Calcium/calmodulin-dependent protein kinase II is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rat nucleus accumbens

Background@#Synaptic plasticity contributes to nociceptive signal transmission and modulation, with calcium/ calmodulin-dependent protein kinase II (CaMK II) playing a fundamental role in neural plasticity. This research was conducted to investigate the role of CaMK II in the transmission and regulation of nociceptive information within the nucleus accumbens (NAc) of naïve and morphine-tolerant rats. @*Methods@#Randall Selitto and hot-plate tests were utilized to measure the hindpaw withdrawal latencies (HWLs) in response to noxious mechanical and thermal stimuli. To induce chronic morphine tolerance, rats received intraperitoneal morphine injection twice per day for seven days. CaMK II expression and activity were assessed using western blotting. @*Results@#Intra-NAc microinjection of autocamtide-2-related inhibitory peptide (AIP) induced an increase in HWLs in naïve rats in response to noxious thermal and mechanical stimuli. Moreover, the expression of the phosphorylated CaMK II (p-CaMK II) was significantly decreased as determined by western blotting. Chronic intraperitoneal injection of morphine resulted in significant morphine tolerance in rats on Day 7, and an increase of p-CaMK II expression in NAc in morphine-tolerant rats was observed. Furthermore, intra-NAc administration of AIP elicited significant antinociceptive responses in morphine-tolerant rats. In addition, compared with naïve rats, AIP induced stronger thermal antinociceptive effects of the same dose in rats exhibiting morphine tolerance. @*Conclusions@#This study shows that CaMK II in the NAc is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rats.

Cloning and expression analysis of superoxide dismutase SmMSD2 gene from Salvia miltiorrhiza / 药学学报

Superoxide dismutase (SOD) is a key enzyme that scavenge superoxide anion free radical (O2·-) in vivo, and plays an important role in plant growth and development and stress. In this study, according to the genome and transcriptome data of Salvia miltiorrhizae, 9 SOD genes were identified and the expression patterns of SOD family genes were further analyzed, including 5 Cu/Zn-SOD, 2 Fe-SOD and 2 Mn-SOD. On the basis of proteomic analysis, combined with transcriptome data, one full-length cDNA of Mn-SOD gene, namely SmMSD2 was cloned from Salvia miltiorrhizae. The results of amino acid sequence alignment and phylogenetic analysis showed that SmMSD2 protein belongs to the manganese superoxide dismutase (Mn-SOD) subfamily, and SmMSD2 protein shares high sequence identity with the Mn-SOD proteins of various plants that all contain a C-terminal conserved metal-binding domain "DVWEHAYY". The prokaryotic expression vector pMAL-c2X-SmMSD2 was constructed and transformed into E. coli BL21 expressing strain, and the target recombinant protein was successfully induced and its enzymatic properties were analyzed. Spatiotemporal expression analysis showed that SmMSD2 gene was expressed in all tissues, indicating that SmMSD2 gene was constitutively expressed at a stable level. Real-time quantitative PCR indicated that drought (15% PEG6000), abscisic acid (ABA) and indole-3-acetic acid (IAA) could induce the expression of SmMSD2 gene, suggesting that SmMSD2 may be involved in the response of Salvia miltiorrhizae to abiotic stress such as drought, as well as the signaling pathways of phytohormone ABA and IAA. These results lay the foundation for further elucidating the involvement of superoxide dismutase in the stress response and accumulation of active components of Salvia miltiorrhiza.

