Objective To investigate the mechanism of Guizhi Tongluo Tablets(GZTLP)on improving atherosclerosis in APOE knockout mice by regulating neutrophil extracellular trapping nets(NETs).Methods After modeling,24 APOE knockout mice aged 8 weeks were randomly divided into 4 groups:GZTLP high-dose group,low-dose group,model control group and normal control group,with 6 mice in each group.GZTLP was given 1.87 mg·g-1 and 0.47 mg·g-1 intragastric administration in high-dose group and low-dose group,respectively.The normal control group and model control group were given 0.9%sodium chloride solution intragastric administration for 6 weeks,and the lipid plaque deposition in aorta was observed by gross oil red O staining.Lipid deposition in aortic root was observed by oil red O staining.The pathological changes of lipid plaques in aortic root were observed by HE staining.The levels of interleukin-1β(IL-1β)and tumor necrosis factor α(TNF-α)in peripheral blood of mice were detected by enzyme-linked immunosorbent assay(ELISA).The expression of lymphocyte antigen 6G(Ly6G),myeloperoxidase(MPO)and citrulinated histone(Cit-H3)in plaques of the aortic arch and the colocalization of Ly6G,MPO and Cit-H3 were detected by immunofluorescence assay.Results Compared with the normal control group,the aorta of mice in the model control group showed serious lipid plaque deposition,morphological damage,and a large number of inflammatory cells infiltration,the contents of serum inflammatory factors IL-1β and TNF-α were increased,and the protein expressions of Ly6G,Cit-H3 and MPO were significantly increased.Compared with model control group,GZTLP group reduced the amount of lipid plaque deposition in aorta,the arrangement of aortic cells was more regular,the inflammatory cell infiltration was improved,and the contents of serum inflammatory factors IL-1β and TNF-α were significantly decreased(P<0.05).The colocalization and the protein expression of Ly6G,MPO and Cit-H3 were significantly decreased in aortic tissues(P<0.01).Conclusions GZTLP can improve atherosclerosis,and its mechanism may be related to the inhibition of neutrophil extracellular trapping nets.

Cadmium is a non-essential,non-degradable heavy metal element,the accumulation of cadmium can cause kidney damage.The purpose of this study was to reveal the ferroptosis mecha-nism induced by cadmium exposure in porcine kidney PK-15 cells.First of all,cell viability of gradi-ent concentration of cadmium chloride(CdCl2)on PK-15 cells was detected by CCK-8 method to screen suitable work concentration of CdCl2.Secondly,PK-15 cells were treated with 10 μmol/L CdCl2 for 3,6 and 12 h.The contents of lactate dehydrogenase(LDH)malondialdehyde(MDA)were detected by colorimetry,the expression of ferroptosis related protein were detected by West-ern blot,and the content of ferrous ion(Fe2+)was detected by fluorescence probe.Finally,PK-15 cells were pretreated with 10 μmol/L HO-1 inhibitor zinc protoporphyrin(ZnPP)for 6 h,and then treated with 10 μmol/L CdCl2 for 12 h.The morphology of PK-15 cells was observed by phase contrast microscope and the expression of ferroptosis related proteins was detected by West-ern blot.The results showed that CdCl2 treatment caused a significant decrease in cell viability.The levels of LDH,MDA and Fe2+,the protein levels of Nrf2,HO-1 and ALOX5,and the expression level of FTH1 protein were significantly decreased in CdCl2 treatment cells(P＜0.01).ZnPP could significantly improve the ferroptosis of PK-15 cells induced by CdCl2 treatment.Compared with CdCl2 treatment cells,the cell morphology was significantly improved,the protein levels of Nrf2,HO-1 and ALOX5 protein were significantly decreased,and the protein levels of FTH1 protein were significantly increased in ZnPP pretreatment group(P＜0.01).The results showed that cad-mium induced iron overload and lipid peroxidation,which result in ferroptosis in PK-15 cells through Nrf2/HO-1 pathway.

