1.Treatment of Sepsis-induced Inflammatory Responses with Xijiao Dihuangtang by Modulation of PKM2-mediated One-carbon Metabolism Pathway
Qixiang YAN ; Yeyan ZHU ; Fan GE ; Qimeng SUN ; Leyao YE ; Fang TIAN ; Jun LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):18-26
ObjectiveTo investigate the effects of Xijiao Dihuangtang (XJDHT) on mice with sepsis and cellular models of sepsis and explore its molecular mechanism in alleviating sepsis-induced inflammatory responses via regulating pyruvate kinase M2 (PKM2)-mediated one-carbon metabolism pathway. MethodsForty C57BL/6N mice were randomly divided into four groups: normal group, model group, low-dose XJDHT group (7.7 g·kg-1), and high-dose XJDHT group (15.4 g·kg-1). After one week of continuous gavage, sepsis was induced using cecal ligation and puncture (CLP) in groups except the normal group. 24 h after the surgery, mortality rates in all groups were recorded, and serum cytokines were measured by enzyme linked immunosorbent assay (ELISA). Lung histopathology was examined by hematoxylin-eosin (HE) staining. During the in vitro experiment, the human monocytic leukemia cell line (THP-1) was exposed to various concentrations of XJDHT and treated with lipopolysaccharide (LPS) at a final concentration of 2 mg·L-1 for 24 h. Cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Protein levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were measured by Western blot. Transcriptome sequencing was performed to analyze differentially expressed genes in all groups and conduct gene ontology (GO) enrichment. Key genes in the one-carbon metabolism pathway, including pyruvate kinase M2 (PKM2), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and phosphoglycerate dehydrogenase (PHGDH), were verified by Western blot. A PKM2 inhibition model was established using shikonin for further protein expression analysis. ResultsAnimal experiments showed that compared with the normal group, the model group exhibited significantly elevated body temperature and lung pathology (P<0.01) and increased serum TNF-α and IL-1β levels (P<0.01). High-dose XJDHT reduced body temperature and lung tissue damage (P<0.01) and significantly decreased serum TNF-α and IL-1β levels (P<0.01). Low-dose XJDHT treatment showed no significant temperature change (P<0.01) but reduced serum TNF-α and IL-1β levels (P<0.01). Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α, IL-1β, and one-carbon metabolism genes (PKM2, MTR, and PHGDH) (P<0.01). Cell experiments demonstrated that compared to the normal group, the model group showed elevated protein expressions of TNF-α and IL-1β in THP-1 cells (P<0.01), decreased Bcl-2/Bax ratio, and increased apoptosis (P<0.01). Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α, IL-1β, and one-carbon metabolism genes (PKM2, MTR, and PHGDH) (P<0.01). Compared to the model group, high-dose XJDHT significantly increased Bax/Bcl-2 ratio and PHGDH protein expression (P<0.01) and effectively reduced cell apoptosis (P<0.01) while down-regulating protein expressions of TNF-α, IL-1β, PKM2, and MTR (P<0.01). Low-dose XJDHT moderately increased Bax/Bcl-2 ratio and PHGDH protein expression (P<0.05), reduced apoptosis (P<0.05), and decreased IL-1β and MTR protein levels (P<0.05, P<0.01), but there were no significant changes in TNF-α and PKM2 expression. After PKM2 inhibition by shikonin in THP-1 cells, the expression of protein related to one-carbon metabolism was detected. Compared with the blank group, the LPS-induced model group showed significantly upregulated PKM2 and MTR protein expression (P<0.01) and downregulated PHGDH expression (P<0.01). Compared with the model group, shikonin treatment significantly reduced PKM2 expression (P<0.05), increased PHGDH expression (P<0.01), and decreased MTR expression (P<0.05). ConclusionXJDHT can inhibit the release of inflammatory factors in sepsis, and its mechanism is related to the intervention of the PKM2-regulated one-carbon metabolism pathway in macrophages.
