Current Research Status and Application Technical Progress of Small Molecule Drug Screening Technology / 医药导报

Small molecule drug screening technology is continuously evolving and expanding along with drug discovery,and the innovation in drug screening technology can improve the research and development efficiency and success rate,shorten the cycle time,and reduce the cost.From traditional screening technologies based on known active compounds and high-throughput screening(HTS)to new technologies such as structure-based drug discovery(SBDD),fragment-based drug discovery(FBDD),DNA encoded compound library(DEL)and proteolysis targeting chimeras(PROTAC),small molecule drug screening technologies are continuously broadening the market potential for small molecule drugs.This article will provide an overview of the current status of small molecule drug screening technology,systematically review each technique along with their advantages and disadvantages,and offer essential insights for the development of new small molecule drug screening technologies.

Analysis of goitrogenic effect of goitrogen in food / 中华地方病学杂志

Goiter is a kind of non-inflammatory and non-neoplastic hyperplasia and enlargement. Many studies have shown that substances such as thiocyanates and isothiocyanates can prevent the development of a variety of tumors. However, some studies have also found that such substances can lead to goiter. In this article, relevant information on common goitrogen in food are collected to explore their mechanism of action, laying a foundation for guiding residents to maintain a healthy and balanced diet.

Association between screen time and psychological behaviors of preschool children in Lanzhou City / 中国儿童保健杂志

【Objective】 To analyze the associations between different types of video screen time and psychological behaviors of preschool children, in order to provide evidence for promoting the development of children′s mental health. 【Methods】 From February to March 2023, a total of 1 361 parents of children aged 3 - 6 years from 6 kindergartens of Lanzhou were surveyed by cluster sampling method.Parents were surveyed to obtain information about the video use, and the children′s Strengths and Difficulties questionnaire (parent version) was used to assess children′s psychological and behavioral problems. 【Results】 The rate of daily screen time exceeding standard was 36.96% (503/1 361).The screen time was mainly spent in watching TV cartoons, followed by educational APP.The detection rate of abnormal total difficulty score was 11.61% (158/1 361), and the abnormalities of peer communication (32.26%) and prosocial behavior (12.34%) were the most prominent.After adjusting for related factors by multiple Logistic regression analysis, total screen time≥2h/d (OR=1.802) was found to be a risk factor for abnormal total difficulty score; watching TV cartoons≥2h/d was a risk factor for abnormal total difficulty score (OR=2.409) and peer communication (OR=2.222); playing games≥1h/d was a risk factor for abnormal total difficulty score, emotional symptoms, conduct problems, hyperactive behavior, and abnormalities of peer communication, the differences were all statistically significant (P<0.05).However, educational APP screen time<1h/d was a protective factor for abnormal total difficulty score(OR=0.615) and prosocial behavior (OR=0.549), but educational APP screen time≥2h/d was a risk factor for conduct problems (OR=2.302), the differences were all statistically significant (P<0.05). 【Conclusions】 The screen time of preschool children in Lanzhou cannot be ignored, and there is a significant correlation between overuse and children′s psychological and behavioral problems.Parents and schools should attach importance to the parent-child and peer interaction of preschool children and strengthen the intervention of preschool children′s video behavior.

Effect of early immunotherapy in preventing conversion of ocular myasthenia gravis to generalized myasthenia gravis / 西安交通大学学报(医学版)

