy of the choroid and retina.The first diagnosis age of the 8 probands was 4-7 years old, and they were all diagnosed as high myopia, with a refractive status ≤-6.00 DS.Genetic tests showed that the 8 probands carried a heterozygous variant c. 313A>G (p.M105Val) in FZD4 gene, a heterozygous variant c. 14_15insAAGA (p.Asp5fs *) in TSPAN12 gene, a heterozygous frameshift variant c. 2234_2237del (p.Arg745fs) in RPGR gene, a compound heterozygous variant of c. 481C>T (p.Gln161Ter *) and c. 355>T (p.Arg119Cys *) in GPR179 gene, a frameshift variant c. 1659_1660insACGGTGACCCTGGCCGTCCTGG (p.Pro554fs *) in COL2A1 gene, a compound heterozygous variant of c. 1811C>T (p.Thr604Ile *) and c. 967G>A (p.Gly323Ser) in PDE6B gene, a compound heterozygous variant of c. 604_619delTCCACGGCACTCAGGG (p.Ser202fs *) and c. 995G>C (p.Arg332Pro) in GUCY2D gene, a homozygous variant c. 772C>T (p.Pro241Leu) in OAT gene.Seven of them were novel variants.Compared with the previous literature, the clinical and gene phenotypes of the 8 families were analyzed in detail in this study, which provided the basis for the diagnosis of hereditary eye diseases with eoHM. Conclusions:EoHM is closely related to some hereditary eye diseases, which may be the reason for the early diagnosis of children and an important clue for clinicians to detect potential hereditary eye diseases.Further clinical evaluations of ocular structure and function as well as genetic screening in children with eoHM are recommended.

The health literacy refers to the ability of individuals to acquire and understand basic health information and services and use them to make the right decisions to maintain and promote their health. Health literacy data focusing on cancer prevention and control was limited in China. In order to understand the health literacy and awareness of cancer risk factors and the cancer screening, early diagnosis and treatment in Chinese urban residents and compare the effect of different stages of the cancer intervention, the Cancer Screening Program in Urban China (CanSPUC) program, supported by the National Key Public Health Program, conducted a survey on the health literacy of the cancer prevention and treatment among urban residents in 16 provinces nationwide from 2015 to 2017. Four subgroups were designed in this survey, including (1) general population who have never participated in any cancer screening programs at a community-level; (2) individuals who have previously attended the CanSPUC program for cancer risk assessment or screening intervention; (3) cancer patients who were receiving treatment in local hospitals; (4) a special group from employees of government and public institutions (non-health system), state-owned enterprises and private enterprises (to have better understand on the impact of socioeconomic factors). The self-designed questionnaire covered six parts, including basic information, consciousness of common risk factors to cancer, awareness of early detection, awareness of early diagnosis, awareness of early treatment, and the needs and approaches for knowledge of cancer prevention and treatment. A total of 32 257 individuals were included in the final analyses. This paper landscaped the overall design of the survey, including participants, domains of the instrument, quality control, basic characteristics of the included individuals. These descriptions are applicable to each individual report of the current special issue of "Health Literacy of Cancer Control in Urban China" and future reports, in which more detailed results are and will be reported. The findings of this survey could provide some useful implications for similar researches in the future.

OBJECTIVE:To establish HPLC-quadrupole/electrostatic field orbitrap high resolution mass spectrometry for rapid determination of aconitine,mesaconitine,hypaconitine,benzoylaconitine,benzoylmesaconine and benzoylhypacoitine in rat plasma. METHODS:Internal standard lappaconitine was added into plasma sample,and methanol precipitated protein was used for pretreatment. HPLC-quadrupole/electrostatic field orbitrap high resolution mass spectrometry was adopted. HPLC condition was as follows as Sinochrom ODS-BP C18column,mobile phase consisted of acetonitrile-1% formic acid solution(50:50,V/V),the flow rate of 0.6 mL/min,sample size of 10 μL,column temperature of 25 ℃,automatic sampler temperature of 4 ℃. Mass spectrum scanning mode was full ion monitoring model,positive ion acquisition,mass charge ratios(m/z)of ion were 646.32(aconitine), 632.30(mesaconitine),616.31(hypaconitine),604.31(benzoylaconitine),590.29(benzoylmesaconine),574.30(benzoylhypacoitine), 585.31(internal standard). Six male Wistar rats were collected and given single dose of total alkaloid extract of Aconitum carmichaeli(4 mg/kg)intragastrically. Blood samples were collected before medication(0 h)and 0.5,0.75,1.25,1.5,2,4,6, 8,10,24 h after medication. Plasma concentration was determined and pharmacokinetic parameters were calculated by using PK-Solver V2.0 software. RESULTS:The linear range of 6 kinds of aconitum alkaloids in plasma were 0.1-10 μ g/L(r>0.992). The limit of quantitation was 0.1 μ g/L. Average recovery was higher than 75%,RSDs of intra-day and inter-day,matrix effects,stability test were all lower than 15%. The tmaxof 6 kinds of aconite alkaloids were about 1.2 h;t1/2were about 10 h;cmaxof monoestertype aconite alkaloids were higher than those of diester-type aconite alkaloids. CONCLUSIONS:Established HPLC-quadrupole/electrostatic field orbitrap high resolution mass spectrometry is accurate,sensitive,simple and rapid, and can be used for plasma concentration monitoring of 6 kinds of aconitum alkaloids.

