Bone and joint infection complicated with sepsis in neonates and infants under three months of age

Abstract Objective: Studies focusing on bone and joint infections (BJIs) in young infants are rare. Some cases of BJI are accompanied by sepsis. This study aimed to identify the clinical and bacteriological features of sepsis in neonates and young infants with BJIs. Methods: Neonates and infants younger than 3 months diagnosed with BJI in the present institution from 2014 to 2021 were retrospectively reviewed. Patient characteristics, clinical data, and outcomes were documented and compared between those with and without sepsis. Results: Twenty-five patients with a mean age of 34.8 days were included. Nine BJI cases had concomitant sepsis (group A), and 16 had BJI without sepsis (group B). Within group A, staphylococcus aureus was the major pathogenic germ (5 cases, of which 4 were of the methicillin-resistant staphylococcus aureus (MRSA) type). There was no statistical difference in male-to-female ratio, age, history of hospitalization, anemia, birth asphyxia, peripheral leukocyte counts, C-reactive protein on admission, and sequelae between groups. Univariate analyses indicated a significant difference in the incidence of septic arthritis (SA) combined with osteomyelitis (OM) (88.9% vs 37.5%), congenital deformities (44.4% vs 0%), and mean duration of symptoms (2.83 days vs 9.21 days) in comparisons between groups A and B. Conclusion: Staphylococcus aureus is the main pathogenic bacteria in BJI cases complicated with sepsis in neonates and young infants. Among infants younger than 3 months diagnosed with BJI, those with concurrent SA and OM, MRSA infection, or congenital deformities are more likely to develop sepsis.

Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1alpha After Treatment: A Cell Regulation Study / Observación del Efecto Clínico de Apatinib Combinado con 131I para el Cáncer de Tiroides Diferenciado Resistente al Yodo Radiactivo y Análisis de Importancia Pronóstica de la Proteína Inflamatoria 1alfa de Macrófagos Después del Tratamiento: Un Estudio de Regulación Celular

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.

The value of high-throughput sequencing data reanalysis in identifying ERBB2 amplification in colorectal cancer patients / 复旦学报（医学版）

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

Prevalence and associated factors of screening positive myopia among elementary and middle school students in Guangdong / 中国学校卫生

Objective@#The study aims to analyze the prevalence and associated factors of myopia among 4 to 9 grade students in Guangdong Province in 2022, so as to provide a scientific basis for targeted intervention measures for myopia in children and adolescents.@*Methods@#From September to October 2022, stratified cluster random sampling was used to select 29 095 of 4 to 9 grade students from Guangzhou, Jiangmen, and Meizhou in Guangdong Province for myopia screening and questionnaire surveys. The Chisquare test was applied to compare the differences between groups, and multivariable Logistic stepwise regression analysis was used to analyze factors associated with myopia.@*Results@#The myopia detection rate of 4 to 9 grade students was 61.7%, with detection rates of 51.5% for 4 to 6 grade primary school students and 71.95% for 7 to 9 grade junior high school students. Multivariable Logistic regression analysis showed that higher myopia rates were detected among girls (OR=1.39, 95%CI=1.30-1.49), students with one (OR=1.82, 95%CI=1.69-1.96) or both parents having myopia (OR=2.86, 95%CI=2.56-3.18), and indoor sedentary time >6 h(OR=1.28, 95%CI=1.17-1.39) in the 4 to 6 grade. Lower myopia rates were detected in the county (OR=0.92, 95%CI=0.86-0.99) and outdoors at recess activities (OR=0.88, 95%CI=0.81-0.95). Meanwhile, higher myopia rates were detected among girls (OR=1.84, 95%CI=1.69-1.99), students with one (OR=1.87, 95%CI=1.71-2.04) or both parents having myopia (OR=3.03, 95%CI=2.63-3.50), and indoor sedentary time >6 h/d (OR=1.11, 95%CI=1.01-1.23) in the 7 to 9 grade. Lower myopia rates were detected in the county (OR=0.74, 95%CI=0.68-0.80), outdoors at recess activities (OR=0.83, 95%CI=0.76-0.91), and outdoor activity time ≥2 h/d(OR=0.87, 95%CI=0.80-0.95)(P<0.05).@*Conclusions@#The detection rate of myopia among 4 to 9 grade students in Guangdong Province is relatively high. Place of recess activities, daily outdoor activity and indoor sedentary duration are associated with myopia. Therefore, targeted intervention measures should be adopted, such as appropriately increasing outdoor activity to reduce the occurrence of myopia among primary and middle school students.

