Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia / 中华儿科杂志

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Research progress on the effects of childhood obstructive sleep apnea syndrome on cognition and brain functions / 生理学报

Obstructive sleep apnea syndrome (OSAS), a prevalent sleep disorder in children, is characterized by recurring upper airway obstruction during sleep. OSAS in children can cause intermittent hypoxia and sleep fragmentation, ultimately affect brain development and further lead to cognitive impairment if lack of timely effective intervention. In recent years, magnetic resonance imaging (MRI) and electroencephalogram (EEG) have been employed to investigate brain structure and function abnormalities in children with OSAS. Previous studies have indicated that children with OSAS showed extensive gray and white matter damage, abnormal brain function in regions such as the frontal lobe and hippocampus, as well as a significant decline in general cognitive function and executive function. However, the existing studies mainly focused on the regional activity, and the mechanism of pediatric OSAS affecting brain networks remains unknown. Moreover, it's unclear whether the alterations in brain structure and function are associated with their cognitive impairment. In this review article, we proposed two future research directions: 1) future studies should utilize the multimodal neuroimaging techniques to reveal the alterations of brain networks organization underlying pediatric OSAS; 2) further investigation is necessary to explore the relationship between brain network alteration and cognitive dysfunction in children with OSAS. With these efforts, it will be promising to identify the neuroimaging biomarkers for monitoring the brain development of children with OSAS as well as aiding its clinical diagnosis, and ultimately develop more effective strategies for intervention, diagnosis, and treatment.

Research progress on neutrophil extracellular traps in oral infectious diseases / 口腔疾病防治

@#Eutrophils are the first innate immune cells to reach the site of inflammation. Neutrophils produce neutrophil extracellular traps (NETs) that can quickly capture and limit the spread of pathogens, facilitating the removal of pathogens and their debris. Neutrophils in the oral cavity are specifically transformed from circulating neutrophils in the blood, and the number of NETs released by oral neutrophils is much higher than that of circulating neutrophils, thus better maintaining the balance of the oral microenvironment. As a bimorphic fungus, only the mycelium phase of Candida albicans can induce NETs, which is related to the neutrophils' ability to sense the size of pathogenic microorganisms through neutrophil elastase. However, spherical Staphylococcus aureus are much smaller than Candida albicans, and they can still induce NETs. Porphyromonas gingivalis, as one of the microorganisms in the periodontitis complex, induces fewer NETs than Streptococcus oralis and Actinomycetes, which are two common oral microorganisms, and there may be a mechanism allowing them to escape neutrophilic immunity in the early stage of periodontitis. Although the two main pathways of NET production have been studied in detail, the mechanisms involved in the induction of NETs by different microorganisms, especially from oral neutrophils, are not well understood. This review describes the mechanism of the immune effects of pathogenic microorganisms on neutrophil NETs in the oral cavity, providing a reference for the search for therapeutic targets and the development of key drugs for treating oral infectious diseases.

Comparison of efficacy of platelet-rich plasma and extracorporeal shock wave for the treatment of chronic insertional Achilles tendinopathy / 中国骨伤

OBJECTIVE@#To compare clinical efficacy of platelet-rich plasma (PRP) and extracorporeal shock wave in treating chronic insertional Achilles tendinopathy.@*METHODS@#From February 2019 to August 2021, 42 patients with chronic insertional Achilles tendinopathy were selected and divided into PRP group(20 patients, 28 feet) and shock wave group (22 patients, 29 feet). In PRP group, there were 12 males and 8 females, aged 47.00(28.00, 50.75) years old, and the courses of disease ranged 7.00(6.00, 7.00) months;PRP injection was performed in the Achilles tendon stop area of the affected side. In shock wave group, there were 16 males and 6 females, aged 42.00(35.75, 47.25) years old;and the courses of disease was 7.00(6.00, 8.00) months;shock wave was performed in Achilles tendon stop area of the affected side and triceps surae area. Visual analogue scale (VAS) and Victorian Institute of Sport Assessment-Achilles (VISA-A) were applied to evaluate clnical effect before treatment, 1, 3 and 6 months after treatment, and satisfaction of patients was investigated.@*RESULTS@#VAS and VISA-A score in both groups were significantly improved at 1, 3 and 6 months after treatment than before treatment (P<0.05), VAS and VISA-A score in PRP group at 6 months after treatment were significantly higher than those at 1 and 3 months after treatment, and VAS and VISA-A score in shock wave group were lower than those at 1 and 3 months after treatment (P<0.05). There was no significant difference in VAS and VISA-A score between two groups before treatment, 1 and 3 months after treatment(P>0.05), while VAS and VISA-A score in PRP group were better than those in shock wave group at 6 months after treatment(P<0.05), and the satisfaction survey in PRP group was better than that in shock wave group(P<0.05).@*CONCLUSION@#PRP injection has a good clinical effect on chronic insertional Achilles tendinopathy with high patient satisfaction, and medium-and long-term effect of PRP injection for the treatment of chronic insertional Achilles tendinopathy is better than that of extracorporeal divergent shock wave.