Objective To explore the application effect of the PICC simple bath protective sleeve in catheter patients.Methods Three hundred home-bathing patients with PICC tube were divided into control group (n =150) and observation group (n =150),given plastic wrap to protect the tube,simple bath protector,respectively.The incidence rates of dampness and looseness,the incidence rate of PICC-related complications,comfort and satisfaction were compared.Results The incidence rates of dampness and looseness in the observation group was lower than that in the control group (P ＜ 0.05).PICC local eczema,puncture point infection,mild and moderate prolapse of catheter and incidence of complications were lower than that in the control group (P ＜ 0.05),comfort and satisfaction were higher than that in the control group (P ＜ 0.05).Conclusion Simple bath cover can effectively avoid dampness and loosening of catheter,reduce PICC prolapse,local eczema and puncture point infection,and improve comfort and nursing satisfaction.

Objective To explore the application effect of the PICC simple bath protective sleeve in catheter patients.Methods Three hundred home-bathing patients with PICC tube were divided into control group (n =150) and observation group (n =150),given plastic wrap to protect the tube,simple bath protector,respectively.The incidence rates of dampness and looseness,the incidence rate of PICC-related complications,comfort and satisfaction were compared.Results The incidence rates of dampness and looseness in the observation group was lower than that in the control group (P ＜ 0.05).PICC local eczema,puncture point infection,mild and moderate prolapse of catheter and incidence of complications were lower than that in the control group (P ＜ 0.05),comfort and satisfaction were higher than that in the control group (P ＜ 0.05).Conclusion Simple bath cover can effectively avoid dampness and loosening of catheter,reduce PICC prolapse,local eczema and puncture point infection,and improve comfort and nursing satisfaction.

Objective To investigate implementing approach and clinical effect of 4-dimensional innovative model basing on JCI standards on health education to elderly patients with CHD.Methods Following JCI standards, a 4-dimensional model was innovated, regarding 4 aspects of health education for elderly patients with CHD:concept, platform, transmission system and technological application. Totals of 120 elderly patients with CHD were divided randomly into observation group and control group. For the patients in the observation group, health education was conducted according to the 4-dimentional innovative model, while in the control group, routine health education approach for CHD was used, which was to hand out health pamphlets explaining knowledge concerning diet, drug, exercise, follow-up visit, etc. After 5 days of intervention, CHD organism functional status and quality of life of the CHD patients in the two groups were evaluated and compared. Indexes, such as self-management skills, were compared 6 months after discharge. Results In SAQ scoring, there were significant differences between observation group and control group regarding limitation degree of motion, attacking condition of angina or stable condition of angina, scores of satisfaction on treatment and awareness of the disease ( P<0. 05 ) . Conclusions Conducting health education to elderly patients with CHD with the 4-dimensional innovative model basing on JCI standards plays a significant role in promoting guarantee of medical safety, prevention of harmful cardiac incidents, and enhancement of treatment compliance, patients′ self-management abilities and patients′satisfaction.

Background Study determined that retinitis pigmentosa has a similar pathogenesis mechanism to Alzheimer disease,and activity of cyclin-dependent kinase 5 (Cdk5) and its activators participates in the degeneration of central nervous system.Roscovitine,an inhibitor of Cdk5,can suppress activity of Cdk5/p25 pathway and therefore inhibit cell apoptosis.However,the influence of roscovitine on retinitis pigmentosa(RP) is unclear.Objective This study was to investigate the expressions of p35,p25 and tau in the retinas of RCS rats.Methods Roscovitine of 4 μl was intravitreally injected in the right eyes of 12 SPF 17-day-old RCS rats,and the fellow eyes were not intervened as the control eyes.The rats were sacrificed on eighth day (postnatal 25 days) and eighteenth day (postnatal 35 days),and whole retinas were isolated to evaluate the relative expressions of Cdk5,p35,p25 and tau phosphorylation by Western blot,and the activity of Cdk5/p25 was analyzed by quantitative colorimetric assay.The results were compared between the right eyes and fellow eyes by paired t test.The use and care of the rats complied with Ethic Statement of Experimental Animal of Ningxia Medical University.Results In the eighth and eighteenth day after injection,the relative expression values (A values) of p35 in rat retinas were 1.186±0.019 and 1.069± 0.019 in the injected eyes,showing significant decreases in comparison with 1.364±0.016 and 1.214±0.008 of the fellow eyes (t =-6.294,-6.477,both at P＜0.05);the relative expression values (A values) of p25 in rat retinas were 0.312±0.009 and 0.269±0.018 in the injected eyes,which was significantly lower than 0.595±0.013 and 0.473±0.011 of the fellow eyes (t=-36.508,-11.879,both at P＜0.05).No significant difference was found in the relative expression of Cdk5 protein between the injected eyes and the fellow eyes in various time points after injection (both at P＞0.05).The activities of Cdk5/p25 were (0.003 83 ±0.000 14) mol/(s · mg) and (0.002 01 ± 0.000 11) mol/(s · mg) in the injected eyes,with significant decreases in comparison with the (0.005 47±0.000 27)mol/(s · mg)and (0.003 35±0.000 15) mol/(s · mg) of the fellow eyes (t=-9.152,P=0.000;t=-9.248,P=0.000),and the tau phosphorylation levels followed the same pattern in the eighth and eighteenth day after injection (t =-9.854,-6.744,both at P＜0.05).Conclusions Intravitreal injection of roscovitine can inhibit the activity of Cdk5/p25 and tau phosphorylation level in retinas of RCS rats to certain extend.