Prevalence and risk factors of dry eye patients with corneal epithelial defects: A hospital-based retrospective study / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the characteristics and correlated risk factors of dry eye patients with corneal epithelial defects.METHODS: Outpatient medical records of dry eye patients with corneal epithelial defects at Peking University Third Hospital from July 2018 to June 2019 were retrospectively analyzed. The patients' data including sex, age, visit date, presence of comorbidities, and meteorological indicators at the same period were statistically analyzed.RESULTS: A total of 291 dry eye patients with corneal epithelial defects, of whom 75.3% were female, were retrospectively analyzed. Young patients aged 21-30 made up the most(26.5%), while the proportion of teenagers(<18 years, 5.8%)and the elderly(≥61 years, 17.2%)was low. However, as the largest proportion of this population, young and middle-aged patients tend to experience fewer visits(5.4±12.4). Spring and winter were the main seasons of complaints. The meteorological indicators at the same period including fine-particulate matter with a median aerometric diameter of less than 10μm(PM10), sulfur dioxide(SO2), nitrogen dioxide(NO2), and reduced average relative humidity were found significantly correlated with dry eye corneal epithelial defects(P<0.05). Conjunctivitis, cataracts, blurred vision, and trichiasis ranked the top four comorbidities.CONCLUSION: Dry eye corneal epithelial defects of young and female population cannot be ignored. PM10, SO2, NO2, and reduced humidity are found significantly correlated with dry eye corneal epithelial defects. For dry eye patients with conjunctivitis, cataracts, blurred vision, and trichiasis, more attention should be paid to their corneal conditions.

Associations between sugar sweetened beverage intake and emotional and behavioral problems in preschoolers / 中国学校卫生

Objective@#To explore the consumption of sugar sweetened beverages (SSBs) and its association with behavioral problems in Chinese preschool children, and to provide a scientific basis for the prevention of behavioral problems of children.@*Methods@#A total of 7 634 children aged 3-6 years were chosen from kindergartens in 3 cities (Yangzhou, Xuzhou, Zhenjiang) in the lower reaches of Yangtze River using method of cluster sampling during October to November in 2017. Parental or guardian questionnaires were used to obtain information regarding child consumption of SSBs. The Strengths and Difficulties Questionnaire (SDQ) was used to assess children s emotional and behavioral problems. Multivariate Logistic regression model was used to explore the association between different SSBs intake frequency and children s behavioral problems.@*Results@#A total of 5 509(72.2%) consumed SSBs less than once a day, 830(10.9%) reported SSBs consumption once a day, and 1 295(16.9%) had 2 times or more intake of sugar sweetened beverages per day. After adjusting for confounding factors including age, sex, BMI, family financial status, parental education, screen time, sleep duration, and physical activities duration, multiple Logistic regression model revealed that intake of SSBs once a day was associated with an increased risk of hyperactivity disorder ( OR =1.26, 95% CI =1.01-1.57) and SDQ total difficulties ( OR =1.44, 95% CI =1.14-1.82) in boys and with an increased risk of emotional symptoms ( OR=1.34, 95%CI =1.02-1.76), conduct problems ( OR=1.53, 95%CI =1.18-2.00), hyperactivity disorder ( OR=1.79, 95%CI =1.42-2.27) and prosocial behavior ( OR=1.48, 95%CI =1.14-1.91) in girls. Intake of SSBs≥2 times per day was associated with an increased risk of emotional symptoms ( OR=1.28, 95%CI =1.02-1.59) and SDQ difficulties ( OR=1.30, 95%CI =1.07-1.58) in boys and not with behavioral problems in girls.@*Conclusion@#Sex differences are observed with respect to the association between SSBs intake and behavioral problems in preschoolers, but no significant dose response relationship was observed. More longitudinal studies are needed to further explore the association between SSBs intake and behavioral problems in preschool children as well as the underlying physiological mechanisms in future.

Simultaneous integrated boost vs. routine IMRT in limited-stage small-cell lung cancer: an open-label, non-inferiority, randomized, phase 3 trial / 中华放射肿瘤学杂志

Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.

