Systematic characterization and identification of the chemical constituents of the Schisandra chinensis decoction based on a hybrid scanning technique of UHPLC/IM-QTOF-MS / 药学学报

italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H2O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS2 data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

Concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma: a clinical study / 中华放射肿瘤学杂志

Objective:To investigate the efficacy and side effects of concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy.Methods:In the prospective study, 100 patients with stage Ⅲ-Ⅳa locally advanced nasopharyngeal carcinoma (except T 3N 0M 0 stage) who met the inclusion criteria were randomly divided into the experimental and control groups using the random number table method. Patients in both groups were treated with neoadjuvant chemotherapy using TPF (paclitaxel liposome, cisplatin, and 5-fluorouracil) regimen for 2 cycles. At 2 weeks after chemotherapy, concurrent chemoradiotherapy plus nimotuzumab targeted therapy was given in the experimental group, and concurrent chemoradiotherapy was delivered in the control group. The main observation index was the distant metastasis-free survival (DMFS) rate. Log-rank test and multivariate Cox regression analysis were used. Results:The objective remission rate and complete remission rate in the experimental and control groups were 100% vs. 98% ( P=1.000) and 92.0% vs. 80% ( P=0.084). The 3-year DMFS in the experimental and control groups were 91.4 % vs. 76.1 % ( P=0.043). The 3-year progression-free survival (PFS), locoregional recurrence-free survival (LRFS) and overall survival (OS) in two groups were 87.3 % vs. 74.1 % ( P=0.097), 94.5 % vs. 85.6 % ( P=0.227) and 90.5% vs. 85.2% ( P=0.444). Subgroup analysis showed that patients with age<60 years ( HR=0.34, 95% CI=0.12-0.94, P=0.037), neutrophil-to-lymphocyte ratio (NLR)≤4 ( HR=0.34, 95% CI=0.13-0.89, P=0.028) received concurrent chemoradiotherapy plus nimotuzumab obtained better PFS. Multivariate analysis showed that NLR was an independent risk factor for disease progression ( HR=5.94, 95% CI=1.18-29.81, P=0.030) and distant metastasis ( HR=13.76, 95% CI=1.52-124.36, P=0.020). Conclusions:Compared with concurrent chemoradiotherapy alone, concurrent chemoradiotherapy combined with nimotuzumab after neoadjuvant chemotherapy can significantly increase DMFS rate for patients with locally advanced nasopharyngeal carcinoma. The incidence of side effects is similar in two groups. Concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy may be a preferred treatment strategy for locally advanced nasopharyngeal carcinoma.

A Rapid Non-invasive Method for Skin Tumor Tissue Early Detection Based on Bioimpedance Spectroscopy / 生物化学与生物物理进展

ObjectiveIn recent years, with the intensification of environmental issues and the depletion of ozone layer, incidence of skin tumors has also significantly increased, becoming one of the major threats to people’s lives and health. However, due to factors such as high concealment in the early stage of skin tumors, unclear symptoms, and large human skin area, most cases are detected in the middle to late stage. Early detection plays a crucial role in postoperative survival of skin tumors, which can significantly improve the treatment and survival rates of patients. We proposed a rapid non-invasive electrical impedance detection method for early screening of skin tumors based on bioimpedance spectroscopy (BIS) technology. MethodsFirstly, we have established a complete skin stratification model, including stratum corneum, epidermis, dermis, and subcutaneous tissue. And the numerical analysis method was used to investigate the effect of dehydrated and dry skin stratum corneum on contact impedance in BIS measurement. Secondly, differentiation effect of different diameter skin tumor tissues was studied using a skin model after removing the stratum corneum. Then, in order to demonstrate that BIS technology can be used for detecting the microinvasion stage of skin tumors, we conducted a simulation study on the differentiation effect of skin tumors under different infiltration depths. Finally, in order to verify that the designed BIS detection system can distinguish between tumor microinvasion periods, we conducted tumor invasion experiments using hydrogel treated pig skin tissue. ResultsThe simulation results show that a dry and high impedance stratum corneum will bring about huge contact impedance, which will lead to larger measurement errors and affect the accuracy of measurement results. We extracted the core evaluation parameter of relaxed imaginary impedance (Zimag-relax) from the simulation results of the skin tumor model. When the tumor radius (Rtumor) and invasion depth (h)>1.5 mm, the designed BIS detection system can distinguish between tumor tissue and normal tissue. At the same time, in order to evaluate the degree of canceration in skin tissue, the degree of tissue lesion (εworse) is defined by the relaxed imaginary impedance (Zimag-relax) of normal and tumor tissue (εworse is the percentage change in virtual impedance of tumor tissue relative to that of normal tissue), and we fitted a Depth-Zimag-relax curve using relaxation imaginary impedance data at different infiltration depths, which can be applied to quickly determine the infiltration depth of skin tumors after being supplemented with a large amount of clinical data in the future. The experimental results proved that when εworse=0.492 0, BIS could identify microinvasive tumor tissue, and the fitting curve correction coefficient of determination was 0.946 8, with good fitting effect. The simulation using pig skin tissue correlated the results of real human skin simulation with the experimental results of pig skin tissue, proving the reliability of this study, and laying the foundation for further clinical research in the future. ConclusionOur proposed BIS method has the advantages of fast, real-time, and non-invasive detection, as well as high sensitivity to skin tumors, which can be identified during the stage of tumor microinvasion.