Social functioning characteristics of children with co occurrence of attention deficit hyperactivity disorder and oppositional defiant disorder / 中国学校卫生

Objective@#To explore the social functioning characteristics of children with co ocurrence of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) for intervention reference.@*Methods@#The Chinese Version of Swanson Nolan and Pelham, Version IV Scale-Parent Form(SNAP-IV), the Chinese Version of Weiss Functional Impairment Scale-Parent(WFIRS-P), and the Questionnaire-Children with Difficulties (QCD) were applied to 192 children with ADHD, 243 children with co occurrence of ADHD and ODD, who firstly visited the Department of Children Psychological Health of Zhuhai Maternal and Child Health Care Hospital, and 118 healthy control children from a school in Zhuhai.@*Results@#The scores of attention deficit factor in SNAP-Ⅳ scale of children in three groups were[1.9(1.7, 2.1), 1.8(1.6, 1.9), 1.0(0.6, 1.2)], the scores of hyperactive impulsivity were[1.8(1.4, 2.1), 1.6(1.1, 1.8), 0.7(0.2, 1.0)] the scores of oppositional defiant were[1.6(1.5, 1.9), 1.0(0.8,1.1), 0.8(0.5, 1.0)], the differences were statistically significant( H=268.44, 237.97, 418.66, P <0.01). The dimensions and total scores of the three groups of children s WFIRS-P scale were family[0.8(0.6, 1.1), 0.6(0.3, 0.8), 0.3(0.1, 0.6)]; learning and school[0.8(0.5, 1.1), 0.8(0.5, 1.0), 0.3(0.1, 0.5)]; life skills[1.0(0.7, 1.2), 0.8(0.6, 1.0), 0.6(0.4, 0.8)]; self management [1.0(0.3, 1.0), 0.7(0.3, 1.0), 0.3(0.0, 0.7)]; social activities [0.7(0.4, 1.0), 0.6(0.3, 0.9), 0.3(0.0, 0.4 )]; adventure activities[0.3(0.2, 0.5), 0.2(0.1, 0.4), 0.1(0.0, 0.2)]; the total score[0.8(0.6, 1.0), 0.6(0.5, 0.8), 0.4( 0.2 , 0.6)], the difference between the groups was statistically significant( H=108.82, 122.45, 60.17, 40.58, 96.17, 76.57, 138.30, P <0.01). The difference between the QCD scale scores of children in the three groups was statistically significant[30.0( 24.0 , 37.0), 32.0(27.0, 40.0), 47.0(37.0, 52.3), H=124.65, P <0.01). Multiple regression analysis showed that attention deficit, and oppositional defiant symptoms were associated with both the total WFIRS-P score and the QCD score of children( R 2= 0.40 , 0.25, P <0.05).@*Conclusion@#Children with co occurrence of ADHD and ODD have more severe deficits in all dimensions of social functioning than children with ADHD, which might be associated with attention deficit and oppositional defiant symptoms.

