Establishment of a high-throughput screening platform based on drug repurposing targeting alpha-1-acid glycoprotein and discovery of potential weight loss drugs / 药学实践杂志

Objective Alpha-1-acid glycoprotein （ORM） was a new target for the development of weight loss drugs. To search for potential weight loss drugs that could target ORM from the compound library of already marketed drugs based on drug repurposing. Methods The pGL4.20-ORM1 promoter recombinant plasmid was contructed and validated, and then a lentiviral vector was utilized to establish stable AML12 cell lines expressing ORM1 promoter-LUC-PURO. This cell line was employed for high-throughput screening of compounds from the marketed drug library, and the luminescence value of the cells was characterized by enzyme marker. Results Primary screening and secondary screening of 1 470 compounds identified 42 compounds that increased ORM1 promoter expression and could be used for further weight loss effect assessment. Conclusion This study successfully constructed LV-AML12-ORM1 promoter-LUC-PURO stable expression cell lines using lentiviral vectors, laying a foundation for efficient and stable screening of weight loss drugs targeting ORM.

CiteSpace knowledge map of research hotspots and frontiers of Polygalae Radix / 中国中药杂志

In this study, the Web of Science and China National Knowledge Infrastructure(CNKI) were searched comprehensively for the literature about the research on Polygalae Radix. After manual screening, 1 207 Chinese articles and 263 English articles were included in this study. Excel was used to draw the line chart of the annual number of relevant publications. CiteSpace 6.1.R3 was used for the visual analysis of author cooperation, publishing institutions, keyword co-occurrence, keyword clustering, and bursts in the research on Polygalae Radix. The results showed that the number of articles published in Chinese and English increased linearly, which indicated the rising research popularity of Polygalae Radix. WANG J and LIU X were the authors publishing the most articles in Chinese and English, respectively. Shanxi University of Chinese Medicine and Chinese Academy of Medical Sciences were the research institutions with the largest number of Chinese and English publications in this field, respectively. The institutions publishing the relevant articles in English formed a system with the Chinese Academy of Medical Sciences as the core. According to the keywords, the research hotspots of Polygalae Radix included variety selection and breeding, quality standard, extraction and identification of active chemical components, prescription compatibility, processing, clinical medication rules, and pharmacological mechanism. The research frontiers were the molecular mechanisms of Polygalae Radix and its active components in exerting the protective effect on brain nerve, regulating receptor pathways, alleviating anxiety and Alzheimer's disease, as well as data mining and clinical medication summary. This study has reference significance for the topic selection and frontier identification of the future research on Polygalae Radix.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project / 老年心脏病学杂志（英文版）

BACKGROUND@#The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).@*METHODS@#A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.@*RESULTS@#A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).@*CONCLUSIONS@#Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Study on the fingerprint of total saponins from Mussaenda pubescens and the spectrum-effect relationship of its hepatoprotective activity / 中国药房

OBJECTIVE To establish the fingerprint of total saponins from Mussaenda pubescens， and to study the spectrum- effect relationship of its hepatoprotective activity. METHODS Ten batches of total saponins from M. pubescens from different origins were prepared using 75% ethanol as solvent. High-performance liquid chromatography （HPLC） and the Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition） were used to draw the fingerprints of 10 batches of total saponins from M. pubescens. The similarity evaluation and identification of common peaks were conducted. The same HPLC method was adopted to determine the contents of five triterpenoid saponins （mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G and mussaendoside O）. The hepatoprotective effect of total saponins from M. pubescens was investigated by establishing carbon tetrachloride-induced acute liver injury model mice， and the spectrum-effect relationship was studied by using grey correlation analysis. RESULTS There were 11 common peaks in 10 batches of total saponins from M. pubescens， 5 of which were identified， i.e. mussaendoside H （peak 3）， mussaendoside U （peak 7）， mussaglaoside C （peak 8）， mussaendoside G （peak 9） and mussaendoside O （peak 11）； the similarities of 10 batches of samples ranged 0.940- 0.991. Average contents of mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G， mussaendoside O were 0.01- 0.05， 0.10-0.21， 0.10-0.18， 0.03-0.08， 0.20-0.40 mg/g， respectively. Ten batches of total saponins from M. pubescens could generally reduce the contents of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum， and tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in liver tissue of model mice （P＜0.05 or P＜0.01）. The E-mail：13878195336@139.com correlation between the common peak areas and the contents of ALT， AST， TNF-α， IL-6 and IL-1β were 0.602-0.757， 0.585-0.833， 0.593-0.795， 0.618-0.820， 0.607-0.804， respectively； the peaks with high correlation were peaks 11， 9 and 8 in order. CONCLUSIONS Ten batches of total saponins from M. pubescens have similar components， and the average contents of mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G and mussaendoside O are different. The batches of samples have a certain degree of hepatoprotective effect； mussaendoside O， mussaendoside G and mussaglaoside C may be its main active components.

