Objective The oxidative damage of DNA can be caused by excessive levels of Reactive oxygen species(ROS).Monitoring of DNA oxidative damage enables effective evaluation of ROS damage effects.Although the detection of DNA damage effects based on microbial sensor allows quantitative analysis of oxidative damage,the ROS clearance mechanism existed in bacterial will affect the sensitive of detection.The work of this article is to knockout the key genes of ROS clearance mechanism and construct an antioxidant gene-knock-out microbial sensor.The microbial sensor can realize sensitive monitoring of DNA damage effects and then evaluates the damage effects of cells by ROS.Methods The antioxidant damage genes of bacterial ahpCF,katE and katG were knocked out by λ-Red homologous recombination and antioxidant gene-knockout microbial sensor was constructed.The nalidixic acid sodium salt and UV irradiation were used to characterize the performance for monitoring of DNA damage effects.Results The antioxidant gene-knockout microbial sensors ΔahpC,ΔahpCF/ΔkatEG and ΔahpCF/ΔkatE/ΔkatG were constructed successfully.The results showed that the microbial sensor ΔahpCF/ΔkatE/ΔkatGl had the highest sensitive of damage effects and the limit of detection for nalidixic acid sodium salt was 0.40 μmol/L.In addition,1.80 min of UV irradiation(254 nm)was sufficient to induce a significant fluorescent expression effect in the engineered bacteria.Conclusion In this article,antioxidant gene-knockout microbial sensors had been constructed to realize active and sensitive monitoring of DNA damage effects such as DNA damage reagents and UV irradiation.The sensors could provide an active,effective,and sensitive potential monitoring method for future evaluation of radiation effects in space.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

Objective:To investigate the clinical characteristics and short-term follow-up outcomes of primary nephrotic syndrome (PNS) children infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Omicron variant outbreak in Shanghai, and to provide a reliable reference for clinicians in the diagnosis and treatment.Methods:It was a case-control study. The clinical data of children with PNS (PNS group) who were diagnosed and followed-up up to 1 year in the nephrology department of four children's medical centers in Shanghai, and the children (control group) who had no underlying diseases and were infected with SARS-CoV-2 in Shanghai Jinshan Public Health Center, including the data when they were infected with SARS-CoV-2, were retrospectively analyzed.Results:(1) From March 30th to April 13th, 2022, 6 PNS children in Shanghai were infected with SARS-CoV-2, including 5 boys and 1 girl. The median age was 4.5 (2.0, 11.0) years old. And 30 children were matched by sex, age and disease type as control group, including 20 males and 10 females. The median age was 4.5 (2.0, 9.0) years. There were no significant differences between the PNS group and the control group in clinical symptoms (including fever duration), treatment regimens, vaccine doses and virus clearance time (all P>0.05). (2) The 6 children with PNS included 3 cases of steroid-sensitive type, 3 cases of steroid-resistant type, 2 cases of minimal change disease, 2 cases of focal segmental glomerulosclerosis and 2 cases with no renal biopsy. Before SARS-CoV-2 infection, their primary disease-PNS were stable, and urine protein was negative, four of them were under maintenance treatment with oral steroids or immunosuppressive drugs. At the time of SARS-CoV-2 infection, the symptoms of all of the 6 cases were mild, no severe, critical or fatal cases, and they were all cured and discharged from hospital through medical isolation observation or symptomatic treatment of infections. (3) Five cases of them still had discomfort symptoms such as cough, anorexia, and fatigue after being discharged from the hospital, which lasted for about 1 week. Within 1 year of follow-up, none of the children have suffered from "recurrent positive PCR results" or "secondary infection" of the SARS-CoV-2. (4) Among them, 4 cases of PNS relapsed after SARS-CoV-2 infection, timely addition of steroids was effective, their urine protein quickly turned negative, and there was no recurrence after 1 year of follow-up. (5) Before infection with SARS-CoV-2, the levels of immunoglobulin IgG were lower than the normal reference value in the 4 cases with PNS recurrence. Conclusions:During the Omicron variant outbreak in Shanghai, the infection of SARS-CoV-2 in children with PNS are resulted in high transmission among household contacts. Most of them have mild symptoms and good prognosis. PNS is prone to relapse after SARS-CoV-2 infection, and steroid therapy is effective and safe for these relapse. IgG may be a potential marker for the prognosis of PNS children infected with SARS-CoV-2.

