1.Effects of meropenem and amikacin on gut microbiota diversity and structure in a neonatal rat model of necrotizing enterocolitis
Chenghuan ZHANG ; Haiyan CHENG ; Leilei SHEN ; Xianyuan YIN ; Min TAO ; Hedan XU ; Sheng CHEN
Journal of Army Medical University 2025;47(17):2088-2096
Objective To investigate the effects of meropenem and amikacin on gut microbiota diversity and composition in a neonatal rat model of necrotizing enterocolitis(NEC).Methods Neonatal SD rats(1~2 d,weighing 5~10 g,both sexes)were subjected to establish a NEC model through artificial formula feeding,hypoxic-cold stress,and lipopolysaccharide(LPS)gavage.The rats were randomly divided into normal control group(Group C,n=12),NEC group(Group N,n=20),meropenem intervention group(Group M,n=20),and amikacin intervention group(Group A,n=20).Following modeling,Group M and Group A received intraperitoneal injections of meropenem(125 mg/kg)or amikacin(468 mg/kg),twice daily for 3 consecutive days.Groups C and N were administered an equal volume of normal saline.At the end of the intervention,colonic contents or fecal samples were collected.The gut microbiota structure was analyzed using 16S rDNA high-throughput sequencing.Bioinformatics analysis was performed using the QIIME2 platform.Alpha diversity was evaluated using Chao1,Shannon,and Simpson indices.Beta diversity was assessed based on Bray-Curtis distance through principal coordinate analysis(PCoA)and non-metric multidimensional scaling(NMDS).Venn and UpSet plots were generated to visualize the composition and overlap of operational taxonomic units(OTUs).Linear discriminant analysis effect size(LEfSe)was applied to identify differentially abundant taxa across groups.Results High-throughput 16S rDNA sequencing showed that the N group had significantly lower 3 indices of α diversity than the C group(P<0.01),that is,a Chao1 index from 230 to 40,a Shannon index from 1.65 to 0.85,and a Simpson index from 0.65 to 0.42.After antibiotic intervention,both the M group and A group obtained obvious increases in the Chao1 index than the N group(P<0.001),with a greater increase observed in the M group than in the A group(P<0.05).However,neither antibiotic group exhibited notable improvements in the Shannon index or Simpson index compared with the N group(P>0.05).Venn and UpSet analyses revealed that the M group had the highest number of unique OTUs(283),while the A group shared the most OTUs(63)with the C group.PCoA and NMDS analyses indicated that the microbial structure of the A group was closer to that of the C group,with better clustering.Taxonomic composition and LEfSe analysis demonstrated that the N group was enriched with potentially pathogenic taxa such as Escherichia coli B2 and Klebsiella under the phylum Proteobacteria,while beneficial bacteria including Lactobacillaceae and Bifidobacteriaceae(phylum Firmicutes)were significantly reduced,indicating severe dysbiosis.In contrast,the A group exhibited a significant increase in beneficial bacteria and a structural tendency toward ecological recovery.The M group,however,was enriched with various conditionally pathogenic and environmentally associated genera,displaying a microbial configuration notably deviating from a healthy state.Conclusion Meropenem and amikacin exhibit differential regulatory effects on the intestinal microbiota in the context of NEC.Amikacin demonstrates superior efficacy in restoring microbial stability and levels of beneficial bacteria,whereas meropenem,although effective for early infection control,warrants caution due to its potential long-term impact on the gut microbiome.
