Clinical characteristics and prognosis of high-risk neuroblastoma patients with skeletal metastases at different sites / 中华实用儿科临床杂志

Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.

Total glucosides of Rhizoma Smilacis Glabrae: a therapeutic approach for psoriasis by regulating Th17/Treg balance / 中国天然药物

Total glucosides of Rhizoma Smilacis Glabrae (RSG) are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells. In this study, we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis. Our findings revealed significant improvements upon administration of RSG in an imiquimod (IMQ)-induced psoriasis model. These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema, ulceration, and flaking. By transcriptome sequencing and T-cell flow sorting assay, we identified notable effects of RSG on the modulation of various cellular processes. Specifically, RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G2 phase cells. Furthermore, RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells. Of particular interest, we discovered that β-sitosterol, sitostenone, stigmasterol, smiglanin, and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells. In summary, our study highlights the therapeutic potential of RSG in the treatment of psoriasis, attributed to its ability to regulate the Th17/Treg balance. These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.

Research progress of microparticles in traditional Chinese medicine decoction / 药学学报

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

Progress in application of adult endogenous neurogenesis in brain injury repair / 生理学报

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.

Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression / 老年心脏病学杂志（英文版）

BACKGROUND@#Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood.@*METHODS@#Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5.@*RESULTS@#In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development.@*CONCLUSIONS@#CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

The mediating effect of resilience on anxiety and subjective well-being in occupational population / 中华劳动卫生职业病杂志

Objective: To explore the current situation of anxiety, subjective well-being in occupational population and the mediating effect of resilience. Methods: From March 24th to 26th, 2020, a cross-sectional survey was conducted among occupational population aged ≥18 years old using online questionnaires. A total of 2134 valid questionnaires were obtained, with respondents from 30 provinces, autonomous regions, and municipalities directly under the Central Government. Their general demographic data, subjective well-being, anxiety, and resilience were collected. Pearson χ(2) test and Spearson correlation analysis were used for data analysis, and structural equation model was used to explore the mediating effect of resilience on anxiety and subjective well-being. Results: The age of the respondents ranged from 18 to 60 years old, with an average age of (31.19±7.09) years old, including 1075 (50.4%) women and 1059 (49.6%) men. The positive rates of low subjective well-being and anxiety were 46.5% (992/2134) and 28.4% (607/2134), respectively. Anxiety scores were significantly negatively correlated with subjective well-being scores and resilience scores (r(s)=-0.52, -0.41, P<0.05), while resilience was significantly positively correlated with subjective well-being (r(s)=0.32, P<0.05). Structural equation models showed that anxiety had a negative predictive effect on subjective well-being, while resilience not only had a positive predictive effect on subjective well-being, but also played a mediating role between anxiety and subjective well-being, with a mediating effect of 9.9%. Conclusion: The situation of anxiety and well-being in the occupational population is still not optimistic, and resilience has a mediating effect between anxiety and subjective well-being.

Expert consensus on late stage of critical care management / 中华内科杂志

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.

Development and validation of prognostic nomogram for malignant pleural mesothelioma / 中华肿瘤杂志

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.

Activation of Yes-associated protein (YAP) improves mouse acute liver failure by alleviating ferroptosis / 细胞与分子免疫学杂志

Objective To investigate the effects of YAP on the occurrence and progression of acute liver failure by regulating the ferroptosis pathway and its underlying mechanism. Methods A total of 20 8-week-old C57BL/6 mice were randomly divided into four groups: a control group, an acute liver failure model group, a YAP agonist XMU-MP-1 treatment group and a YAP inhibitor verteporfin treatment group, five mice for each group. HE staining was used to observe the pathological changes of hepatic inflammation and necrosis. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by liver biochemistry. Iron (Fe), malondialdehyde (MDA), glutathione (GSH) determination kits were used to measure their levels in liver tissues of each group. The changes of hepatocyte mitochondrial in each group were observed by electron microscopy. Real time PCR and Western blot analysis were used to detect the mRNA and protein expressions of YAP, glutathione peroxidase 4 (GPX4) and 5-lipoxygenase (5-LOX). Results Compared with the control group, mice in the acute liver failure model group and the YAP inhibitor verteporfin treatment group showed severe liver tissue congestion with inflammatory cell infiltration and structural damage to hepatic lobules. Liver injury was alleviated in the XMU-MP-1 treatment group. With the occurrence of liver failure, plasma ALT and AST levels significantly increased, and liver function was improved in XMU-MP-1 treatment group. Electron microscopy showed that mitochondria in hepatocytes of mice with liver failure became smaller and bilayer membrane density increased, while mitochondria changes in the XMU-MP-1 group were alleviated. In addition, the acute liver failure model group showed an increase in Fe and MDA contents, decreased protein expressions of GPX4, and enhanced expression of 5-LOX, suggesting that ferroptosis was involved in acute liver failure in C57BL/6 mice. Ferroptosis was inhibited by activation of YAP. Conclusion Activation of YAP may ameliorate liver injury by inhibiting ferroptosis.

