During the development of whole-cell microbial sensors,factors such as cellular metabolic activity and signal output modes play pivotal roles in the stability and repeatability of the sensors,presenting numerous challenges for the standardization of sensor applications. This research focused on the arsenic ion sensor based on the RepL amplifier,adjusting the reporter genes,culture media,growth stages,and induction times of arsenic ions,aiming to investigate how these factors affect the sensor's detection performance. The results indicated that the cell's culturing environment,growth status (e.g.,different growth phases),type of reporter,and induction time all had significant impacts on the performance of the arsenic ion sensor. First,the stability of the sensors varied greatly in different media,all the three sensors displayed greater stability in LB culture medium. Meanwhile,the cells in different growth stages also exhibited different performance advantages. Cells at the stationary growth phase exhibited better detection sensitivity and linearity,while cells in the logarithmic growth phase had lower limit of detection (LOD) . Moreover,there was an optimal induction time for the response of the sensor,overly long or short induction time could interfere with its response. The optimal induction time for the arsenic sensor in this work was about 2-3 h. By comparing three types of fluorescent protein reporters,it was found that although their detection limits were fairly similar,all within the range of 5-10μg/L,but their response times varied,ranging from 40 min to 2 h. The fluorescent proteins with higher brightness exhibited faster sensor response. These research outcomes provided a solid foundation for the practical application of microbes in detection. In practice,we could choose cells in specific states based on particular purpose,maximizing the performance of the cell sensors and further broadening the application scope of such sensors.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

OBJECTIVE To predict the amount of colorants used in the preparation of placebo of Chinese medicine by construc-ting particle swarm optimization-back propagation neural network PSO-BPNN compound granules,and to provide a new idea for the simulation of placebo color of Chinese medicine compound granules.METHODS The BP neural network was used to establish the model of sample color parameters L,a?,b?and pigment mass fraction.The global search ability of particle swarm optimization algo-rithm was used to optimize the weight and bias of BP neural network to prevent the local minimum value of the model.The linear reduc-tion weight coefficient method and the introduction of mutation operator were used to improve the global optimization ability of particle swarm optimization algorithm.The color comprehensive evaluation index(ΔE)was used as the objective evaluation standard to verify the test results.RESULTS The training results show that the fitting accuracy of the improved PSO-BP neural network was up to 98.31%.The prediction results show that the prediction error of the improved PSO-BP neural network was the smallest,and the mean absolute percentage error(MAPE),root mean square error(RMSE)and mean color difference(ΔE)were 0.411 5,2.164 6 and 2.56,respectively.The verification samples of three kinds of particles were prepared for verification.The ΔE of the verification sample and the model drug were 1.73,2.63 and 4.11,respectively.The color difference between the two groups and the model drug was small by visual evaluation.CONCLUSION The BP neural network based on the improved particle swarm optimization algorithm can simulate the prediction of the amount of colorants used in the preparation of Chinese medicine compound granules,and can be used as a recommended optimization model for placebo color matching research.

Objective To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle frac-tures in children.Methods A systematic search was conducted in PubMed,Embase,the Cochrane library,Web of Science,China National Knowledge Internet(CNKI),Wanfang Datebase from in ception to February 2022.Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included.Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality,their excellent and good rate of fracture healing,malunion,delayed union or nonunion,infection,limitation of elbow flexion or extension(＞10°)were ex-tracted and analyzed using software Rev Man 5.3.Results A total of 9 retrospective studies involving 647 patients were includ-ed,with 255 patients in the screw fixation group(including screw combined with Kirschner wire)and 392 patients in the Kirschner wire fixation group.Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22,95％CI(0.09,0.56),P=0.001].There were no significant differences between the 2 groups in excellent and good rate of fracture healing,malunion rate(P＞0.05).Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18,95％CI(0.05,0.65),P=0.009].Conclusion For lateral humeral condyle fractures,Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation.There were no significant differences in the excellent and good rate of fracture healing,malunion.In terms of postoperative efficacy and safety of internal fixation,orthopaedic surgeons are more like-ly to recommend screws for fixation of lateral humeral condyle fractures in children.

Objective To compare the clinical efficacies of unilateral biportal endoscopy(UBE)technique and percutaneous endoscopic lumbar discectomy(PELD)technique in the treatment of lumbar disc herniation.Methods The clinical data of 149 patients with lumbar disc herniation in our hospital were retrospectively analyzed and divided into the UBE group(n=80)and the PELD group(n=69)according to different surgical methods.The operation time,intraoperative fluoroscopy frequency,intraoperative blood loss,hospital stay,postoperative complications,visual analogue scale(VAS)score,Oswestry disability index(ODI)score,intervertebral disc height and vertebral canal area of the two groups were compared.Results The operation time in the UBE group was longer than that in the PELD group,and the intraoperative fluoroscopy frequency was fewer than that in the PELD group,the differences were statistically significant(P<0.001).There was no significant difference in the intraoperative blood loss or hospital stay between the two groups(P>0.05).There was no significant difference in the VAS or ODI scores at each time point between the two groups(P>0.05).There was no significant difference in the intervertebral disc height or vertebral canal area at each time point between the two groups(P>0.05).The postoperative vertebral canal areas of patients in the two groups were greater than those before surgery,and the differences were statistically significant(P<0.05).The incidence of postoperative complications in the UBE group was lower than that in the PELD group,the difference was statistically significant(P<0.05).Conclusion In terms of short-term efficacy,both PELD technique and UBE technique can effectively relieve the symptoms of low back and leg pain caused by lumbar disc herniation,and the UBE technique has longer operation time,but with fewer intraoperative fluoroscopy frequency,and lower incidence of postoperative complications.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.