2.Transcatheter endocardial alginate-hydrogel implantation for the treatment of a patient with non-responsive heart failure on cardiac resynchronization therapy defibrillator:a case report
Cun-Jun ZHU ; Bo WANG ; Chao GAO ; Min SHEN ; Tao SU ; Ru-Tao WANG ; Fang-Jun MOU ; Xiao-Na CHEN ; Fei LI ; Ling TAO
Chinese Journal of Interventional Cardiology 2024;32(8):468-471
Heart failure(HF)is the end stage of almost all cardiovascular diseases,including coronary heart disease and structural heart disease.For end-stage HF,medications and cardiac assist devices have limited therapeutic effects,and heart transplantation is associated with donor shortage and immune rejection.Alginate hydrogel has the ability to mechanically support and induce cardiac tissue regeneration and repair.In March 2021,we conducted the world's first transcatheter endocardial alginate-hydrogel implantation in patients with end-stage heart failure,and explored the safety and feasibility of the treatment.Given that patients with heart failure who had undergone cardiac resynchronization therapy defibrillator(CRT-D)were excluded from previous studies,this paper is the first to report a case of transcatheter endocardial alginate-hydrogel implantation in a patient with heart failure who did not respond to CRT-D,with a significant reduction in the number of visits to the doctor and a significant improvement in the quality of life during the post-procedure follow-up,which may expand the indications for the use of this technology.
3.Extracorporeal membrane oxygenation support during transcatheter aortic valve replacement in patients with reduced left ventricular ejection fraction
Cun-Jun ZHU ; Chao GAO ; Bo WANG ; Tao SU ; Ru-Tao WANG ; Yuan HE ; Fang-Jun MOU ; Xiao-Na CHEN ; Fei LI ; Ling TAO
Chinese Journal of Interventional Cardiology 2024;32(11):642-647
Objective To evaluate the efficacy of extracorporeal membrane oxygenation(ECMO)in patients with reduced left ventricular ejection fraction(LVEF)undergoing transcatheter aortic valve implantation(TAVR).Methods This was a single-center,retrospective study enrolling a total of 30 patients with reduced LVEF undergoing TAVR from January 2020 to January 2024.Of these,12 patients underwent TAVR with ECMO.Baseline clinical characteristics,preprocedural echocardiographic and computed tomographic(CT)measurements,TAVR procedural details,and follow-up data at 60-day and 6-month were collected.Results Among the 30 patients,there were 20 males with an average age of(67.0±10.4)years,an average STS score of(8.2±1.8)points,and an average LVEF of(21.2±5.3)%.This study included 11 AR patients,all of whom were in the group without ECMO implantation,and the difference between the two groups was statistically significant(P=0.027).During the operation,there were 0 cases of circulatory collapse in the ECMO group,and 5 cases(5/18)of circulatory collapse in the non ECMO group.All 5 patients underwent emergency ECMO placement.There were statistically significant differences(P<0.05)in the comparison of two groups with circulatory collapse and salvage ECMO implantation.The technical success rate of 30 patients was 76.7%(23/30),and the instrument success rate was 60.0%(18/30).Among them,the technical success rate and instrument success rate of the ECMO group were higher than those of the non ECMO group,but the differences were not statistically significant(both P>0.05).During a 30 day follow-up,there were 0 all-cause deaths in the ECMO group and 9 all-cause deaths(9/18)in the non ECMO group.Among them,7 cases(7/18)died from cardiovascular causes.The differences in all-cause and cardiovascular cause deaths between the two groups were statistically significant(both P<0.05).During a 6-month follow-up,one patient with ECMO died due to extensive cerebral infarction.The all-cause mortality rate during the 6-month follow-up was 1/12(8.3%),while the all-cause mortality rate without ECMO was 9/18(5.0%).The difference between the two groups was statistically significant(P=0.024).The incidence of stroke with ECMO was 1/12(8.3%),while without ECMO it was 0.There was no statistically significant difference between the two groups(P=0.978).Conclusions In patients with reduced LVEF undergoing TAVR,periprocedural ECMO support does seem to improve patient outcome.