Aiming at the current situation of high cost, huge volume, complex operation and difficulty in real application of pulse analyzer, this study designs and implements a portable pulse detection system based on IoT. The design utilizes Raspberry Pi 3B+, STM32 series MCU and cloud server to collect, store, display and recognize pulse signals at CUN, GUAN and CHI. The system is small in size and low in cost, which can be connected with cloud server through network to make full use of resources. The experimental results show that the recognition accuracy of the main feature points of the pulse signal by the portable pulse analyzer is higher than 97%, which has a broad prospect of development and application.
Computers ; Heart Rate

Objective : To prepare the La-doped TiO2 film on the surface of 3Y-TZP ceramics in order to observe its antibacterial properties, providing an experimental basis for the application of antibacterial zirconia ceramics in the clinic. Method: A cylindrical 3Y-TZP specimen with a diameter of 20 mm and a height of 3 mm was prepared. The sol-gel method was used to prepare 1% lanthanum (La)-doped TiO2 sol, and the La-TiO2 film-3Y-TZP ceramic was prepared by dip coating on the surface of 3Y-TZP. The TiO2 thin film-3Y-TZP ceramic was prepared by adding no lanthanum nitrate solution in the same way. The surface morphology of 3Y-TZP ceramic specimens (3Y-TZP group), TiO2 thin film-3Y-TZP ceramic specimens (TiO2 film group), and La-TiO2 thin film-3Y-TZP ceramic specimens (La-TiO2 film group) was observed by scanning electron microscopy, and photocatalysis, antibacterial and cytotoxicity experiments were carried out. For the photocatalytic experiment, four specimens were randomly selected from the La-TiO2 film group and TiO2 film group to observe the degradation rate of methylene blue at different time points under sunlight. In the antimicrobial experiment, five specimens were randomly selected from the La-TiO2 film group, TiO2 film group and 3Y-TZP group. The antimicrobial activity of each group was tested using the bacteriostatic circle method, and the bacteriostatic distance of each group was compared. In the cytotoxicity experiment, three samples were randomly selected from the La-TiO2 film group, TiO2 film group and 3Y-TZP group (negative control group), and the extracts were prepared. Here, 0.064% phenol solution were served as the positive control group. Morphological observation of L-929 cells in four groups was performed after 3 d of culture. Cell viability and relative cell proliferation were measured by MTT assay. Results: La-TiO2 films with uniform distribution can be prepared on a 3Y-TZP surface by the dipping-drawing method. Photocatalytic experiments showed that the degradation rate of methylene blue in the La-TiO2 film group was (41.2 ± 1.5)% in daylight for 2 hours, which was higher than that in TiO2 film group (36.5 ± 2.4)%. A significant difference was noted between the two groups (t=3.321, P=0.016). The antimicrobial experiment showed that the antimicrobial distance of La-TiO2 group was (0.34 ± 0.08) mm, which was larger than that of TiO2 group (0.12 ± 0.02) mm. No obvious antimicrobial circle was noted in 3Y-TZP group, and the antimicrobial distance of the La-TiO2 film group was larger than that of TiO2 film group (F=63.798, P < 0.001). Cytotoxicity test showed that the relative proliferation rate of cells in La-TiO2 film group was (89.5 ± 1.3)%, and the cytotoxicity rating was grade 1. Significant differences were noted among the four groups (F=68.250, P < 0.001). Conclusion The La-doped TiO2 film can improve its photocatalytic activity and enhance the antibacterial activity of 3Y-TZP without obvious cytotoxicity.

Objective To explore the risk factors of nosocomial infections to provide a reference for prevention and control of nosocomial infection.Methods The data of 680 patients with nosocomial infection in this hospital from January 2015 to December 2016 were retrospectively collected.The characteristics of nosocomial infection were analyzed from the aspects of age,hospitalization department,infection site,etc.Results A total of 680 cases of nosocomial infection accounted for 1.67％(680/40 657) of all hospitalization patients,including 316 cases(nosocomial infection rate was 2.47％) of 61-80 years old.The infection rate was the highest in ICU(24.90％),followed by the nephrology department(4.99％).For infection sites,the maximal cases-times in infection site was lower respiratory tract(413 case-times),followed by urinary tract and superficial incision(each 68 case-times).The pathogenic detection rate was 45.03％,and 190 strains of pathogens were detected.The top five places were Escherichia coli(47 strains),Klebsiella pneumoniae(28 strains),Pseudomonas aeruginosa (23 strains),Staphylococcus aureus (22 strains) and Bauman Acinetobacter (16 strains).Logistic regression analysis showed that age larger than 60 years old,hospitalization time longer than 60 d,indwelling urinary catheter,peripherally inserted central catheter(PICC),tracheotomy and enteral nutrition were the risk factors for nosocomial infection occurrence.Conclusion Hospital should put the emphasis on preventing nosocomial infection of lower respiratory tract and strengthen the nosocomial infection management of key departments like ICU.