2.Research Progress of Selective Nerve Root Block in the Treatment of Lumbosacral Radiculopathy
Leilei GAO ; Jun LIU ; Xiaoxia HUANG ; Tao LIU ; Yong TENG
Medical Journal of Peking Union Medical College Hospital 2025;16(3):739-748
Lumbosacral radiculopathy refers to the pain syndrome caused by inflammation or mechanical compression of the lumbar nerve root, mainly manifested as low back pain, and radiating to the lower limbs in cutaneous mode, which can be accompanied by numbness, paresthesia, tingling, muscle weakness and loss of specific reflexes and other symptoms, which not only bring physical pain and life inconvenience to the patients, but also bring huge economic burden to the social medical care. Selective nerve root block(SNRB), as a safe, effective, low-cost, precise and minimally invasive clinical technique, can accurately intervene in specific nerve roots and quickly relieve pain symptoms by reducing inflammation and improving the surrounding environment of nerves. However, there are still many challenges and controversies in practice, such as precise targeting requirements, drug selection, potential risks and complications, and differences in efficacy among different patient populations. The purpose of this review is to systematically review and analyze the existing research results on SNRB, so as to provide useful reference and guidance for the further development of this field.
3.Exploration on the Onset of Acute Lymphoblastic Leukemia in Children Based on the Five-Circuit and Six-Qi Theory
Yunyun SUN ; Liang LI ; Leilei CHU ; Ke YANG ; Zhexiu JIANG ; Tian LIU ; Jianmin ZHANG ; Jian PAN ; Yanfang TAO
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(1):32-38
Objective To explore the five-circuit and six-qi features of birth time and onset time of children with acute lymphoblastic leukemia(ALL).Methods A total of 877 cases of children with ALL from Children's Hospital of Soochow University from June 2021 to February 2023 were collected,and their five-circuit and six-qi features of birth time and onset time were analyzed.And then the correlation of five-circuit and six-qi features of birth time and onset time with ALL was explored preliminarily,and the pathogenic characteristics of congenital factors and acquired pathogenic factors were revealed.Results(1)The children who were born in the year with the heavenly stems being bing(the 3rd of the ten heavenly stems)and ding(the 4th of the ten heavenly stems)and with the earthly branches being shen(the 8th of the twelve earthly branches)and you(the 9th of the twelve earthly branches)are prone to suffer from ALL,and the birth year of children with ALL had the five-circuit and six-qi features of the joining of guest circuit with dominant circuit being rebellious.ALL is commonly seen in the year with the heavenly stems being geng(the 7th of the ten heavenly stems)and xin(the 8th of the ten heavenly stems)and with the earthly branches being zi(the 1st of the twelve earthly branches)and chou(the 2nd of the twelve earthly branches),and the onset year of ALL in children had the five-circuit and six-qi features of the yearly circuit being gold-circuit and water-circuit,sitian-zaiquan yearly circuit qi being shaoyin monarch-fire with yangming dryness-gold,taiyin damp-earth with taiyang cold-water,and the qi-circuit assimilation relationship being celestial correspondence,same celestial correspondence,celestial correspondence in convergent year,disharmony,mildly-rebellious,and celestial restriction.Conclusion Gold-dryness and water-cold are the congenital factors and acquired pathogenic factors of ALL.The onset of ALL in children is closely related to qi insufficiency and qi stagnation of wood and fire in five-circuit and six-qi theory.
4.Recurrence mechanisms and treatment strategies for IDH wild-type glioblastoma
Tao WANRU ; Lv LEI ; Wang ZIJUN ; Bao LEILEI
Chinese Journal of Clinical Oncology 2025;52(6):309-313
Isocitrate dehydrogenase(IDH)wild-type glioma is a type of highly invasive brain tumor with poor prognosis and a high recur-rence rate.The recurrence process is driven by multiple complex and interwoven factors.Although the current standard treatment regi-mens can temporarily alleviate patients'symptoms,they still face significant challenges in effectively preventing tumor recurrence.The re-currence mechanism of this tumor is intricate and covers multiple aspects such as genomic instability,maintenance of stem cell characterist-ics and mesenchymal transformation,as well as dynamic changes in the tumor microenvironment.This article aims to comprehensively sum-marize the recurrence mechanism of glioblastoma and deeply explore potential countermeasures targeting these mechanisms,hoping to open up new perspectives and approaches for the treatment of recurrent tumors.