Effect of dexmedetomidine on TXNIP/ASK1 signaling pathway in a mouse model of intestinal ischemia-reperfusion / 中华麻醉学杂志

Objective:To evaluate the effect of dexmedetomidine on the thioredoxin-interacting protein (TXNIP)/apoptosis signal-regulated kinase 1 (ASK1) signaling pathway in a mouse model of intestinal ischemia-reperfusion (I/R).Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), TXNIP inhibitor resveratrol group (Res group) and dexmedetomidine group (Dex group). The mouse model of intestinal I/R injury was developed by clamping the superior mesenteric artery for 45 min followed by 120-min reperfusion in anesthetized animals. Resveratrol 30 mg/kg was intraperitoneally injected before developing the model in Res group, and dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before ischemia in Dex group. Blood samples were collected by cardiac puncture at the end of 120-min reperfusion, then the mice were sacrificed, and the small intestine tissues were removed for microscopic examination and for determination of the serum diamine oxidase (DAO) concentration (by enzyme-linked immunosorbent assay) and expression of TXNIP, ASK1 and cleaved-caspase-3 in small intestinal tissues (by Western blot). The apoptosis rate of intestinal epithelial cells was calculated. The intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score, serum DAO concentrations and apoptosis rate of intestinal epithelial cells were significantly increased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was up-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in group Res ( P<0.05). Compared with I/R group, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in Dex group ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates intestinal I/R injury may be related to inhibition of the TXNIP/ASK1 signaling pathway and reduction of cell apoptosis in mice.

A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance / 药物分析学报

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50％of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine le-sions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glio-blastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell char-acteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

Effect of hemopurification on acute chlorfenapyr poisoning / 中华急诊医学杂志

Objective:To evaluate the therapeutic effect of hemopurification on acute chlorfenapyr poisoning according to the blood concentration of chlorfenapyr and to provide experience for clinical treatment.Methods:Two patients who presented to our Emergency Department following an ingestion of chlorfenapyr and then were treated with hemopurification in 2022 were included. The concentrations of chlorfenapyr and its highly toxic metabolite tralopyril were dynamically monitored, and the clinical data of the patients were collected.Results:Case 1 was given hemoperfusion for the first time 13 hours after ingestion. During l hour hemoperfusion, the tralopyril decreased by 28.82%. The concentration increased and exceeded the pre-perfusion level after 2 hours of hemoperfusion. After three times of hemoperfusion, the concentrations of chlorfenapyr and tralopyril were still higher than those before the first time, reaching 248 ng/mL and 1 307 ng/mL respectively. The concentration of chlorfenapyr showed a downward trend after 130 h, and the tralopyril in blood reached the peak 3 164 ng/mL at 130 h and decreased to 2 707 ng/mL at 178 h. In case 2, the blood chlorfenapyr and tralopyril concentration was 392 ng/mL and 7 598 ng/mL respectively 150 hours after ingestion. The blood chlorfenapyr concentration decreased by 37.75% respectively after first hemoperfusion, and the tralopyril concentration decreased by 38.02% respectively. During 85 hours of continuous veno-venous hemodiafiltration (CVVHDF), the concentration of tralopyril was maintained at 4 234~6 410 ng/mL. Case 1 was followed up to 12 days and lost follow-up. Case 2 died and the survival time was 247 hours.Conclusions:Hemoperfusion can scavenge tralopyril, but CVVHDF has poor scavenging ability for tralopyril. And the apparent volume of distribution (Vd) of chlorfenapyr and tralopyril are large. After ingestion, chlorfenapyr spreads to various tissues quickly, and it is easy to accumulate in the adipose tissue. The chlorfenapyr in the tissue slowly is released back to the blood and stays in the blood for a long time. The peak concentration of chlorfenapyr appeared earlier than that of tralopyril. Clinicians should pay attention to the early removal of toxins from the digestive tract.

