Toward precision medicine: Prospect of asthma diagnosis related technology / 中国综合临床

Bronchial asthma is a heterogeneous disease characterized by chronic airway inflammation. In recent years, the diagnosis and treatment of asthma tend to be precision medicine, and the individualized treatment of asthma is mainly based on individualized diagnosis. However, the pathogenesis of asthma is complex and the clinical phenotype is different, and its high heterogeneity also brings great challenges to realize individualized diagnosis and treatment, Diagnosis and evaluation based on multi-dimensional and multi-means is an important practical development direction.

Effect of follicular unit transplantation on hair loss of the head and face / 中华医学美学美容杂志

Objective:To explore the therapeutic effect of follicular unit excision on the hair loss of head and face.Methods:From September 2019 to September 2020, 24 patients with hair loss of head and face who were treated in the plastic and aesthetic surgery of Henan Provincial People′s Hospital were used as the research objects. According to the characteristics of the patients′ hair loss areas, hair follicles were obtained from healthy scalp by using the follicular unit excision. After the operation, the survival of transplanted hair follicles, the direction of hair growth, and patient satisfaction were followed up to observe the repair effect.Results:Fifteen cases of partial scalp loss hair, 8 cases of partial loss of eyelashes, and 1 case of partial lack of eyelashes, after hair transplantation, the hair growth in the operation area was good, the direction was basically the same as that of the original hair, and the cosmetic effect of hair coverage was satisfactory. After 9-18 months of follow-up, the hair survived well.Conclusions:The use of follicular unit excision technology to repair the hair loss on the head and face is an ideal treatment method, with less trauma, quick recovery, and satisfactory cosmetic effects.

Association between perfluorinated alkyl substances and depression / 环境与职业医学

Background Perfluorinated alkyl substances (PFAS) are a class of synthetic organic fluorides, which have adverse health effects on brain function, and limited research has been conducted on their effects on depression. Objective To assess potential correlation between serum PFAS and depression. Methods Using the 2015—2016 and 2017—2018 National Health and Nutrition Examination Survey (NHANES) datasets, 2626 subjects with complete relevant information in people ≥20 years old were selected. Logistic regression and restricted cubic splines were used to analyze the association and dose-response relationship between serum PFAS concentration and depression. Subgroup analysis was performed on sex, age, race, education level, marital status, family income to poverty ratio, moderate exercise, body mass index, and drinking status. Results Among the 2626 subjects, there were 666 patients (25.4%) with mild or above depression. After adjusting for race, education level, marital status, body mass index, moderate exercise, drinking history, cotinine, and other types of PFAS, serum perfluorooctane sulfonate (PFOS) was positively associated with the risk of depression (OR=1.85, 95%CI: 1.14, 3.02), and showed a nonlinear dose-response relationship (χ2=6.37, Pnonlinear=0.012). Perfluorononanoic acid (PFNA) was inversely associated with the risk of depression (OR=0.23, 95%CI: 0.14, 0.39), and showed a linear dose-response relationship (Ptrend<0.001, χ2=35.13, Poverall<0.001). After subgroup analysis, it was found that males, 20-39 year-olds and 40-64 year-olds were more sensitive to PFNA exposure (OR=0.15, 95%CI: 0.06, 0.37; OR=0.16, 95%CI: 0.06, 0.40; OR=0.18, 95%CI: 0.08, 0.39). PFOS only showed a statistically significant health effect in people aged 20-39 years (OR=3.00, 95%CI: 1.14, 7.94). In addition, among subgroups of non-Hispanic blacks, cohabitants, current drinkers, high school graduates, and obese patients, exposure to PFAS was significantly associated with the risk of depression. Conclusion PFOS exposure may be associated with increased levels of depression, whereas PFNA exposure may be protective.

Detection of IgG protein in human urine based on vertical flow paper microfluidic chip / 生物工程学报

The kidney is the body's most important organ and the protein components in urine could be detected for diagnosing certain diseases. The amount of IgG protein in urine could be used to determine the degree of kidney function damage. IgG protein in human urine was detected by vertical flow paper-based microfluidic chip, double-antibody sandwich immunoreaction, and cell phone image processing. The results showed that using an IgG antibody concentration of 500 μg/mL and a gold standard antibody concentration of 100 μg/mL, the image signal showed a good linear relationship in the range of IgG concentration of 0.2-3.2 μg/mL, with R2=0.973 3 achieved. A complete set of detection devices were designed and the detection method showed good non-specificity.