5.Therapeutic effect of Formononetin on Mycoplasma pneumoniae pneumonia in mice based on the MAPK/NF-κB signaling pathway
Shuang ZHANG ; Ran TAO ; Xiaojian CUI ; Leilei SHI
Immunological Journal 2025;41(8):535-540
Objective To investigate the therapeutic effect of Formononetin on mice with Mycoplasma pneumoniae pneumonia(MPP)by regulating the mitogen-activated protein kinase(MAPK)/nuclear factor κB(NF-κB)signaling pathway.Methods Six-week-old SPF-grade male BALB/c mice were selected.The MPP mouse model was established as the model group by instillating Mycoplasma pneumoniae bacterial solution through the nose.On the second day after successful modeling,mice were intraperitoneally injected with 15,30,and 60 mg/kg of Formononetin and 60 mg/kg of Formononetin+20 mg/kg of Anisomycin respectively as the low-dose,medium-dose,and high-dose Formononetin groups and the high-dose Formononetin+Anisomycin group,with 12 mice in each group.Another 12 mice were intraperitoneally injected with the same amount of 0.9%sodium chloride injection as the control group.The cough frequency of mice in each group was detected through the cough induction test.The partial pressure of carbon dioxide(PCO2)and partial pressure of oxygen(PO2)in each group of mice were detected by a blood gas analyzer,and the oxygenation index(OI)was calculated.The levels of inflammatory factors in each group were detected by ELISA,and the apoptosis of lung tissue cells in each group of mice was detected by TUNEL.HE staining was performed to observe the pathological changes of lung tissues in each group.The expression of MAPK/NF-κB pathway-related proteins in the lung tissues of mice in each group was detected by Western blot method.Results The lung tissue morphology of the mice in the control group was normal.The alveolar ducts and alveolar structures of mice in the model group were damaged,the alveolar septa thickened,and there was a large amount of inflammatory cell infiltration.Compared with the model group,the lung tissue morphology was improved in the low-dose,medium-dose and high-dose Formononetin groups.The lung tissue injury in the high-dose Formononetin+Anisamycin group was more severe compared with the high-dose Formononetin group.Compared with the control group,the cough latency period in the model group was shortened,and PO2,OI,and interleukin-10(IL-10)were decreased,while the frequency of coughing,PCO2,interleukin-18(IL-18),tumor necrosis factor-α(TNF-α),apoptosis rate,and the ratios of p-P38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,p-extracellular signal-regulated kinase 1/2(ERK1/2)/ERK1/2,and p-C-jun N-terminal kinase(p-JNK)/JNK increased(P<0.05).Compared with the model group,the low-,medium-and high-dose Formononetin groups had improved lung tissue morphology,prolonged cough latency,increased PO2,OI and IL-10,and reduced cough frequency.The PCO2,IL-18,TNF-α,apoptosis rate,and the ratios of p-p38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,ERK1/2/ERK1/2,and p-JNK/JNK decreased(P<0.05).In the low-,medium-,and high-dose Formononetin groups,with the increase of Formononetin dose,the cough latency gradually prolonged,the cough frequency gradually decreased,and the PO2,oxygenation index,and IL-10 gradually increased.The PCO2,IL-18,TNF-α,apoptosis rate and the ratios of p-p38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,p-ERK1/2/ERK1/2,and p-JNK/JNK gradually decreased(P<0.05).Compared with the high-dose Formononetin group,the high-dose Formononetin+Anisamycin group had shorter cough latency,lower PO2,OI and IL-10.The frequency of coughing,PCO2,IL-18,TNF-α,apoptosis rate,and the ratios of p-p38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,p-ERK1/2/ERK1/2,and p-JNK/JNK increased(P<0.05).Conclusion Formononetin may improve lung injury in MPP mice by inhibiting the MAPK/NF-κB signaling pathway.