Porcine kidney cell line(PK-15)with HO-1 gene knockout was constructed by CRISPR/Cas9 system to provide experimental materials for exploring the role and molecular mechanism of HO-1 in cadmium-induced ferroptosis in PK-15 cells.Three sgRNA targeting HO-1 gene were de-signed,synthesized and ligated to lentiviral vector Lenti CRISPRv2.The constructed lentiviral plas-mid was transfected into human embryonic cells(HEK293FT)to obtain recombinant lentivirus,which was used to infect PK-15 cells.The monoclonal cell line with HO-1 knockout was obtained by puromycin screening and limited dilution method.The knockout effect was analyzed by sequencing and Western blot detection.The HO-1 gene knockout cells were treated with 10 μmol/L cadmium chloride(CdCl2).The cell viability was detected by CCK-8 method,the cell morpholo-gy was observed by phase contrast microscope,and the content of ferrous ion(Fe2+)was detected by fluorescence probe.The results showed that sgRNA2 possessed the highest editing efficiency.The base insertion or deletion of HO-1 gene and the frameshift of the target gene occurred in all five knockout cells.Western blot results showed that no expression of HO-1 protein was detected,indicating that the PK-15 cell line with HO-1 gene knockout was successfully constructed.After CdCl2 treatment,compared with the control cells,the cell viability was significantly increased and the Fe2+content was significantly decreased in PK-15 cells with HO-1 gene deletion,indicating that HO-1 gene knockout could significantly alleviate the abnormal iron metabolism caused by cadmium treatment.In conclusion,this study successfully constructed a PK-15 cell line knocking out HO-1 gene by using CRISPR/Cas9 gene editing technique,and confirmed that HO-1 plays an important role in iron metabolism abnormality in PK-15 cells induced by cadmium treatment,which lays a foundation for further study on the regulatory mechanism of HO-1 in ferroptosis in PK-15 cells induced by cadmium exposure.

Objective To explore the clinical efficacy and safety of betaquiline fumarate tablets in the treatment of multi drug resistant pulmonary tuberculosis.Methods Patients with multidrug-resistant tuberculosis(MDR-TB)admitted to the Third People's Hospital of Kunming from March 2019 to September 2022 were selected as the research objects.They were divided into two groups by random number table method.The observation group(n = 93)received anti tuberculosis treatment with a regimen containing bedaquiline fumarate tablets,while the control group(n = 90)received anti tuberculosis treatment with a regimen without bedaquiline fumarate tablets.The lesion absorption rate,sputum negative conversion rate,cavity reduction rate,treatment efficiency,and adverse drug reactions during treatment were collected at the end of 24 weeks.Results At the end of the 24th week of treatment,the differences between the observation group and the control group in the rates of lesion absorption rate(85.7%,63.3%),negative conversion of sputum smears(89.7%,71.4%),negative conversion of sputum cultures(82.1%,68.6%),cavity shrinkage rate(88.2%,69.4%),and total treatment efficacy(81.9%,60.2%)were statistically significant(P<0.05).The difference in the incidence of adverse drug reactions between the observation group and the control group(69.9%and 83.4%)was statistically significant(P<0.05),but the difference in the severity of adverse reactions was not statistically significant(P>0.05).Conclusion The regimen containing betaquiline fumarate tablets has good efficacy and is safe in the treatment of multidrug-resistant pulmonary tuberculosis.

Objective:To explore the correlation among psychological flexibility, pain stimulation and adaptation of patients with chronic pain.Methods:From July to September 2020, convenience sampling was used to select 491 patients admitted to the Department of Orthopedics in 5 Class Ⅲ Grade A hospitals in Beijing and Shanghai. The survey was conducted with the self-designed General Information Questionnaire, Psychological Inflexibility in Pain Scale (PIPS) , Pain Disability Index (PDI) , Tampa Scale of Kinesiophobia (TSK-11) and the Chinese version of World Health Organization Quality of Life-BREF (WHOQOL-BRIF) , and the structural equation model hypothesis was proposed.Results:Among patients with chronic pain, the total PIPS score, PDI score, and the total TSK-11 score were (51.06±14.35) , (31.41±18.31) and (30.42±6.43) respectively. The scores of physical health, psychological health, social relationships, environment, overall quality of life and general health were (12.55±2.19) , (13.04±2.42) , (14.29±2.97) , (12.98±2.79) , (3.17±0.98) and (2.73±0.99) respectively. Painful stimulation could produce exercise fear ( β=3.382, t=21.754, P<0.05) , and exercise fear affected stereotype psychology ( β=3.382, t=21.754, P<0.05) , and stereotype psychology had a direct negative impact on the quality of life ( β=-0.092, t=-6.516, P<0.05) . Conclusions:The pain stimulus of patients with chronic pain affects the patient's psychological flexibility through exercise fear, thereby further affecting the patient's quality of life.