Effect of continuous shaping and compression in the comprehensive treatment of auricle keloids / 中华医学美学美容杂志

Objective:To observe the effect of continuous shaping and compression in the comprehensive treatment of auricle keloids.Methods:From June 2018 to April 2020, 40 patients with auricular keloids (53 ears) admitted to the Plastic Surgery Department of Henan Provincial People＇s Hospital were divided into surgical injection group (20 cases, 27 ears) and surgical injection compression group (20 cases, 26 ears) according to the treatment method. The patients were followed up for more than 18 months continuously; the clinical efficacy, satisfaction with auricle morphology, and the occurrence of infection and recurrence were observed in the two groups.Results:The effective rate of surgical injection compression group (24 ears, 92.31%) was higher than that of surgical injection group (16 ears, 59.26%), and the difference was statistically significant (χ 2=5.121, P<0.05). The Vancouver scar scale (VSS) scores of the two groups at 6 months and 12 months after treatment were significantly lower than that before treatment, and the VSS score of the surgical injection compression group was lower than that of the surgical injection group, the difference was also statistically significant ( P<0.05). The satisfactory rate of the surgical injection compression group (22 ears, 84.62%) was higher than that of the surgical injection group (13 ears, 48.15%), and the difference was statistically significant (χ 2=4.048, P<0.05). The recurrence rate of the surgical injection compression group was significantly lower than that of the surgical injection group (χ 2=5.779, P<0.05); there was no significant difference in the infection rate between the two groups of patients after treatment (χ 2=0.001, P>0.05). Conclusions:Surgical resection of auricle keloids combined with local injection of corticosteroids and local shaping and compression can significantly improve the clinical efficacy, maintain the shape of the auricle, and the therapeutic effect is satisfactory.

Isothermal amplification technology based on microfluidic chip / 生物工程学报

Polymerase chain reaction (PCR) is the gold standard for nucleic acid amplification in molecular diagnostics. The PCR includes multiple reaction stages (denaturation, annealing, and extension), and a complicated thermalcycler is required to repetitively provide different temperatures for different stages for 30-40 cycles within at least 1-2 hours. Due to the complicated devices and the long amplification time, it is difficult to adopt conventional PCR in point-of-care testing (POCT). Comparing to conventional PCR, isothermal amplification is able to provide a much faster and more convenient nucleic acid detection because of highly efficient amplification at a constant reaction temperature provided by a simple heating device. When isothermal amplification is combined with microfluidics, a more competent platform for POCT can be established. For example, various diagnosis devices based on isothermal amplification have been used to rapidly and conveniently detect SARS-CoV-2 viruses. This review summarized the recent development and applications of the microfluidics-based isothermal amplification. First, different typical isothermal amplification methods and related detection methods have been introduced. Subsequently, different types of microfluidic systems with isothermal amplification were discussed based on their characteristics, for example, functionality, system structure, flow control, and operation principles. Furthermore, detection of pathogens (e.g. SARS-CoV-2 viruses) based on isothermal amplification was introduced. Finally, the combination of isothermal amplification with other new technologies, e.g. CRISPR, has been introduced as well.

Whole-body PET tracking of a d-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors

Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [64Cu]DPA and investigated the tumor engagement of [64Cu/68Ga]DPA in mouse models. Our results revealed that intact [64Cu/68Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [64Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.

Environmental exposure to e-cigarettes among adolescents and its preventive countermeasures / 环境与职业医学

In recent years, with the vigorous marketing of e-cigarette manufacturers, e-cigarettes have become a popular tobacco product for adolescents. The problem of e-cigarette environmental exposure among adolescents is also getting worse and its associated adverse impacts cannot be ignored. However, domestic research on the environmental exposure to e-cigarettes among youth is insufficient, and experience on e-cigarette regulation is also limited. This review first briefly introduced the definition and sources of e-cigarette environment exposure, then focused on the differences of e-cigarette environmental exposure among adolescents with different characteristics to identify possible influencing factors, as well as the impacts of e-cigarette environmental exposure on adolescents, and finally summarized international countermeasures to prevent e-cigarette environmental exposure in adolescents, aiming to provide directional guidance for China to conduct e-cigarette control activities among adolescents.

Research progress of neutrophil extracellular traps in the pathogenesis of ischemic stroke / 中华神经科杂志

Ischemic stroke is one of the primary causes of death and disability worldwide. Neutrophils can release depolymerized chromatin and proteins to form neutrophil extracellular traps (NETs) and participate in intravascular thrombus formation. In recent years, NETs have received increasing attention in the study of acute ischemic stroke. The results indicate that NETs play an important role in the pathogenesis of acute ischemic stroke. This review presented recent advances in the study of NETs in acute ischemic stroke.