Objective To investigate the molecular characteristic of fluoroquinolone resistant Streptococcus agalactiae (GBS) isolates in Suzhou.Methods Totally 46 fluoroquinolone resistant GBS strains were collected,and then subjected into PCR and two resistance genes were sequenced and their high frequency mutation sites,gyrA and parC were analysed.Results Among these isolates,the most frequent gyrA mutation was gyrA_S81L (TCA→TTA),which displayed 93.4％ (43/46) with substituted at No.81 site of amino acid from Ser to Leu.However,the most frequent parC mutation was mutated at No.79 site of amino acid from Ser to Tyr orPhe,with two mutations parC_S79Y (73.9％,34/46) and parC_S79F(17.4％,8/46).The analysis showed that the major mutation patterns are gyrA_S81L with parC_S79Y (73.9％,34/46),gyrA_S81L with parC(13.0％,6/46).Conclusion The most frequent mutations of fluoroquinolone resistant gene in Suzhou are gyrA and parC and the major mutation patterns are gyrA_S81L/parC_S79Y and gyrA_S81L/parC_S79F.

OBJECTIVETo assess the application value in prenatal diagnosis using karyotype analysis combined with BACs-on-Beads (BoBs) assay.

METHODSNine hundred sixty five pregnant women were subjected to amniocentesis, chromosomal karyotype analysis and detection of BoBs were employed simultaneously for abnormal number of chromosomes and 9 chromosome microdeletion syndrome in prenatal diagnosis.

RESULTSFifty cases common chromosome aneupoidies were successfully detected by both karyotype analysis and BoBs which included 31 cases of trisomy 21,10 cases of trisomy 18 and 9 cases with sex chromosome abnormality. BoBs in addition detected 1 case of DiGeorge-1 microdeletion syndrome and 1 case of 7q11.23 microduplication syndrome. All 9 fetuses with chromosome abnormalities detected by karyotyping were missed by BoBs, including 2 cases of marker chromosomes,4 cases of chromosomal translocation,1 case of chromosomal inversion, 2 cases of Sex chromosome mosaicism; 2 cases of fetal inherited from the parents,7 cases for novel mutations.

CONCLUSIONKaryotype analysis combined with BoBs dedtection is a rapid, effective and highly accurate prenatal diagnosis model that may should be widely used in clinical diagnosis.

OBJECTIVETo explore the application of combined techniques for the prenatal diagnosis of a case with 7q11.23 duplication.

METHODSAmniocentesis was performed in the second trimester for a mother with a high risk suggested by serological prenatal screening. G-banded chromosomal analysis was performed on cultured amniocytes and peripheral blood samples from both parents. DNA from amniotic fluid sample was isolated for a BACs-on-Beads (BoBs) assay. To define the range of duplication, copy number variation was determined with single nucleotide polymorphism array (SNP array, Affymetrix CytoScan 750K) and fluorescence in situ hybridization (FISH) analysis.

RESULTSChromosomal analysis suggested that the fetus and both parents all had a normal karyotype, while a duplication of 7q11.23 was detected by the BoBs assay. SNP array revealed a 1.5 Mb duplication in chromosome 7q11.23, which was confirmed by FISH.

CONCLUSIONCombined prenatal BoBs, SNP array and FISH has enabled effective diagnose of a case with 7q11.23 syndrome.

Adult ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Male ; Middle Aged ; Pregnancy ; Prenatal Diagnosis ; Trisomy ; genetics

Based on the chemical structures of magnolol and honokiol,a series of small molecular derivatives were designed for the treatment of Alzheimer's disease.Through the Discovery Studio,five compounds (6a-6e) exhibited the inhibitory activity against Aβ and Tau proteins in all of the designed compounds.Then the five compounds are chemically synthesized and their biological activities were tested by thioflavin T.The result showed that compound 6a had inhibitory effect on the aggregation of two kinds of target proteins at the concentration of 100 μmol/L,which deserves further research.