Safety of thoracic radiotherapy followed by PD-1/PD-L1 inhibitor after induction therapy for extensive-stage small cell lung cancer / 中华放射肿瘤学杂志

Objective:To evaluate the safety and tolerance of sequential thoracic radiotherapy combined with PD-1/PD-L1 inhibitors in patients with extensive-stage small cell lung cancer (ES-SCLC) after induction systemic therapy.Methods:ES-SCLC patients from a phase I trial and a real-world study were enrolled for those who received thoracic radiotherapy after induction systemic treatment (chemotherapy/chemotherapy combined with PD-1/PD-L1 inhibitors) and consolidated with PD-1/PD-L1 inhibitors. These two studies were both approved by the Ethics Committee of Chinese Academy of Medical Sciences Cancer Hospital (Clinical Trials.gov number, NCT03971214, NCT04947774).Results:Between January 2019 and March 2021, a total of 11 patients with ES-SCLC were analyzed, aged 52-73 years, with a median age of 62 years. Among them, five patients (45.5%) received induction chemotherapy and six patients (54.5%) received chemotherapy combined with PD-1/PD-L1 inhibitor, and then all received intensity-modulated thoracic radiotherapy after evaluation of systemic treatment efficacy. Two patients developed treatment-related grade G3-5 toxicity (18.2%, 1 treatment-related pneumonitis and 1 radiation esophagitis). G 1-G 2 hematologic toxicity, pneumonia, and anorexia were common mild toxicities. Only one patient (9.1%) terminated immunotherapy due to immune-related pneumonitis. During a median follow-up time of 12.5 months (range: 3.5-16.4 months), the median disease progression-free survival and overall survival was 7.4 months (95% CI: 6.9-8.0 months) and 14.6 months (95% CI: 9.0-20.2 months), respectively. Conclusions:Sequential thoracic radiotherapy followed by PD-1/PD-L1 inhibitor is safe and feasible in patients with ES-SCLC after induction therapy. Given that both thoracic radiotherapy and immunotherapy benefits the ES-SCLC in survival, this comprehensive treatment modality warrants further investigation.

Optimizing the target volume to boost the efficacy of radiation-induced immunomodulatory effects / 中华放射肿瘤学杂志

Radiotherapy is a pivotal method in cancer treatment harbouring immunomodulatory effects. Radiotherapy combined with immunotherapy has been proven to yield promising preliminary results in certain types of tumors. Most studies have concentrated on the dose fractionation of radiotherapy and timing of radiotherapy and immunotherapy. With the development of related studies, attention has been gradually paid to the influence of target volume upon circulating lymphocytes and tumor microenvironment. The interaction between target volume and immunotherapy has been valued. For tumors not suitable for hypofractionated radiotherapy, such as advanced esophageal cancer, conventional fractionated radiotherapy has been adopted. The volume and planning of target volume play a pivotal role in radiotherapy combined with immunotherapy. This article illustrates the feasibility of radiotherapy combined with immunotherapy, theory and conception of optimizing target volume.

Research progress on radical hypofractionated radiotherapy for prostate cancer / 中华放射肿瘤学杂志

Radiotherapy is one of the important treatment strategies for localized prostate cancer. Conventional fractionated external beam radiotherapy is the standard dose-fraction regimen of radical radiotherapy for localized prostate cancer. In recent years, hypofractionated radiotherapy technique has been developed rapidly. The moderately hypofractionated radiotherapy has been considered as an alternative to conventional fractionated radiotherapy in conditional institutions. Increasing evidence has been obtained in the application of ultra-hypofractionated radiotherapy (also known as stereotactic body radiotherapy, SBRT) in patients with low-and intermediate-risk prostate cancer. However, the efficacy and safety of SBRT for high-risk prostate cancer have not been fully demonstrated. In this review, research progressess on the efficacy and safety of radical hypofractionated radiotherapy and the techniques of SBRT for prostate cancer were summarized.

