Effects of lead exposure on development of heart and spine in zebrafish embryos / 环境与职业医学

Background Lead is widely distributed. Lead exposure interferes with early life development in zebrafish, but the mechanisms by which lead exposure affects skeletal development and cardiac development are not clear as yet. Objective To investigate the molecular mechanisms of bone development and cardiac development toxicity induced by lead acetate exposure. Methods Zebrafish embryos were exposed to different concentrations of lead acetate (0, 6, 12, 24, and 48 μmol·L−1) for 3 h post-fertilization (3 hpf) until 5 d post-fertilization (5 dpf). The malformation phenotypes of 5 dpf were counted, and the mRNA expressions of spinal development-related genes (bmp2b, bmp4, bmp9, runx2a, runx2b) and heart development-related genes (nkx2.5, myh6, myh7) were detected by quantitative PCR (qPCR). Expressions of genes of development-related regulatory pathways including Wnt/β-catenin pathway (wnt5a, wnt8a, wnt10a, β-catenin) and TGF-β pathway (tgf-β1, tgf-β2) as well as key molecule eph of Eph-Ephrin signaling were analyzed. Results At 5 dpf, the zebrafish in the lead acetate treated groups showed deformed phenotypes including spinal curvature and pericardial sac edema compared to the control group. In the lead acetate groups at 24 and 48 μmol·L−1, the spinal curvature deformity rates reached 26.47% and 71.52% (P<0.01) respectively. The qPCR results revealed that the expression levels of spinal development-related genes bmp2b, bmp4, bmp9, runx2a, and runx2b were downregulated in the 48 μmol·L−1 exposure group compared to the control group by 82.8%, 58.0%, 88.7%, 85.5%, and 69.2%, respectively (P<0.05 or P<0.01); the expression levels of heart development-related genes myh6, myh7, and nkx2.5 were down-regulated by 63.7%, 58.9%, and 55.2%, respectively (P<0.01); the expression levels of wnt8a and β-catenin in the Wnt/β-catenin pathway were down-regulated by 71.5% and 47.3% (P < 0.05 or P < 0.01), respectively; the expression level of tgf- β1 in the TGF-β pathway was down-regulated by 67.5% (P<0.01); the expression level of eph was down-regulated by 86.9% (P<0.01). Conclusion Lead acetate exerts developmental toxic effects on zebrafish heart and bone by down-regulating the expressions of genes related to spinal development and heart development, as well as inhibiting development-related Wnt/β-catenin and TGF-β pathways and Eph-Ephrin signaling, causing malformed phenotypes such as spinal curvature and pericardial sac edema.

Meta-analysis of the efficacy and safety of 0.05% cyclosporine A in the treatment of dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To systematically evaluate the safety and efficacy of 0.05% cyclosporine A(CsA)in the treatment of dry eye.METHODS: PubMed, Web of Science, Cochrane Library, Embase, Chinese Bio-Medical Literature Database, CNKI, VIP, and Wan Fang Database were retrieved. Randomized controlled trials related to the treatment of dry eye with 0.05%CsA from January 1, 2016 to March 28, 2022 in each database were included. The CsA group was treated with 0.05% CsA eye drops, and the control group was treated with artificial tears and placebo. ReMan 5.3 was used for Meta-analysis of post-treatment Schirmer Ⅰ test(SⅠt), break up time(BUT), corneal fluorescein staining(CFS), ocular surface disease index(OSDI)and adverse effects.RESULTS: A total of 13 literatures were included, which included 1 164 cases(2 057 eyes). Compared with the control group, the SIt in the CsA group was prolonged(MD=2.04, 95%CI: 1.75～2.33, P&#x0026;#x003C;0.00001), BUT was longer(MD=1.32, 95%CI: 0.87～1.76, P&#x0026;#x003C;0.00001), CFS decreased(MD=-0.79, 95%CI: -1.20～-0.39, P=0.0001)and OSDI decreased(MD=-5.52, 95%CI: -9.14～-1.91, P=0.003). However, the CsA group had more adverse reactions(OR=1.69, 95%CI: 1.06～2.72, P=0.03).CONCLUSION: 0.05% CsA can improve the subjective symptoms and various objective indicators of dry eye patients. However, 0.05% CsA seems to produce more adverse effects, like ocular burning sensation when compared to drugs such as artificial tears.