Research on risk factors for microcirculation obstruction after acute myocardial infarction reperfusion / 实用放射学杂志

Objective To investigate the risk factors of microcirculation obstruction(MVO)after reperfusion in patients with acute myocardial infarction(AMI).Methods Forty-one patients with AMI who received treatment with myocardial reperfusion were retrospectively selected.Cardiac magnetic resonance(CMR)was used to determine whether the patients had MVO.The patients were divided into MVO and non-MVO groups.The basic data,laboratory examination and CMR parameters of patients were collected and compared between the groups,and the risk factors related to MVO were screened out by logistic regression analysis.Results Delayed myocardial enhancement was observed in all 41 patients,among which 11 cases(26.8%)were with MVO.A total of 206 delayed myocardial enhancement segments were observed,of which 77 segments combined with MVO and 129 segments without MVO.AMI patients with MVO had a higher rate of transmural myocardial infarction,greater infarct volume,left ventricular myocardial mass(LVMM)and edema degree,as well as lower ejection fraction of left and right ventricles(P<0.05).Multivariate logistic regression analysis indicated that infarct volume[odds ratio(OR)=1.116,95%confidence interval(CI)1.017-1.224,P=0.020]was an independent risk factor for MVO after AMI reperfusion.Conclusion Infarct volume is an independent risk factor for MVO after AMI reperfusion,and MVO is associated with left and right ventricular function impairment.

Natural collapse course of ARCO Ⅱ stage osteonecrosis of the femoral head based on China-Japan Friendship Hospital classification / 中国组织工程研究

BACKGROUND:Osteonecrosis of the femoral head is one of the refractory diseases in orthopedic diseases.The natural collapse course of osteonecrosis of the femoral head under different stages and types affects the progression and prognosis of the disease. OBJECTIVE:To explore the progression of natural collapse within 5 years in patients under the different classifications of China-Japan Friendship Hospital(CJFH)with stage Ⅱ osteonecrosis of the International Association for Research Circulation Osseous(ARCO),and to analyze the collapse rate and collapse risk of the femoral head under the different classifications of CJFH. METHODS:A retrospective study was performed to select patients diagnosed with ARCO Ⅱ stage osteonecrosis of the femoral head without collapse in the Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2016 to October 2017.According to whether it collapsed,the number of hips was divided into the collapse group(n=82)and the non-collapsed group(n=70).The collapse risk of patients with osteonecrosis of the femoral head under different CJFH classifications,as well as the collapse time,number of collapses,and collapse rate within 5 years were counted,and then the Kaplan-Meier survival curve of the femoral head under different classification of CJFH was plotted. RESULTS AND CONCLUSION:(1)A total of 97 patients with 152 hips were enrolled,and 82 hips collapsed during the follow-up period,with a total collapse rate of 53.9%,of which the collapse rates of M type,C type,L1 type,L2 type,and L3 type were 0.0%,36.7%,51.4%,72.2%,and 77.8%,respectively,and the comparison between the groups was statistically significant(P<0.05).(2)In terms of collapse risk,the collapse risk of L1 type was 1.704 times that of C-type(P>0.05),while the collapse risks of L2 type and L3 type were 3.866 times and 6.423 times that of C type(P<0.05),respectively.(3)In terms of the Kaplan-Meier survival curve,the median survival time of the femoral head of ARCO Ⅱ stage patients was 3 years,with a 95%confidence interval of 2.885-3.471 years,and the survival rates of the femoral head at the first,third and fifth years were 65.1%(99/152),50.7%(77/152),and 46.1%(70/152),respectively.(4)These findings conclude that different CJFH classifications affect the collapse rate of ARCO Ⅱ stage osteonecrosis of the femoral head patients,among which L3 type patients have the highest collapse rate,followed by L2 type and L1 type patients;C type patients have a lower collapse rate,and M type patients do not collapse,which indicates that the preservation of the lateral column of the femoral head is of great significance for the natural collapse course of osteonecrosis of the femoral head.