6.Therapeutic effect of Formononetin on Mycoplasma pneumoniae pneumonia in mice based on the MAPK/NF-κB signaling pathway
Shuang ZHANG ; Ran TAO ; Xiaojian CUI ; Leilei SHI
Immunological Journal 2025;41(8):535-540
Objective To investigate the therapeutic effect of Formononetin on mice with Mycoplasma pneumoniae pneumonia(MPP)by regulating the mitogen-activated protein kinase(MAPK)/nuclear factor κB(NF-κB)signaling pathway.Methods Six-week-old SPF-grade male BALB/c mice were selected.The MPP mouse model was established as the model group by instillating Mycoplasma pneumoniae bacterial solution through the nose.On the second day after successful modeling,mice were intraperitoneally injected with 15,30,and 60 mg/kg of Formononetin and 60 mg/kg of Formononetin+20 mg/kg of Anisomycin respectively as the low-dose,medium-dose,and high-dose Formononetin groups and the high-dose Formononetin+Anisomycin group,with 12 mice in each group.Another 12 mice were intraperitoneally injected with the same amount of 0.9%sodium chloride injection as the control group.The cough frequency of mice in each group was detected through the cough induction test.The partial pressure of carbon dioxide(PCO2)and partial pressure of oxygen(PO2)in each group of mice were detected by a blood gas analyzer,and the oxygenation index(OI)was calculated.The levels of inflammatory factors in each group were detected by ELISA,and the apoptosis of lung tissue cells in each group of mice was detected by TUNEL.HE staining was performed to observe the pathological changes of lung tissues in each group.The expression of MAPK/NF-κB pathway-related proteins in the lung tissues of mice in each group was detected by Western blot method.Results The lung tissue morphology of the mice in the control group was normal.The alveolar ducts and alveolar structures of mice in the model group were damaged,the alveolar septa thickened,and there was a large amount of inflammatory cell infiltration.Compared with the model group,the lung tissue morphology was improved in the low-dose,medium-dose and high-dose Formononetin groups.The lung tissue injury in the high-dose Formononetin+Anisamycin group was more severe compared with the high-dose Formononetin group.Compared with the control group,the cough latency period in the model group was shortened,and PO2,OI,and interleukin-10(IL-10)were decreased,while the frequency of coughing,PCO2,interleukin-18(IL-18),tumor necrosis factor-α(TNF-α),apoptosis rate,and the ratios of p-P38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,p-extracellular signal-regulated kinase 1/2(ERK1/2)/ERK1/2,and p-C-jun N-terminal kinase(p-JNK)/JNK increased(P<0.05).Compared with the model group,the low-,medium-and high-dose Formononetin groups had improved lung tissue morphology,prolonged cough latency,increased PO2,OI and IL-10,and reduced cough frequency.The PCO2,IL-18,TNF-α,apoptosis rate,and the ratios of p-p38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,ERK1/2/ERK1/2,and p-JNK/JNK decreased(P<0.05).In the low-,medium-,and high-dose Formononetin groups,with the increase of Formononetin dose,the cough latency gradually prolonged,the cough frequency gradually decreased,and the PO2,oxygenation index,and IL-10 gradually increased.The PCO2,IL-18,TNF-α,apoptosis rate and the ratios of p-p38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,p-ERK1/2/ERK1/2,and p-JNK/JNK gradually decreased(P<0.05).Compared with the high-dose Formononetin group,the high-dose Formononetin+Anisamycin group had shorter cough latency,lower PO2,OI and IL-10.The frequency of coughing,PCO2,IL-18,TNF-α,apoptosis rate,and the ratios of p-p38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,p-ERK1/2/ERK1/2,and p-JNK/JNK increased(P<0.05).Conclusion Formononetin may improve lung injury in MPP mice by inhibiting the MAPK/NF-κB signaling pathway.