Correlation of serum creatinine, blood urea nitrogen and uric acid levels in patients with nephrotic syndrome / 公共卫生与预防医学

Objective To explore the correlation between serum creatinine, blood urea nitrogen content and uric acid level in adult nephrotie syndrome (AS) patients of different ages, in order to provide a theoretical basis for the prevention and control of uric acid metabolism. Methods Individuals of different ages who were diagnosed with nephrotic syndrome from March 2018 to August 2020 in the outpatient department of our hospital were selected as research subjects by stratified random sampling,healthy individuals who underwent physical examination during the same period were selected as controls .The age range of the subjects was 18-55 years old. The biochemical test results of serum creatinine, blood urea nitrogen and uric acid were retrospectively collected from patients of different ages. Pearson correlation analysis of adult serum creatinine, blood urea nitrogen and uric acid levels. Results The levels of creatinine and blood urea nitrogen in healthy adults showed an upward trend at the age of 18-40, and reached a plateau at the age of 40; while the level of uric acid showed an upward trend with age. The levels of serum creatinine, blood urea nitrogen and uric acid in AS patients at different ages were higher than those in healthy controls, and the increase was most pronounced between the ages of 45 and 55. The t-test results showed that the serum creatinine, blood urea nitrogen and uric acid contents of healthy controls were different from those of AS patients except for the 18-22 age group. The main performance was that AS patients had higher measured values than healthy controls. Pearson correlation was used to analyze the correlation between serum creatinine and blood urea nitrogen levels and uric acid in AS patients of different ages. The results showed that the 41-45-year-old patients had the strongest correlation with uric acid, r was 0.584; The patients' blood urea nitrogen level had the strongest correlation with uric acid, with r of 0.373. The age groups with the correlation between serum creatinine, blood urea nitrogen and uric acid content in AS patients were stratified according to gender. There was a significant positive correlation (r>0.45, P0.30, P<0.05). Conclusion The expression level of serum creatinine in 34-45 years old patients with nephrotic syndrome can effectively predict the level of uric acid, and the predictive value of women is higher than that of men.

Study on the mechanism of Wenyang huazhuo tongluo formula contained serum inhibiting the proliferation of Th17 cells in scleroderma patients / 中国药房

OBJECTIVE To study the effects of Wenyang huazhuo tongluo formula conta ined serum on the expression and methylation of retinoic acid related nuclear orphan receptor （RORγt），and to explore the mechanism of its regulation of Th 17 cell proliferation in the treatment of scleroderma. METHODS Wistar rats were given 15，30，60 g/（kg·d）Wenyang huazhuo tongluo formula intragastrically to prepare different doses of drug-contained serum ，and peripheral blood of scleroderma patients were collected to sort Th 17 cells. Using blank serum as blank control ，methyltransferase inhibitor decitabine （DCA）as positive control ， Th17 cells were treated with different concentrations of drug-contained serum ，and then the proliferation of Th 17 cells was detected by CCK- 8；mRNA expressions of RORγt and IL-17 were detected by qRT-PCR ，and the protein expression of RORγt was detected by Western blot assay ；the protein expression of IL- 17 in the cell supernatant was detected by ELISA ，and the methylation level of RORγt gene promoter was detected by methylation-specific PCR. The transcriptional activity of RORγt gene promoter was detected by dual-luciferase assay. RESULTS Compared with blank control ，Wenyang huazhuo tongluo formula contained serum and DCA could inhibit the proliferation of Th 17 cells（P＜0.05），reduced the mRNA and protein expressions of RORγt and IL-17，enhanced the methylation level of RORγt gene promoter and attenuated ， the transcription activity of RORγt gene promoter. Except for mRNA expression of Th 17 and the methylation level of RORγt gene promoter in drug-contained serum low-dose group ，there were statistical significance in above indexes of other groups（P＜0.05）. CONCLUSIONS Wenyang huazhuo tongluo formula can promote the methylation lev el of RORγt gene，and inhibit the expression of RORγt and the secretion of IL-17，so as to inhibit the proliferation of Th 17 cells.