Comparison of preparation for 177Lu-labeled radiopharmaceutical and its preliminary clinical application / 中华核医学与分子影像杂志

Objective:To investigate the preparation methods and quality control of 177Lu-labeled radiopharmaceuticals, and conduct preliminary clinical application research. Methods:177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)- D-Phe1-Tyr3-octreotide (TOC) and 177Lu-prostate specific membrane antigen (PSMA)-I&T were labeled by manual labeling and automatic labeling, respectively. Factors such as the amount of precursor and nuclide, reaction temperature, pH value, reaction time, labeling yield and specific activity were investigated. Quality control of the products were carried out, such as clarity, pH value, sterility, bacterial endotoxin and stability in vitro. 177Lu-PSMA-I&T was applied to the treatment of prostate cancer patients, and the efficacy was evaluated by SPECT/CT imaging. Paired t test was used to analyze the data. Results:The amount of precursor and nuclide, reaction temperature, pH value and reaction time of the two methods were basically the same, both with high yield and specific activity. The yield of 177Lu-DOTA-TOC automatic labeling was significantly higher than that of manual labeling (99.2±0.4)% vs (95.3±1.5)% ( t=7.17, P<0.001), and the specific activity were (91.6±13.7) vs (89.1±13.2) GBq/μmol. The yield of 177Lu-PSMA-I&T automatic labeling was also significantly higher than that of manual labeling (99.6±0.3)% vs (95.7±1.3)% ( t=8.24, P<0.001), and the specific activity were (96.1±14.3) vs (93.2±13.8) GBq/μmol. The labeled products were colorless clear solution with pH value of 6.5-7.0. The sterility and bacterial endotoxin met the requirements. The radiochemical purity of the labeled products was more than 95% after 48 h, which showed good stability. The clinical application of 177Lu-PSMA-I&T in patients with prostate cancer showed that both primary and metastatic lesions had good uptake. Conclusions:The labeling of 177Lu radiopharmaceuticals is simple and has high yield and stability. The application of automatic labeling can simplify the process, improve the yield and reduce irradiation.

Effect of endogenous nitric oxide on superoxide dismutase-1 activity and apoptosis of vascular endothelial cells / 中华实用儿科临床杂志

Objective:To investigate the regulatory effects of endogenous nitric oxide (NO) on the activity of superoxide dismutase-1 (SOD1) and apoptosis of human umbilical vein endothelial cells (HUVECs).Methods:HUVECs were taken as the research object.The endothelial NO synthase (eNOS) short hairpin RNA(shRNA) lentivirus was employed to transfect HUVECs to knock down eNOS.HUVECs were divided in 4 groups: the scramble group, the eNOS shRNA group, the eNOS shRNA + sodium nitroprusside(SNP) group and the eNOS shRNA+ SNP+ tris (2-carboxyethyl) phosphine hydrochloride (TCEP) group.The protein expressions of eNOS and SOD1 dimer/monomer in cells were detected by western blot.The activity of SOD was detected by the enzyme-linked immunosorbent assay.The NO content in cells was detected with NO fluorescence probe.The level of superoxide anion in HUVECs was detected with dihydropyridine (DHE). The terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay was adopted to detect the apoptosis of HUVECs in situ.Results:Compared with the scramble group, the endogenous NO content (2.690±0.420 vs.15.029±2.193, P<0.01), eNOS protein expression (1.000±0.778 vs.3.141±0.199, P<0.01), SOD1 dimer/monomer ratio (4.6±1.0 vs.7.6±2.0, P<0.05) and SOD activity [(0.432±0.254) Carmen′s unit/10 4 cell vs.(1.000±0.116) Carmen′s unit/10 4 cell, P<0.01] were significantly decreased, while the level of intracellular superoxide anion (11.180±1.560 vs.6.146±1.007, P<0.01) and HUVECs apoptosis [75.0 (55.0, 100.0)% vs.0 (0, 0)%, P<0.01] were significantly increased in the eNOS shRNA group.Compared with the eNOS shRNA group, the content of endogenous NO (16.705±0.116 vs.2.690±0.420, P<0.01), the ratio of SOD1 dimer/monomer (7.3±2.0 vs.4.6±1.0, P<0.05) and the activity of SOD [(0.737±0.060) Carmen′s unit/10 4 cell vs.(0.432±0.254) Carmen′s unit/10 4 cell, P<0.05] were significantly increased, while the level of superoxide anion (6.897±1.648 vs.11.180±1.560, P<0.01) and the HUVECs apoptosis [0 (0, 0)% vs.75.0 (55.0, 100.0)%, P<0.01] were significantly decreased in the eNOS shRNA+ SNP group.Compared with the eNOS shRNA + SNP group, the ratio of SOD1 dimer/monomer (4.4±0.9 vs.7.3±2.0, P<0.05) and the activity of SOD [(0.214±0.084) Carmen′s unit/10 4 cell vs.(0.737±0.060) Carmen′s unit/10 4 cell, P<0.01] were significantly decreased, while the level of superoxide anion (10.917±1.552 vs.6.897±1.640, P<0.01) and the apoptosis level of HUVECs[63.6 (55.0, 90.0)% vs.0 (0, 0)%, P<0.01] were significantly increased in the eNOS shRNA+ SNP+ TCEP group.However, there was no significant difference in the NO content (16.112±0.926 vs.16.705±0.116, P>0.05). Conclusions:Endogenous NO could effectively antagonize the apoptosis of endothelial cells by increasing the cysteine-dependent SOD1 dimer/monomer ratio, enhancing SOD activity and inhibiting the accumulation of reactive oxygen species.