Construction of an evaluation index system of public health emergency preparedness capacity in county-level centers for disease control and prevention / 预防医学

Objective@#To construct an evaluation index system of public health emergency preparedness capacity in county-level centers for disease control and prevention (CDC), so as to provide the evidence for improving the public health emergency preparedness capacity in county-level CDC.@*Methods@#An index system framework was created based on review of health emergency policies, laws and regulations released in China from 2003 to 2023. The importance, sensitivity and accessibility of indicators were scored and screened through two rounds of Delphi expert consultations, and the weights of indicators were calculated using precedence charts. The efficiency of Delphi expert consultations was evaluated using the active coefficient, authority coefficient and coordination coefficient. @*Results@#Eighteen experts participated in consultations, including 9 men, 15 with educational levels of master degree and higher, 12 with preventive medicine or public health as the specialty, and 12 with deputy senior professional titles and higher. The active coefficients of two rounds of consultations were 100.00% and 94.44%, and the authority coefficients were 0.83 and 0.84, respectively. The coordination coefficients of secondary and tertiary indicators during the second round consultation were 0.341 and 0.241, which were both higher than those during the first round (both P<0.05). The final evaluation index system included 8 primary indicators, 21 secondary indicators and 58 tertiary indicators. Among primary indicators, health emergency organization and management (0.203 1), health emergency team building (0.203 1) and financial support for health emergency (0.203 1) had the highest weights, and of secondary indicators, completion degree of health emergency administration regulations (initial weight/global weight: 0.750 0/0.152 3), health emergency team building (0.750 0/0.152 3) and financial support for emergency (0.750 0/0.152 3) had the highest weights, while among tertiary indicators, defining the duty of health emergency administration sectors had the highest weight (0.750 0/0.114 2). @*Conclusion@#The created evaluation index system is feasible for evaluation of the public health emergency preparedness capacity in county-level CDC.

Interferon-α mediating the functional damage of CD56dimCD57+natural killer cells in peripheral blood of systemic lupus erythematosuss / 北京大学学报(医学版)

OBJECTIVE@#To investigate the regulatory effect of interferon-α (IFN-α) on the apoptosis and killing function of CD56dimCD57+ natural killer (NK) cells in systemic lupus erythematosus (SLE) patients, and to explore the specific mechanism.@*METHODS@#A total of sixty-four newly treated SLE patients and sixteen healthy controls (HC) enrolled in the Second Hospital of Dalian Medical University were selected as the research subjects. And the gene expression levels of molecules related to NK cell-killing function were detected by real-time quantitative polymerase chain reaction. CD56dimCD57+ NK cells were co-cultured with the K562 cells, and the apoptotic K562 cells were labeled with Annexin-Ⅴ and 7-amino-actinomycin D. Peripheral blood mononuclear cells were treated with 20, 40, and 80 μmol/L hydrogen peroxide (H2O2), and treated without H2O2 as control, the expression level of perforin (PRF) was detected by flow cytometry. The concentration of IFN-α in serum was determined by enzyme linked immunosorbent assay. The expression levels of IFN-α receptors (IFNAR) on the surface of CD56dimCD57+ NK cells were detected by flow cytometry, and were represented by mean fluorescence intensity (MFI). CD56dimCD57+ NK cells were treated with 1 000 U/mL IFN-α for 24, 48 and 72 h, and no IFN-α treatment was used as the control, the apoptosis and the expression levels of mitochondrial reactive oxygen species (mtROS) were measured by flow cytometry and represented by MFI.@*RESULTS@#Compared with HC(n=3), the expression levels of PRF1 gene in peripheral blood NK cells of the SLE patients (n=3) were decreased (1.24±0.41 vs. 0.57±0.12, P=0.05). Compared with HC(n=5), the ability of peripheral blood CD56dimCD57+ NK cells in the SLE patients (n=5) to kill K562 cells was significantly decreased (58.61%±10.60% vs. 36.74%±6.27%, P < 0.01). Compared with the control (n=5, 97.51%±1.67%), different concentrations of H2O2 treatment significantly down-regulated the PRF expression levels of CD56dimCD57+ NK cells in a dose-dependent manner, the 20 μmol/L H2O2 PRF was 83.23%±8.48% (n=5, P < 0.05), the 40 μmol/L H2O2 PRF was 79.53%±8.56% (n=5, P < 0.01), the 80 μmol/L H2O2 PRF was 76.67%±7.16% (n=5, P < 0.01). Compared to HC (n=16), the serum IFN-α levels were significantly increased in the SLE patients (n=45) with moderate to high systemic lupus erythematosus disease activity index (SLEDAI≥10) [(55.07±50.36) ng/L vs. (328.2±276.3) ng/L, P < 0.001]. Meanwhile, compared with HC (n=6), IFNAR1 expression in peripheral blood CD56dimCD57+ NK cells of the SLE patients (n=6) were increased (MFI: 292.7±91.9 vs. 483.2±160.3, P < 0.05), and compared with HC (n=6), IFNAR2 expression in peripheral blood CD56dimCD57+ NK cells of the SLE patients (n=7) were increased (MFI: 643.5±113.7 vs. 919.0±246.9, P < 0.05). Compared with control (n=6), the stimulation of IFN-α (n=6) significantly promoted the apoptosis of CD56dimCD57+ NK cells (20.48%±7.01% vs. 37.82%±5.84%, P < 0.05). In addition, compared with the control (n=4, MFI: 1 049±174.5), stimulation of CD56dimCD57+ NK cells with IFN-α at different times significantly promoted the production of mtROS in a time-dependent manner, 48 h MFI was 3 437±1 472 (n=4, P < 0.05), 72 h MFI was 6 495±1 089 (n=4, P < 0.000 1), but there was no significant difference at 24 h of stimulation.@*CONCLUSION@#High serum IFN-α level in SLE patients may induce apoptosis by promoting mtROS production and inhibit perforin expression, which can down-regulate CD56dimCD57+ NK killing function.

