Objective To estimate and optimize the dosage regimen of vancomycin and linezolid for treatment in different Gram-positive cocci infections. Methods The pharmacokinetic data of vancomycin and linezolid were collected, and the pharmacodynamics in vitro of these drugs for staphylococcus epidermidis, staphylococcus aureus, enterococcus faecalis and enterococcus faecium were analysed. The cumulative response fraction (CFR) was evaluated in different dosage regimens of two drugs against four types of bacteria. Results The regimen of 3 500 mg/d vancomycin was recommended for patients with staphylococcus epidermidis infection. The regimen of 2 500 mg/d vancomycin was recommended for patients with staphylococcus aureus infection. The regimens of 3 000 mg/d vancomycin and 400 mg linezolid given 2 times/day were recommended for patients with enterococcus faecalis infection. The regimens of 2 500 mg/d vancomycin and 400 mg linezolid given 2 times/day were recommended for patients with enterococcus faecium infection. Conclusion In application of vancomycin and linezolid for treatment of Gram-positive cocci infections, different dosage regimens should be used in different types of infections.

Objective To develop a new method for establishing a temperature gradient field in the microchannel on a glass-polydimethylsiloxane ( PDMS ) microfluidic chip and to verify its applicability in the study of cellular thermal biological effect.Methods The establishment and control of the temperature gradient field in the microchannel were implemented by a peripheral indium tin oxide ( ITO) heater and a heating micro-wire embedded in the PDMS chip.The temperature gradient field established in the microchannel was represented by the finite element numerical analysis and temperature-dependent fluorescent dye rhodamine B.Finally, the thermal biological effect, which used cell survival rate of human prostate cancer cells T24 as an indicator, was investigated in the microchannel.Results The results of finite element numerical analysis proved that this method established a temperature gradient field along the length of the microchannel successfully.The distribution range of the temperature gradient field was controlled by the ITO heater, while the gradient of the temperature gradient field was controlled by the heating micro-wire.The measurement result of rhodamine B was identical with the result of the finite element numerical analysis.The thermal biological effect of T24 tumor cell research showed that the cell survival rate decreased with the rise of the regional temperature in the microchannel.Conclusion The method developed in this paper for establishing a temperature gradient field in the microchannel on a glass-PDMS microfluidic chip is simple and easy to implement, and it can be used for parallel study of the cellular thermal biological effect on the microfluidic chip in the future.

Objective:To explore the function of the cya gene and the preliminary mechanism of attenuated strain.Methods:The biological characteristics of cya mutant in acid and alkali resistant,salt resistance,motility,biofilm components,poisonous to the cells of epithelial cell adhesion,invasion were analysis.Results:The mobility capabilities,acid and alkali resistance and salt tolerance of cya mutant were significantly lower than the parent strain;the composition testing revealed that the cya mutant did not produce cellulose,curli and biofilm;at the same time the adhesion and invasion to epithelial cells of cya mutant had a prominent depression,and the toxicity to HeLa cells was weaker than the parent strain.Conclusion:The function of cya gene is closely related to athletic ability, penetration of cell membrane, the formation biofilm and virulence.It will provide a theory reference to the functional research of Salmonella typhimurium cya gene and the mechanism of attenuated strain.This will contribute to the development of oral vaccine using attenuated Salmonella typhimurium as vector.

Objective To evaluate the value of DTI in mild articular cartilage injury in patellofemoral joint.Methods The DTI and arthroscopy data of 82 patients wih routine MRI diagnosed as mild articular cartilage injury were analyzed retrospectively.According to the results of arthroscopy,40 cases of mild articular cartilage injury with Outerbridge classification Ⅰ or Ⅱ were divided into experimental group,and 33 cases with normal patellofemoral articular cartilage were divided into control group.There were 8 articular cartilage injury patients with Outerbridge classification Ⅲ or Ⅳ in patello-femoral join were excluded.The DTI data were analyzed compared with arthroscopy.Results Arthroscopy detected 62 lesions of cartilage injury in experimental group.Totally 49 lesions (49/62,79.03 ％) were detected by ADC pseudocolor image and 51 lesions (51/62,82.25 ％) were detected by FA pseudocolor image.The DTI pseudocolor images of articular cartilage injury showed uneven levels.The red or pink levels can been observed.Compared with the control group,ADC value increased and FA value decreased significantly in experimental group (both P＜0.05).Conclusion DTI can clearly display and detect mild articular cartilage injury in patellofemoral joint,which provide valuable information for early cartilaginous injury.

OBJECTIVE: To explore the clinical and genetic features of a patient suspected with Juvenile Parkinson's syndrome (JP). METHODS: Clinical features of the patient were analyzed. Genomic DNA of the patient and his parents was extracted from peripheral blood samples and sequenced by exome capture sequencing. The nature and impact of detected mutations were predicted and validated. RESULTS: The patient displayed typical features including resting tremor, bradykinesia, rigidity, but with excellent response to low dose levodopa. DNA sequencing showed that she has carried compound heterozygous mutations of the Parkin gene, namely c.1381dupC and c.619-1G>C, which were respectively inherited from his mother and father. Neither mutation was reported previously. Bioinformatic analysis predicted that both mutations are pathogenic. CONCLUSION The patient has JP caused by mutations of the Parkin gene. Exome capture sequencing is an accurate and efficient method for genetic diagnosis of such disease.
Adolescent ; Base Sequence ; Female ; Humans ; Mutation ; Parkinson Disease ; Ubiquitin-Protein Ligases ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis for a family with non-syndromic autosomal recessive deafness. METHODS: The proband and her parents were subjected to physical and audiological examinations. With genomic DNA extracted from peripheral blood samples, next-generation sequencing was carried out using a panel for deafness genes. Suspected mutation was validated by Sanger sequencing and qPCR analysis of her parents. RESULTS: The proband presented bilateral severe sensorineural hearing loss at three days after birth. Her auditory threshold was 110-120 dBnHL but with absence of vestibular and retinal symptoms. Her brother also had deafness but her parents were normal. No abnormality was found upon physical examination of her family members, while audiological examination showed no middle ear or retrocochlear diseases. Next-generation sequencing identified compound heterozygous mutations of the MYO7A gene, including a previously known c.462C>A (p. Cys154Ter) and a novel EX43_46 Del, which were respectively derived from her mother and father. CONCLUSION The compound heterozygous mutations of the MYO7A gene probably underlie the disease in this family. Our findings has enriched the mutation spectrum for non-syndromic autosomal recessive deafness 2.
Female ; Hearing Loss, Sensorineural ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mutation ; Myosins ; genetics ; Pedigree