4.Antimicrobial resistance and molecular epidemiological characteristics of Campylobacter in children in Guangdong Province from 2020 to 2022
Jia-Jun LIU ; Dong-Mei HE ; Jing XU ; Qi CHENG ; Ya-Hui SHI ; Fang-Zhu OUYANG ; Bi-Xia KE
Chinese Journal of Zoonoses 2024;40(10):950-958
This study was aimed at understanding the detection rate,drug resistance characteristics,virulence characteris-tics,multi-locus sequence typing,and other molecular epidemic and pathogenic characteristics of Campylobacter jejuni and Campylobacter coli in children in Guangdong Province from 2020 to 2022.Anal swabs or stool samples of suspected infection cases in children from 2020 to 2022 were collected from two hospitals in Guangzhou,Guangdong Province.Campylobacter was isolated and cultured through the filtration method,and identified with a microbial mass spectrometry system;antibiotic resist-ance was analyzed with the agar dilution method;bacterial genome nucleic acids were extracted,and whole-genome sequencing was conducted;and drug resistance genes,virulence genes,multi-locus sequence typing,and phylogenetic analysis based on whole-genome single nucleotide polymorphisms were analyzed from whole-genome sequencing results.First,53 strains of Campy-lobacter were detected through continuous routine monitoring in this study,with a positive detection rate of 2.94%.Among them,Campylobacter jejuni accounted for 81.13%(43/53)and Campylobacter coli accounted for 18.87%(10/53).In addition,16 strains of Campylobacter were screened through multi-pathogen surveillance,including 11 strains of Campylobacter jejuni and 5 strains of Campylobacter coli.Drug resistance ex-periments and whole genome sequencing were conducted on 46 Campylobacter isolates,including 33 isolates of Campylobacter jejuni and 13 isolates of Campylobacter coli.The resistance rate of Campylobacter to erythromycin,a widely used clinical treatment,was21.73%(10/46);that to tetracycline was 80.43%(37/46);those to the quinolone antibiotics nalidixic acid and ciprofloxacin were 76.08%(35/46)and 71.73%(33/46)respectively;and that to chloramphenicol was lowest,at 2.17%(1/46).The drug resistance rate was generally higher for Campylobacter coli than Campylobacter jejuni,and the differences in the indicators of erythromycin,gentamicin,streptomycin,telithromycin,and clindamycin were statistically significant.A total of 30 isolates of multidrug-resistant Campylobacter were detected,including nine multidrug-resistant phenotypes.Whole-ge-nome sequence analysis indicated that 46 Campylobacter isolates carried antibiotic resistance genes for antibiotics such as quino-lones,tetracyclines,β-lactams,and aminoglycosides,and carried 128 virulence factor genes in five categories.All 46 isolates of Campylobacter were identified as 35 ST type through MLST typing,and phylogenetic analysis indicated no obvious dominant ST type.Campylobacter coli had more SNPs than Campylobacter jejuni.In conclusion,the positive detection rate of Campy-lobacter in Guangzhou City,Guangdong Province stabilized from 2020 to 2022,and the detection rate of Campylobacter jejuni was higher than that of Campylobacter coli.Campylobacter isolates were resistant to tetracyclines and quinolone,and showed a wide spectrum of multi-drug resistance,which was relatively severe among Campylobacter coli.Resistance genes and drug-resistant phenotypes were correlated and had predictive significance.The virulence genes of Campylobacter jejuni were more a-bundant than those of Campylobacter coli,possibly because of the higher detection rate and pathogenicity of Campylobacter jejuni.The phylogenetic tree showed clear branches with high genetic diversity and no clearly dominant clonal group.