Use a leaflet flap of foot to severed multi-finger with segmental injury / 中国骨伤

OBJECTIVE@#To explore asurgical methods for replantation of severed finger.@*METHODS@#From January 2018 to November 2022, 8 amputated-finger patients were performed surgical reconstructions by using polyfoliate free flaps with the first dorsal metatarsal artery, including 7 males and 1 female, aged from 20 to 55 years old, and defect areas ranged from (1.0 to 2.0) cm×(3.0 to 4.5) cm. Finger pulp sensation, shape and other relevant parameters were assessed following the upper extremity functional evaluation standard, which was put forward by Hand Surgery Branch of Chinese Medical Association. And maryland foot functional score was used to evaluate foot function.@*RESULTS@#Amputated fingers and flaps of all the 8 patients were survived. All patients were followed up for 4 to 20 months, their finger color and temperature tured to normal, with good wear-resistance and cold-resistance. According to Hand Surgery Branch of Chinese Medical Association, functional score ranged 61 to 92;4 patients got excellent result and 4 good. Maryland foot functional score ranged from 93 to 100;and 8 patients got excellent result.@*CONCLUSION@#It is feasible to repair severed fingers with soft tissue defects using polyfoliate free flaps that driven by the flippers of the first and second toes of the foot. This method ccould bridge blood vessels, increase soft tissue volume of the injured finger, and avoid finger shortening, with high patient satisfaction.

Design and application of intelligent bedside mobile payment from the perspective of industry and finance integration / 中华医院管理杂志

Based on the ideas of management systemization, system standardization, process specialisation, post accountability, duty formalization, form informatization, information digitization and digital intelligence, the smart, mobile and paperless bedside billing service was developed which incorporated both functional and financial prospects. The innovation was realized by Internet+ bedside billing and an integrated information platform, so that the inter-hospital billing system could be connected to the medical insurance system, electrical receive system and commercial insurance system. This saved manpower and equipment deployment, and improved service quality. The bedside intelligent mobile billing system of a hospital was launched in January 2021, and the average discharge billing time of inpatients in 2020 and 2021 was 44.36 min and 30.59 min, respectively, and the online billing fee time was significantly shorter than offline billing in 2021, and the differences were all significant( P<0.01).

The experience of surgical methods without repairing the fistula for 92 cases with gastrointestinal intrathoracic fistula / 中华胸心血管外科杂志

Objective:To summarize the experience of surgical methods without repairing the fistula for 92 cases with gastrointestinal intrathoracic fistula.Methods:The surgical methods without repairing the fistula were performed through VATS, small incision assisted with VATS or thoracotomy. The focus of the surgery was to promote lung expansion, eliminate the residual cavity of chest cavity and keep effective drainage. After entering the chest cavity from the affected side, wash chest cavity with a large amount of warm normal saline and sterilize intermittently with iodophor to ensure the sterile environment in the pus cavity. Then completely remove the pleural cellulose or fiberboard on visceral pleura to promote lung expansion, eliminate the residual cavity of the chest cavity. The fistula was covered tightly and supported firmly by the visceral pleura on the lung. Multiple T-tubes were placed in thoracic cavity and fistula to keep effective postoperative drainage.Results:Among 92 cases, 85 cases were cured and the cure rate was 92.4% (85/92).7 cases died and the mortality rate was 7.61% (7/92). The 7 dead cases include 5 cases with esophagogastric anastomotic fistula (the death of 3 cases was cause by aortic esophagogastric fistula, the death of 1 case was cause by thoracic gastric tracheal fistula and 1 case was dead because of pulmonary infection and respiratory failure), 1 case with esophageal rupture (the cause of death was septic shock ), and 1 case with esophageal perforation(the cause of death was pulmonary infection and respiratory failure).Conclusion:Most of the surgeries without repairing gastrointestinal intrathoracic fistula are conducted simply through VATS or small incision assisted with VATS., which is safe and effective.