Pathogenesis, prenatal diagnosis and clinical features of fetal cardiomyopathies / 中华超声影像学杂志

Objective:To summarize the etiological mechanism, echocardiographic and clinical features of fetal cardiomyopathies (FCMs).Methods:According to the data of echocardiography in Maternal-Fetal Medicine Center in Fetal Heart Disease of Beijing Anzhen Hospital during 2015 January to 2020 December, 70 cases with FCMs were retrospectively reviewed, and the clinical, ultrasonic, pathological and clinical outcome data were collected. Whole exome sequencing and whole genome sequencing were used to identify the genetic changes.Results:Primary FCMs were diagnosed in 55 cases (78.6%, 55/70), including 39 fetuses with non-compaction of the ventricular myocardium (NVM), 10 with dilated cardiomyopathy (DCM), 5 with hypertrophic cardiomyopathy (HCM), and 1 with restricted cardiomyopathy (RCM). Secondary FCMs were diagnosed in 15 cases (21.4%, 15/70), including 7 fetuses with maternal anti-Ro/La antibodies (presenting with DCM), 4 with twin-twin transfusion syndrome (2 with DCM and 2 with HCM), 2 with fetal anemia (presenting with DCM), 1 with maternal diabetes (presenting with HCM) and 1 with chorioangioma of the placenta (presenting with DCM). In all cases, 9 cases were born, 3 cases died in perinatal period, and 58 pregnancies were terminated due to ineffective treatment or the decisions of pregnant women. Thirty cases with primary FCMs were performed with genetic tests, and 13 of them were identified with positive genetic changes related to FCMs, including 12 cases with NVM and 1 with HCM.Conclusions:Primary FCMs are more common than secondary FCMs in fetal period. The genetic disorders have a high proportion in fetal NVM. Fetal DCM and HCM have a large spectrum of intrinsic and extrinsic causes.

Effects of repetitive transcranial magnetic stimulation on attention to the cues for male patients with alcohol use disorder after acute withdrawal / 中华行为医学与脑科学杂志

Objective:To investigate the effect of high-frequency repetitive transcranial magnetic stimulation(rTMS)on cue attention in male patients with alcohol use disorder (AUD) after the acute withdrawal.Methods:A total of 90 male patients AUD who were hospitalized in the Second Affiliated Hospital of Kunming Medical University and Psychiatric Hospital of Yunnan province from May 2020 to December 2020 were enrolled, then they were divided into study group and control group using random number table.Because 18 cases fell out during the study, 36 cases were included in each of the two groups.After the alcohol withdrawal syndrome eliminated, the study group received high-frequency rTMS at 10 Hz for 14 consecutive days, and the control group was administrated by sham rTMS.At baseline and after true or sham rTMS, the cognitive psychology experiment Oddball paradigm was completed, and the behavioral data of the subjects were collected.Paired-sample t-test was used to compare the changes of the two groups before and after treatment.Data analysis were conducted using SPSS 21.0 software. Results:There was no statistical difference between the study group and the control group in terms of drinking level, cognition level and demographic data(all P>0.05). In the Oddball paradigm, compared with the control group((526.72±75.30)ms, (0.98±0.02))the reaction time((497.93±64.51)ms, t=3.145, P=0.008) and accuracy rate((0.99±0.01), t=-2.803, P=0.016) in alcohol-related cues were significantly improved in the study group after rTMS intervention, but in the control group, there were no statistical differences(both P>0.05), whether the cue was alcohol related or not. Conclusion:The results suggest that the rTMS can enhance the attention bias of alcohol-related cues and change the impulse process partly.

Correlation between personality traits and clinical symptoms in patients with anxious depression / 中华行为医学与脑科学杂志