Alternative Biological Material for Tissue Engineering of the Vagina: Porcine-Derived Acellular Vaginal Matrix

BACKGROUND@#Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. @*METHODS@#In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. @*RESULTS@#Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and a-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of b-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the b-catenin/cMyc/cyclin D1 pathway. @*CONCLUSION@#This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

Distribution and comparison of warfarin drug-gene polymorphism in Han children from Beijing area / 中国药房

OBJECTIVE To analyze the distribution characteristics of warfarin drug-gene polymorphism in Han children from Beijing area. METHODS Data of nine warfarin drug-gene loci about VKORC1 rs9923231， CYP2C9 rs1799853*2 and rs1057910*3， CYP4F2 rs2108622， APOE rs429358 and rs7412， ABCB1 rs1045642， EPHX1 rs1051740 and rs2234922 were collected from dept. of cardiovascular medicine， Children’s Hospital Affiliated to Capital Institute of Pediatrics from March 2019 to March 2023， and the population data reported in domestic and foreign literature were compared. RESULTS In Beijing area， the frequency of APOE rs429358 mutant genotype was higher in males （19.8%） than in females （13.5%）（P＜0.05）. VKORC1 rs9923231 was dominated by homozygous mutant genotype （83.3%）， which was consistent with children in Japan （82.2%）， and higher than that of predominantly Caucasian children in the UK， Sweden， the United States， and Germany （10.4%-18.3%）（P＜ 0.05）； CYP2C9 was dominated by *1/*1 type （91.9%）， which was consistent with children in Japan （94.6%）， and higher than that of predominantly Caucasian children in the UK， Sweden， the United States， and Germany （66.1%-73.4%）（P＜0.05）. The frequency of EPHX1 rs1051740 mutant genotype was higher in adults （78.5%） than in children （63.5%）（P＜0.05）. CONCLUSIONS More mutations of VKORC1 rs9923231 and ABCB1 rs1045642 are found in Han children from Beijing area. The distribution of warfarin drug-gene polymorphisms in Han children from Beijing area is different among different genders， as well as compared with other countries， and Chinese Han adults. Therefore， caution should be exercised when using the reported data.

Distribution characteristics of pathogenic bacteria in hospitalized HIV/AIDS patients with wound infection in Yunnan / 中国热带医学

@#Abstract: Objective　To analyze the distribution characteristics of the main pathogens of HIV/AIDS patients with wound infections and provide basis for clinical diagnosis and treatment. Methods　The clinical data of 294 patients with positive secretions or pus specimens from 2016 to 2020 were analyzed retrospectively. Results　A total of 357 strains of pathogenic bacteria were isolated from 294 cases, of which 123 strains of Gram-negative bacilli (G-b), accounting for 34.5%, were mainly Escherichia coli (15.4%), Klebsiella pneumoniae (3.9%), and Pseudomonas aeruginosa (3.6%); Gram-positive bacilli (G+b) 14 strains, accounting for 3.9%; 108 Gram-positive cocci (G+c), accounting for 30.3%, of which 44 strains were coagulase-positive Staphylococcus aureus (12.3%), Coagulase-negative staphylococci were mainly Staphylococcus epidermidis (4.2%) and Staphylococcus hemolyticus (2.8%); 37 strains of fungi, accounting for 10.4%, were mainly Candida albicans (5.9%); 75 strains of Mycobacterium, accounting for 21.0%, including 41 strains of Mycobacterium tuberculosis (11.5%) and 34 strains of non-tuberculosis mycobacteria (9.5%). 52 of the 294 HIV/AIDS patients had mixed infections, accounting for 17.7%. There was significant difference in the distribution of G+c, G-b, mycobacteria and mixed infection among different specimen sources (P<0.05), and there was significant difference in the distribution of mycobacteria among different CD4+T lymphocyte counts (P<0.05). There was significant difference in the level of CD4+T lymphocytes between patients of different ages (P<0.05), and there was significant difference in the level of CD4+T lymphocytes from postoperative incision and other parts (P<0.05). Conclusions　Patients with HIV/AIDS are prone to combined wound infections with various pathogenic bacteria. We should strengthen the research on wound infection in HIV/AIDS patients, and timely send patients with a low number of CD4+T lymphocytes for secretion or pus culture, so as to carry out targeted treatment and improve the prognosis of patients.

