AI-ENABLED ASSESSMENT OF CARDIAC FUNCTION AND VIDEO QUALITY IN EMERGENCY DEPARTMENT POINT-OF-CARE ECHOCARDIOGRAMS.

BACKGROUND: The adoption of point-of-care ultrasound (POCUS) has greatly improved the ability to rapidly evaluate unstable emergency department (ED) patients at the bedside. One major use of POCUS is to obtain echocardiograms to assess cardiac function. OBJECTIVES: We developed EchoNet-POCUS, a novel deep learning system, to aid emergency physicians (EPs) in interpreting POCUS echocardiograms and to reduce operator-to-operator variability. METHODS: We collected a new dataset of POCUS echocardiogram videos obtained in the ED by EPs and annotated the cardiac function and quality of each video. Using this dataset, we train EchoNet-POCUS to evaluate both cardiac function and video quality in POCUS echocardiograms. RESULTS: EchoNet-POCUS achieves an area under the receiver operating characteristic curve (AUROC) of 0.92 (0.89-0.94) for predicting whether cardiac function is abnormal and an AUROC of 0.81 (0.78-0.85) for predicting video quality. CONCLUSIONS: EchoNet-POCUS can be applied to bedside echocardiogram videos in real time using commodity hardware, as we demonstrate in a prospective pilot study.

Tumor endothelial markers1 mediate endothelial cell angiogenesis and heart failure myocardial remodeling via MAPKs pathway / 实用医学杂志

Objective To explore the role of endothelial cells in angiogenesis and myocardial remodeling in heart failure based on MAPKs pathway mediated by tumor endothelial marker 1(TEM1).Methods Sixty-four mice were equally randomized into four groups:sham operation,myocardial infarction(MI),MI+sh-NC and MI+ sh-TEM1.On the 7th day after MI,the changes of EndMT in the infarct border area were detected by immunofluo-rescence staining,and the cardiac function of mice was evaluated by echocardiography on the 28th day.Mouse aortic endothelial cells(MAECs)were divided into three groups:control,Vector and rTEM1.In addition,MAECs were pretreated with MAPK inhibitor SB203580,and the cells were treated with rTEM1 for 48 h.The changes of EndMT and MAPKs signaling pathways in endothelial cells were evaluated by Western blot.Results In the myocardium at the border of infarction,the level of TEM1-1 increased slightly on the 1st day after MI,reached the peak on the 7th day,and then decreased on the 28th day.Compared with Vector group,the expression of VE-Cadherin protein in the rTEM1 group decreased significantly(P<0.05),and the levels of α-SMA and vimentin,relative migration distance,the number of invading cells,and the number of branching formation increased signifi-cantly(P<0.05).SB203580 reversed these changes of MAECs induced by rTEM1.Compared with the MI group,the co-staining level of CD31+Vimentin+ in the MI+sh-TEM1 group decreased significantly(P<0.01).On the 28th day,the LVEF and LVFS in the MI+sh-TEM1 group were significantly higher than those in MI group(P<0.05).Compared with the MI group,the expressions of p-P38/P38 and p-JNK/JNK in the endothelial cells of the MI+sh-TEM1 group decreased.Conclusion EndMT and angiogenesis induced by TEM1 participate in the pathogenesis of cardiac fibroblasts induced by MI,which may be mechanically related to the activation of MAPKs signaling pathway.

A case of pituitary crisis caused by cadonilimab treatment of advanced gastric cancer / 药物流行病学杂志

A 75-year-old female patient with gastric cancer received cadonilimab(500 mg,iv,d1)combined with albumin-bound paclitaxel(300 mg,iv,d2)and tegafur,gimeracil and oteracil potassium(40 mg,po,bid,d2-15)and 21 days was a cycle.Admission examination at the end of 4 cycles of treatment,laboratory tests showed adrenocorticotropic hormone＜1.00 pg,mL-1,cortisol 0.42 μg·dL-1 and serum sodium 131 mmol·L-1.Immune checkpoint inhibitor-related hypophysitis was diagnosed,and pituitary crisis was developed on the 4th day.The diagnosis of hypophysitis concurrent with pituitary crisis was considered to be related to cadonilimab.High-dose glucocorticoids replacement and symptomatic treatment such as rehydration to maintain electrolyte imbalance were given.On the 9th day after admission,the patient was basically in remission.The administration of cadonilimab may cause pituitary crisis,which is relatively rare in clinical practice.This case reminds that the possibility of hypophysitis when patients emerge with the symptom of fatigue and anorexia along with hyponatremia.Assessment of endocrine gland function,correct diagnosis and proper therapy are of significant clinical value to improve the patients'prognosis.