Economic burden of healthcare-associated infection in low birth weight in-fants / 中国感染控制杂志

Objective To analyze the economic burden due to healthcare-associated infection(HAI)in low birth weight(LBW)infants,and provide theoretical basis for formulating HAI related policies.Methods The data of LBW infants in a tertiary first-class hospital from January 2018 to December 2022 were retrospectively collected.Propensity score matching method and marginal analysis were adopted to evaluate the economic losses in LBW in-fants and hospitals due to HAI.Results A total of 1 048 LBW infants were included in analysis,124 of whom had HAI,with HAI incidence of 11.8％.A total of 109 pairs were successfully matched using the propensity score matching method.The median length of hospital stay for LBW infants in the HAI group and non-HAI group were 34.0 and 11.0 days,respectively,the length of hospital extended 23 days in LBW infants in the HAI group(P＜0.001).The median hospitalization expenses for LBW infants in HAI group and non-HAI group were 38 067.6 and 12 375.7 Yuan,respectively,the hospitalization expense for LBW infants in HAI group was 25 691.9 Yuan more than non-HAI group(P＜0.001).The major increased expenses were examination,treatment and medication fees.The total hospitalization expenses in different birth weight LBW infants in HAI group were all higher than non-HAI group,and the differences were all statistically significant(all P＜0.05).LBW infants with gestational age＜32 weeks had longer length of hospital stay and higher total hospitalization expense,differences were all statistically significant(all P＜0.05).When the marginal profit ratios were 5％,10％,and 15％,respectively,the economic losses caused by HAI were 371 000 Yuan,742 000 Yuan,and 1 114 000 Yuan,respectively;The ratios of loss-profit and loss-profit to infection coefficient were 0.33 and 2.79,respectively.Conclusion HAI cause significant economic losses to both LBW infants and hospitals.Infants with a birth weight ≤1 000 g and those with a gestational age＜32 weeks are key populations for prevention and control.The lost-profit to infection coefficient can be used to estimate the economic loss of the hospital,timely adjust infection control measures,and reduce the incidence of HAI.

Investigation,traceability analysis,and discussion of food poisoning caused by Salmonella typhimurium ST19 / 中国人兽共患病学报