Objective:To investigate the personality traits of patients with anxious depression and the relationship between personality traits and clinical symptoms.Methods:From December 2011 to October 2014, 177 first-episode untreated patients with depression from the psychiatric department of the First Affiliated Hospital of Kunming Medical University and 185 healthy controls(HC group) recruited by the community were included.All patients were divided into anxious depression group ( n=92) and non-anxious depression group ( n=85) according to whether the anxiety/somatization factor score ≥7.The simplified version of Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI) and the Hamilton depression scale-17 (HAMD-17) were used to assess all the subjects.Statistical analyses were conducted in SPSS 21.0.Analysis of covariance was used to compare the differences of the scores on personality dimensions among the three groups.The relationship between personality dimensions and anxious depression was confirmed by Logistic regression, linear regression analysis and generalized linear models. Results:The differences of the scores on the four dimensions of neuroticism ( F=108.863, P<0.01), extraversion ( F=86.357, P<0.01), agreeableness ( F=50.615, P<0.01), and conscientiousness ( F=24.730, P<0.01) among the three groups were statistically significant.Further pairwise comparision showed, the score of neuroticisms was higher in the anxious depression group(43.05±8.92) and non-anxious depression group(39.85±7.21) than that in the HC group (30.16±6.25)( P<0.01, Bonferroni corrected). The scores of extroversion (31.22±6.33, 32.61±6.83), agreeableness (38.66±5.80, 39.46±6.19) and conscientiousness (39.75±6.89, 38.85±7.26) were lower in the anxious depression group and non-anxious depression group than those in the HC group (40.29±5.37, 44.79±4.68, 44.09±5.66, all P<0.01, Bonferroni corrected). The score of neuroticisms in anxious depression group was higher than that in non-anxious depression group, and the difference was statistically significant ( P<0.01, Bonferroni corrected). Logistic regression analysis with age, gender and years of education controlled showed that the score of neuroticism ( B=0.082, OR=1.085, 95% CI=1.020-1.154, P=0.009) and conscientiousness ( B=0.060, OR=1.062, 95% CI=1.006-1.120, P=0.028) were risk factors for anxiety symptoms in patients with depression.Linear regression analysis showed that the scores on neuroticism had positive predictive effects on the anxiety/somatization factor score ( B=0.055, 95% CI=0.021-0.089, P=0.002) and cognitive impairment factor score ( B=0.074, 95% CI=0.023-0.125, P=0.005) in the anxious depression group. Conclusion:Compared to non-anxious depression, patients with anxious depression show higher level of neuroticism, and the level of neuroticism can positively predict the symptoms of anxiety and cognitive impairment.The high level of neuroticism and conscientiousness may be risk factors for the occurrence of anxiety symptoms in patients with depressed.

Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese Population / 生物医学与环境科学（英文）

OBJECTIVE@#Traditional epidemiological studies have shown that C-reactive protein (CRP) is associated with the risk of cardiovascular diseases (CVDs). However, whether this association is causal remains unclear. Therefore, Mendelian randomization (MR) was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke, atrial fibrillation, arrhythmia and congestive heart failure.@*METHODS@#We performed two-sample MR by using summary-level data obtained from Japanese Encyclopedia of Genetic association by Riken (JENGER), and we selected four single-nucleotide polymorphisms associated with CRP level as instrumental variables. MR estimates were calculated with the inverse-variance weighted (IVW), penalized weighted median and weighted median. MR-Egger regression was used to explore pleiotropy.@*RESULTS@#No significant causal association of genetically determined CRP level with ischemic stroke, atrial fibrillation or arrhythmia was found with all four MR methods (all Ps > 0.05). The IVW method indicated suggestive evidence of a causal association between CRP and congestive heart failure ( OR: 1.337, 95% CI: 1.005-1.780, P = 0.046), whereas the other three methods did not. No clear pleiotropy or heterogeneity were observed.@*CONCLUSIONS@#Suggestive evidence was found only in analysis of congestive heart failure; therefore, further studies are necessary. Furthermore, no causal association was found between CRP and the other three cardiovascular outcomes.