Analysis of epidemiology and clinical characteristics of patients with poisons purchase online / 中华急诊医学杂志

Objective:To explore the clinical characteristics of poisoned patients with poisons purchase online.Methods:A retrospective case-control study was conducted on poisoned patients purchased poisons online from 1st January 2021 to 31th May 2022 in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University. The clinical data including sex, age, way of medical treatment, cause of poisoning, exposure routes, category of toxic drugs, gastric lavage, toxic detection and prognosis of patients were collected and compared with those patients obtained poisons at stores as the control group.Results:Totally 318 poisoned patients were included in this study, of which 44 (13.8%) were obtained poisons online. Compared with the patients obtained poisons at stores, the patients obtained poisons online were younger ( P<0.001), and had higher proportion of suicide intention ( P=0.006), more oral route exposure ( P=0.029), and more proportions of receiving gastric lavage before transfer to the hospital ( P=0.001). Pesticides and fertilizers with organic heterocycles were the main types of poisons in the online group, and there was no statistical difference in the distribution of poisons compared with the control group. Mixed drug poisoning was the leading cause in both online group (27.8%) and control group (38.8%) in drug overdose poisoned types, followed by dextromethorphan (16.7%) and estazolam (15.5%) in the online group. Conclusions:Young people are the main group getting poisons through the Internet. Health education should be strengthened for this group, and online shopping platforms should pay attention to the poisoning risk of potential overdose drugs or poisons transactions.

Clinical value of sodium dithionite reduction method in the diagnosis and treatment of diquat poisoning / 中华急诊医学杂志

Objective:To explore the clinical value of urine semi-quantitative colorimetry by sodium dithionite reduction method in the diagnosis and treatment of diquat poisoning.Methods:The data of 49 patients with acute diquat poisoning treated in the First Affiliated Hospital of Nanjing Medical University from December 3, 2020 to November 23, 2022 were retrospectively analyzed, the correlation between urine colorimetric results and plasma diquat concentration was observed, and the predictive value of urine colorimetric results for target organ damage and prognosis were evaluated.Results:There was a significant correlation between urine colorimetric results and plasma diquat concentration, the correlation coefficient was r=0.89, P <0.01. The cut-off value of urine colorimetry for the predicting the damage of gastrointestinal tract, liver, kidney, and central nervous system injury were 2.5, 3.5, 3.5, 5.5, respectively; in which the urine colorimetric results showed the highest sensitivity in predicting digestive tract injury [ AUC 0.93 (95% CI:0.89-1.00)]. The cut-off value of urine colorimetry for the prognosis of death was 4.5, the positive predictive value was 64.2%, and the negative predictive value was 95.2%. Conclusions:The urine semi-quantitative method can be used for rapid prediction of the plasma diquat concentration range on admission. The urine colorimetry results can also effectively predict the occurrence of organ injury and clinical outcome related to diquat poisoning, which provides evidence for the clinical diagnosis and therapy.

Application of toxicant and drug detection in 895 patients with clinical poisoning diseases / 中华急诊医学杂志

Objective:To explore the diagnostic value of the toxicant and drug detection in clinical poisoning diseases and analyze the clinical characteristics of patients with positive poison test.Methods:This study was a multicenter retrospective cohort study. Sampling and clinical information data were collected between October 1, 2020 and September 30, 2022 from 41 tertiary hospitals in and around Jiangsu province. The clinical characteristics of patients with positive toxicology tests were analyzed, and the correlation between the drug sampling situation and the test results was analyzed..Results:A total of 895 patients with clinical diagnosis or suspected poisoning were enrolled in this study. Among them, 652 patients had positive results, accounting for 72.85%. Among all positive patients, 506 patients were exposed to a single poison and 147 patients were exposed to multiple poisons. The top three poisons were pesticide herbicides (202 cases, 30.98%), sedative and psychotropic drugs (151 cases, 23.16%), and pesticide insecticides (97 cases, 14.88%). Among 541 patients with clear exposure history, the positive rate was 78.19%, and among 354 patients with unclear exposure history, the positive rate was 64.69%. The top three poisons (drugs) of patients with unclear exposure history were sedative and psychotropic (82, 12.58%), herbicide (26, 3.99%), and rodenticide (22, 3.37%). Patients who admitted to hospital for unexplained consciousness disorder, abnormal blood coagulation function and multiple organ dysfunction were more likely to obtain positive poison test results.Conclusions:There is uncertainty in the exposure history of poisoning diseases, so it is necessary to improve the detection of toxic substances as soon as possible. Toxicant testing should be considered when patients have impaired consciousness, abnormal coagulation function and multiple organ dysfunction.