【Objective】 To compare the risk of generalization in patients with ocular myasthenia gravis (OMG) receiving or not receiving immunosuppressive treatment. 【Methods】 The data of patients with OMG registered in Tangdu Hospital of Air Force Military Medical University from January 1, 2015 to May 1, 2019 were reviewed; the patients were divided into treatment group and control group according to whether they had received immunosuppressive treatment. The multivariate Cox proportional hazards regression model analysis was used to compare the risk of generalization between the two groups of patients within 2 years of onset. Sensitivity analysis was used to evaluate the duration of immunosuppressive treatment and the risk of generalization under different immunotherapy regimens. By using stratified analysis, the consistency of the main results across different levels of subgroup factors was evaluated. 【Results】 A total of 702 OMG patients were collected. Of them 367 patients (52.3%) were included in the treatment group, with an average onset age of (50.54±15.1) years, and 159 (43.3%) being female. Another 335 patients (47.7%) were included in the control group, with an average age of (49.1±14.6) years, and 159 ones (47.5%) were female. A total of 28 cases (7.7%) in the treatment group and 106 cases (31.6%) in the control group developed generalization during the observation period. After multivariate-adjusted Cox model analysis, patients who had received immunosuppressive treatment had a significantly lower risk of generalization compared with the control group (HR=0.24; 95% CI: 0.15-0.37; P<0.001). Sensitivity analysis found that the longer the duration of immunosuppression, the lower the risk of generalization (HR=0.88; 95% CI: 0.85-0.91; P<0.001). Stratified analysis showed that immunosuppressive therapy reduced the risk of generalization in different subgroups of patients. 【Conclusion】 Early immunosuppressive treatment can significantly reduce the risk of generalization in patients with OMG.

The role of Nrf2 in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated MMP9 / 中华劳动卫生职业病杂志

Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.

The pathological role of hypersplenism in the course of liver cirrhosis / 中华肝胆外科杂志

Hypersplenism is an important complication of cirrhotic portal hypertension, and splenectomy is an important means to treat hypersplenism in cirrhosis. It is realized that hypersplenism played a pathological role in the course of cirrhosis. This article analyzes and compares the changes in the condition of patients with cirrhosis between splenectomy with and without hyperfunction, and comprehensively discusses the pathological role and mechanism of hypersplenism in the course of cirrhosis, in order to strengthen the clinical prevention and treatment of hypersplenism in cirrhosis and to better improve the condition and prognosis of patients with cirrhosis.

Research progress of DNA methylation in the diagnosis of early colorectal cancer / 国际外科学杂志

Colorectal cancer is a common tumor of the digestive system with a high degree of malignancy. Most patients are in the advanced stages of the disease when they develop symptoms. Although the detection rate of traditional screening methods is improving with advances in imaging and the popularity of colonoscopy, the diagnosis of early, asymptomatic colon cancer is still unsatisfactory. Therefore, it is particularly important to further study the occurrence and development mechanism of colorectal cancer and obtain new ideas for the diagnosis and treatment.? In recent years, with the deepening of epigenetics research, the role of DNA methylation in the pathogenesis of colorectal cancer has gradually attracted attention. This paper will review the research progress of DNA methylation in colorectal cancer′s diagnosis and treatment.

Visualization analysis of microfluidics research status / 生物医学工程学杂志

Microfluidics is the science and technology to manipulate small amounts of fluids in micro/nano-scale space. Multiple modules could be integrated into microfluidic device, and due to its advantages of microminiaturization and controllability, microfluidics has drawn extensive attention since its birth. In this paper, the literature data related to microfluidics research from January 1, 2006 to December 31, 2021 were obtained from Web of Science Core Collection database. CiteSpace 5.8.R3 software was used for bibliometrics analysis, so as to explore the research progress and development trends of microfluidics research at home and abroad. Based on the analysis of 50 129 articles, it could be seen that microfluidics was a hot topic of global concern, and the United States had a certain degree of authority in this field. Massachusetts Institute of Technology and Harvard University not only had a high number of publications, but also had strong influence and extensive cooperation network. Combined with ultrasonic, surface modification and sensor technology, researchers constructed paper-based microfluidic, droplet microfluidic and digital microfluidic platforms, which were applied in the field of immediate diagnosis, nucleic acid and circulating tumor cell analysis of in vitro diagnosis and organ-on-a-chip. China was one of the countries with a high level of research in the field of microfluidics, while the industrialization of high-end products needed to be improved. As people's demand for disease risk prediction and health management increased, promoting microfluidic technological innovation and achievement transformation is of great significance to safeguard people's life and health.