TRIM21 suppresses invasion of hepatocellular carcinoma cells by promoting β-catenin ubiquitylation and degradation / 南方医科大学学报

OBJECTIVE@#To explore the role of TRIM21 in modulating the invasive phenotype of hepatocellular carcinoma (HCC) cells and its mechanism of action.@*METHODS@#RNA interference technique was used to knock down the expression of TRIM21 and β-catenin, alone or in combination, in HCC cell lines 97H and LM3, and the interfering efficiency and the activity of closely related pathways were determined using Western blotting. The two cells with TRIM21 knockdown (siTRIM21 97H and siTRIM21 LM3 cells) were assessed for their invasion ability in vitro using Transwell invasion assay, and the lung metastasis capacity of siTRIM21 LM3 cells following tail vein injection was evaluated in nude mice. The binding of TRIM21 with β-catenin and the ubiquitylation level of β-catenin in TRIM21-overexpressing HEK293 cells were determined with Western blotting and co-immunoprecipitation assay. We also compared the overall survival of patients with CTNNB1highTRIM21high and CTNNB1highTRIM21low HCC subtypes using Kaplan-Meier method based on filtrated and grouped HCC clinical data from TCGA database.@*RESULTS@#TRIM21 knockdown significantly enhanced the invasion ability of 97H and LM3 cells in vitro (P < 0.01 or 0.05) and the lung metastasis ability of LM3 cells in nude mice (P < 0.01), and simultaneous knockdown of β -catenin obviously suppressed the in vitro invasiveness of the cells (P < 0.0001 or 0.05). Co-immunoprecipitation assay showed that TRIM21 was capable of directly binding with β-catenin protein to accelerate the ubiquitination and degradation of the latter, leading to inhibition of nuclear translocation of β-catenin and hence reduced invasiveness of HCC cells. Bioinformatic analysis showed that compared patients with CTNNB1highTRIM21low HCC subtype where Wnt pathway was activated, the patients with CTNNB1highTRIM21high HCC subtype had a significantly better survival outcomes (P < 0.05).@*CONCLUSION@#A high expression of TRIM21 suppresses the invasion of HCC cells by promoting β-catenin ubiquitylation and degradation, which possibly explains the poor prognosis of CTNNB1highTRIM21low HCC patients.

Short-term effects and seasonal variation of ozone on daily hospital outpatient visits for childhood asthma in Lanzhou / 北京大学学报(医学版)

OBJECTIVE@#To analyze the effects of ozone (O3) concentrations measured with different approaches across different seasons on the total number of childhood asthma-related clinical visits, as well as the differentiation of such effects across different groups of patients.@*METHODS@#The outpatient data of three grade A tertiary hospitals in Lanzhou City spanning from 1 January 2014 to 31 December 2017, as well as air pollution and meteorological data during the same period were collected. Considering the nonlinear relationship between O3 concentrations and the total number of childhood asthma-related clinical visits and meteorological factors, a generalized additive temporal sequence model was employed to analyze the short-term association between changes in O3 concentrations and the total number of childhood asthma-related clinical visits. Taking into account of the variations in O3 concentrations within 1 day, this study adopted different measurement approaches to address the three types of O3 exposures, namely, the maximum 1 h daily concentration (O3max1h), the maximum 8 h daily concentration (O38h) and the mean 24 h daily concentration (O324h) as the short term exposure indicators to O3, followed by a model-based analysis.@*RESULTS@#The increase in short-term exposure levels to O3 in summer had a significant effect on the increase in the total number of childhood asthma-related clinical visits. With lag0 for the current day, every 10 μg/m3 increase in atmospheric concentration of O3max1h was associated with an increase in the total number of childhood asthma-related clinical visits by 3.351% (95%CI: 1.231%-5.516%); for every 10 μg/m3 increase in O38h concentration, the total number of childhood asthma-related clinical visits increased by 3.320% (95%CI: 0.197%-3.829%); for every 10 μg/m3increase in O324h concentration, the total number of childhood asthma-related clinical visits in summer increased by 6.600% (95%CI: 0.914%-12.607%); moreover, an increase in exposure to O3max1h also led to a significant rise in the total number of childhood asthma-related clinical visits among the males.@*CONCLUSION@#The increase in short-term exposure levels to O3 in summer in Lanzhou City has a significant effect on the increase in the total number of childhood asthma-related clinical visits; O3max1h is more closely correlated with the increase in the total number of childhood asthma-related clinical visits.