Skin recurrence after remission of primary nasopharyngeal myeloid sarcoma: report of one case and review of literature / 白血病·淋巴瘤

Objective:To improve the awareness of primary myeloid sarcoma.Methods:The clinical data of one primary myeloid sarcoma patient with first symptom involving nasopharynx who was admitted to the Second Affiliated Hospital of Anhui Medical University in June 2017 were retrospectively analyzed, and the related literature was reviewed.Results:The patient presented with nasal congestion with tinnitus; it took half a year for the myeloid sarcoma diagnosis to be clear with biopsy and immunohistochemical examinations for many times. The patient was treated with chemotherapy regimens for acute myeloid leukemia (AML). Isolated myeloid sarcoma relapsed with skin masses after remission for more than 2 years. Further improvement of the bone marrow-related examinations showed that the bone marrow was not involved, and it was still isolated myeloid sarcoma. The skin mass disappeared completely after the induction chemotherapy of AML. Six months after the recurrence, the patient was in stable condition and was still under follow-up treatment.Conclusions:The primary nasopharyngeal myeloid sarcoma lacks specificity and is easy to be misdiagnosed. The prognosis of isolated myeloid sarcoma is better than that of AML. Isolated recurrence after chemotherapy remission is rare, and usually progresses to the leukemia stage quickly. Early and correct diagnosis is very important for the prognosis, and clinicians should improve the awareness of primary myeloid sarcoma.

Effectiveness of systematic sex education for adolescent students from the perspective of sexual mental health / 中国学校卫生

Objective@#To conduct a comparative study on the specific effects of systematic sex education on adolescent students in terms of sexual cognition, sexual values, and sexual adaptation, and to provide the support for conducting a comprehensive education in middle schools.@*Methods@#A whole group sampling method was used to select 3 369 middle and high school students from six general and vocational middle schools in Sichuan Province, which were divided into systematic sex education schools and non systematic sex education schools, and a comparative study was conducted using the Adolescent Mental Health Scale.@*Results@#The results showed that the adolescent students who received systematic sex education were significantly different from those who did not receive systematic sex education in terms of sex related cognition (7.18±6.24, 5.65±7.40), sexual values(7.60±1.17，7.30±1.24), and sexual adjustment (11.49±1.29，11.10±1.41). All differed significantly ( t =5.95, 6.80,7.57, P <0.01). The students who received systematic education in junior middle school were higher than those who received non systematic education in sex related cognition, sexual values and sexual adaptation ( P <0.01). However, in senior high school, the differences in systematic education are only shown in sexual values control and self adaptation in sexual adjustment ( P <0.01). There were significant differences in sex related cognition, sexual values and sexual adjustment between male and female students who received systematic education and non systematic education ( P <0.01).@*Conclusion@#Systematic sex education is more beneficial to the psychosexual health of adolescent students than non systematic sex education in schools.