Diagnostic value of machine learning model based on 18F-FDG PET/CT for polymyalgia rheumatic / 中华核医学与分子影像杂志

Objective:To investigate the diagnostic value of machine learning model based on 18F-FDG PET/CT for polymyalgia rheumatica (PMR). Methods:From November 2014 to December 2022, 177 patients (119 males, 58 females; age: 67.0 ( 61.0, 72.0) years) admitted to the Department of Rheumatology and Immunology, the First People′s Hospital of Changzhou, with suspected PMR and undergoing 18F-FDG PET/CT examination were retrospectively analyzed. Patients were randomly divided into training set and validation set at the ratio of 7∶3. Three machine learning models, including classification and regression tree (CART), the least absolute shrinkage and selection operator (LASSO) algorithm, and logistic regression, were established based on the PET/CT imaging features to aid in the diagnosis of PMR. The diagnostic efficacy of each model was evaluated by ROC curve analysis and differences among AUCs were analyzed by Delong test. Results:There were 78(44.1%, 78/177) PMR patients and 99(55.9%, 99/177) non-PMR patients, and 124 patients in the training set and 53 patients in the validation set. The logistic regression model (training set: AUC=0.961; validation set: AUC=0.930) was superior to the CART (training set: AUC=0.902, z=2.96, P=0.003; validation set: AUC=0.844, z=2.46, P=0.014) in diagnosing PMR, and was similar to LASSO algorithm (training set: AUC=0.957, z=0.95, P=0.340; validation set: AUC=0.930, z=0.00, P=1.000), but with fewer sites evaluated. The simplified PMR-Logit score had the AUC of 0.951 in the overall population, with the sensitivity of 89.74%(70/78) and the specificity of 90.91%(90/99). Conclusion:Machine learning models based on 18F-FDG PET/CT imaging features are expected to be an effective diagnostic tool for PMR.

Clinical application and evaluation of rapid detection of carbapenem resistance genes in blood cultures by Xpert Carba-R / 中华检验医学杂志

This work aims to evaluate a rapid detection method of carbapenem resistance genes in blood cultures based on Xpert Carba-R and preliminarily evaluate its clinical application.Methods:Sixteen strains of Enterobacterales carrying different carbapenem resistance genes were selected to prepare simulated positive blood culture samples and Xpert Carba-R was used to directly detect carbapenem resistance genes in the simulated positive blood culture. From January 2022 to June, a prospective study was conducted on a total of 117 Enterobacteriaceae-positive blood culture samples in the First Affiliated Hospital of Nanjing Medical University. Xpert Carba-R, detecting five kinds of carbapenem resistance genes in these samples, was evaluated in sensitivity and specificity compared to polymerase chain reaction sequencing. Meanwhile clinical data of positive patients was collected for prognostic analysis. Results:Of the 16 simulated specimens, 14 strains had carbapenem resistance genes detected by Xpert Carba-R, including 8 bla KPC, 5 bla NDM and 1 bla IMP, showing 100% agreement with the known results. As of the 117 clinical specimens, 28 cases were determined to be Enterobacterales harboring carbapenem resistance genes, including 24 bla KPC, 2 bla NDM and 2 bla KPC+ bla NDM. In comparison to the PCR sequencing, the sensitivity and specificity of Xpert Carba-R were both 100% for blood culture samples, and furthermore, the detection time was significantly reduced. Of the 25 positive patients, 9 cases were treated with monotherapy and 5 cases were effective, other 16 cases received combined treatment and 12 cases were effective. A total of 17 cases were effective, 8 cases were ineffective and 3 of them died, the mortality rate was 12% (3/25). Conclusion:Xpert Carba-R can rapidly and accurately detect carbapenem resistance genes in blood culture, which can provide evidence for rational drug therapy in early clinical stage.