Technical progress and industrial development of in vitro diagnostic / 中华检验医学杂志

In vitro diagnosis (IVD) is an important source of clinical diagnostic information, and provides an important decision basis for disease prevention, diagnosis and treatment. IVD is a necessary tool for promoting graded diagnosis and treatment, realizing precision medicine, constructing a "Healthy China" and responding to major public health emergencies. Combining the great progress made in the development of in vitro diagnostics in China and the shortcomings and weaknesses faced by it, this article analyzed the demand for IVD, policy support, technical and industrial development trends, and the ways to accelerate the industrialization development, aiming to promote the development and improvement of IVD in China.

Seed oil of Brucea javanica induces apoptosis through the PI3K/Akt signaling pathway in acute lymphocytic leukemia Jurkat cells / 中国天然药物

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3β was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.

Clinical screening and genetic diagnosis for Prader-Willi syndrome / 中国当代儿科杂志

OBJECTIVE@#To study the clinical screening and genetic diagnosis of children suspected of Prader-Willi syndrome (PWS), as well as the differences in the scores of clinical diagnostic criteria among the children with a confirmed diagnosis of PWS.@*METHODS@#A total of 94 children suspected of PWS who were admitted from July 2016 to December 2018 were enrolled as subjects. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to confirm the diagnosis. For the children with a confirmed diagnosis of PWS, the scores of clinical diagnostic criteria were determined, and the perinatal characteristics were analyzed.@*RESULTS@#A total of 11 children with PWS were confirmed by MS-MLPA, with a detection rate of 12%, among whom there were 7 boys and 4 girls, with a median age of 3 years and 4 months (range 25 days to 6 years and 8 months) at the time of confirmed diagnosis. Among the 11 children with PWS, only 5 children (45%) met the criteria for clinical diagnosis. The main perinatal characteristics of the children with PWS were decreased fetal movement (9 cases, 82%), cesarean section birth (11 cases, 100%), hypotonia (11 cases, 100%), feeding difficulties (11 cases, 100%), and weak crying (11 cases, 100%).@*CONCLUSIONS@#Gene testing should be performed as early as possible for children suspected of PWS by clinical screening. PWS may be missed if only based on the scores of clinical diagnostic criteria.

Relationship between hemoglobin level and nonalcoholic fatty liver disease in male patients with primary gout / 中华全科医师杂志

Four hundred and four male patients with primary gout were enrolled. According to the degree of nonalcoholic fatty liver diseases (NAFLD), the patients were divided into simple gout ( n=121), gout combined with mild NAFLD ( n=149) and gout combined with moderate-severe NAFLD ( n=134). The height, weight, waist, hip, blood pressure and blood biochemistry parameters of patients were measured. The degree of NAFLD was negatively correlated with the age of patients in three groups. The BMI, ratio of waist/hip, count of red cells, hemoglobin, hematocrit, red blood cell distribution width ( SD and CV), triglyceride, alanine aminotransferase and HOMA-IR were increased with the increasing of NAFLD severity (all P<0.05). Red blood cell count, hemoglobin, alanine aminotransferase, serum uric acid increased with the increasing of NAFLD severity (all P<0.05). Platelet, serum urea nitrogen and serum creatinine were decreased with the increase of NAFLD severity. Logistic regression showed that BMI, hemoglobin and HOMA-IR were independent risk factors for NAFLD. The prevalence and the severity of NAFLD was increased with increasing quadrates of hemoglobin. Taking group Q1 as a control, OR of NAFLD in group Q2 was 1.166(95 %CI:0.638-2.133), OR in group Q3 was 2.011(95 %CI:1.122-3.605)and OR in group Q4 was 3.120(95 %CI:1.613-6.034). The result indicates that hemoglobin levels are associated with the development and the severity of NAFLD in male patients with primary gout.