Causes of False-Positive Results in 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT Imaging / 中国医学科学院学报

Objective To investigate the causes of false-positive results in the 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) PET/CT imaging. Methods The imaging data of 547 patients undergoing 68Ga-FAPI-04 PET/CT examination in the Department of Nuclear Medicine of the Affiliated Hospital of Southwest Medical University from September 2020 to May 2021 were retrospectively collected.Two experienced nuclear medicine diagnostic physicians analyzed the clinical data,relevant imaging examinations,laboratory examinations,pathological results and follow-up results of the patients with false-positive results. Results The 68Ga-FAPI-04 PET/CT imaging of 547 patients showed false-positive results in 99 (18.1%) patients,including 56 males and 43 females.The postoperative pathological examination confirmed false-positive results in 13 patients,including 1 patient of thyroiditis,2 patients of pulmonary tuberculosis,1 patient of bone tuberculosis,2 patients of pulmonary inflammatory pseudotumor,1 patient of pulmonary sarcoidosis,1 patient of pulmonary benign fibroma,1 patient of organic pneumonia,2 patients of renal angiomyolipoma,1 patient of mass pancreatitis,and 1 patient of pancreatic mucinous cystadenoma.The medical history,relevant imaging examination,and long-term follow-up confirmed false-positive results in 86 patients.Specifically,the false-positive uptake in the neck,chest,abdomen,bone joint,and skin occurred in 8 (9.3%),13 (15.1%),5 (5.8%),57 (66.3%),and 3 (3.5%) patients,respectively.Inflammation-related uptake appeared in 83 (83.8%) patients with false-positive imaging results,of which arthritis (23 patients) and osteophyte (29 patients) were the most common.Sixteen (16.2%) patients showed the false-positive uptake related to fibroblasts. Conclusion 68Ga-FAPI-04 PET/CT imaging will show non-malignant tumor false-positive results,which are mainly associated with inflammation and fibroblasts.

Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry / 药物分析学报

Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca2+,reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca2+overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.

Antitussive Effect of Shegan Zhike Capsule and Its Effect on RARs Receptor,HA and 5-HT / 世界科学技术-中医药现代化

Objective To explore the antitussive action site and potential mechanism of Shegan Zhike Capsule.Methods The mouse cough model induced by concentrated ammonia was used to observe the dose effect relationship of the antitussive effect of Shegan Zhike capsule.The central antitussive effect of Shegan Zhike capsule was observed by using the cough model induced by electrical stimulation of superior laryngeal nerve in guinea pigs.The peripheral antitussive effect of Shegan Zhike capsule was observed by using the cough model of capsaicin desensitized guinea pigs induced by mechanical stimulation.The model of chronic bronchitis in guinea pigs was established by smoking,and the effects of Shegan Zhike Capsule on vasoactive amines histamine(HA)and 5-hydroxytryptamine(5-HT)were observed.Results Shegan Zhike capsule could significantly reduce the number of coughs in mice at the doses of 43.00,86.00 and 172.00 mg extract·kg-1(P<0.05 or P<0.01).The low-dose group,the middle-dose group,and the high-dose group of Shegan Zhike Capsule did not significantly inhibit the cough inducing effect of electrical stimulation of guinea pig superior laryngeal nerve at 30 min and 60 min after administration.Shegan Zhike capsule could significantly inhibit the cough of capsaicin desensitized guinea pigs caused by mechanical stimulation in the low dose group at 60 min,the medium dose group at 30 min and the high dose group at 30 min and 60 min(P<0.05).Compared with the model control group,the content of HA in serum of guinea pigs in low,medium and high dose groups of Shegan Zhike capsule decreased significantly(P<0.05 or P<0.01).The content of serum 5-HT in the high dose group decreased significantly(P<0.05).Conclusion The antitussive effect of Shegan Zhike Capsule was not in the center,and its peripheral antitussive effect was related to the inhibition of RARs receptors,and vasoactive amines such as HA and 5-HT were also involved.