Analysis and thought on reaching the consensus during the development of acupuncture and moxibustion clinical practice guidelines in China / 中国针灸

Based on the 28 Chinese clinical practice guidelines of acupuncture and moxibustion, this study summarized and analyzed the contents related to reaching consensus during the development process. The results indicated that all the 28 guidelines reported they have used consensus in the "recommendations" section, and provided details on consensus personnel, consensus methods, consensus process and consensus materials. However, it was found that the reporting of consensus was in need of further improvement. The limitations included unclear definition and responsibilities of "expert group", obscure concept between "consensus meeting" and "expert discussion", non-rigorous process of reaching consensus when generating recommendations and lacking of detailed reporting of the consensus reaching process. As such, we suggested that future researchers should conduct researches to further standardized the consensus process when developing acupuncture and moxibustion clinical practice guidelines, so as to improve the quality and clinical applicability of guidelines．.

Professor YANG Ji-guo's experience in treatment of functional gastrointestinal diseases with acupuncture combined with umbilicus moxibustion / 中国针灸

Professor YANG Ji-guo's clinical experience in treatment of functional gastrointestinal diseases was summerized. Professor YANG Ji-guo believes that this disease is caused by the deficiency of six fu organs. Dysfunction of six fu organs in descending transportation is the basic pathogenesis. The principle of acupoint selection includes benefiting gastrointestinal functions, unblocking and purging six fu, soothing liver qi and calming down the mind. In treatment, acupuncture is combined with umbilicus moxibustion. In acupuncture, the deqi promoting technique by rotating and trembling needle is adopted. Focusing on the deficiency of six fu organs, umbilicus moxibustion is adopted to benefit the spleen and stomach and harmonize the functions of six fu organs for both biao (symptoms) and ben (root cause).

The Biocompatibility of Multi-Source Stem Cells and GelatinCarboxymethyl Chitosan-Sodium Alginate Hybrid Biomaterials

BACKGROUND@#Nowadays, biological tissue engineering is a growing field of research. Biocompatibility is a key indicator for measuring tissue engineering biomaterials, which is of great significance for the replacement and repair of damaged tissues. @*METHODS@#In this study, using gelatin, carboxymethyl chitosan, and sodium alginate, a tissue engineering material scaffold that can carry cells was successfully prepared. The material was characterized by Fourier transforms infrared spectroscopy. In addition, the prepared scaffolds have physicochemical properties, such as swelling ratio, biodegradability.we observed the biocompatibility of the hydrogel to different adult stem cells (BMSCs and ADSCs) in vivo and in vitro. Adult stem cells were planted on gelatin-carboxymethyl chitosan-sodium alginate (Gel/SA/CMCS) hydrogels for 7 days in vitro, and the survival of stem cells in vitro was observed by live/died staining. Gel/SA/CMCS hydrogels loaded with stem cells were subcutaneously transplanted into nude mice for 14 days of in vivo culture observation. The survival of adult stem cells was observed by staining for stem cell surface markers (CD29, CD90) and Ki67. @*RESULTS@#The scaffolds had a microporous structure with an appropriate pore size (about 80 lm). Live/died staining showed that adult stem cells could stably survive in Gel/SA/CMCS hydrogels for at least 7 days. After 14 days of culture in nude mice, Ki67 staining showed that the stem cells supported by Gel/SA/CMCS hydrogel still had high proliferation activity. @*CONCLUSION@#Gel/SA/CMCSs hydrogel has a stable interpenetrating porous structure, suitable swelling performance and degradation rate, can promote and support the survival of adult stem cells in vivo and in vitro, and has good biocompatibility. Therefore, Gel/SA/CMCS hydrogel is a strong candidate for biological tissue engineering materials.