A preliminary study of apoptosis in tongue squamous cell carcinoma cells induced by hyperthermia via downregulation of Notch1/Jagged1/Hes1 / 中华放射肿瘤学杂志

Objective:To observe the optimal time interval of multiple short-term hyperthermia in tongue squamous carcinoma Cal-27 cells, and investigate the role of Notch signaling pathway in hyperthermia-induced apoptosis of Cal-27 cells.Methods:Cal-27 cells were placed into a 42℃ incubator for 45 min, and the second hyperthermia was performed at 6 h,12 h, 24 h, 48 h and 72 h later, respectively. Cell proliferation capacity was detected by CCK-8 assay at 0 h, 12 h and 24 h after the end of hyperthermia. After determining the optimal time interval of hyperthermia, multiple cycles of hyperthermia were performed, and the effects of hyperthermia on the proliferation and apoptosis of Cal-27 cells were detected by CCK-8 assay and flow cytometry, respectively. The changes in the expression of Notch1, Jagged1 and hairy and enhancer of split homolog-1 (Hes1) mRNA and proteins were analyzed by real-time reverse transcription PCR (qRT-PCR) and Western blot. All data were expressed as mean±SD. Two-group comparison was performed by one-way ANOVA.Results:Hyperthermia at 42℃ for 45 min every 12 h consistently inhibited the proliferation of Cal-27 cells ( P<0.05). Compared with the control group, hyperthermia in the experiment group significantly inhibited the proliferation and induced the apoptosis of Cal-27 cells after 7 cycles of hyperthermia ( P<0.05), and the expression levels of Notch1, Jagged1 and Hes1 mRNA and proteins in the hyperthermia group were significantly down-regulated (all P<0.05). Conclusions:The optimal time interval of hyperthermia to inhibit the proliferation of tongue squamous cells carcinoma Cal-27 cells is 12 h. Hyperthermia might induce the apoptosis of Cal-27 cells by inhibiting the Notch signaling pathway.

Progress of new anti-seizure medications in elderly patients with epilepsy / 中华神经科杂志

With the rapid aging of the population, elderly epilepsy probably becomes one of the most common forms of epilepsy. Lacosamide, brivaracetam, eslicarbazepine acetate, and perampanel have been approved by the United States Food and Drug Administration and the European Medicines Agency for monotherapy and (or) adjunctive treatment of seizures in the last few years. This review summarizes the efficacy and tolerability of third-generation anti-seizure medications in elderly epilepsy patients and introduces the effects of anti-seizure medications on cognitive function and mood, as well as drug-drug interactions, aiming to provide a reliable basis for clinicians to choose third-generation anti-seizure medications.