The expression and prognostic value of vascular endothelial growth factor receptor-2 and microRNA-378 in cervical cancer patients / 中国医师进修杂志

Objective:To investigate the expression and prognostic value of vascular endothelial growth factor receptor-2 (VEGFR-2) and microRNA-378 (miR-378) in cervical cancer patients.Methods:A total of 105 patients with cervical cancer diagnosed and treated in Shaoxing Central Hospital from September 2019 to September 2021 were selected. Cervical cancer tissues and adjacent normal tissues (at least 2 cm distant from the tumor tissue) were collected, respectively. Immunohistochemistry was used to detect the expression of VEGFR-2, and reverse transcription-polymerase chain reaction(RT-PCR) method was used to detect the expression of miR-378 in tissues. The positive expression rate of VEGFR-2 and the expression of miR-378 in cervical cancer tissues and adjacent normal tissues were compared, and the relationship of VEGFR-2 and miR-378 with pathological parameters and prognosis of cervical cancer was analyzed. Kaplan-Meier method was used to plot the survival curve, and univariate and multivariate Cox regression analysis was used to analyze the risk factors affecting the prognosis of patients with cervical cancer.Results:The positive expression rate of VEGFR-2 in the cervical cancer tissues was higher than that in the adjacent normal tissues: 86.67% (91/105) vs. 62.86%(66/105); the expression level of miR-378 in the cervical cancer tissues was higher than that in the adjacent normal tissues: 1.46 ± 0.35 vs. 0.68 ± 0.12, there were statistical differences ( χ2 = 15.77, t = 21.60, P<0.05). The positive expression rate of VEGFR-2 and the expression level of miR-378 in cervical cancer tissues had no relationship with age, pathological type and tumor size ( P>0.05), but with the increase of clinical stage, the decrease of differentiation and the occurrence of lymph node metastasis, the positive expression rate of VEGFR-2 and the expression level of miR-378 increased ( P<0.05). Survival curve was drawn by Kaplan-Meier method, the results showed that the overall survival time (OS) of patients with miR-378 high expression was significantly lower than patients with miR-378 low expression, and the OS of patients with VEGFR-2 positive expression was significantly lower than patients with VEGFR-2 negative expression, there were statistical differences ( P<0.05). Univariate and multivariate Cox regression analysis confirmed that clinical stage Ⅲ-Ⅳ, low differentiation, lymph node metastasis, positive expression of VEGFR-2 and high expression of miR-378 were independent risk factors for poor prognosis of cervical cancer patients ( P<0.05). Conclusions:The positive expression of VEFGR-2 and high expression of miR-378 in cervical cancer tissues are related to clinical stage, differentiation degree and lymph node metastasis. At the same time, the positive expression of VEGFR-2 and high expression of miR-378 will affect the survival of patients with cervical cancer, which is a risk factor for the poor prognosis of cervical cancer.

Left Ventricle Longitudinal Strain Parameters Are Effective for Differentiating Cardiac Amyloidosis from Primary Hypertensive Left Ventricular Hypertrophy / 中山大学学报(医学科学版)