Thermosensitive Hydrogel Loaded with Primary ChondrocyteDerived Exosomes Promotes Cartilage Repair by Regulating Macrophage Polarization in Osteoarthritis

BACKGROUND@#Intra-articular injection is a classic strategy for the treatment of early osteoarthritis (OA). However, the local delivery of traditional therapeutic agents has limited benefits for alleviating OA. Exosomes, an important type of extracellular nanovesicle, show great potential for suppressing cartilage destruction in OA to replace drugs and stem cellbased administration. @*METHODS@#In this study, we developed a thermosensitive, injectable hydrogel by in situ crosslinking of Pluronic F-127 and hyaluronic acid, which can be used as a slow-release carrier to durably retain primary chondrocyte-derived exosomes at damaged cartilage sites to effectively magnify their reparative effect. @*RESULTS@#It was found that the hydrogel can sustainedly release exosomes, positively regulate chondrocytes on the proliferation, migration and differentiation, as well as efficiently induce polarization of M1 to M2 macrophages. Intraarticular injection of this exosomes-incorporated hydrogel significantly prevented cartilage destruction by promoting cartilage matrix formation. This strategy also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+ regenerative M2 macrophages over CD86+ M1 macrophages in synovial and chondral tissue, with a concomitant reduction in pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and increase in anti-inflammatory cytokine (IL-10) in synovial fluid. @*CONCLUSION@#Our results demonstrated that local sustained-release primary chondrocyte-derived exosomes may relieve OA by promoting the phenotypic transformation of macrophages from M1 to M2, which suggesting a great potential for the application in OA.

Expression and Clinical Significance of CAS in Acute Myeloid Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the expression of cellular apoptosis susceptibility protein （CAS） in acute myeloid leukemia （AML） and its correlation with clinical characteristics.@*METHODS@#The expression of CAS in bone marrow tissue of 54 patients with AML and 24 patients with non-hematological malignant diseases was detected by Western blot and immune-histochemical method, and compared between AML group and control group. Also the relationship of CAS expression in AML and sex, age, WBC count, Hb, platelet count, bone marrow blast cell ratio, ki-67 index, cytogenetic and molecular biological prognostic risk stratification, extramedullary infiltration and other clinical characteristics was analyzed.@*RESULTS@#Western blot showed that the expression of CAS protein in bone marrow biopsies of AML patients was significantly higher than that in control group (P<0.05). Immune-histochemical method revealed that CAS was mainly located in the cytoplasm in both AML group and control group. Among 54 AML patients, 14 patients (25.9%) showed high expression of CAS, while all the 24 patients in the control group showed low expression of CAS. The high expression rate of CAS in AML patients was significantly higher than that in the control group (P<0.05). There were statistically significant differences in prognostic risk stratification and the remission rate of the first chemotherapy between CAS high expression group and CAS low expression group in AML (P<0.05). The proportion of high risk patients and unremission patients after the first chemotherapy in CAS high expression group were significantly higher than those in CAS low expression group (57.1% vs 27.5%, 30.8% vs 7.9%), while the proportion of low risk patients and complete remission patients after the first chemotherapy were significantly lower than those in CAS low expression group (14.3% vs 37.5%, 53.8% vs 84.2%). In AML patients, the ki-67 index of bone marrow tissue in CAS high expression group was higher than that in CAS low expression group (60% vs 50%) (P<0.05).@*CONCLUSION@#CAS is localized in cytoplasm in both AML and non-hematological malignant diseases, and its expression increases in AML. CAS is related to the risk stratification of cytogenetics and molecular biology, the remission rate after the first chemotherapy and ki-67 index in AML, which suggests that CAS may be involved in the occurrence and development of AML.

Application of "kindergarten effect" in radiotherapy for children with tumor aged 3-5 years / 中国当代儿科杂志

OBJECTIVES@#To study the clinical application effect of "kindergarten effect" in radiotherapy for children with tumor based on the psychology of preschool children aged 3-5 years.@*METHODS@#A total of 30 children, aged 3-5 years, who were admitted to the Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, from January 2020 to August 2021 were enrolled in this prospective study. The children were randomly divided into a control group and a test group, with 15 children in each group. The children in the test group were treated in "kindergarten mode", i.e., all children were treated together at a specified time and left together after all children completed treatment. Those in the control group were treated alternately with adult patients according to the treatment time based on the type of radiotherapy fixation device. The treatment compliance was evaluated for both groups, and the two groups were compared in terms of the setup errors in the superior-inferior (SI), left-right (LR), and anterior-posterior (AP) directions.@*RESULTS@#Compared with the control group, the test group showed a significantly shorter time for finishing the treatment (P<0.05) and a significantly lower proportion of children with treatment interruption (P<0.05). Compared with the control group, the test group showed smaller mean errors in the SI, LR and AP directions after image-guided radiotherapy, with significant differences in the mean errors in the SI and LR directions (P<0.05).@*CONCLUSIONS@#With the application of the "kindergarten effect", most children can actively cooperate in radiotherapy, and it can also improve the accuracy and repeatability of positioning and help to achieve the desired treatment outcome.