Analysis of sense of security and anxiety of students in Sichuan Province under major public crisis / 四川精神卫生

ObjectiveTo take COVID-19 as an example to understand the sense of security and anxiety of students in Sichuan province under major public crisis events， and to provide references for psychological education and intervention under the situation of normalized COVID-19 prevention and control. MethodsIn June 2020， a total of 7 319 students from colleges， middle schools and primary schools in Sichuan province were surveyed via Wenjuanxing platform by Security-Insecurity Questionnaire （S-I） and Self-rating Anxiety Scale （SAS）. ResultsThe SAS score of students in Sichuan province was （41.52±9.90）， and the S-I score was （29.88±11.60）， the S-I score of male students was higher than that of female students， and the SAS score was lower than that of female students， the differences were statistically significant （t=5.961， -2.430， P<0.01）. There were significant differences in the total scores of S-I and SAS among students in different academic stages （F=122.579， 60.950， P<0.01）. The total score of S-I and the scores of each dimension were negatively correlated with SAS score （r=-0.553~-0.471， P<0.01）. Linear regression analysis showed that the regression model fitted well （adjusted R2=0.274）， and the model was statistically significant （F=40.802， P<0.01）. Emotional security （β=-0.441， P<0.01） was a significant negative predictor of anxiety. ConclusionUnder major public crisis events， students have a high level of anxiety and a low sense of security. Anxiety and security level are significantly different regarding different genders and school levels. Security has a negative predictive effect on anxiety.

Investigation and case analysis of an occupational chronic benzene poisoning accident / 中华劳动卫生职业病杂志

This article investigated an occupational chronic benzene poisoning incident that occurred in a sealing material factory in Hebei Province in September 2019, analyzed the clinical data of workers, to explore the causes of occupational chronic benzene poisoning, and summarize the diagnosis and treatment characteristics and treatment outcome. According to GBZ 68-2013 "Diagnosis of Occupational Benzene Poisoning", a total of 12 cases of occupational chronic benzene poisoning were diagnosed among the 20 workers, including 2 cases of occupational chronic mild benzene poisoning, 7 cases of moderate benzene poisoning, and 3 cases of severe benzene poisoning. Both mild and moderate poisoning patients had recovered after treatment. Severely poisoned patients had recovered more slowly, and the white blood cell count was still 2.0×10(9)-3.0×10(9)/L during the 1-year follow-up. This benzene poisoning incident was caused by illegal operations. The responsibility of the employer, the supervision of the administrative agency, and the awareness of personal protection of employees should be strengthened to avoid or reduce the occurrence of poisoning incidents and ensure the health of workers.

Effects of low dose hormone replacement therapy on bone mineral density and estrogen level in the treatment of perimenopausal women with osteoporosis / 中国医师进修杂志

Objective:To study the effect of low dose hormone replacement therapy (HRT) on bone mineral density and estrogen level in perimenopausal women with osteoporosis (OP).Methods:A total of 105 perimenopausal OP patients diagnosed and treated in Guangrao County People′s Hospital from March 2019 to May 2020 were selected and divided into the conventional group (51 cases) and the hormone group (54 cases) according to the non-randomized clinical concurrent control study and the principle of patient voluntary. The former group was given conventional drug therapy, while the latter group was given low-dose HRT. Bone mineral density (BMD), bone metabolic markers, endometrial thickness, and hormone levels were compared between the two groups before and after the treatment, and the safety was assessed.Results:After the treatment, bone mineral density values of lumbar L 2 - L 4 and greater trochanter in the hormone group were higher than those in the conventional group: (1.23 ± 0.25) g/cm 2 vs. (1.12 ± 0.27) g/cm 2, (0.62 ± 0.16) g/cm 2 vs. (0.55 ± 0.17) g/cm 2, the differences were statistically significant ( P<0.05). After treatment, the level of bone alkaline phosphatase (BAP) in the hormone group was higher than that in the conventional group: (6.71 ± 1.20) μg/L vs.(5.82 ± 1.04) μg/L; the levels of tartrate resistant acid phosphatase-5b (TRACP-5b), osteocalcin (BGP) in the hormone group were lower than those in the conventional group: (501.42 ± 36.66) pg/L vs. (536.63 ± 38.58) pg/L, (75.86 ± 6.39) U/L vs. (79.32 ± 7.13) U/L, the differences were statistically significant ( P<0.05). After treatment, the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the hormone group were lower than those in the conventional group: (11.23 ± 2.21) U/L vs. (13.31 ± 1.98) U/L, (13.64 ± 3.68) U/L vs. (16.47 ± 4.04) U/L; the level of estradiol (E 2) in the hormone group was higher than that in the conventional group: (98.46 ± 18.34) nmol/L vs. (91.38 ± 17.59) nmol/L, the differences were statistically significant ( P<0.05). There was no significant difference in endometrial thickness between the two groups before and after the treatment ( P>0.05). There were no statistically significant differences in the incidence of adverse reaction and adverse event ( P>0.05). Conclusions:The application of low-dose HRT in the treatment of perimenopausal OP patients can effectively increase the body mineral density value, improve the level of sex hormone and bone metabolism markers, and do not increase the endometrial thickness, with a higher safety.