Efficacy of 177Lu-PSMA-I&T in the treatment of prostate cancer / 中华核医学与分子影像杂志

Objective:To evaluate the therapeutic effect of 177Lu-prostate specific membrane antigen (PSMA)-I&T on prostate cancer. Methods:The culture medium of 1.85, 18.50, 185.00, 555.00 and 925.00 MBq/L 177Lu-PSMA-I&T was added into LNCaP cells (200 μl/well, 5 experimental groups and 1 control group, 3 replicates in each group) for 24 h, and the cell viability in each group was detected. The culture medium of 3.7 MBq 177Lu-PSMA-I&T was added into LNCaP cells (1 experimental group, 1 control group, 3 replicates in each group) for 48 h to detect the changes of cell cycle. LNCaP cells (3 experimental groups and 1 control group, 3 replicates in each group) were added into the culture medium of 3.7, 19.5 and 37.0 MBq 177Lu-PSMA-I&T for 48 h to detect cell apoptosis. Tumor-bearing mice models were established (BALB/c-nu/nu nude mice, n=32). The changes of tumor volume and body mass of tumor-bearing mice were observed within 20 d after treatment. On the 7th day after treatment, tumor tissues of tumor-bearing mice were stained with HE staining and fluorescently stained with Ki-67 protein, and apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) assay. On the 20th day after treatment, pathological analysis was performed on the main viscera of the tumor-bearing mice. One-way analysis of variance, the least significant difference t test and paired t test were used to analyze the data. Results:Compared with the control group ((100.00±12.35)%), the cell survival rates were significantly decreased after 177Lu-PSMA-I&T intervention in 185.00, 555.00, 925.00 MBq/L groups ((57.56±6.35)%, (38.65±3.39)%, (27.95±4.48)%; F=78.91, t values: 8.312-14.106, all P<0.01). Cell survival rates were significantly reduced in 185.00 MBq/L group at different time points (24, 48 and 72 h; F=78.28, t values: 6.628-14.384, all P<0.01). The proportion of LNCaP cells in G2/M phase was increased from (12.36±0.28)% to (19.92±0.48)% ( t=17.180, P<0.01). The apoptosis rates of cells were significantly increased in 18.5 and 37.0 MBq groups ( F=71.86, t values: -6.138, -13.050, both P<0.05). The difference of relative tumor volume (RTV%) was statistically significant among 3.7, 14.8 and 29.6 MBq groups and control group (136.7±7.4, 59.2±23.8, 47.3±13.8 vs 240.3±3.7; F=78.20, t values: 7.549-13.345, all P<0.01). But there was no significant difference in body mass of tumor-bearing mice among groups. Compared with the control group, the positive rates of Ki-67 staining cells ((37.23±3.04)% vs (14.89±3.80)%, (5.60±1.83)%, (3.46±0.71)%) and TUNEL-fluorescein isothiocyanate (TUNEL-FITC) staining ((0.74±0.18)% vs (1.61±0.30)%, (3.19±0.44)%, (3.54±0.47)%) in tumor tissues of 3.7, 14.8 and 29.6 MBq groups were statistically significant ( F=103.91, t values: 10.429-15.762; F=38.66, t values: from -9.312 to -2.881, all P<0.01). Conclusions:177Lu-PSMA-I&T has a good therapeutic effect on prostate cancer, with no obvious therapeutic side effects. Therefore, 177Lu-PSMA-I&T is expected to be an ideal drug for treating prostate cancer.

Regional leptomeningeal collateral score on CT angiography predicts the outcome after endovascular therapy in patients with late window anterior circulation stroke / 国际脑血管病杂志

Objective:To investigate the predictive value of regional leptomeningeal collateral (rLMC) score on CT angiography (CTA) for the outcome after endovascular therapy in patients with late window anterior circulation stroke.Methods:Patients with acute anterior circulation large vessel occlusive stroke received endovascular treatment 6 to 24 h after onset in the Department of Neurology, the First Affiliated Hospital of Soochow University from January 2018 to July 2021 were enrolled retrospectively. At 3 months after onset, the outcome was evaluated according to the modified Rankin Scale. A score of ≤ 2 was defined as good outcome, and a score of >2 was defined as poor outcome. The clinical data, non-enhanced CT and CTA parameters of the patients were collected. Multivariate logistic analysis was used to determine the independent influencing factors of poor outcomes after endovascular treatment. Results:A total of 74 patients with acute anterior circulation large vessel occlusive stroke treated with endovascular treatment in the late window were enrolled. Their age was 64.41±12.98 years, 43 were males (58.1%). The baseline National Institutes of Health Stroke Scale (NIHSS) score was 13.18±5.22, and the median time from onset to puncture was 527.5 min. Fifty-three patients (71.6%) chose direct thrombectomy and 21 (28.4%) chose intravenous thrombolysis and bridging thrombectomy. Thirty-six patients (48.6%) had a good outcome and 38 (51.4%) had a poor outcome, including 4 (5.4%) died. Univariate analysis showed that there were significant differences in age, atrial fibrillation, fasting blood glucose, NIHSS score, Alberta Stroke Program Early CT Score (ASPECTS), rLMC score and clot burden score between the good outcome group and the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that higher ASPECTS (odds ratio 0.352, 95% confidence interval 0.157-0.791; P=0.012) and rLMC score (odds ratio 0.550, 95% confidence interval 0.329-0.919; P=0.022) were the independent predictors of good outcomes after endovascular therapy. Conclusion:ASPECTS and rLMC scores were the independent predictors of clinical outcomes after endovascular therapy in patients with late window anterior circulation large vessel occlusive stroke. It had certain guiding value for the decision-making of endovascular treatment in such patients.