Research progress of nuclear factor erythroid 2-related factor 2 in pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a common chronic interstitial lung disease. It is characterized by excessive deposition of extracellular matrix and remodeling of lung tissue structure, resulting in severe impairment of lung function. The cause of its pathogenesis is still unclear. Therefore, it is urgent to explore its pathogenesis and find new targets to combat pulmonary fibrosis. Studies have shown that nuclear factor erythroid 2-related factor 2 can maintain the body's redox homeostasis by regulating antioxidant genes and combining antioxidant response components, thereby protecting tissues and cells from oxidative stress. In recent years, many studies have proved that nuclear factor erythroid 2 -related factor 2 can play an anti-fibrotic role by alleviating oxidative stress, inhibiting macrophage polarization, activating autophagy, inhibiting ferroptosis, and blocking epithelial-mesenchymal transition. This paper provides a brief review of the association and research progress of nuclear factor erythroid 2-related factor 2 with pulmonary fibrosis, with the aim of providing a new direction for the precise treatment of pulmonary fibrosis.

Research progress of metformin in the pathogenesis of pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a chronic, progressive and irreversible respiratory disease characterized by hyperposition of extracellular matrix leading to inflammation and extensive lung remodeling. There is currently no effective treatment. Multiple studies have shown that metformin is a classic antiglycemic drug with antifibrotic potential. However, at present, there is no consensus on the specific mechanism of metformin's anti-fibrosis effect, and this paper reviews the research progress of metformin in the field of pulmonary fibrosis in recent years, mainly from IGF-1/IGF-1R/PI3K signaling, AMPK/mTOR signaling, TGF-β/Smad signaling pathway, and intervening in myofibroblast proliferation and apoptosis, improving oxidative stress, inhibiting epithelial interstitial transformation and transglutaminase. In order to be able to more deeply and comprehensively understand the antifibrosis mechanism and clinical application scope of metformin in the future, and provide new ideas for the treatment of pulmonary fibrosis.

Effectss of hyperoside on traumatic brain injury rats by regulating RhoA/ROCK signaling pathway / 中国临床药理学与治疗学

AIM: To investigate the effects of hyperoside on traumatic brain injury (TBI) rats by regulating the Ras homolog gene family, member A (RhoA)/Rho-associated coiled coil-forming kinase (ROCK) signal pathway. METHODS: The TBI rat model was established by modified Feeney free fall hit method, and was randomly divided into model group, low-dose hyperoside (60 mg / kg) group, high-dose hyperoside (120 mg / kg) group, high-dose hyperoside (120 mg / kg) + no load group, and high-dose hyperoside (120 mg / kg) + RhoA overexpression group, with 10 rats in each group, another 10 healthy rats were set as sham operation group, after hyperoside and plasmid were grouped, the nerve injury was detected by modified neurological deficit score (mNSS) and dark avoidance test; Evans blue (EB) quantitative method was used to detect the permeability of blood brain barrier in rats; ultrastructural damage of blood-brain barrier was observed by transmission electron microscopy; the levels of tumor necrosis factor- α (TNF- α), interleukin-8 (IL-8), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and brain tissue of rats were measured with the kit; and the expression of RhoA/ROCK pathway related proteins in rat brain was detected by Western blot. RESULTS: Compared with the sham operation group, the blood brain barrier structure of the model group rats was damaged, the step-through latency and SOD level decreased obviously (P0.05). CONCLUSION: Hyperoside can inhibit neuroinflammation and oxidative stress in TBI rats by down-regulating RhoA / ROCK signal pathway, thereby reducing the damage of blood brain barrier and repairing its neural function.

Research progress in sodium calcium exchanger and heart failure with preserved ejection fraction / 中国临床药理学与治疗学

Sodium calcium exchanger (NCX) is encoded by the SCL8 family genes and belongs to the cation/Ca

Advances in potential drugs for improvement of energy metabolism in heart failure / 药学实践杂志

Heart failure (HF) is a global public health problem with high morbidity and mortality. Numerous studies have shown that HF is caused by severe disturbance of energy metabolism, resulting in insufficient cardiac energy supply. This lack of energy could lead to a failure of the heart to pump blood and a failure of energy metabolism in other organs throughout the body. Currently, therapeutics of HF work by reducing heart rate and cardiac preload and afterload, symptomatic treatment, or delaying the progression of the disease. However, drugs targeting heart energy metabolism have not been developed. the main characteristics of cardiac energy metabolism, metabolic changes during HF were summarized and drugs that improve cardiac function through energy metabolism were discussed, which could provide a new research direction for the development and application of drugs in treatment of heart failure.