Objective:To investigate the value of serum free light chain(sFLC)and serum calcium ion in the diagnosis and prognosis of multiple myeloma(MM).Methods:Forty patients with MM treated in Henan Provincial People's Hospital from January 2018 to January 2022 were selected as the observation group,and 40 healthy volunteers were selected as the control group.The differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc between the two groups were compared.Meanwhile,the differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc in different international staging systems(ISS),chemotherapy efficacy and prognosis patients were analyzed.Results:The levels of sFLC-κ[(98.39±21.19)vs(12.01±4.45)mg/L],sFLC-λ[(210.20±45.54)vs(14.10±5.11)mg/L]and proportions of hypocalcemia(65％vs 0)in the observation group were significantly higher than those in the control group(P＜0.05),while sFLC-κ/λ ratio[(0.44±0.10)vs(0.87±0.12)]and serum calcium ions[(1.98±0.46)vs(2.42±0.40)mmol/L]were significantly lower than those in the control group(P＜0.05).The sFLC-κ,sFLC-λ,the proportion of hypocalcemia and the course of hypocalcemia in ISS stage Ⅲ patients in the observation group were significantly higher than those in stage Ⅰ and Ⅱ patients(P＜0.05),while sFLC-κ/λ ratio,and serum calcium ions were significantly lower than those in stage Ⅰ and Ⅱ patients(P＜0.05).The levels of sFLC-κ[(107.76±21.22)vs(94.67 ±20.11)mg/L],sFLC-λ[(245.54±41.12)vs(205.54±50.22)mg/L]of patients with hypocalcemia in the observation group was significantly higher than those without hypocalcemia(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those without hypocalcemia[(0.42±0.04)vs(0.47±0.06);P＜0.05].The levels of sFLC-κ[(107.29±20.14)vs(91.11±18.92)mg/L],sFLC-λ[(247.98±42.26)vs(179.29±39.32)mg/L]in patients with ineffective chemotherapy were significantly higher than those in patients with effective chemotherapy(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those in patients with effective chemotherapy[(0.43± 0.10)vs(0.50±0.09);P＜0.05)].The area under the ROC curve for sFLC-κ,sFLC-λ,sFLC-κ/λ predicting ineffective chemotherapy was 0.803,0.793 and 0.699 respectively,P＜0.05.There was no significant difference in sFLC-κ,sFLC-λ,sFLC-κ/λ ratio,serum calcium ion,hypocalcemia ratio and hypocalcemia course between survival and death patients(P＞0.05).Conclusion:sFLC and serum calcium are related to 1SS stage of MM patients.sFLC level has a certain value to predict the curative effect of chemotherapy in MM patients.However,the prognostic values of sFLC and serum calcium are not yet confirmed for MM patients.

Objective To compare the efficacy and safety between thermal ablation combined with synchronous transcatheter arterial chemoembolization(TACE)and TACE in patients with liver metastasis of neuroendocrine tumors of different pathologic grades.Methods A retrospective analysis was performed on patients with liver metastases of neuroendocrine tumors admitted to Department of Interventional Radiology,Zhongshan Hospital,Fudan University from Nov 1,2006 to Jul 31,2022.The patients were divided into synchronous ablation group and TACE group according to treatment mode and subgroups according to pathological grade.The lesions were evaluated by postoperative imaging examination.The patients were followed up until Jul 31,2023,and surgery-related complications were recorded.The endpoint of prognosis were progression-free survival(PFS)and overall survival(OS).Results A total of 86 patients with neuroendocrine tumor were collected,including 34 patients in simultaneous ablation group and 52 patients in TACE group.According to WHO classification,21 patients at G1 stage,45 patients at G2 stage and 20 patients at G3 stage were included.No serious postoperative complications occurred in all patients.The median OS was 47.0(95%CI:31.2-62.8)months in the TACE group and 56.0(95%CI:8.3-73.4)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.50).The median PFS was 18.0(95%CI:6.0-30.0)months in the TACE group and 29.0(95%CI:10.0-48.0)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.22).Of the 45 patients at G2 stage,27 received TACE with a median OS of 47.0 months,and 18 received synchronous ablation with a median OS of 59.0 months,and there was no statistical difference between the two groups(P=0.45).The median PFS was 12.0 months in the TACE group and 32.0 months in the synchronous ablation group,and the difference between the two groups was statistically significant(P=0.03).Conclusion Comparing with TACE,simultaneous ablation can delay disease progression in patients with liver metastasis of neuroendocrine tumors to a certain extent and has good safety,especially for patients with liver metastases of neuroendocrine tumors with intermediate or low grade.