Rapamycin may inhibit murine S180 sarcoma growth by regulating the pathways associated with autophagy and cancer stem cells

Objective: The objective of this study was to investigate the molecular mechanisms involved in rapamycin-induced inhibition of tumor growth. Materials and Methods: Murine S180 sarcoma cells were subcutaneously injected into mice, and the tumor-bearing mice were randomly divided into three groups (vehicle control, 2 mg/kg rapamycin, and 4 mg/kg rapamycin). The effect of rapamycin on tumor growth was determined by measuring tumor volume. Mammalian target of rapamycin (mTOR), Beclin1, ULK1, LC3, Notch1, CD133, and CD90 expressions was confirmed using confocal microscopy and Western blotting. Results: The tumor growth inhibition rates induced by high-dose and low-dose rapamycin were 48.8% and 30.1%, respectively. Beclin1 and ULK1 expressions and the LC3-II/LC3-I ratio in tumor tissues were altered by rapamycin, whereas mTOR, Notch1, CD133, and CD90 expressions were significantly inhibited by rapamycin in immunofluorescence assays. Western blotting also showed similar results. Conclusion: Tumor growth delay induced by rapamycin may be associated with the suppression of the cancer stem cell phenotype (Notch1, CD133, and CD90) and promotion of autophagy (mTOR, Beclin1, ULK1, and LC3-II/LC3-I ratio) in the murine S180 sarcoma model

Safety and efficacy of 177Lu-PSMA-617 therapy in metastatic castration-resistant prostate cancer / 中华核医学与分子影像杂志

Objective To investigate the safety and efficacy of 177Lu-prostate specific membrane antigen (PSMA)-617 in the treatment of metastatic castration-resistant prostate cancer (mCRPC).Methods From August 2017 to September 2018,11 patients(average age 70.6 years) with mCRPC who underwent 177Lu-PSMA-617 therapy in Nanjing First Hospital were studied.All patients underwent 68Ga-PSMA-11 PET/CT before therapy to assess the tumor radioactive uptake.Blood routine examination and renal function test results were documented before and after therapy to assess the safety.The efficacy was reflected by the changes of prostate specific antigen (PSA) levels and maximum standardized uptake value (SUVmax) on 68Ga-PSMA-11 PET/CT imaging.Paired t test and Wilcoxon's sign rank test were used to analyze the data.Results No acute side effects were observed after therapy of 177Lu-PSMA-617.There were no statistically significant differences after therapy in WBC counts,RBC counts,and PLT,as well as Hb levels (t values:-0.28-1.11,all P＞ 0.05).No kidney toxicity was found.The PSA level after 177Lu-PSMA-617 therapy was significantly lower than that before therapy (80.70 (14.29,1 538.00) μg/L vs 604.60 (88.41,3 980.00) μg/L;u =59,P =0.023).Of the 11 patients,only 2 had elevated PSA levels and disease progression,while the other 9 patients had varying decreases,of which 2/11 decreased by ＞30％ and 7/11 decreased by ＞50％.After therapy,SUVmax of metastatic lesions and metastatic lymph nodes were decreased in 9 and 2 patients respectively.Conclusions 177Lu-PSMA-617 has a good therapeutic value for mCRPC.It is safe and has no obvious side effects.