ObjectiveTo clarify the value of the left ventricular longitudinal strain（LVLS）parameters in patients with cardiac amyloidosis （CA） and primary hypertension with left ventricular hypertrophy （HLVH）. MethodsForty-one patients confirmed with CA were selected and assigned to CA with hypertension group （n =14） and pure CA group （n=27） based on the initial diagnosis with or without hypertension. Twenty patients with primary hypertension-induced left ventricular hypertrophy （HLVH group） and twenty healthy controls were also selected， matching for gender， age， and body surface area. Clinical data， conventional echocardiography parameters were collected and LVLS parameters were measured. Within-group variations were compared among the four groups， and pairwise comparisons were conducted between groups. The sensitivity and specificity of each parameter in predicting CA were judged by the receiver operator characteristic （ROC） curvy in CA and HLVH patients with left ventricular ejection fraction （LVEF） preserved. ResultsAmong the conventional echocardiography parameters， LVEF and left ventricular end-diastolic diameter （LVEDD） were lower in the CA with hypertension group and pure CA group compared with the higher values in the HLVH group and control group. Whereas， left ventricular posterior wall thickness （LVPWT）， relative wall thickness （RWT）， and average E/e' were higher in the two CA groups compared with the HLVH group （all P＜0.05）.Among the LVLS parameters， Global longitudinal strain （GLS） was the worst in the CA with hypertension group so as pure CA group， modest in the HLVH group， and highest in the control group. On the contrary， relative longitudinal strain and ejection fraction strain ratio （EFSR） were the highest in the CA with hypertension group so as to pure CA group， modest in the HLVH group， and lowest in the control group （all P＜0.05）. ROC analysis showed that when LVEF was preserved， the absolute value of GLS less than 14.35% and EFSR higher than 4.28 could effectively distinguish CA from HLVH （all AUCs＞0.9，all P＜0.05）； meanwhile GLS showed high sensitivity（100%） and EFSR showed great specificity（95%）. There were not statistically significance in any parameter between CA with hypertension group and pure CA group（all P＞0.05）. ConclusionWhether CA was complicated with hypertension or not， there were statistically significance among routine echocardiography and LVLS parameters compared with HLVH. In particular， GLS and EFSR are accurate in predicting CA in patients with myocardial hypertrophy and preserved LVEF.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Risk Factors for in-Hospital Mortality in Patients with Takotsubo Syndrome / 中山大学学报(医学科学版)

ObjectiveTo analyze the risk factors for in-hospital mortality in patients with Takotsubo Syndrome （TTS）. MethodsHospitalization data of consecutive patients with TTS from February 2009 to January 2022 were retrospectively collected and analyzed. Patients were divided into survival group and death group according to outcomes. The basic clinical information， triggering factors， laboratory examinations， electrocardiogram， echocardiography， complications and treatments of the two groups were compared. Univariable logistic regression analysis was used to screen the possible risk factors for in-hospital mortality in TTS patients， and multivariable logistic regression analysis was used to determine the independent risk factors for in-hospital mortality in TTS patients. ResultsA total of 62 TTS patients were included in our study， including 21 males （33.9%）， 41 females （66.1%） and 26 postmenopausal women （41.9%）， with the mean age of （55.6±16.2） years， and physical triggers were found in 50 patients （80.6%）. 17 patients （27.4%） died while 45 patients （72.6%） survived during hospitalization. The death group had lower systolic blood pressure and left ventricular ejection fraction （LVEF）， higher incidence rate of syncope， higher level of N-terminal pro-B natriuretic peptide （NT-proBNP） and hypersensitive troponin T （hs TnT） when compared with survival group （all P value <0.05）. As for the triggering factors， the proportion of TTS induced by neurologic disorders in the death group was higher than that in the survival group （P<0.05）. The death group had higher rates of cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， and respiratory failure （all P value <0.05）. Compared with the survival group， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were higher in the death group （all P value <0.05）. Univariable logistic regression analysis suggested that syncope， NT-proBNP， LVEF， neurologic disorders， cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， respiratory failure， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were potential risk factors for in-hospital mortality in TTS patients （all P value <0.05）. Multivariable logistic regression analysis indicated that neurologic disorders ［OR（95%CI）=5.651（1.195，26.715），P=0.029］， atrial fibrillation ［OR（95%CI）=6.217（1.276，30.298）， P=0.024）］ and therapeutic norepinephrin ［OR（95%CI）=8.847（1.912，40.949）， P=0.005］ were independent risk factors for in-hospital mortality in TTS patients. ConclusionsNeurologic disorders， atrial fibrillation and therapeutic norepinephrin are independent risk factors for in-hospital mortality in patients with Takotsubo Syndrome. Clinically， attention should be paid to the prevention and treatment of neurologic disorders and atrial fibrillation； norepinephrine should be carefully used in patients with diagnosed TTS complicated with hemodynamic instability.

Pitfalls in clinical genetics

With the increasing availability of genetic tests, more doctors are offering and ordering such tests for their patients. Ordering a genetic test appears to be a simple process of filling in paperwork, drawing 3 mL of blood in an ethylenediaminetetraacetic acid tube and receiving a test report. This is identical to sending off a full blood count. However, it is far more complex than that. There are many potential pitfalls, as shown by the increasing number of complaints and lawsuits filed against doctors and allied health staff. Furthermore, clinical genetics involves more than just ordering tests; in fact, focusing on genetic tests alone is a potential pitfall. In this review, we discuss the common pitfalls in clinical genetics and how doctors can avoid these pitfalls to ensure patient safety and to safeguard their practice.