Transformation of epilepsy treatment model: anti-epileptogenesis and disease-modifying therapy / 中华神经科杂志

Most anti-seizure medications do not change the course of epilepsy and are basically "symptomatic treatment". Even if a variety of new anti-seizure medications continue to come out, there are still more than 30% of patients develop drug-resistant epilepsy. Therefore, investigating new therapeutic targets and developing effective drugs to prevent or reverse the onset and progression of epilepsy are important goals of clinical and preclinical researches. Based on the current studies, to realize the transformation from anti-seizure to anti-epileptogenesis and disease-modifying therapy, it not only needs standardized animal models and biomarkers that can predict the epileptogenesis or progression but also needs sufficient patients, rigorous design schemes, and cutting-edge analysis methods to successfully transform preclinical research into clinical practice. There is no doubt that in the future, targeting various nerve injury pathways to achieve anti-epileptogenesis and disease-modifying therapy probably becomes a truly effective means of treating and preventing epilepsy.

Investigation and analysis on multidimensional health status of elderly residents in the Meiyuan community, Beijing / 中华老年医学杂志

Objective:To evaluate and analyze elderly health on the physical, psychological and social dimensions, so as to understand the health status and care needs of community-dwelling elderly residents.Methods:A cross-sectional study was carried out in the Meiyuan community, Malianwa Street, Haidian District of Beijing during July 22 to August 26, 2021.A total of 404 people aged 60 and above(70.6±8.6 years old)including 169 men and 235 women were enrolled through cluster sampling.All information about community-dwelling elderly residents was collected with face-to-face interviews and a standardized structured questionnaire for the evaluation and analysis of their physical, mental, social and overall health.Results:The rate of overall healthy residents was 21.3%(86), and the rates of physically, mentally and socially healthy residents were 66.8%(270), 86.6%(350) and 24.3%(98), respectively, in this community.There was a sex difference in social health in the whole group( χ2=9.008, P=0.011)and a higher proportion of men than women were considered generally healthy( χ2=8.963, P=0.003). People in the three age groups(224 in the 60-69 group, 109 in the 70-79 group and 71 in the ≥80 group)showed statistically significant differences in overall, physical, mental and social health( χ2=18.473, 61.186, 43.026 and 18.310, P<0.001), which declined with increasing age( χ2=13.172, 23.515, 26.806 and 10.068, P<0.001 or 0.01). Conclusions:s The overall healthy rate is not high among community-dwelling elderly residents in Beijing.The health status of the elderly gradually deteriorates with age.Health assessment for the elderly should be emphasized and targeted health education and prevention should be provided to promote disease prevention and mental health.

Effect of polydatin on the proliferation and apoptosis of THP-1 cells and the mechanism / 中国当代儿科杂志

OBJECTIVES@#To explore the effect of polydatin on the proliferation and apoptosis of acute monocytic leukemia cell line THP-1 and the possible mechanism.@*METHODS@#After THP-1 cells were treated with polydatin at gradient concentrations for 24 hours and 48 hours, their proliferation was determined by CCK-8 assay, and half maximal inhibitory concentration (IC50) was calculated. Logarithmically growing THP-1 cells were divided into two groups, a polydatin treatment group (treated with IC50 of polydatin) and a blank control group (treated without polydatin solution), and incubated for 48 hours. Cell apoptosis and cell cycle were measured by flow cytometry. The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins were measured by Western blotting.@*RESULTS@#After treatment with polydatin, the proliferation of THP-1 cells was strongly inhibited, and the IC50 at 48 hours was 1 800 μmol/L. After treatment with 1 800 μmol/L polydatin solution for 48 hours, the apoptosis rate of THP-1 cells increased significantly compared with the blank control group (P<0.05). The cell cycle was arrested in the G0/G1 and S phases, with a significantly increased proportion of cells in the G0/G1 phase and a significantly decreased proportion of cells in the S phase, as compared with the blank control group (P<0.05). The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins decreased significantly compared with the blank control group (P<0.05).@*CONCLUSIONS@#Polydatin can effectively inhibit the proliferation, block the cell cycle, and induce the apoptosis of THP-1 cells, which may be related to inhibition of the PI3K/AKT/mTOR signaling pathway.

Effect of Daoqi Tongjing needling method on intra-uterine residue after drug abortion from the perspectives of Hegu (LI 4) and Sanyinjiao (SP 6) / 中国针灸

The paper introduces professor ZHUANG Li-xing's clinical experience in treatment of intra-uterine residue and lochia after drug abortion. Professor ZHUANG believes that this disorder is related to "dysfunction of the thoroughfare vessel and the conception vessel, qi deficiency and blood stagnation, and retention of turbid qi in the uterus" in pathogenesis. The treating principle should focus on "regulating the functions of the thoroughfare vessel and the conception vessel, tonifying qi and eliminating stasis, as well as promoting qi movement". Besides Hegu (LI 4) and Sanyinjiao (SP 6), the acupoints are added from the conception vessel. The Daoqi Tongjing needling technique (the specific technique for directing qi and preserving essence) is exerted flexibly instead of traditional reinforcing and reducing technique of acupuncture to tonify qi and remove stasis.