5.Clinical Characteristics and Prognosis of Patients with Acute Leukemia Complicated with Mucormycosis after Chemotherapy
Ping-Ping ZHANG ; Meng WANG ; Yan JIN ; Jun-Feng ZHU ; Fang-Bing ZHU ; Li-Li HAN ; Yan-Li YANG ; Feng ZHANG ; Jia-Jia LI
Journal of Experimental Hematology 2024;32(3):685-692
Objective:To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia,and to strengthen understanding of the disease.Methods:7 cases of acute leukemia(AL)patients diagnosed with mucormycosis by metagenomic next generation sequencing(mNGS)after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected,and their clinical data,including clinical characteristics,diagnosis,treatment,and prognosis,were retrospectively analyzed.Results:Among the 7 patients with AL complicated with mucormycosis,there were 3 males and 4 females,with a median age of 52(20-59)years.There were 6 cases of acute myeloid leukemia(AML)and 1 case of acute lymphocytic leukemia(ALL).Extrapulmonary involvement in 4 cases,including 1 case suspected of central nervous system involvement.The median time for the occurrence of mucor infection was 16(6-69)days after chemotherapy and 19(14-154)days after agranulocytosis.The main clinical manifestations of mucormycosis were fever(7/7),cough(3/7),chest pain(3/7)and dyspnea(1/7).The most common chest CT imaging findings were nodules,patchy or mass consolidation(6/7).All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase.5 patients died within 8 months,and the median time from diagnosis to death was 1 month.Conclusion:Although prophylactic antifungal therapy is adopted,patients with acute leukemia still have a risk of mucor infection during the neutropenia phase.Fever is the main manifestation in the early stage of mucor infection.The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.
6.On-site rapid detection of multiple pesticide residues in tea leaves by lateral flow immunoassay
Gao JUNXIA ; Zhang TIANYI ; Fang YIHUA ; Zhao YING ; Yang MEI ; Zhao LI ; Li YE ; Huang JUN ; Zhu GUONIAN ; Guo YIRONG
Journal of Pharmaceutical Analysis 2024;14(2):276-283
The application of pesticides(mostly insecticides and fungicides)during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea.Thus,it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits.However,the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues.In this study,nine types of lateral flow immunochromatographic strips(LFICSs)were developed to detect the pesticides of interest(fenpropathrin,chlorpyrifos,imidacloprid,thiamethoxam,acet-amiprid,carbendazim,chlorothalonil,pyraclostrobin,and iprodione).To reduce the interference of tea substrates on the assay sensitivity,the pretreatment conditions for tea samples,including the extraction solvent,extraction time,and purification agent,were optimized for the simultaneous detection of these pesticides.The entire testing procedure(including pretreatment and detection)could be completed within 30 min.The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.
7.Clinical characteristics of children on prolonged mechanical ventilation due to different primary diseases
Jun-Zhen ZHU ; Zheng LI ; Li-Dan CUI ; Shi-Yue MEI ; Xiao-Lei LI ; Bing FANG ; Su-Yun QIAN ; Yi-Bing CHENG
Chinese Journal of Contemporary Pediatrics 2024;26(5):481-485
Objective To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation(PMV)due to different primary diseases.Methods A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022.According to the primary disease,they were divided into respiratory disease(RD)group,central nervous system(CNS)group,neuromuscular disease(NMD)group,and other disease group.The four groups were compared in terms of general information,treatment,and outcome.Results There were significant differences among the four groups in age,body weight,Pediatric Logistic Organ Dysfunction-2(PELOD-2)score,Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score,analgesic and sedative treatment,nutrition supply,rehabilitation treatment,tracheotomy,successful ventilator weaning,and outcomes(P<0.05).Compared with the RD group,the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment,and the CNS group had a significantly higher proportion of children receiving tracheotomy(P<0.008).Compared with the other disease group,the CNS group and the NMD group had significantly lower PELOD-2 and PRISM Ⅲ scores,and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged(P<0.008).Conclusions There are differences in clinical characteristics among children receiving PMV due to different etiologies.Most children in the RD group have a younger age,and children in the CNS group have a relatively good prognosis.