Effect of silencing troponin I3 gene expression on biological property of rat embryonic H9C2 cardiomyocytes / 中华实用儿科临床杂志

Objective@#To investigate the effect of silencing troponin I3 (Tnni3) gene expression on biological property of rat embryonic H9C2 cardiomyocytes.@*Methods@#The rat embryonic H9C2 cardiomyocytes were cultured and divided into 2 groups: control group transfected with negative control small interfering RNA (NC-siRNA group) and experimental group transfected with Tnni3 small interfering RNA (Tnni3-siRNA group). At 48 h, 72 h after transfection, the cells were collected, and real time quantitative polymerase chain reaction (qPCR)was used to detect the mRNA expressions of Tnni3 and Caspase-3, and Western blot was used to detect the protein expressions of Tnni3, Cyclin A1 and Cyclin B1.Annexin V-fluorescein isothiocyanate(FITC) apoptosis detection kit was used to analyze cell apoptosis.Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) solution and cell cycle was detected by flow cytometry.@*Results@#At 48 h post-transfection with Tnni3-siRNA, H9C2 cells exhibited a significant decrease in Tnni3 mRNA (0.27±0.05 vs. 1.00±0.00) and protein (0.18±0.03 vs. 1.00±0.00) compared with those transfected with NC-siRNA, and the differences were statistically significant (t=25.26, 47.40, all P<0.01). Apoptotic cells were observed in the NC-siRNA group and the Tnni3-siRNA group.At 72 h post-transfection, the percentage of apoptotic cells significantly increased in H9C2 cells transfected with Tnni3-siRNA [(11.30±1.85)% vs. (0.33±0.15)%] compared with those transfected with NC-siRNA, an increased expression of Caspase-3 mRNA was also observed in Tnni3-siRNA-transfected H9C2 cells (1.39±0.13 vs. 1.00±0.00), and the differences were statistically significant (t=10.24, 5.19, all P<0.01). Compared with NC-siRNA-transfected H9C2 cells, a time-dependent reduction in cell proliferation was observed in Tnni3-siRNA-transfected H9C2 cells (48 h: 0.32±0.06 vs. 0.46±0.03; 72 h: 0.31±0.01 vs. 0.63±0.04; 96 h: 0.36±0.01 vs 0.75±0.04), and the differences were statistically significant (t=3.62, 13.45, 16.39, all P<0.01). At 72 h post-transfection with Tnni3-siRNA, the percentage of G1 phase, S phase and G2 phase cells was (71.25±3.82)%, (18.28±2.78)% and (9.94±1.09)%, respectively.There was a significant increase in the proportion of G2 phase cells [(9.94±1.09)% vs. (4.54±0.99)%] in H9C2 cells transfected with Tnni3-siRNA compared with those transfected with NC-siRNA, an increased expression of Cyclin A1 protein (1.89±0.09 vs.1.00±0.00) and a decreased expression of Cyclin B1 protein (0.47±0.06 vs.1.00±0.00) were observed in Tnni3-siRNA-transfected H9C2 cells, respectively, and the differences were statistically significant (t=6.35, 17.12, 15.32, all P<0.01).@*Conclusions@#Silencing Tnni3 gene expression in rat embryonic H9C2 cardiomyocytes can induce cell apoptosis, suppress cell proliferation, and led to G2 cell cycle arrest.

Relationship between total cerebral small vessel disease burden and hemorrhagic transformation of acute ischemic stroke patients after intravenous thrombolysis / 中华神经科杂志

Objective To investigate the relationship between total cerebral small vessel disease (CSVD) burden and intracranial hemorrhage transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods One hundred and fifty-four patients who suffered from ischemic stroke within 4.5 hours of onset and received recombinant tissue plasminogen activator thrombolytic therapy in the emergency green channel of the First Affiliated Hospital of Soochow University from August 2016 to January 2018 were enrolled.HT examined by computed tomography scan within 24 hours after thrombolysis was included.The magnetic resonance imaging examination was performed within 48 hours.The patients were divided into two groups:HT group and control group according to the presence or absence of HT.Periventricular white-matter hyperintensities (WMH) with Fazekas score of 3 or deep WMH with Fasekas score of 2 or 3 was recorded as 1 point,MRI of cerebral microbleeds (CMBs) or lacunar infarction (LI) was recorded as 1 point respectively,and peripheral vascular space (PVS) in basal ganglia graded 2-4 (≥11)was counted 1 point.Single-factor analysis was used to compare total CSVD burden score,baseline data and clinical data between the two groups.Multivariate Logistic regression analysis was performed to explore the relationship between total CSVD burden score and HT.Results The age of the 154 patients was 66.00(59.00,74.25) years,males accounted for 66.9％ (103/154),onset to treatment time (OTT) was 174.50 (131.50,200.00) minutes and the NIHSS score before thrombolytic therapy was 6.00 (3.00,10.25).There were 43 cases (27.9％) with moderate to severe WMH,35 cases (22.7％) with CMBs,52 cases (33.8％) with PVS graded 2-4,and 96 cases (62.3％) with LI.There were 21 enrolled patients (13.6％) who suffered from HT.Symptomatic intracranial hemorrhage occurred in nine cases (5.8％).In the multivariate Logistic regression model,the results demonstrated that baseline diastolic pressure (OR=1.072,95％CI 1.027-1.118,P=0.001)and atrial fibrillation (OR=28.564,95％CI 6.217-131.241,P=0.000) were independently associated with HT.After using the mild CSVD burden score as a reference,moderate CSVD burden (OR=0.810,95％ CI 0.154-4.257,P=0.804) was not associated with HT after thrombolysis,and severe CSVD burden (OR=8.429,95％ CI 1.643-43.227,P=0.011) was independently associated with HT.Conclusions The severity of total CSVD burden in patients with AIS was closely related to HT after thrombolysis.Severe CSVD was an independent risk factor for HT after thrombolysis.