Study on the Distribution Characteristics of Traditional Chinese Medicine Syndrome Types in Girls with Idiopathic Central Precocious Puberty from Hainan Province / 广州中医药大学学报

Objective To investigate the distribution characteristics of traditional Chinese medicine(TCM)syndromes in girls with idiopathic central precocious puberty(ICPP)from Hainan province.Methods A total of 216 cases of ICPP girls admitted to Hainan Women and Children's Medical Centre from January 2019 to December 2021 were retrospectively collected.The frequency statistics and grading of TCM syndromes in the included ICPP girls were carried out,and the distribution characteristics of TCM syndromes were discussed on the basis of the analysis of the three TCM syndrome types of yin deficiency and fire exuberance syndrome,qi and blood insufficiency syndrome and incoordination between heart and kidney syndrome.Results(1)The age of ICPP onset in 216 girls were between 4 and 10 years old,with an average onset age of(7.15±1.06)years.The highest incidence rate of ICPP was found in the girls aged over 7 years old while less than 8 years old,which was 49.54%.(2)Of the three TCM syndrome types,yin deficiency and fire exuberance syndrome accounted for the highest proportion(147 cases,68.06%),followed by the qi and blood insufficiency syndrome(41 cases,18.98%)and the incoordination between heart and kidney syndrome(28 cases,12.96%).(3)The common 16 TCM symptoms(frequency＞25.0%)in descending order of frequency were aversion to heat and night sweating,feverish sensation in soles and palms,breast distension and pain,irritability,thready and rapid pulse,dry stools,dry throat and mouth,hot flushes,excessive intake of fat and sweet food,red tongue with less fur,depression,mental weakness,flushed cheeks,insomnia and dreaminess,red tongue with yellow fur,and bitterness and dryness in the mouth.(4)The distribution of the age in ICPP girls with various syndromes was as follows:yin deficiency and fire exuberance syndrome and qi and blood insufficiency syndrome were more common in the ICPP girls aged over 7 years old while less than 8 years old(accounting for 58.50%and 51.22%),and incoordination between heart and kidney syndrome was more common in ICPP girls aged over 8 years old while less than 9 years old(accounting for 89.29%).Conclusion Yin deficiency and fire exuberance syndrome is the common TCM syndrome that accounts for the highest proportion in ICPP girls from Hainan province.The study of the distribution of TCM syndromes in girls with precocious puberty will be helpful for the observation of the early clinical symptoms of precocious puberty and early diagnosis of the disease,and can provide clues and evidence for the clinical diagnosis and medication for girls with ICPP.

A Retrospective Study on the Qianyang Fengsui Dan Combined with Flying Needle Therapy in the Treatment of Kidney-Yang Deficiency Type of Insomnia / 广州中医药大学学报