8.A Sensor for Detection of Breast Tumor with Three-dimensional Electrical Impedance Tomography
Kai LIU ; An-Qi LI ; Fang LI ; Cheng-Jun ZHU ; Hang TIAN ; Jia-Feng YAO
Chinese Journal of Analytical Chemistry 2024;52(2):248-255,中插16-中插18
An intensive breast array sensor was designed based on three-dimensional electrical impedance tomography in this work.Firstly,an electrical impedance sensor for detection of breast cancer was developed.The sensor adopted the integrated design of excitation electrode array and ground electrode to achieve structural simplification.It realized electric field densification through conical matrix and double-layer circumferentially arranged electrode array and improved the detection accuracy of target object through taper optimization.Secondly,the imaging system was designed,and the sensor was optimized by numerical simulation.The simulation results showed that halving the number of electrodes did not affect imaging accuracy of the sensor,but could improve the imaging speed.Finally,the performance of the sensor was verified by experiment.The signal-to-noise ratio and channel consistency of the system were at a good level.The sensor was used to reconstruct three-dimensional image of the experimental model with relative volume of the detection field of 0.4%.The image correlation coefficient of the single target imaging was above 0.6 and the position of the double target object could be clearly identified,and thus the visual detection of breast cancer was realized.
9.The value of synthetic MRI combined with field of view optimized and constrained undistorted single shot diffusion weighted imaging in differential diagnosis of BI-RADS 4 breast lesions
Shu FANG ; Guiqian WANG ; Jun ZHU ; Ziyang WANG ; Wei ZHANG ; Yafeng WANG ; Tingyan LIU
Journal of Practical Radiology 2024;40(1):51-55
Objective To evaluate the differential diagnostic value of synthetic magnetic resonance imaging(syMRI)and field of view optimized and constrained undistorted single shot diffusion weighted imaging(FOCUS DWI)in patient with breast imaging reporting and data system(BI-RADS)4 breast lesions.Methods A total of 68 patients who underwent breast MRI and were classified as BI-RADS category 4 were prospectively enrolled.Among them,there were 31 cases of benign lesions(benign group)and 37 cases of malignant lesions(malignant group).All patients underwent T1WI,T2WI,FOCUS DWI,dynamic contrast-enhanced magnetic resonance ima-ging(DCE-MRI)and syMRI.Two radiologists delineated the region of interest(ROI)on quantitative parameters images of syMRI and the apparent diffusion coefficient(ADC)images generated from FOCUS DWI and calculated T1,T2,proton density(PD)and ADC values,respectively.The thresholds and diagnostic efficacy of syMRI and FOCUS DWI parameters were evaluated by the receiver op-erating characteristic(ROC)curve.Logistic regression analysis was used to combine the parameters of the two sequences and evalu-ate the diagnostic efficacy.Results The T2,PD,and ADC values in the malignant group were significantly lower than those in the benign group(P<0.05),but there were no statistically significant difference in T1 values between the groups(P>0.05).T2 and ADC values could be used as important diagnostic indexes in patient with malignant lesions of BI-RADS 4 breast lesions,and the area under the curve(AUC)of T2 and ADC was 0.833 and 0.867,respec-tively.There was no significant difference in AUC of T2 and ADC between benign and malignant groups(Z=0.485,P=0.627).The AUC of T2 value combined with ADC value was 0.910,and the sensitivity and specificity was 90.3%and 89.2%,respectively.Conclusion T2 value of syMRI and ADC value of FOCUS DWI can be used as quantitative diagnostic indicators in patients with BI-RADS 4 breast lesions.The combination of T2 and ADC values can further improve the differential diagnosis efficiency.
10.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

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