Effect of silencing troponin Ⅰ3 gene expression on biological property of rat embryonic H9C2 cardiomyocytes / 中华实用儿科临床杂志

Objective To investigate the effect of silencing troponin Ⅰ3 (Tnni3) gene expression on biological property of rat embryonic H9C2 cardiomyocytes.Methods The rat embryonic H9C2 cardiomyocytes were cultured and divided into 2 groups:control group transfected with negative control small interfering RNA (NC-siRNA group) and experimental group transfected with Tnni3 small interfering RNA (Tnni3-siRNA group).At 48 h,72 h after transfection,the cells were collected,and real time quantitative polymerase chain reaction (qPCR)was used to detect the mRNA expressions of Tnni3 and Caspase-3,and Western blot was used to detect the protein expressions of Tnni3,Cyclin A1 and Cyclin B1.Annexin V-fluorescein isothiocyanate(FITC) apoptosis detection kit was used to analyze cell apoptosis.Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) solution and cell cycle was detected by flow cytometry.Results At 48 h post-transfection with Tnni3-siRNA,H9C2 cells exhibited a significant decrease in Tnni3 mRNA (0.27 ± 0.05 vs.1.00 ± 0.00) and protein (0.18 ± 0.03 vs.1.00 ± 0.00) compared with those transfected with NC-siRNA,and the differences were statistically significant (t =25.26,47.40,all P ＜ 0.01).Apoptotic cells were observed in the NC-siRNA group and the Tnai3-siRNA group.At 72 h post-transfection,the percentage of apoptotic cells significantly increased in H9C2 cells transfected with Tnni3-siRNA [(11.30 ± 1.85) ％ vs.(0.33 ± 0.15) ％] compared with those transfected with NC-siRNA,an increased expression of Caspase-3 mRNA was also observed in Tnni3-siRNA-transfected H9C2 cells (1.39 ±0.13 vs.1.00 ±0.00),and the differences were statistically significant (t =10.24,5.19,all P ＜ 0.01).Compared with NC-siRNA-transfected H9C2 cells,a time-dependent reduction in cell proliferation was observed in Tnni3-siRNA-transfected H9C2 cells (48 h:0.32 ± 0.06 vs.0.46 ± 0.03;72 h:0.31 ± 0.01 vs.0.63 ±0.04;96 h:0.36 ± 0.01 vs 0.75 ± 0.04),and the differences were statistically significant (t =3.62,13.45,16.39,all P ＜ 0.01).At 72 h post-transfection with Tnni3-siRNA,the percentage of G1 phase,S phase and G2 phase cells was (71.25 ± 3.82) ％,(18.28 ± 2.78) ％ and (9.94 ± 1.09) ％,respectively.There was a significant increase in the proportion of G2 phase cells [(9.94 ± 1.09) ％ vs.(4.54 ±0.99) ％] in H9C2 cells transfected with Tnni3-siRNA compared with those transfected with NC-siRNA,an increased expression of Cyclin A1 protein (1.89 ±0.09 vs.1.00 ±0.00) and a decreased expression of Cyclin B1 protein (0.47 ± 0.06 vs.1.00 ± 0.00) were observed in Tnni3-siRNA-transfected H9C2 cells,respectively,and the differences were statistically significant (t =6.35,17.12,15.32,all P＜0.01).Conclusions Silencing Tnni3 gene expression in rat embryonic H9C2 cardiomyocytes can induce cell apoptosis,suppress cell proliferation,and led to G2 cell cycle arrest.