The effects of early exercise on the cortical spinal tract after cerebral infarction / 中华物理医学与康复杂志

Objective:To observe the effect of early exercise intervention on the corticospinal tract of rats with cerebral infarction.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sedentary group (SED), a 1 day later exercise group (1D) and a 1 week later exercise group (1W), each of 6. A modified Longa′s method was used to occlude the middle cerebral artery to model a stroke. Rats in the 1D and 1W groups started exercising 1 day and 1 week after the modeling, while those in the sedentary group were placed on a stationary treadmill for 30 minutes every day. Modified neurological severity scores (mNSSs) were used to quantify neurological functioning after 1, 4 and 8 weeks. Magnetic resonance imaging was used to calculate the infarct volume ratio, and diffusion tensor imaging was used to detect the fractional anisotropy ratio (rFA) of the corticospinal tract for correlation with the mNSS scores. The corticospinal cord′s morphology was observed using DTT.Results:After 1 week the average mNSS score of the 1D group was significantly lower than the other two groups′ averages. At 4 weeks the average mNSS scores of both the 1D and the 1W group were significantly lower than the sedentary group′s average. At 8 weeks the 1D group′s average mNSS score was significantly lower than those of the other two groups, while that of the 1W group was significantly lower than the sedentary group′s average. At 1 and 4 weeks after modeling the average infarct volume ratio in the 1D group was significantly lower than those of the other groups. By 4 weeks the average infarct volume ratio of the 1W group was significantly lower than that of the sedentary group, and by 8 weeks the average infarct volume ratios of both the 1D and 1W groups was significantly lower than that of the sedentary group. After 1 week the average rFA of the 1D group was significantly lower than that of the sedentary group, but by 4 weeks the averages of the 1D group and the 1W group were both significantly higher than the sedentary group′s average. At 8 weeks the 1D group′s average rFA was significantly above that of the 1W group and of the sedentary group, and that of the 1W group was significantly higher than that of the sedentary group. After 8 weeks the corticospinal tracts in the 1D group appeared to be more symmetrical than those of the other 2 groups. The rFA results correlated strongly with the mNSS scores ( r=-0.707). Conclusions:Exercise can promote corticospinal cord remodeling and improve neurological function after cerebral infarction, at least in rats. It should be started as early as possible.

Awareness of Autonomic Dysreflexia post Spinal Cord Injury in Surgeons / 中国康复理论与实践

Objective To investigate the levels of knowledge on autonomic dysreflexia (AD) following spinal cord injury (SCI) from surgeons.Methods September 1st to 30th, 71 surgeons from seven departments were tested with the knowledge about AD with a questionnaire.Results Only 35％ of them gave the correct answer above 60％ of the items. The items that got respondence less than 60％ involved in those about causes, clinical signs and symptoms, diagnosis, and treatment for AD. The respondence about knowledge of causes, clinical signs and symptoms, and treatment for AD was different among departments (F＞ 2.270, P ＜ 0.05). The respondence about knowledge of treatment for AD was different among the surgeons who had managed different numbers of SCI patients (F = 4.043, P ＜ 0.05). The knowledge of clinical signs and symptoms, and treatment was different among the surgeons with their self-reported knowledge level of AD (F = 5.519, P ＜ 0.01). There was no difference in knowledge for AD among the surgeons with different educational background, technological position and length of career (F ＜ 2.107, P＞ 0.05).Conclusion The knowledge about AD needs to improve in the surgeons.

Non-coding RNA and tumor immune regulation / 药学学报

non-coding RNA (ncRNA) is a kind of non-protein coding RNA, which plays a vital role in the initiation and development of tumor. The immune system also exhibits more complex function in tumor development. It can not only inhibit the development of tumor, but also create conditions for tumor growth. As an important means of tumor therapy, tumor immunotherapy can be regulated by non-coding RNA to achieve the goal of treatment. This article summarizes the regulation of tumor immunity by non-coding RNA.