Objective To analyze the clinical efficacy of the Qianyang Fengsui Dan(combined with flying needle therapy)in the treatment of kidney-yang deficiency type of insomnia.Methods A retrospective study was conducted to select 82 patients with insomnia admitted to the Department of Traditional Chinese Medicine of Dezhou Hospital of Traditional Chinese Medicine from November 2020 to November 2021,and they were divided into an observation group and a control group according to whether or not they were treated with Qianyang Fengsui Dan combined with flying needle therapy,with 41 cases in each group.The control group was treated with Estazolam,while the observation group was treated with Qianyang Fengsui Dan combined with flying needle therapy on the basis of the treatment of the control group,and the course of treatment was 1 month.The changes of Pittsburgh Sleep Quality Index(PSQI)scores and Epworth Sleepiness Scale(ESS)scores,as well as polysomnographic parameters were observed before and after treatment in the two groups.The changes of γ-aminobutyric acid(GABA),glutamate(GA),substance P(SP),and neuropeptide Y(NPY)levels were compared before and after treatment between the two groups.And followed up for 1 year to compare the incidence of relapce of the two groups of patients.Results(1)The total effective rate was 95.12%(39/41)in the observation group and 63.41%(26/41)in the control group,and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,PSQI scores and ESS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI scores and ESS scores,and the differences were statistically significant(P＜0.05).(3)After treatment,sleep efficiency,awakening time,sleep latency,REM,and total sleep time were significantly improved in the two groups(P＜0.05),and the observation group was significantly superior to the control group in improving sleep efficiency,awakening time,sleep latency,REM,and total sleep time,and the differences were statistically significant(P＜0.05).(4)After treatment,the serum GABA,GA,SP,and NPY levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum GABA,GA,SP,and NPY levels,and the differences were all statistically significant(P＜0.05).(5)After treatment,follow-up for 1 year,the recurrence rate of the observation group was 0,and there were 7 cases of recurrence in the control group,and the recurrence rate of the control group was 17.07%(7/41),and the recurrence rate of the observation group was lower than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The combination of flying needle therapy and Qianyang Fengsui Dan can effectively relieve insomnia and fatigue in patients with insomnia,reduce daytime drowsiness,regulate the release of blood monoamine neurotransmitters,and reduce the relapse rate,and its efficacy is superior to that of simple western medicine treatment.

Expression levels and clinical significance of autophagy related proteins in placenta tissues of pregnant women with fetal growth restriction / 基础医学与临床

Objective To explore the expression and clinical significance of autophagy related proteins Beclin-1,microtubule-associated protein 1 light chain 3(LC3)in placenta tissues of pregnant women with fetal growth restric-tion(FGR).Methods A total of 40 pregnant women undergoing delivery due to FGR and 40 pregnant women un-dergoing normal delivery in the Second Affiliated Hospital of Zhengzhou University were enrolled as FGR group and healthy group between August 2022 and August 2023.The general clinical data in the two groups were collected.The levels of Beclin-1 and LC3 mRNA in placenta tissues were detected by PCR,and expressions of Beclin-1 and LC3 proteins were detected by immunohistochemistry.The differences in positive of Beclin-1 and LC3 proteins among patients with different clinical data were analyzed.Results The placental thickness,placental mass and neonatal weight in FGR group were lower than those in healthy group(P＜0.05).The mRNA levels of Beclin-1 and LC3 in FGR group were higher than those in healthy group(P＜0.05)and positive expression rates of Beclin-1 and LC3 proteins were significantly higher than those in healthy group(P＜0.05).There was significant difference in positive expression profile of Beclin-1 and LC3 proteins among patients with different placental thickness,placental mass and neonatal weight(P＜0.05).Conclusions The positive expressions of autophagy genes(Beclin-1 and LC3)are related to FGR,and their specific expression levels are closely related to fetal growth and development.

Effect of miR-141-5p/ZNF705A on adhesion of bone marrow mesenchymal stem cells in chronic myeloid leukemia cell-derived exosomes / 中国药理学通报

Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.

Psychological states and needs among post-allogeneic hematopoietic stem cell transplantation survivors.

OBJECTIVES: To analyze psychological states and needs of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Questionnaires were sent to 101 allo-HSCT survivors and 96 questionnaires were returned. The questionnaire covered several categories: (1) demographics and general information, (2) physical conditions, (3) psychologic status and sleep quality, (4) survivor's comments on transplantation, (5) demands and needs, (6) preferred forms and channels of information. RESULTS: Depression and poor sleep quality were major concerns troubling allo-HSCT survivors. A notable discrepancy exists between clinically diagnosed depression (4.2%) and self- reported depression based on BDI-13 (55.2%). Young adults (18-49 years old), chronic graft-versus-host disease, the ECOG performance score of 2-4, surviving within 5 years since HSCT, no or low dose of ATG used and being single were significantly associated with self-reported depression. Based on the PSQI score, 75% of survivors experienced varying degrees of sleep quality impairment. Young adults, chronic GVHD and the ECOG score of 2-4 were significantly associated with worse sleep quality. The majority of patients reported unmet needs on physical and psychosocial aspects. Nutrition information was the most important topic, followed by disease treatments and fatigue. Differences in informational needs were found in the survivors according to age, time since HSCT and gender. WeChat public account and WeChat applet, mobile interactive platform and one-to-one conversation were the favorite channel for information. CONCLUSIONS: Clinicians should establish more appropriate survivorship care plans focusing on survivors' psychologic states, demands and needs.