To perform a comprehensive analysis of the pathogenic causes of a food poisoning case in a district of Wuhan Cit-y,we investigated the molecular epidemiological relationships among pathogenic bacteria,to aid in traceability analysis of food-borne disease outbreaks,as well as clinical diagnosis and treatment.The pathogenic bacteria in this food poisoning case were i-solated and identified according to GB789.4-2016.The isolated strains were subjected to genotyping with pulsed field gel elec-trophoresis(PFGE).Drug resistance gene analysis,multi-locus sequence typing(MLST),and genome-wide single-nucleotide polymorphism analysis(wgSNP)were conducted via whole genome sequencing(WGS).The evolutionary tree for cluster analy-sis was constructed in fasttree software.Drug susceptibility testing was conducted with the broth microdilution method.A total of 12 strains of Salmonella were detected in seven anal swab samples and two fecal samples from the case,as well as three anal swab samples from unaffected individuals.The serotype of the strains was Salmonella typhimurium.The strain exhibited severe multiple drug resistance,including resistance to amikacin,ampi-cillin,cefazolin,gentamicin,piperacillin,and tetracycline,but susceptibility to other antibiotics.The coincidence rate between drug resistance genes and drug resistance phenotypes was high.PFGE revealed that nine strains from this food poisoning case were highly homologous.WGS revealed that the MLST type was ST19,and varying numbers of SNPs(1-6)were present a-mong strains.The phylogenetic tree revealed nine isolated strains forming a distinct cluster,differing from other Salmonella strains in the database and belonging to a novel clonal branch.The single nucleotide site in the strains was highly homologous to that of GCF in Jiangxi_020221795.1.The food poisoning case was caused by Salmonella typhimurium ST19,and all nine iso-lated strains originated from the same source.The chef is closely connected to this food poisoning case.This strain of Salmo-nella typhimurium belongs to a new clonal branch and exhibits multiple drug resistance.

Role of Ca2+in electromagnetic field regulation on osteoblast proliferation and differentiation / 中国医学物理学杂志

Objective To explore the effects of electromagnetic field(EMF)on thechange of Ca2+ in osteolbast from the qualitative and quantitative perspectives,and try to identify the role of Ca2+in EMF regulation on osteoblast proliferation and differentiation.Methods A platform was established for generating sine EMF with a frequency of 38.7 Hz and a strength of 1.5 mT.The MC3T3-E1 osteoblasts were randomly divided into control group and experimental group(EMF intervention for 8 h per day).CCK8 was used to detect osteoblast proliferation,ALP staining to detect osteoblast differentiation,and Ca2+fluorescence probes and flow cytometer to detect the Ca2+concentration in osteoblasts.Results CCK8 result showed that EMF intervention for 48,72,96 and 120 h could significantly promote osteoblast proliferation.After 14 days of EMF intervention,the positive expression of ALP was significantly higher in EMF group than in control group.Ca2+fluorescent staining and flow cytometry results revealed that EMF intervention could increase the Ca2+in osteoblasts.Conclusion The EMF-induced upregulation of Ca2+ signal in osteoblasts may be closely related to the promotions of osteoblast proliferation and differentiation by EMF,but which Ca2+-related biosignaling pathways are involved in the EMF promoting osteoblast proliferation and differentiation remains to be further investigated.

Effects of salidroside on cerebral vascular endothelial cells in MCAO rats / 中国药理学通报

Aim To study the effect of salidroside (SAL) on cerebral vascular endothelial cells of rats with ischemic brain injury and its mechanism of action. Methods Twenty-four healthy adult SD male rats were prepared by bolt plugging method to prepare MCAO models,and randomly divided into sham surgery group ( Sham ) , model group ( MCAO ) , and SAL administration group (MCAO + SAL) ,and the concentration of SAL was 50 mg • kg ~ , with a continuous administration for six days. Western blot was used to detect the protein expression of ICAM-1, VCAM-1 , E-se-lectin,and P-selectin in injured brain tissue of rats. In vitro cell experiments using HUVECs were subjected to different concentrations of salidroside (0. 1,1,10 jjunol • L ) and LPS (100

GLPS improves EAE demyelination through inhibition of TLR4/NF-KB pathway / 中国药理学通报

Aim To explore the protective effects of ganoderma lucidum polysaccharides (GLPS) on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS) and the underlying mechanism. Methods Thirty C57BL/6 mice were randomly divided into three groups: normal control group, EAE model group and GLPS group (5 mg • kg

Advances in the study of the pathogenesis of ophthalmic surgery-related dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

With the rapid development and widespread implementation of all types of ophthalmic surgery, more attention is being paid to the quality of post-operative vision. Dry eye is a common complication after ophthalmic surgery, often causing eye discomfort, blurred vision and other dry eye symptoms. Ophthalmic surgery-related dry eye is a common type of dry eye and is usually caused by a combination of surgical injury to the conjunctival tissue and nerves, destabilisation of the tear film, postoperative inflammatory reaction and perioperative topical medication. This article reviews the risk factors for ophthalmic surgery-related dry eye, the pathogenesis of dry eye due to different ophthalmic surgeries and the prevention of this type of dry eye, with the aim of reducing the occurrence and development of ophthalmic surgery-related dry eye and improving the quality of vision and life after ophthalmic surgery in the clinical setting.