Establishment of a microtubule-fluorescent fusion protein mosaically labeled zebrafish motor neuron system / 生理学报

Motor neurons are an important type of neurons that control movement. The transgenic fluorescent protein (FP)-labeled motor neurons of zebrafish line is disadvantageous for studying the morphogenesis of motor neurons. For example, the individual motor neuron is indistinguishable in this transgenic line due to the high density of the motor neurons and the interlaced synapses. In order to optimize the in vivo imaging methods for the analysis of motor neurons, the present study was aimed to establish a microtubule-fluorescent fusion protein mosaic system that can label motor neurons in zebrafish. Firstly, the promotor of mnx1, which was highly expressed in the spinal cord motor neurons, was subcloned into pDestTol2pA2 construct combined with the GFP-α-Tubulin fusion protein sequence by Gateway cloning technique. Then the recombinant constructs were co-injected with transposase mRNA into the 4-8 cell zebrafish embryos. Confocal imaging analysis was performed at 72 hours post fertilization (hpf). The results showed that the GFP fusion protein was expressed in three different types of motor neurons, and individual motor neurons were mosaically labeled. Further, the present study analyzed the correlation between the injection dose and the number and distribution of the mosaically labeled neurons. Fifteen nanograms of the recombinant constructs were suggested as an appropriate injection dose. Also, the defects of the motor neuron caused by the down-regulation of insm1a and kif15 were verified with this system. These results indicate that our novel microtubule-fluorescent fusion protein mosaic system can efficiently label motor neurons in zebrafish, which provides a more effective model for exploring the development and morphogenesis of motor neurons. It may also help to decipher the mechanisms underlying motor neuron disease and can be potentially utilized in drug screening.

Application of formative assessment combined with Ladder type teaching in the teaching of standardized training of nephrology and endocrinology / 中华医学教育探索杂志

Objective:To explore the application effect of formative assessment combined with Ladder type teaching on the teaching of standardized training of nephropathy and endocrinology.Methods:A total of 39 residents who rotated in the Department of Nephrology and Endocrinology, Sichuan Science City Hospital from March 2019 to March 2020 were included in the control group and were taught routinely, and another 42 residents who rotated from April 2020 to April 2021 were classified as a research group and were given formative assessment and Ladder type teaching. The out-department assessment results between the two groups were compared, and the mini-clinical exercise evaluation (Mini-CEX), normal performance assessment and 360-degree evaluation results of the research group when entering and exiting the department were compared. The students' satisfaction with teaching between the two groups was also compared. SPSS 24.0 was used for t test, chi-square test and rank sum test. Results:The scores of theory, skill manipulation and case analysis in the research group were higher than those in the control group, and the differences were statistically significant ( P<0.05). The Mini-CEX score, usual performance assessment score and 360-degree evaluation score in the research group when exiting the department were all higher than those when entering the department, with statistically significant difference ( P<0.05). There were significant differences in the grades distribution of teaching satisfaction degrees between the two groups ( P<0.05), and the total satisfaction rate of the research group was higher than that of the control group. Conclusion:The use of formative assessment combined with Ladder type teaching in the standardized training of nephropathy and endocrinology can significantly improve the scores of the residents and their clinical comprehensive literacy, and increase the satisfaction of teaching, with great value of popularization and application.