CiteSpace knowledge map of research hotspots and frontiers of traditional Chinese medicine intervention in psoriasis in recent ten years / 中国中药杂志

This study aimed to investigate the development status of traditional Chinese medicine(TCM) intervention in psoriasis in recent ten years, analyze the research hotspots, and summarize the development trends to provide reference materials for scholars in this field. Taking the available literature related to the field of TCM intervention in psoriasis as the research object, the trends, contents, and source publications were statistically analyzed based on bibliometrics. The research cooperation and co-occurrence of keywords in this field were studied by the knowledge map analysis method based on CiteSpace. The total number of Chinese papers was 2 993 and English papers 285. In terms of publication trend, the annual publication of English papers was low but showed an obvious upward trend, while the increase in Chinese papers fluctuated and tended to be flat. In terms of the content of Chinese papers published, TCM ranked first according to the discipline(2 415). In English papers, the number of publications in pharmacology and pharmaceutical science was the highest(87). Literature source analysis showed that the Chinese and English journals with the most publications were China Journal of Traditional Chinese Medicine and Pharmacy and Evidence Based Complementary and Alternative Medicine, respectively. Beijing University of Chinese Medicine published the most dissertations in China(99). The authors with the most publications in Chinese and English were LI Bin(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine) and LU Chuan-jian(Guangdong Hospital of Traditional Chinese Medicine). As revealed by the CiteSpace analysis of the research cooperation network, there were four mature and stable core teams in this field, but the cooperation intensity between different teams was weak. According to the keywords co-occurrence knowledge graph constructed by CiteSpace, the current hot keywords in this field are as follows: psoriasis, blood-heat syndrome, blood-stasis syndrome, fire needle, blood-dryness type, imiquimod, TCM bath, etiology and pathogenesis, cytokines, cupping therapy, etc. In summary, Chinese scholars have conducted active exploration and research in the field of TCM intervention in psoriasis in recent ten years. The overall development trend is good, and the breadth and depth of the research are constantly extending. It is suggested that relevant research should be free from discipline restrictions and strive for interdisciplinary integration.

Signal detection and analysis of the adverse events of ustekinumab based on OpenFDA database / 中国药房

OBJECTIVE To analyze the risk of adverse drug reaction of ustekinumab， so as to provide reference for rational drug use in clinic. METHODS The adverse events （AE） reports related to ustekinumab included in the FDA public data program （OpenFDA） database were analyzed after marketing （from September 25th 2009 to December 30th 2021）. The risk signals were mined for top 100 AE by the method of reporting odds ratio （ROR） and proportional reporting ratio （PRR）. RESULTS A total of 62 356 AE reports related to ustekinumab were retrieved， male patients （51.79%） were more than female patients （39.51%）. Results of ROR method and PRR method showed that 31 suspicious signals were mined， mainly infections and infectious diseases （9 kinds）， general disorders and administration site conditions （5 kinds）， skin and subcutaneous tissue disorders diseases （4 kinds）， musculoskeletal and connective tissue disorders （4 kinds）， etc. Fourteen suspicious signals were not included in the instructions， such as hepatic enzyme increase， basal cell carcinoma， pericarditis， pemphigus， hair loss， synovitis， glossodynia， etc. CONCLUSIONS During clinical dosing of ustekinumab， in addition to ADR mentioned in package inserts， great attention should be paid to the patient’s liver function， skin status， hair loss and cardiovascular-related risks，which is helpful to discover AE early and ensure the safety medication of patients.