The role of MYCN and PHOX2B gene combined with plasma cell-free DNA detection in risk stratification and predicting the prognosis of high-risk neuroblastoma / 中华实用儿科临床杂志

Objective:To explore the clinical significance of the MYCN gene, PHOX2B gene and plasma cell-free DNA (cfDNA) in risk stratification and predicting the prognosis of high-risk neuroblastoma (NB). Methods:This was a prospective study involving 94 high-risk NB children admitted to Beijing Children′s Hospital, Capital Medical University from August 2017 to December 2018.Relative levels of MYCN and PHOX2B and cfDNA at diagnosis, and 4 and 6 cycles of chemotherapy were detected, and their differences were compared by the Chi- square test.Kaplan-Meier survival analysis was performed to explore their prognostic potential in high-risk NB. Results:Among the 94 high-risk NB children, 14 cases (14.9%) had MYCN amplification, 76 cases (80.8%) had positive expression of PHOX2B and 56 cases (59.6%) had cfDNA level higher than 100 μg/L.The proportion of high lactate dehydrogenase (LDH, ≥1 500 U/L) level in the MYCN gene amplification group (6/14 cases) was higher than that in the normal group (9/80 cases) ( P=0.009). The proportion of multi-site metastasis (54/76 cases) and high neuron specific enolase (NSE) level (NSE≥370 μg/L, 37/76 cases) in PHOX2B positive group were significantly higher than those in the negative group (5/14 cases, 2/14 cases) ( P=0.015, 0.020). The proportion of high LDH and high NSE in high cfDNA concentration (≥229.6 μg/L)group (13/37 cases, 28/37 cases) were significantly higher than those in low cfDNA concentration group (2/48 cases, 10/48 cases) (all P<0.001). With the decreased tumor burden during the treatment, the copy number of PHOX2B gene and cfDNA level were significantly lower than those at the initial diagnosis [0 (0-719.6) copies vs.1 723.5 (0-186 000.0) copies; 19.0 (1.1-225.5) μg/L vs.200.6 (8.0-5 247.4) μg/L, all P<0.001]. The 2-year event-free survival (EFS) rate of the MYCN gene amplification group was significantly lower than that of the normal group[(33.3±13.1)% vs.(58.5±7.1)%, P=0.020]. The 2-year EFS rate of PHOX2B positive group was significantly lower than that of the negative group[(47.9±7.1)% vs.(79.1±11.1)%, P=0.043]. EFS rate in high cfDNA concentration group was significantly lower than that in cfDNA low concentration group[(38.6±9.8)% vs.( 71.7±8.2)%, P=0.001]. After 6 cycles of chemotherapy, EFS rate in the PHOX2B positive group was significantly lower than that in the negative group [(16.7±14.4)% vs.( 60.6±6.6)%, P=0.014]; which was significantly lower in the Metaiodobenzylguanidine (MIBG) positive group than that of the negative group[(35.2±11.7)% vs.(65.8±7.1)%, P=0.037]. The MYCN gene and cfDNA concentration were not correlated with the prognosis of high-risk NB.Survival analysis of the combination of PHOX2B and MYCN gene ( PHOX2B+ /MIBG + , PHOX2B+ or MIBG + , PHOX2B-/MIBG -) showed a significant difference in the survival among three groups[0 vs.(53.6±1.2)% vs.(65.5±7.4)%, P=0.003]. Conclusions:The MYCN and PHOX2B gene and cfDNA concentration are of significance in risk stratification and predicting the prognosis of high-risk NB.Compared with the MYCN gene and cfDNA concentration, the PHOX2B gene is more suitable for monitoring the curative effect of chemotherapy on high-risk NB.A combined analysis of PHOX2B gene and MIBG before treatment can be more accurate in evaluating the treatment effect and residual lesions.