7.Recurrence mechanisms and treatment strategies for IDH wild-type glioblastoma
Tao WANRU ; Lv LEI ; Wang ZIJUN ; Bao LEILEI
Chinese Journal of Clinical Oncology 2025;52(6):309-313
Isocitrate dehydrogenase(IDH)wild-type glioma is a type of highly invasive brain tumor with poor prognosis and a high recur-rence rate.The recurrence process is driven by multiple complex and interwoven factors.Although the current standard treatment regi-mens can temporarily alleviate patients'symptoms,they still face significant challenges in effectively preventing tumor recurrence.The re-currence mechanism of this tumor is intricate and covers multiple aspects such as genomic instability,maintenance of stem cell characterist-ics and mesenchymal transformation,as well as dynamic changes in the tumor microenvironment.This article aims to comprehensively sum-marize the recurrence mechanism of glioblastoma and deeply explore potential countermeasures targeting these mechanisms,hoping to open up new perspectives and approaches for the treatment of recurrent tumors.
8.Significance of echocardiography in distinguishing between two main subtypes of myocardial amyloidosis
Chong FAN ; Leilei PEI ; Chun YANG ; Tao ZHANG ; Wenjin ZHU ; Shun WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):789-793
Objective To explore the application value of echocardiography in the differential diagnosis of transthyretin cardiac amyloidosis(ATTR-CA)and immunoglobulin light chain cardiac amyloidosis(AL-CA).Methods We conducted a retrospective analysis of echocardiographic parameters of 50 confirmed CA patients diagnosed between November 2021 and January 2024 at The First Affiliated Hospital of Xi'an Jiaotong University,including 6 cases of ATTR and 44 cases of AL.Parameters that could potentially distinguish between the two subtypes were selected using t-tests and x2 tests,and the diagnostic capabilities of these parameters for the two subtypes were analyzed using receiver operating characteristic(ROC)curves.Results There were no statistically significant differences in general characteristics,global longitudinal strain(GLS),ratio of apical to basal strain,ejection fraction to GLS ratio(EFSR),maximum thickness of left ventricular myocardium,relative thickness of left ventricular wall,presence of thickened atrioventricular valves,or presence of enlarged atria between ATTR and AL groups(P>0.05).The interventricular septal thickness was greater than in ATTR group than in AL group(P<0.05),and the E/e'ratio(ratio of spectral Doppler early diastolic peak velocity to tissue Doppler early diastolic peak velocity)was greater in ATTR group than in AL group(P<0.05).ROC curve analysis showed that the areas under the curve for distinguishing between the two subtypes based on interventricular septal thickness and E/e'ratio were 0.891(95%CI:0.792-0.991)and 0.826(95%CI:0.698-0.955),respectively,with a sensitivity of 100.00%and specificity of 95.24%for combined diagnosis.Conclusion Echocardiographic parameters,including E/e'ratio and interventricular septal thickness,may have clinical significance in distinguishing between the two main subtypes of CA in patients.