Content determination of ten flavonoids and alkaloids in Gleditsiae Sinensis Fructus, Gleditsiae Fructus Abnormalis, and Gleditsiae Spina / 中国中药杂志

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 μm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 μg·g~(-1)) was higher than that in GFA(0.03-10.41 μg·g~(-1)) and GS(0.04-13.66 μg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.

Content analysis and quality evaluation of main active components and mineral elements of Cynomorium songaricum in different habitats / 中国中药杂志

To clarify the content characteristics of the main active components and mineral elements of Cynomorium songaricum under different habitat conditions, and further explore the relationship between the quality of C. songaricum and habitats, this study took C. songaricum from 25 different habitats in China as the research object, and measured the contents of 8 main active components and 12 mineral elements separately. Diversity analysis, correlation analysis, principal component analysis and cluster analysis were carried out. The results showed that the genetic diversity of total flavonoids, ursolic acid, ether extract, potassium(K), phosphorus(P) and zinc(Zn) in C. songaricum was high. The coefficient of variation of crude polysaccharide, ether extract, gallic acid, protocatechuic aldehyde, catechin, epicatechin, calcium(Ca), sodium(Na), magnesium(Mg), sulfur(S), iron(Fe), manganese(Mn), selenium(Se) and nickel(Ni) were all over 36%, indicating that the quality of C. songaricum was significantly affected by habitats. There were strong synergistic and weak antagonistic effects among the contents of the 8 active components, and complex antagonistic and synergistic effects among the contents of the 12 mineral elements. Principal component analysis revealed that crude polysaccharide, ursolic acid, catechin, epicatechin and total flavonoids could be used as the characteristic components to evaluate the quality of C. songaricum, and Na, copper(Cu), Mn and Ni were the characteristic elements to evaluate the quality of C. songaricum. In cluster ana-lysis, the second group with the main active components as cluster center had better quality in terms of the content of active substances, and the second group with the mineral elements as cluster center had higher utilization potential in the exploitation of mineral elements. This study could provide a basis for resource evaluation and breeding of excellent varieties of C. songaricum in different habitats, and provide a reference for cultivation and identification of C. songaricum.

Association Analysis between Genotype and Phenotype of α,β-Thalassaemia Carriers in Huizhou Area of Guangdong Province / 中国实验血液学杂志

OBJECTIVE@#To analyze the prevalence, genotype distribution and hematological characteristics of α,β-thalassaemia carriers in Huizhou area of Guangdong Province.@*METHODS@#10 809 carriers of simple β-thalassaemia and 1 757 carriers of α,β-thalassaemia were enrolled as our study cohort. The hematological parameters were detected by automated blood cell counters and automatic capillary electrophoresis. Suspension array technology, gap-polymerase chain reaction (gap-PCR) and PCR-reverse dot blot were used for the genotyping of thalassaemia carriers.@*RESULTS@#The prevalence of α,β-thalassaemia in Huizhou area of Guangdong Province was 1.99%. A total of 62 genotypes were detected, and the most prevalent genotype was --SEA/ αα, βCD41-42/ βN (19.29%), the next was --SEA/ αα, βIVS-II-654/ βN (16.73%). Significant differences in mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were found between different genotype groups for simple β-thalassaemia and α,β-thalassaemia. Violin plots showed that carriers with co-inheritance of β-thalassaemia and mild α-thalassaemia expressed the lightest anemia, and carriers with co-inheritance of β-thalassaemia and hemoglobin H (Hb H) disease expressed the most severe anemia.@*CONCLUSION@#There is a high prevalence of α,β-thalassaemia in Huizhou area of Guangdong Province. Because of the lack of specific hematological makers for diagnosis of α,β-thalassaemia, it is necessary to distinguish it from simple β-thalassaemia by genotyping of α- and β-thalassaemia in order to correctly guide genetic counseling and prenatal disgnosis.