Progress of genes related to persistent pulmonary hypertension of the newborn / 国际儿科学杂志

Persistent pulmonary hypertension of the newborn(PPHN)is a disease that seriously endangers the life of the newborn caused by one or more factors.The causes mainly include respiratory distress syndrome, meconium aspiration syndrome, infection, congenital diaphragmatic hernia, etc.The pathogenesis of PPHN is still not completely clear, and neurobiochemical, internal environment, genetics and other factors are currently recognized as influencing factors.In recent years, with the rapid development and wide application of genetic testing technology, more and more studies have shown that the occurrence of PPHN may be related to the polymorphism and/or mutation of some genes.This article reviews the research progress of six gene loci that may be related to PPHN in order to provide reference for clinical research.

MF2ResU-Net: a multi-feature fusion deep learning architecture for retinal blood vessel segmentation / 数字中医药（英文）

Objective@#For computer-aided Chinese medical diagnosis and aiming at the problem of insufficient segmentation, a novel multi-level method based on the multi-scale fusion residual neural network (MF2ResU-Net) model is proposed.@*Methods@#To obtain refined features of retinal blood vessels, three cascade connected U-Net networks are employed. To deal with the problem of difference between the parts of encoder and decoder, in MF2ResU-Net, shortcut connections are used to combine the encoder and decoder layers in the blocks. To refine the feature of segmentation, atrous spatial pyramid pooling (ASPP) is embedded to achieve multi-scale features for the final segmentation networks.@*Results@#The MF2ResU-Net was superior to the existing methods on the criteria of sensitivity (Sen), specificity (Spe), accuracy (ACC), and area under curve (AUC), the values of which are 0.8013 and 0.8102, 0.9842 and 0.9809, 0.9700 and 0.9776, and 0.9797 and 0.9837, respectively for DRIVE and CHASE DB1. The results of experiments demonstrated the effectiveness and robustness of the model in the segmentation of complex curvature and small blood vessels.@*Conclusion@#Based on residual connections and multi-feature fusion, the proposed method can obtain accurate segmentation of retinal blood vessels by refining the segmentation features, which can provide another diagnosis method for computer-aided Chinese medical diagnosis.

Significance of serum circRNA hsa_circ_0000437 in the auxiliary diagnosis and prognosis of gastric cancer / 中华检验医学杂志

Objective:To investigate the expression of hsa_circ_0000437 in the serum of patients with gastric cancer and its clinical value.Methods:The serum samples from 80 patients (57 males and 23 females) with pathologically confirmed gastric cancer (GC), 50 gastric benign disease (28 males and 22 females) and 80 healthy controls (46 males and 34 females) were collected from October 2018 to December 2020 in Affiliated Hospital of Nantong University.Serum samples from 35 of 80 gastric cancer patients after operation were collected. The expression of serum hsa_circ_0000437 was determined by real-time fluorescent quantitative PCR (RT-qPCR). Serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA 199) and carbohydrate antigen 724 (CA724) were determined by chemiluminescence method.Comparisons of serum hsa_circ_0000437 between groups were performed by Mann-Whitney U test.The correlation between serum expression of hsa_circ_0000437 in gastric cancer patients and its clinical pathological characteristics was performed by χ 2 test.Receiver operating characteristic (ROC) curve and the area under the curve of ROC (AUC) were used to evaluate their diagnosis efficiency. Kaplan-Meier survival curve analysis was used to analyze the relationship between the expression level of serum hsa_circ_0000437 and the prognosis of patients. Results:The relative expression of hsa_circ_0000437 in GC, gastric benign disease, healthy controls were 2.252 (1.235, 4.765), 1.598(1.139, 1.982) and 1.000 (0.818, 1.385) respectively.The relative expression of hsa_circ_0000437 in GC was significantly higher than that in gastric benign disease ( P<0.001) and healthy controls ( P<0.001). The difference between gastric benign disease and healthy controls was also statistically significant ( P<0.001).The differences of serum hsa_circ_0000437 expression in GC patients between T stage, N stage, and tumor differentiation were statistically significant. The AUC of hsa_circ_0000437, CEA, CA199 and CA724 in GC patients were 0.863, 0.619, 657 and 0.608 respectively compared with healthy controls. The AUC of above four-parameter panel was 0.892 and the sensitivity was up to 97.5% (78/80). Kaplan-Meier survival curve showed that the overall survival rate of patients with high serum hsa_circ_0000437 expression was significantly lower than that of patients with low expression ( P=0.008). Conclusion:Serum hsa_circ_0000437 could be a biomarker for the auxiliary diagnosis and prognosis of GC.