9.Development and validation of a nomogram diagnostic model for the diagnosis of Prosthetic Joint Infections based on serum and joint fluid inflammatory markers
Leilei QIN ; Jianye YANG ; Tao ZHANG ; Chen ZHAO ; Ning HU ; Wei HUANG
Chinese Journal of Orthopaedics 2024;44(4):250-259
Objective:To construct a column-line diagram diagnostic model based on serum and joint fluid inflammatory markers for the diagnosis of periprosthetic joint infections (PJI) after joint arthroplasty and to validate its predictive ability.Methods:The clinical data of 181 patients diagnosed with PJI or aseptic loosening in the Department of Orthopedics of the First Affiliated Hospital of Chongqing Medical University from January 2015 to June 2020 were retrospectively collected as a modeling group. The best indicators for diagnosing PJI were screened by lasso regression, single-factor and multifactor analysis. By comprehensively considering the weights and intrinsic connections of the indicators, a column-line diagram diagnostic model was constructed and used to develop a clinical decision support system (CDSS). Prospectively, the clinical data of patients diagnosed with PJI or aseptic loosening in the Department of Orthopedics of the First Hospital of Chongqing Medical University from July 2020 to December 2022 were collected as a validation group, and the diagnostic performance of the column-line diagram model was externally validated by methods such as receiver operating characteristic curve (ROC).Results:There were 85 cases of PJI in the 181 cases modeling group and 23 cases of PJI in the 49 cases validation group. Among the 27 potential factors analyzed by lasso regression analysis, body mass index (BMI), blood tests including platelet (PLT), absolute lymphocyte value, interferon γ (IFN-γ), ESR, IL-6, C-reactive protein, D-dimer, and joint fluid tests including C-reactive protein, IL-1, IL-4, IL-6, percentage of multinucleated neutrophils (PMN%), and CD64 may be potential indicators for the diagnosis of PJI. Univariate found significant differences between hematologic tests including sedimentation, C-reactive protein, IL-6, D-dimer and joint fluid tests including C-reactive protein, joint fluid CD64 index, C-reactive protein, IL-1, IL-4, IL-6, PMN%( P<0.05). Further multifactorial regression analysis screened serum IL-6, D-dimer, joint fluid CD64 index, C-reactive protein, IL-1, IL-4, IL-6, and percentage of multinucleated neutrophils, and based on that, the column-line graph model and CDSS system were constructed. The area under the ROC in the validation group was 0.978, and the AUC in the internal validation was 0.995; the C-index of the calibration curve was 99.50%, and the C-index of the internal validation was 99.53%, suggesting that the column-line diagram model has a good predictive ability. Conclusions:The column-line diagram for diagnosing PJI based on multiple diagnostic indicators showed good diagnostic performance. The CDSS system constructed by column-line diagrams could assist clinicians in diagnosing PJI and making reasonable strategies in time.
10.Genetic characterization of varicella-zoster virus in Jilin province from 2010 to 2023
Xiang LI ; Leilei WEI ; Biao HUANG ; Tao CHENG ; Yuanchun SHAN ; Guixiang QIN ; Hongyan SUN ; Shangwei JI ; Xin TIAN ; Simei FU ; Shuang WANG
Chinese Journal of Experimental and Clinical Virology 2024;38(5):521-526
Objective:This study aimed to analyze the genomic characteristics of Varicella-Zoster Virus (VZV) strains circulating in Jilin province from 2010 to 2023.Methods:Vesicle fluid from 78 sporadic cases with VZV infection were collected in Jilin province from 2010 to 2023, after detecting by Real-time PCR, 26 specimens (CT<25) were detected by PCR. Open reading frame 22(ORF22), ORF38 and ORF62 were amplified and analyzed. Genotyping was confirmed by SNPs ORF22 (37902, 38019, 38055, 38081 and 38177) and ORF38 (69424). Vaccine strains were indentified from wild-type strains according to ORF38 (69349) and ORF62 (106262, 107252, and 108111). Sequences were analyzed by homologous comparison and phylogenetic analysis.Results:The comparison with Dumas sequence revealed that SNPs (37902, 38055, 38081 and 38177) in ORF22 and ORF38 (69424) have mutations similar to the pOka strain, which belong to clade 2. Compared to the Dumas and Baike strains, all 26 samples were wild-type strains. JL2016-4 strain changes from threonine to asparaginyl at position 38059, JL2021-4 strain changes from arginine to proline at position 37933, from aspartic acid to tyrosine at position 37935, and from aspartic acid at base 38031 to tyrosine. JL2023-1 strain changes from arginine to leucine at position 37933.Conclusions:VZV has been prevalent for 14 years in Jilin province. The main epidemic strains belong to the clade 2. We should strengthen the monitoring of VZV outbreaks and raise the coverage rate of VZV vaccination.

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