Modified Bascom cleft lift procedure for chronic pilonidal sinus / 中华普通外科杂志

Objective To evaluate the clinical efficacy of modified Bascom cleft lift procedure in the treatment of chronic sinus.Methods Modified Bascom cleft lift procedure was performed in 53 patients admitted from Oct 2012 to Jul 2016.49 cases were male and 4 were female.The average age was (25.4± 2.3) years.Results All patients were satisfied with the operation.There were 49 cases of primary healing and 4 cases of incision complications.The average follow-up was (12.1 ±4.3) months,no recurrence was observed.Conclusion The modified Bascom cleft lift technique is effective and reliable,with less complications and a lower recurrence rate.

Clinical Characteristics and Treatment of Autonomic Dysreflexia after Spinal Cord Injury (review) / 中国康复理论与实践

@#Autonomic dysreflexia (AD) is an emergency commonly happened in patients with spinal cord injury (SCI) above T6 and especially in chronic SCI patients. AD is usually triggered by stimuli below the injury level. Sudden elevated blood pressure is the main clinical symptom and cardiovascular and/or cerebral complication even death if effective treatments are not provided. Mechanisms contributed to AD possibly are dysfunction of supra spinal control, plastic changes of neurons and receptors. Preventive measures and managements such as removal of risk factor, adjustment of body position, and pharmacological treatment are now in use.

Two new C steroidal glycosides isolated from Cynanchum komarovii / 中国天然药物

The present study was designed to further investigate the C steroidal glycosides in Cynanchum plants. Two new steroidal glycosides based on a 13, 14:14, 15-disecopregnane-type aglycone, komaroside P (1) and komaroside Q (2), together with three known compounds (3-5) were isolated from the whole herbs of Cynanchum komarovii. The aglycones of compounds 1 and 2 were two new disecopregnane. Their structures were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. All the compounds (1-5) showed potent inhibitory activities against human leukemia cell lines (HL-60) with IC values ranging from 16.6 to 26.3 μmol·L, compared to the positive control 5-fluorouracil (6.4 μmol·L).

Analysis of human genetic resources project application for examination and approval / 中华医学科研管理杂志

Objective To summarize the characteristic of projects accepted by human genetic resources management office in 2016 and put forward further measures.Methods Statistic analyses were carried out based on the overall projects application,then Chinese application units and partners were analyzed separately.Results 1 138 international cooperation projects were approved in total,mainly on clinical research.24 countries were involved with increasing trend of globalization.Conclusions The human genetic resources management played a positive role in the development of the biomedical research and industry.

Association of +45 and +276 polymorphisms in the adiponectin gene with the development of Kawasaki disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the distribution of adiponectin +45T/G and +276G/T polymorphisms and its association with the development of Kawasaki disease and coronary artery lesion (CAL).</p><p><b>METHODS</b>A total of 81 children with Kawasaki disease (among whom 11 had CAL) and 100 normal children who underwent physical examination (control group) were enrolled in a case-control study. Sequencing was performed to investigate the distribution of adiponectin +45T/G and +276G/T polymorphisms.</p><p><b>RESULTS</b>There were no significant differences between the Kawasaki disease and control groups in the frequencies of TT, TG, and GG genotypes and T/G alleles of +45T/G polymorphism in the adiponectin gene (P>0.05). In the Kawasaki disease group, there were also no significant differences in the genotype and allele frequencies of the +45T/G polymorphism between the children with CAL and those without (P>0.05). There were significant differences between the Kawasaki disease and control groups in the frequencies of GG, GT, and TT genotypes and G/T alleles of +276G/T polymorphism in the adiponectin gene (P<0.05). GG genotype was a risk factor for the development of Kawasaki disease (OR=2.313, P=0.006). In the Kawasaki disease group, there was no significant difference in the genotype distribution of the +276G/T polymorphism between the children with CAL and those without (P>0.05).</p><p><b>CONCLUSIONS</b>The adiponectin +276G/T polymorphism may be associated with the development of Kawasaki disease, but not associated with CAL. The adiponectin +45T/G polymorphism may not be associated with Kawasaki disease or CAL.</p>