Diagnostic Efficacy of 68Ga-Labeled Prostate-Specific Membrane Antigen and 18F-Labeled Sodium Fluoride PET/CT in Prostate Cancer With Bone Metastasis / 中国医学科学院学报

Objective To compare the efficiency of 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) and 18F-labeled sodium fluoride (18F-NaF) PET/CT in the diagnosis of bone metastasis in the patients with prostate cancer.Methods The prostate cancer patients suspected of bone metastasis who underwent 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT from January 2018 to January 2021 were included in this study.The number of lesions,maximum standardized uptake value (SUVmax),and tumor-to-background (T/B) ratio were compared between the two methods.Results 18F-NaF PET/CT detected more metastases than 68Ga-PSMA-11 PET/CT (310 vs.264,P<0.001).The median SUVmax[23.2 (16.4,33.4) vs.4.1 (2.5,5.6)] and median T/B ratio[7.0 (4.9,9.9) vs.6.7 (3.7,9.6)] of 18F-NaF PET/CT were higher than those of 68Ga-PSMA-11 PET/CT (all P<0.001).With the number of lesions as the indicator,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of 18F-NaF PET/CT were 100.0%,92.0%,92.0%,98.7%,and 100.0% respectively,and those of 68Ga-PSMA-11 PET/CT were 85.2%,94.0%,79.2%,98.9%,and 50.5%,respectively.Conclusion 18F-NaF PET/CT is superior to 68Ga-PSMA-11 PET/CT in the detection of bone metastases of prostate cancer.

Palliative Care for End-Stage Renal Disease:A Case Report and Literature Review / 中国医学科学院学报

Since end-stage renal disease leads to a variety of problems such as disability,reduced quality of life,and mental and psychological disorders,it has become a serious public health problem around the globe.Renal palliative care integrates palliative care philosophy in the care for patients with end-stage renal disease.As a planned,comprehensive,patient-centered care,renal palliative care focuses on the patient's symptoms and needs,aiming to reduce the suffering throughout the course of the disease,including but not limited to end-of-life care.This study reports the palliative care practice for a patient on maintenance dialysis in the Blood Purification Center of Peking Union Medical College Hospital and reviews the present situation of palliative care in end-stage renal disease.

An experimental study of acute toxicity and pharmacology of fermented Platycodonis Radix / 中国中药杂志

This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 μL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.

Immunophenotypic and Clinical Characteristics of SET-CAN Fusion Gene Positive Acute Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the flow immunophenotype and clinical characteristics of leukemia patients with positive SET-CAN fusion gene.@*METHODS@#A total of 7 newly diagnosed acute leukemia patients with SET-CAN fusion gene admitted to Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from February 2016 to February 2020 were collected. Multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of SET-CAN fusion gene. The immunophenotype was detected by four-color flow cytometry. The case information of 17 literatures published at home and abroad was extracted for statistical analysis.@*RESULTS@#Among the 7 patients, 2 cases were diagnosed as mixed phenotype acute leukemia (MPAL), 2 cases as acute myeloid leukemia (AML), and 3 cases as T-acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Leukemia cells in bone marrow specimens of all cases expressed or partially expressed CD34, CD33 and CD7. CD5 and cytoplasmic CD3 were expressed in 5 patients except 2 patients diagnosed with AML. Bone marrow and lymph node specimens were both detected in 2 patients, and the immunophenotypes of the two specimens were not completely consistent, with differences in lineage or maturity related markers. Two patients with MPAL showed differentiated response to treatment. One AML patient gave up treatment, and another AML patient with FLT3-ITD gene mutation had a poor prognosis. All three T-ALL/LBL patients maintained a long duration of remission after induced remission, and one case underwent allogeneic hematopoietic stem cell transplantation.@*CONCLUSIONS@#There are common characteristics of immunophenotype in patients with positive SET-CAN fusion gene. Differential expression of immunophenotype in samples from different parts is observed in some cases. The prognosis of these diseases varies.

Animal study on left bundle branch current of injury and anatomic location of leads in His-purkinje conduction system pacing / 中华心血管病杂志

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.