Objective To explore basement membrane markers and potential drugs for treatment in idiopathic pulmona-ry fibrosis(IPF).Methods IPF-related datasets were downloaded from the Gene Expression Omnibus(GEO)database,processed to construct basement membrane gene expression matrices associated with IPF,and screened for differential basement membrane genes(DEBMs);DEBMs were enriched for function and pathways,and machine learning algorithms were used to ob-tain candidate signature genes,receiver operating characteristic(ROC)curves were used to identify signature genes and con-struct a nomogram.We performed ssGSEA analysis to explore the correlation between signature genes and immune cells and their functions and predicted the corresponding miRNAs and therapeutic drugs by signature genes.Results A total of 56 DEBMs were extracted;enrichment analysis showed that DEBMs were mainly enriched in"extracellular matrix tissue","extracellular structural tissue",etc.,and were closely related to"ECM-receptor interaction"and"local adhesion spot"pathways.The ma-chine learning has identified six candidate signature genes(TIMP3,P3H2,ITGA7,ITGA4,ADAMTS2,COL8A2),all of which meet the requirements of the signature genes by the ROC curve test,and the nomogram diagnostic value was outstanding(AUC=0.991 523);B cells and Macrophages in IPF were significantly different from the normal group.Finally,miRNAs were predicted to be dominated by miR-4305,miR-3684,progesterone,and tert-butyl hydroperoxide as therapeutic agents with strong relevance to IPF.Conclusion Signature genes and predictive miRNAs may serve as novel markers for IPF diagnosis,and pre-dictive drugs may be a potential source of drugs for treating IPF.

Objective To investigate the effect and mechanism of lycium barbarum polysaccharide(LBP)on hepatocyte injury induced by homocysteine(Hcy).Methods Normal C3H/An mouse hepatocytes(NCTC 1469)were cultured in vitro and treated with different concentrations of Hcy(0,50,100,200,500 μmol/L).The optimal concentrations of Hcy-treated NCTC 1469 cells were detected by MTT assay.When the cells reached the logarithmic growth stage,the conditions were set up as follows:(1)control group(cultured with DMEM medium supplemented with 10%horse serum)and Hcy group(treated with 100 μmol/L Hcy solution for 48 h),and the cells were collected.Cell viability staining was used to detect apoptosis,aspartate aminotransferase(AST)/alanine aminotransferase(ALT)activity detection kit was used to detect AST and ALT activities,RT-qPCR was used to detect the expression levels of YAP1,DNMT1,DNMT3a and DNMT3b mRAN,and Western blotting was used to detect the expression of YAP1 protein,nested methylation specific PCR(nMS-PCR)was used to detect DNA methylation rates in the YAP1 promoter region.(2)Control group,LBP group,Hcy group and Hcy+LBP group.LBP group was treated with 4 mg/ml LBP solution for 2 h,Hcy group and Hcy+LBP group were treated with 100 μmol/L Hcy solution for 48 h,and Hcy+LBP group was treated with 4 mg/ml LBP solution at 46 h,and the cells were collected.The expression levels of YAP1,DNMT1,DNMT3a and DNMT3b mRAN were detected by RT-qPCR;the expression of YAP1,Bax and Bcl-2 proteins was detected by Western blotting;AST/ALT activity detection kit was used to detect AST and ALT activities.Prediction of DNA methylation CpG islands in YAP1 promoter region by bioinformatics.Results NCTC 1469 cells were treated with 100 μmol/L Hcy according to the results of MTT assay.Compared with control group,the apoptosis rate of Hcy group increased(P<0.01),the activities of ALT and AST increased(P<0.001),the mRAN and protein expression levels of YAP1 decreased(P<0.001),and the methylation rate of YAP1 promoter region increased(P<0.01),the mRNA expression levels of DNMT1,DNMT3a and DNMT3b increased(P<0.01 or P<0.001).Compared with Hcy group,the mRNA expression levels of DNMT1,DNMT3a and DNMT3b in the Hcy+LBP group decreased(P<0.001),the mRAN and protein expression levels of YAP1 significantly increased(P<0.01 or P<0.001).In addition,in the Hcy+LBP group,cells showed significantly elevated of Bcl-2 protein(P<0.001),but decreased Bax protein(P<0.001),and decreased activities of ALT and AST(P<0.001).Conclusions The decrease of YAP1 expression may be the key process of Hcy induced injury of NCTC 1469 cells,and the methylation of the YAP1 promoter region may be the molecular mechanism of Hcy induced YAP1 expression change.LBP may improve NCTC 1469 cell damage induced by Hcy by positively regulating YAP1 expression.