Objective:To explore the role of Mycoplasma pneumoniae (MP) in hospitalized children with community-acquired pneumonia (CAP) in Suzhou.Methods:Pathogen data of 2 367 patients with bronchiolitis, bronchopneumonia, lobar pneumonia, and interstitial pneumonia were retrospectively analyzed from January 2017 to December 2018 in Children′s Hospital of Soochow University. The detected pathogens were MP, respiratory syncytial virus (RSV), adenovirus (Adv), influenza A, B, parainfluenza virus (PIV) 1, 2 and 3, human metapneumovirus (hMPV), boca virus (HBoV) and bacteria.Results:The most common pathogen of bronchiolitis was RSV (34.9%, 249/713), followed by MP (15.8%, 113/713) and hMPV (11.4%, 85/713). The most common pathogen of bronchial pneumonia was Streptococcus pneumoniae (Sp, 14.8%, 180/1 220), followed by RSV (13.1%, 160/1 220) and MP (10.2%, 124/1 220). The most common pathogen of lobar pneumonia was MP (47.8%, 141/295), followed by Sp(12.9%, 38/295). The most common pathogen of interstitial pneumonia was MP (35.3%, 49/139), followed by RSV (23.0%, 32/139) and Adv (6.5%, 9/139). Compared with non-MP infections, children with MP infections were older, and had higher percentage of fever and less shortness of breath. The adjusted OR(95% CI) was 2.4 (1.1-3.5), 5.1 (3.2-10.4) and 0.2 (0.0-0.4), respectively. Conclusions:MP is the most common pathogen of lobar pneumonia and interstitial pneumonia and the second most common cause of bronchiolitis. MP infections are usually associated with older age, higher percentage of fever and less shortness of breath.

The main purposes of translational Medicine is to break the barrier among the basic medicine,clinical medicine and drug R&D in order to establish direct and close connection and cooperation between them.However,so far almost in the world wide,translational medicine is still at the exploration stage and far away from the real transformation.This article reviewed the difficult position of translational medicine cooperation from the three aspects of cooperative resources,sponsor and domestic culture,and then suggested to promote clinical medicine research,set up new assessment systems which focus on classified evaluation and representative work,as well as create the culture of cooperation.

Objective To investigate the reliability and validity of Hospice care quality assessment scale. Methods Eight experts in the field of hospice revised the Scale after Chinese localization. The scale data were analyzed after collation of 181 families fulfill the scale. Results The total scale Cronbach′s a coefficient was 0.851. The first dimension′s coefficient was 0.796. The second dimension′s coefficient was 0.622 and the third dimension′s coefficient was 0.827. In factor analysis of the scale, after varimax rotation, the number of characteristic roots>1 was 10 and made up of 70.88%of the total variance. Conclusions The hospice care quality assessment scale after Chinese localization has good reliability and validity and could be a tool to evaluate the clinical quality of care for dying patients.

Objective To determine the weight coefficient of the customer requirements of emergency infusion equipment.Methods Customer requirements were made clear using methods of literature research, personal interviews and expert meeting. Analytic hierarchy process approach was adopted to establish the hierarchical structure model, construct paired comparison matrix structure, calculate the weight coefficient and make logic consistency check.Results The weight coefficients were determined for 8 primary and 36 secondary customer requirements, which all met the logical consistency check (CR<0.1).Conclusion The research and development of emergency infusion equipment has to pay attention to such key requirements firstly as safety, efficacy and portability, and the intelligence has to be supported by the key requirements and intermediate needs.

Differentiation strategy includes self examination on ability,location and intention,strengthening self rarity according to its own characteristics,and improving core competitive power.This article reviewed several related issues in R&D fields,and suggested to set up new evaluation systems which focus on discipline construction,scientific research output,classified evaluation and representative work.