OBJECTIVETo prepare and characterize rabbit polyclonal antibodies against Toxoplasma gondii vacuolar proton pyrophosphatase type I (TgVP1).

METHODS AND RESULTSTwo synthesized peptides TgVP1-1 and TgVP1-2 as the haptens were conjugated with KLH to immunize rabbits. Indirect ELISA showed that the titers of rabbit anti-TgVP1-1 polyclonal antibody and rabbit anti-TgVP1-2 polyclonal antibody reached 1:128 000. Western blotting results revealed that both purified polyclonal antibodies could specifically bind to a purified 85 kD T. gondii protein predicted as TgVP1. The protein detected by these two polyclonal antibodies was distributed in the cytoplasm of T. gondii tachyzoite, and this distribution pattern was consistent with that of acidocalcisome.

CONCLUSIONThe peptide-based method of antibody generation is efficient and the obtained TgVP1 polyclonal antibodies possess a high specificity to facilitate further study of T. gondii acidocalcisome and the diagnosis of toxoplasmosis.

Animals ; Antibodies ; immunology ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Protozoan Proteins ; immunology ; Pyrophosphatases ; immunology ; Rabbits ; Toxoplasma ; enzymology

Objective To systematically evaluate the efficacy and safety of hydroxychloroquine(HCQ)in obstetric antiphospholipid syndrome(OAPS).Methods PubMed,Embase,Cochrane Library,Web of Science,SinoMed,Wanfang Data,CNKI,and VIP databases were searched electronically to collect clinical research on HCQ treatment for OAPS from inception to January 31,2023.Two researchers independently screened the literature,extracted data,and assessed the risk of bias of the included studies,Meta-analysis and GRADE evaluation were performed using RevMan 5.4 software and GRADE Profile 3.6 softwares.Results Five cohort studies and three randomized controlled trias(RCTs)were included,with a total of 644 OAPS patients(732 pregnancies).The results of Meta-analysis showed that compared with conventional treatment,HCQ supplementation significantly increased the live birth rate of OAPS(RR=1.29,95％CI 1.10 to 1.51,P=0.001),the negative conversion rate of lupus anticoagulant(RR=1.29,95％CI 1.13 to 1.47,P＜0.001),the anticardiolipin antibody negative conversion rate(RR=1.27,95％CI 1.12 to 1.45,P＜0.001)and the anti-β2 glycoprotein I antibody negative conversion rate(RR=1.31,95％CI 1.12 to 1.52,P＜0.001),the rate of early abortion(＜10 weeks)was significantly reduced(RR=0.31,95％CI 0.10 to 0.93,P=0.04).However,there was no significant difference between the two groups in reducing the rate of premature birth,late abortion(＞10 weeks)and the incidence of preeclampsia(P＞0.05).In terms of safety analysis,two studies described HCQ adverse effects including skin reactions and dry eyes,symptoms are mild.Three RCTs were used to compare the incidence of adverse reactions between the two groups,the incidence of adverse reaction of HCQ group was lower than that of control group(RR=0.40,95％CI 0.25 to 0.66,P＜0.001),and no serious adverse reactions occurred in both groups.The sensitivity analysis results were robust and reliable.The results of GRADE evaluation showed that the quality of index evidence included in this study were low or very low,with weak recommendations.Conclusion HCQ can significantly improve the live birth rate of OAPS and the negative conversion rate of antiphospholipid antibody,and reduce the fetal abortion rate before 10 weeks with fewer adverse reactions,but there is insufficient evidence to reduce the incidence of premature birth,fetal abortion after 10 weeks and preeclampsia.Due to the limited number and quality of included studies,the above conclusions need to be confirmed by more high-quality studies.

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

Objective: To explore the genetic basis for a family with non-syndromic autosomal recessive deafness. Methods: The proband and her parents were subjected to physical and audiological examinations. With genomic DNA extracted from peripheral blood samples, next-generation sequencing was carried out using a panel for deafness genes. Suspected mutation was validated by Sanger sequencing and qPCR analysis of her parents. Results: The proband presented bilateral severe sensorineural hearing loss at three days after birth. Her auditory threshold was 110-120 dBnHL but with absence of vestibular and retinal symptoms. Her brother also had deafness but her parents were normal. No abnormality was found upon physical examination of her family members, while audiological examination showed no middle ear or retrocochlear diseases. Next-generation sequencing identified compound heterozygous mutations of the MYO7A gene, including a previously known c. 462C>A (p. Cys154Ter) and a novel EX43_46 Del, which were respectively derived from her mother and father. Conclusion The compound heterozygous mutations of the MYO7A gene probably underlie the disease in this family. Our findings has enriched the mutation spectrum for non-syndromic autosomal recessive deafness 2.