Progress of miR-196 in the development and diagnosis of non-small cell lung cancer / 国际外科学杂志

Microribonucleic acid (miRNAs) is a widely existing endogenous single-stranded non-coding small RNA, which is stably expressed in tissues and body fluids. By complementing messenger RNA(mRNA) sequences, miRNAs degrade target mRNA and block the expression of protein-coding genes, playing a key role in post-transcriptional regulation and different biological processes. In recent years, more and more studies have shown that miRNAs are closely related to the occurrence and development of tumors. Among them, as a member of the miRNAs family, microribonucleic acid-196 (miR-196) is abnormally expressed in the serum, tissues and cells of patients with non-small cell lung cancer, participating in the occurrence and development of non-small cell lung cancer and playing an important regulatory role in various biological processes such as proliferation, invasion and metastasis, providing diagnostic evidence for early screening of non-small cell lung cancer.This paper reviews the progress of miR-196 in the development and diagnosis of non-small cell lung cancer.

Anatomical analysis of muscle spindles in tibialis anterior and extensor digitorum longus muscle of C57BL/6 mice / 解剖学报

Objective To locate the distribution of muscle spindles in tibialis anterior (TA) and extensor digitorum longus muscle (EDL) and the anchoring mode of muscle spindles in skeletal muscles, and perform statistics analysis of their morphological character by anatomical parameters. Methods Five adult wild type C57BL/6 mice were sacrificed, and TA and EDL were dissected and frozen with improved ultra-low temperature cryopreservation technology avoiding myofibers damaged by possible ice crystal. Continuous frozen transections were obtained and operated by HE staining, followed by microimaging to spot the muscle spindles location. Some parameters including regions length and cross section area (CSA) of muscle spindles were noticed for the discovery of some general characteristics of spindles by statistics. Results For TA and EDL, the scattered characters of muscle spindles were distributed as follows: the spindles were located at the upper third of the mid-belly of both TA and EDL from caudal to rostral position, while near the enter point to muscle of the deep peroneal nerve in dorsal-ventral orientation. The peripheral of muscle spindles anchored to extrafusal fibers to hold in the muscle. And in term of length, region A, connected with sensory nerve ending, demonstrated a significant correlation with region B, which located at the poles of region A and twined by motor nerve ending (correlation index = 0. 75) when considering the muscle spindles with four intrafusal fibers only. And no correlation was discovered in any others pairwise parameters. Conclusion The scattered diagram of muscle spindles in TA and EDL of C57BL/6 mice might provide anatomic basis for evaluation of lower limb motor function, especially for the spinal cord injury and recovery research. And the correlationship between the length of region A and B might improve exploring the variability of electrophysiological characters.

Effect of Suanzaoren Decoction on molecular levels of bile acids in serum, liver, and ileum of insomnia mice / 中国中药杂志

To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.

Discovery of novel 4-phenylquinazoline-based BRD4 inhibitors for cardiac fibrosis

Bromodomain containing protein 4 (BRD4), as an epigenetic reader, can specifically bind to the acetyl lysine residues of histones and has emerged as an attractive therapeutic target for various diseases, including cancer, cardiac remodeling and heart failure. Herein, we described the discovery of hit 5 bearing 4-phenylquinazoline skeleton through a high-throughput virtual screen using 2,003,400 compound library (enamine). Then, structure-activity relationship (SAR) study was performed and 47 new 4-phenylquinazoline derivatives toward BRD4 were further designed, synthesized and evaluated, using HTRF assay set up in our lab. Eventually, we identified compound C-34, which possessed better pharmacokinetic and physicochemical properties as well as lower cytotoxicity against NRCF and NRCM cells, compared to the positive control JQ1. Using computer-based molecular docking and cellular thermal shift assay, we further verified that C-34 could target BRD4 at molecular and cellular levels. Furthermore, treatment with C-34 effectively alleviated fibroblast activation in vitro and cardiac fibrosis in vivo, which was correlated with the decreased expression of BRD4 downstream target c-MYC as well as the depressed TGF-β1/Smad2/3 signaling pathway. Taken together, our findings indicate that novel BRD4 inhibitor C-34 tethering a 4-phenylquinazoline scaffold can serve as a lead compound for further development to treat fibrotic cardiovascular disease.