In vivo study of strontium-doped calcium phosphate cement for biological properties / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the biocompatibility and osteogenic effect of new calcium phosphate cement (CPC) in vivo and to provide experimental basis for its further clinical application.@*METHODS@#Thirty New Zealand white rabbits were randomly divided into four groups: CPC group, CPC+Bio-Oss group, Bio-Oss group and blank control group. Bone defect models of 6 mm in diameter and 7 mm in depth were made on the lateral condyle of bilateral hind legs of the rabbits. CPC, Bio-Oss and CPC+Bio-Oss mixture were implanted into the bone defect according to the group, and the mass ratio of CPC and Bio-Oss was 4 ∶ 1. The experimental animals were sacrificed the 4th, 12th and 24th week after operation. The tissue around the bone defect was taken for histological evaluation by H&E staining. Bone ingrowth fraction (BIF) was calculated. The expression of BMP-2 and COL-Ⅰ was detected by immunohis- tochemical staining by calculating the mean optical density (MOD) of the positive area the 4th week after operation, and the bone healing of each group was evaluated at different time points. The measurement data were analyzed by one-way ANOVA and LSD test was used for multiple comparison of the differences between the means by SPSS 19.0. P < 0.05 was considered to be statistically significant.@*RESULTS@#The results of H&E staining showed that the BIF values of CPC group, CPC + Bio-Oss group and Bio-Oss group were significantly higher than those of blank control group at the same time point (P < 0.01). The BIF values of CPC group were lower than those of Bio-Oss group and CPC + Bio-Oss group (P < 0.01). There was no significant difference between CPC + Bio-Oss group and Bio-Oss group. Immunohistochemical staining showed that the MOD values of BMP-2 and COL-Ⅰ in CPC group were higher than those in blank control group, but lower than those in Bio-Oss group and CPC+Bio-Oss group (P < 0.01). There was no significant difference between BMP-2 and COL-Ⅰ in CPC+Bio-Oss group and Bio-Oss group.@*CONCLUSION@#The new calcium phosphate cement has good biocompatibility and can promote early osteogenesis with stable and long-term effect.

Optimization of the Extraction Technology of Zhideke Granules / 中国药房

OBJECTIVE：To optimize the extraction technology of Zhideke granules. ME THODS：The extraction technology （water extraction ，alcohol extraction ，water extraction and ethanol precipitation ）of Zhideke granules was initially screened by ammonia-induced cough experiment and xylene-induced ear swelling experiment in mice. Based on its preparation route ，the immersion time of medicinal materials containing volatile oil was investigated with water absorption as index firstly. The single factor test was adopted to investigate the amount of water added and the extraction time taking the volatile oil yield as index to optimize the extraction technology of medicinal materials containing volatile oil. Taking the contents of irisflorentin and total flavonoids as indicators ，on the basis of single factor investigation ，orthogonal test was adopted to examine the influence of three factors including the amount of water added ，extraction time and extraction frequency ，so as to optimize the water extraction technology of Zhideke granules and the validation tests were conducted. RESULTS ：The results of pharmacodynamics experiment showed that the cough latency of mice in water extract low-dose and high-dose groups （6.34，12.68 g/kg，by crude drug ）and water-extraction alcohol-precipitation extract high-dose group （12.68 g/kg，by crude drug ）were significantly longer than those inmodel group ，and the number of cough within 2 minutes was significantly reduced （P＜0.05 or P＜0.01）. Compared with model group ， the ear swelling of mice in water extract low-dose and high-dose groups （6.34，12.68 g/kg，by crude drug），ethanol extract high-dose group （12.68 g/kg，by crude drug） and water-extraction alcohol-precipitation extract hig dose group （12.68 g/kg，by crude drug ） were decreased significantly （P＜0.05 or P＜0.01）. The swelling inhibition rates were 42.26％，55.08％，33.49％，51.56％，39.57％ and 44.36％ in low-dose and high-dose groups of water extract ，alcohol extract ， water-extraction and alcohol-precipitation extract respectively ，indicating that the water extract had better antitussive and anti-inflammatory effects. The optimal extraction technology of volatile oil was adding 5-fold water ，soaking for 30 minutes，and extracting for 3 hours. The optimal water extraction technology was adding 12-fold water ，extracting for 3 times after soaked for 50 min，lasting for 1 h each time. Results of 3 times of validation tests showed that average content of irisflorentin in the extract obtained by optimal technology was 76.47 μg/g（RSD＝ 2.15％，n＝3）and the average content of total flavonoids was 92.45 mg/g（RSD＝0.48％，n＝3）. CONCLUSIONS ：The optimal extraction technology of Zhideke granules is stable and feasible.