Effect of co-morbid chronic kidney disease on the accuracy of cardiac troponin levels for diagnosis of acute myocardial infarction / 南方医科大学学报

OBJECTIVE@#To evaluate the accuracy of cardiac troponin (cTn) levels in the diagnosis of acute myocardial infarction (AMI) in patients with chronic kidney disease (CKD) and explore a potential strategy for improving the diagnostic accuracy.@*METHODS@#We retrospectively analyzed the data from patients with high-risk chest pain admitted in Zhujiang Hospital from January, 2018 to December, 2020, including 126 patients with and 272 patients without CKD, and 122 patients diagnosed to have AMI and 276 patients without AMI. The baseline clinical data of the patients and blood test results within 12 h after admission were collected.@*RESULTS@#In patients without AMI, cTnT level was significantly higher in those with co-morbid CKD than in those without CKD (P < 0.001), and showed a moderate negative correlation with eGFR (rs=- 0.501, P < 0.001), while cTnI level did not differ significantly between the two groups (P=0.72). In patients with CKD, the optimal cutoff level was 0.177 μg/L for cTnT and 0.415 ng/mL for cTnI for diagnosis of AMI, for which cTnI had a higher specificity than cTnT. The diagnostic model combining both cTnT and cTnI levels [P=eY/(1+ eY), Y=6.928 (cTnT)-0.5 (cTnI)-1.491] had a higher AUC value than cTn level alone.@*CONCLUSION@#In CKD patients, the cutoff level of cTn is increased for diagnosing AMI, and cTnI has a higher diagnostic specificity than cTnT. The combination of cTnT and cTnI levels may further improve diagnostic efficacy for AMI.

A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring / 中国当代儿科杂志

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.

Solid Tumors With Cold Agglutinins:Report of Two Cases and Literature Review / 中国医学科学院学报

Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.

Clinicopathological Features and Prognosis of Patients Newly Diagnosed With Lung Adenocarcinoma With Both EGFR Mutation and C-MET Amplification / 中国医学科学院学报

Objective To explore the clinicopathological features and prognosis of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification.Methods The pathological sections were reviewed.EGFR mutation was detected by amplification refractory mutation system-quantitative real-time polymerase chain reaction,and C-MET amplification by fluorescence in situ hybridization.The clinicopathological features and survival data of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification were analyzed retrospectively.Results In 11 cases of EGFR mutation combined with C-MET amplification,complex glands and solid high-grade components were observed under a microscope in 10 cases except for one case with a cell block,the tissue structure of which was difficult to be evaluated.The incidence of lung adenocarcinoma in the patients with EGFR mutation combined with C-MET amplification at clinical stage Ⅳ was higher than that in the EGFR mutation or C-MET amplification group (all P<0.001),whereas the difference was not statistically significant between the EGFR mutation group and C-MET amplification group at each clinical stage (all P>0.05).There was no significant difference in the trend of survival rate between EGFR gene group and C-MET amplification group (χ2=0.042,P=0.838),while the survival of the patients with EGFR mutation combined with C-MET amplification was worse than that of the patients with EGFR mutation (χ2=246.72,P<0.001) or C-MET amplification (χ2=236.41,P<0.001).Conclusions The patients newly diagnosed with lung adenocarcinoma with EGFR mutation plus C-MET amplification demonstrate poor histological differentiation,rapid progress,and poor prognosis.The patients are often in the advanced stage when being diagnosed with cancer.Attention should be paid to this concurrent adverse driving molecular event in clinical work.With increasing availability,the inhibitors targeting C-MET may serve as an option to benefit these patients in the near future.

Association between Fruit and Vegetable Intake and Arterial Stiffness: The China-PAR Project / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the association between fruit and vegetable intake and arterial stiffness.@*METHODS@#We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. A semi-quantitative food-frequency questionnaire was used to assess baseline (2007-2008) and recent (2018-2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from 2007-2008 to 2018-2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity-pulse index (AVI) and arterial pressure-volume index (API). Elevated AVI and API values were defined according to diverse age reference ranges.@*RESULTS@#Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI ( B= -0.11; 95% confidence interval [ CI]: -0.20, -0.02) on average, rather than API ( B = 0.02; 95% CI: -0.09, 0.13). The risk of elevated AVI (odds ratio [ OR] = 0.82; 95% CI: 0.70, 0.97) is 18% lower in individuals with high intake (≥ 500 g/d) than in those with low intake (< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5 years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up ( OR = 0.64; 95% CI: 0.49, 0.83).@*CONCLUSION@#Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.