Mechanism of Schisandra Chinensis-mediated microglia phenotypic transformation by regulation of the TLR4 pathway based on miR-124 / 药学学报

To investigate the mechanism by which Schisandra Chinensis mediates the phenotypic transformation of microglia via microRNA-124 (miR-124)-based regulation of the Toll-like receptor 4 (TLR4) pathway, a model was established using lipopolysaccharide (LPS) stimulation of BV2 cells. Cells were treated with different doses of Schisandra Chinensis extract (SCE). MiR-124 inhibitors and negative control sequences (NC inhibitor) were transfected into LPS-induced BV2 cells and treated with SCE. The MTT assay was used for cell activity detection; an NO kit was used to measure NO release; ELISA kits were used to measure the levels of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). Microglia markers, including ionized calcium binding adapter molecule-1 (IBA-1) and arginase-1 (Arg-1), and the nuclear translocation of nuclear factor-kappa B (NF-κB) were evaluated by immunofluorescent staining. NF-κB p65, IBA-1, Arg-1, TLR4, myeloid differentiation primary factor 88 (MyD88), inhibitor of nuclear factor-kappa B kinases-α (IKK-α), IL-10, TNF-α were detected by immunoblot. SCE at concentrations ranging from 31.25 to 250 μg·mL-1 had no significant effect on cell activity. SCE treatment significantly inhibited NO release induced by LPS (P < 0.001, P < 0.01), increased the level of IL-10 (P < 0.05), and decreased the level of TNF-α (P < 0.001). In addition, SCE significantly reduced the expression of TNF-α, IBA-1, TLR4, and MyD88 (P < 0.01, P < 0.001) and elevated the expression of IL-10, Arg-1, NF-κB P65 and IKK-α (P < 0.001, P < 0.01, P < 0.05). SCE treatment could also promote the expression of miR-124 (P < 0.01). However, transfection with the miR-124 inhibitor increased TNF-α (P < 0.001), decreased the level of IL-10 (P < 0.05), increased the mRNA level and the protein expression of TNF-α and IBA-1 (P < 0.05, P < 0.01, P < 0.001), and decreased the mRNA level and protein expression of IL-10 and Arg-1 (P < 0.001, P < 0.01). In addition, the inhibition of TLR4 and MyD88 was attenuated. In conclusion, SCE appears to inhibit the activation of TLR4 signaling pathway by upregulating miR-124 so as to inhibit microglia M1 polarization and promote microglia M2 polarization.

Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). @*Materials and Methods@#An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. @*Results@#Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. @*Conclusion@#Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

Comparison of three design methods of hybrid boost plan based on Monaco in radiotherapy for nasopharyngeal carcinoma / 医疗卫生装备

Objective To analyze the differences of three design methods of hybrid boost(HB)plan based on Monaco in radiotherapy for nasopharyngeal carcinoma.Methods Ten patients who underwent intensity-modulated radiotherapy(IMRT)for nasopharyngeal carcinoma in some hospital from January to December 2021 were selected,and Monaco planning system was used to design a simultaneous integrated boost(SIB)IMRT plan SIB-IMRT33f with a prescription fraction of 33f for each patient,keeping the fraction dose unchanged and modifying the prescription fraction to 28f to obtain a SIB-IMRT28f plan.SIB-IMRT5f1,SIB-IMRT5f2 and SIB-IMRT5f3 plans were formed based on the SIB-IMRT28f plan respectively by using the Bias Plan function,adding a prescription with a prescription fraction of 5f or copying the SIB-IMRT33f plan,modifying the prescription fraction to 5f and executing re-optimization after deleting PTV2 optimization function,then Plan_HB1,Plan_HB2 and Plan_HB3 were got by fusing SIB-IMRT28f with SIB-IMRT5e,SIB-IMRT5f2 and SIB-IM RT5f3 plans.Differences in dosimetric and therapeutic parameters were compared among the three HB plans and statistically analyzed using SPSS 20.0 software.Results The dose distributions of the three HB plans all met clinical treatment requirements,and the dose distribution of Plan_HB2 was roughly equivalent to that of Plan_HB3.Plan-HB1 behaved better significantly than Plan_HB2 and Plan_HB3 in D2％of planning gross tumor volume(PGTV)and PGTV1 target area and D2％,Dmean homogeneity index and VPTV2,56 of PTV2 target area(P＜0.05);Plan_HB2 and Plan_HB3 both had Dmean of parotid gland,V55 of cochlea,Dmean of oral cavity,Dmean of larynx and Vbody-PTV outside the target area increased significantly when compared with Plan_HB1 plan(P＜0.05);SIB-IMRT5f2 and SIB-IMRT5G had the number of segments,number of monitor units and delivery time decreased when com-pared with SIB-IMRT5f1(P＜0.05).Conclusion All the three HB plan design methods based on Monaco planning system are feasible in nasopharyngeal cancer radiotherapy.In terms of dosimetric and therapeutic parameters,Plan_HB2 is roughly equivalent to Plan_HB3,with some dosimetric parameters inferior to while some therapeutic parameters superior to those of Plan_HB1.[Chinese Medical Equipment Journal,2023,44(11):50-55]