Recent Advance of Newly Therapy for Chronic Myeloid Leukemia with BCR-ABLT315I Mutation--Review / 中国实验血液学杂志

BCR-ABLT315I mutation is the main mechanism of resistance to the first and second generation tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML). Ponatinib as the third generation TKI has been found that can significantly improve the prognosis of CML patients with T315I mutation. However, the latest report has discovered that the T315I compound mutant is even resistant to ponatinib, which aroused the enthusiasm of research on the mechanism of CML resistance and targeted therapy once again. Previous studies have shown that TKI combined with other targeted drugs is effective to CML patients with drug resistance or relapse due to T315I mutation. The latest research has found that the allosteric inhibitor asciminib combined with TKI therapy is equally effective to CML patients with T315I compound mutant, but the specific mechanism is not yet clarified. This review will focus on the latest research progress of therapy for CML with BCR-ABLT315I mutation, hoping to provide reference for researching new drugs and improve therapy for treating CML with T315I mutation.

Detection of BCR-ABL Fusion Gene in Chronic Myeloid Leukemia by Novel Digital PCR / 中国实验血液学杂志

OBJECTIVE@#To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230.@*METHODS@#A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared.@*RESULTS@#Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal.@*CONCLUSIONS@#This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.

Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that CRLF1 was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of CRLF1 had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for CRLF1 up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.

Detection performance of Al 18F-PSMA-BCH PET/CT in early relapsed prostate cancer after radical prostatectomy / 中华核医学与分子影像杂志

Objective:To assess the performance of Al 18F-prostate specific membrane antigen (PSMA)-BCH PET/CT in the detection and localization of early recurrent prostate cancer after radical prostatectomy. Methods:From July 2021 to July 2022, a cohort of 51 patients (age: 49-80(64.8±6.9) years) who underwent Al 18F-PSMA-BCH for biochemical recurrence with the prostate specific antigen (PSA) level less than 2 μg/L in Peking University Cancer Hospital & Institute were retrospectively analyzed. The patients were stratified into 4 groups (PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L, 1 μg/L≤PSA<2 μg/L groups) according to different PSA levels. Lesions detected by Al 18F-PSMA-BCH PET/CT were recorded as prostate bed (including bed of seminal vesicles); pelvic, paraaortic, mediastinal/supraclavicular and axillary lymph nodes; bone lesions and visceral lesions. The detection rates among different groups were compared by Fisher exact test. Results:Of 51 patients, 30(58.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer, with 60.0%(18/30) had disease confined to the pelvis, including 26.7%(8/30) had prostate bed recurrence, 26.7%(8/30) had pelvic lymph nodes, 6.6%(2/30) had prostate bed recurrence with pelvic lymph nodes, while 40.0%(12/30) had extra pelvic disease. The detection rates of Al 18F-PSMA-BCH PET/CT in PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L and 1 μg/L≤PSA<2 μg/L groups were 39.1%(9/23), 6/11, 8/9 and 7/8, respectively. There were no significant differences of detection rates between PSA<0.2 μg/L group and 0.2 μg/L≤PSA<0.5 μg/L group ( P=0.397) and also between 0.5 μg/L≤PSA<1 μg/L group and 1 μg/L≤PSA<2 μg/L group ( P=0.929). Conclusion:Al 18F-PSMA-BCH has a high detection rate for early recurrent prostate cancer, even at low PSA levels less than 0.2 μg/L.

Evaluation of the effect of linker on novel targeted PSMA PET probe / 中华核医学与分子影像杂志