Primary Study on Chronic Myeloid Leukemia in NCG Mice from Qinba Mushroom / 中国实验血液学杂志

OBJECTIVE@#The present study was to evaluate the anti-tumor effects of acidic RNA protein complex (FA-2-b-β) extracted from the wild edible Qinba mushroom in inducing of apoptosis and immunoregulation of tumor cell.@*METHODS@#Cell proliferation inducing rate of FA-2-b-β to K562 cell was measured using CCK-8. Apoptosis rate was detected by using flow cytometry. Chronic myeloid leukemia model was developed by tail vein injection/subcutaneous inoculation of K562 cells in NCG mice. The tumor burden of mice was observed. The general condition of the mice was monitored twice daily. The peripherivcal full blood counts of mice was tested daily. RT-qPCR and Western blot was FA-2-b-β performed to determine involvement of apoptotic-related gene and protenin, Immunofluorescence and immunohistochemistry was used to detected the expression of CD3, CD4 and CD8.@*RESULTS@#The proliferation and apoptosis of K562 cell could be inhibitied and induced by FA-2-b-β, there was 100% successful in the tumor formation in vivo, after treated by drug for 21 days there were significantly increased peripheral leucocytes, but decreased hemoglobin of mice treated by FA-2-b-β as compared with those in control group. The CD3, CD4 and CD8 showed positive in mice, and the propotation was imbalance, but it showed reserved after treated by FA-2-b-β.@*CONCLUSION@#FA-2-b-β is strong anti-leukemia effect in vitro and in vivo, suggesting the traditional Chinese medicine maybe contribute to the anti-cancer and immunoregulation research.

Critical quality attribute assessment of big brand traditional Chinese medicine: online NIR quality control research on boiling time during extraction process / 中国中药杂志

Assessment of the status property(boiling time) is a challenge for the quality control of extraction process in pharmaceutical enterprises. In this study, the pilot extraction process of Phellodendron chinense was used as the research carrier to develop an online near-infrared(NIR) quality control method based on the status property(boiling time). First, the NIR spectra of P. chinense were collected during the two pilot-scale extraction processes, and the status property(boiling time) was assessed by observing the state of bubbles in the extraction tank using a transparent window during the extraction process, which was then used as a reference standard. Based on the moving block standard deviation(MBSD) algorithm, the assessment model using online NIR spectra for boiling time during extraction process was established. In addition, the model was optimized as follows: standard normal variable(SNV) for spectral pretreatment, modeling band of 800-2 200 nm, and window size of 4. The results showed that, with 0.002 0 as the MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process. Furthermore, the principal component analysis-moving block standard deviation(PCA-MBSD) model was developed by our group to reduce the influence of online NIR spectral noise and background signal on the model, and the number of principal components was optimized into 2 in the PCA-MBSD model. The results showed that, with 0.000 075 as the PCA-MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process, with improved reliability. This study can provide a assessment method for boiling time during extraction process using online NIR spectra, which can replace the empirical judgment in manual observation, and realize the digitalization of the extraction process for big brand traditional Chinese medicine.