Mechanism of Mongolian drug Naru-3 in initiation of neuroinflammation of neuropathic pain from MMP9/IL-1β signaling pathway / 中国中药杂志

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.

Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining / 中国中药杂志

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain / 神经科学通报·英文版

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.

Effect of hyperthermia on biological behavior of squamous cell carcinoma of the tongue by regulating ferroptosis pathway / 中华放射肿瘤学杂志

Objective:To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL-27.Methods:Half maximal inhibitory concentration (IC 50) of Fer-1, an inhibitor of ferroptosis, was detected by CCK-8 assay and used for subsequent experiments. CAL-27 cells were divided into the HT, control, Fer-1 and HT+ Fer-1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real-time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results:HT significantly up-regulated the ROS levels ( P<0.01) and iron ion concentration ( P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased ( P<0.001), whereas cell apoptosis rate was increased by HT ( P<0.01). In the HT+Fer-1 group, the ROS levels ( P<0.001), iron ion concentration ( P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down-regulated, the cell migration ability was recovered ( P<0.01), and cell apoptosis rate was decreased ( P<0.01) compared with those in the HT group, respectively. Conclusions:HT may induce the ferroptosis of CAL-27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.

Influencing factors of lower urinary tract symptoms in patients with prostate hyperplasia after transurethral holmium laser enucleation / 中华全科医师杂志

A total of 360 patients with prostate hyperplasia underwent transurethral holmium laser enucleation of the prostate in Department of Urology of Jinhua People′s Hospital from July 2019 to December 2022. Among 360 patients, lower urinary tract symptoms occurred one month after operation in 40 cases with an incidence rate of 11.11%. The age, body mass index (BMI), course of disease, nature of disease, preoperative prostate volume, postoperative prostate volume, preoperative IPSS score, postoperative IPSS score, preoperative maximum urine flow rate, postoperative maximum urine flow rate, preoperative residual urine volume, postoperative residual urine volume, postoperative urinary tract infection, operative time, postoperative catheter retention time were compared between patients with lower urinary tract symptoms (study group) and those without (control group). There were significant differences in the course of disease, preoperative prostate volume, preoperative IPSS score, preoperative maximum urine flow rate, preoperative residual urine volume, postoperative urinary tract infection and postoperative catheter retention time between two groups ( t=28.01, 6.35, 8.79, 17.92, 34.84, 11.45;all P<0.05). Multivariate logistic analysis showed that the course of disease, preoperative prostate volume, preoperative IPSS score, postoperative urinary tract infection, and postoperative catheter retention time were independent risk factors for postoperative lower urinary tract symptoms ( OR=6.964, 3.442, 1.944, 4.836, 4.225, 4.894; all P<0.05); while the preoperative maximum urinary flow rate was the protective factor( OR=0.043, P<0.05). The incidence of postoperative lower urinary tract symptoms in patients undergoing transurethral holmium laser enucleation of prostate is high. Effective protective measures should be taken based on the risk factors to reduce the incidence of postoperative lower urinary tract symptoms and to promote the early recovery of patients.