Objective:To prepare a novel targeted prostate specific membrane antigen (PSMA) molecular probe Al 18F-PSMA-136, and evaluate the effects of the change in linker on the biological behavior and tumor targeting ability. Methods:Al 18F-PSMA-136 was prepared by replacing the phenyl of Al 18F-PSMA-137 with cyclohexyl in 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA). The inhibition abilities of PSMA of NOTA-PSMA-136 and NOTA-PSMA-137 were determined by N-acetylated-α-linked acidic dipeptidase (NAALADase) method. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio-high-performance liquid chromatography. The PSMA specificity and tumor targeting capability of the probes were investigated in 22Rv1 (PSMA positive-expressing) cells and mouse models. Independent-sample t test was used to analyze the data. Results:The Ki values of NOTA-PSMA-136 and NOTA-PSMA-137 were 3.41 and 0.30 nmol/L, respectively. The labeling yield of Al 18F-PSMA-136 was (30.1±8.4)% and the specific activity was (18.7±5.3) GBq/μmol. The radiochemical purities of the two probes were both greater than 95% and the stabilities in vitro were both good. Both probes showed PSMA-specific in 22Rv1 cells, but the uptake of Al 18F-PSMA-137 was significantly higher than that of Al 18F-PSMA-136 (1 h: (1.67±0.24) vs (1.00±0.01) percentage injected activity per 1×10 5 cells (%IA/1×10 5 cells): t=4.78, P=0.003; 2 h: (2.11±0.06) vs (1.03±0.06) %IA/1×10 5 cells; t=19.90, P<0.001). MicroPET/CT imaging showed that Al 18F-PSMA-136 and Al 18F-PSMA-137 had similar distribution in vivo, mainly concentrated in kidneys, intestine, gallbladder, bladder and tumor. However, the uptake of Al 18F-PSMA-137 in tumor was significantly higher than that of Al 18F-PSMA-136 (1 h: 1.78±0.10 vs 0.54±0.08; t=13.29, P<0.001; 2 h: 1.95±0.01 vs 0.52±0.11; t=18.53, P<0.001). Conclusion:Changes in the NOTA-conjugated linker can significantly affect the PSMA inhibition ability and tumor targeting, and the imaging effect of Al 18F-PSMA-137 with strong lipophilicity is superior.

Comparison of effects of absolute scatter correction and relative scatter correction on image quality in PET reconstruction / 中华核医学与分子影像杂志

Objective:To study the impact of different scattering correction algorithms in the reconstruction of PET/CT images on image artifacts and the precision of quantitative parameters.Methods:The phantom as described in the National Electrical Manufacturers Association (NEMA) NU2 standard was filled with 18F. The background activity was fixed, and the activity of the solution in the spheres was adjusted to obtain several configurations, including the normal ratio group (4.08∶1) and the extreme ratio group (200∶1). The surface contamination group with the same ratio as the extreme ratio group contained a small radioactive source with different doses of 18F (74, 37, 3.7 and 0.37 MBq) placed at the surface of the phantom. PET/CT images of 30 patients (21 males, 9 females, age: (44.5±10.2) years) from Peking University Cancer Hospital & Institute between July 2012 and December 2021 were retrospectively analyzed, including 10 with normal images ( 18F-FDG) and 20 with abnormal images (10 with dislocation during acquisition, 10 with surface contamination). The images were reconstructed with relative and absolute scattering correction. The phantom was evaluated using the target to background ratio (TBR) and the artifact classification. CV as well as the artifact classification were used to compare the clinical image quality. Mann-Whitney U test and χ2 test were used to analyze data. Results:In the normal ratio group and the extreme ratio group, the TBRs of phantom images reconstructed with relative correction were significantly higher than those with absolute correction (normal ratio group: 3.30(1.94, 4.53) vs 2.72(1.56, 3.56); z=-2.20, P=0.028; extreme ratio group: 105.47(45.62, 162.82) vs 101.36(43.96, 155.57); z=-1.99, P=0.046). In the surface contamination group, with the increase of the activity of the small source, the artifact became more obvious, and the artifact classification score of absolute correction was significantly better than that of relative correction (1.5(1.0, 2.0) vs 2.5(2.0, 3.0); z=-2.00, P=0.046). In the 10 normal 18F-FDG PET/CT patients, the CVliver of the relative correction (9.67%(8.00%, 11.00%)) was significantly lower than that of absolute correction (11.00%(9.00%, 12.00%); z=-2.57, P=0.010), indicating the higher image quality of images with relative correction. In abnormal images, the image quality of absolute correction was significantly higher than that of relative correction with fewer and less severe artifacts (dislocation cases: 9/10 vs 4/10; χ2=5.50, P=0.019; surface contamination cases: 9/10 vs 4/10; χ2=5.50, P=0.019). Conclusions:The relative scattering correction is suitable for normal situations in clinical PET acquisition. However, with dislocation or surface contamination, the absolute scattering correction helps to reduce the artifacts and improve the image quality.