Research advances on the role of competing endogenous RNAs in wound healing / 中华烧伤杂志

Wound healing, as one of the important public health issues, has been a worldwide problem. Due to the unique biological wound environment, wound healing is a very complex process with current treatments requiring long cycles, being poorly effective, and bringing high economic burden to patients. An increasing number of studies have shown that non-coding RNAs (ncRNAs) play important roles in wound healing process. The competing endogenous RNAs (ceRNAs) hypothesis in recent years is a new proposal on the inter-regulation of RNAs, which suggests a "mode of communication" between different RNAs. ceRNA regulatory network (ceRNET) combines the functions of protein-coding mRNA with ncRNA (e.g., microRNA, long non-coding RNA, pseudogenes, and circular RNA). Recent studies have shown that ceRNAs play important roles in wound healing, which may provide new effective therapeutic targets for wound healing. This paper starting with ceRNET systematically reviewed the research progress on the effects of various ceRNAs in wound healing and the future research challenges, with the aim to deeply explore the molecular mechanisms and clinical significance of ceRNAs in the process of wound healing.

Consensus of experts on the medical risk prevention for the patients with cardiovascular diseases during dental treatment (2022 edition) / 中华口腔医学杂志

With the aging process of population in the society, the prevalence of cardiovascular diseases (CVD) in China is increasing continuously and the number of dental patients with CVD is increasing gradually too. Due to the lack of guidelines for dental patients with CVD in our country, how to implement standardized preoperative evaluation and perioperative risk prevention remains a problem to be solved for dentists at present. The present expert consensus was reached by combining the clinical experiences of the expert group of the Fifth General Dentistry Special Committee, Chinese Stomatological Association and respiratory and cardiology experts in diagnosis and treatment for CVD patients, and by systematically summarizing the relevant international guidelines and literature regarding the relationship between CVD and oral diseases and the diagnosis and treatment of dental patients with heart failure, hypertension and antithrombotic therapy. The consensus aims to provide, for the dental clinicians, the criteria on diagnosis and treatment of CVD in dental patients in China so as to reduce the risk and complications, and finally to improve the treatment levels of dental patients with CVD in China.

Analysis of serum immunoglobulin level in children with Burkitt lymphoma / 中华儿科杂志

Objective: To summarize changes of serum immunoglobulin levels before and after chemotherapy in children with Burkitt lymphoma (BL), so as to investigate the effects of chemotherapy and rituximab on serum immunoglobulin levels in children with BL. Methods: Clinical data of 223 children with newly diagnosed Burkitt lymphoma at Beijing Children's Hospital from January 2009 to April 2017 were analyzed retrospectively. They were treated according to the modified LMB 89 regimen and some of them received combined rituximab therapy during the chemotherapy. The serum immunoglobulin (IgA, IgM, IgG) before chemotherapy, at the time of discontinuing chemotherapy, as well as 6, 12, 24, 36 months after chemotherapy were collected. Changes of serum IgA, IgM and IgG with time among different treatment groups were compared using repeated measures ANOVA. Results: According to risk group, 223 children were devided into group B（n=53）and group C（n=170）. Before chemotherapy, 109 cases (48.9%) were combined with hypogammaglobulinemia. The serum IgA, IgM, and IgG levels of all the patients were (0.9±0.7), 1.2 (0.5, 1.3) and (7.2±2.9) g/L before chemotherapy, (0.5±0.4), 0.2 (0.1, 0.3) and (6.3±2.3) g/L at the time of discontinuing chemotherapy (t=13.63, Z=-11.99, t=4.57, all P<0.05). There were statistical difference in IgA, IgM levels of group B and IgA, IgM, IgG levels of group C before chemotherapy and at the time of discontinuing chemotherapy (t=8.86, Z=-6.28, t=11.19, Z=-10.15, t=4.50, all P<0.05). The differences of serum IgA and IgG levels at the time after chemotherapy among patients treated with chemotherapy alone and those treated with chemotherapy combined rituximab in group B and C were significant (F=5.38, P=0.002 and F=4.22, P=0.007). Conclusions: Approximately half of children with BL have already existed hypogammaglobulinemia at initial diagnosis prior to the start of treatment. The modified LMB 89 regimen have significant effect on humoral immunity of children with BL. In the process of immune reconstruction after chemotherapy, rituximab has more significant effect on serum IgA and IgG levels in BL patients.

Pay attention to the detection and evaluation of CD30 in pathological diagnosis of lymphoma / 中华病理学杂志

CD30 is a transmembrane glycoprotein of tumor necrosis factor receptor family, which is expressed differently in various lymphomas. It has specific effects on the proliferation and function of tumor cells. However, the significance of CD30 expression has not been fully recognized by clinicians and pathologists, and the detection and evaluation of CD30 have not been standardized. The role of CD30 in the diagnosis of lymphoma, detection methods and reporting standards are summarized in the paper to improve the understanding of CD30.

Progress in the practice of surveillance and early warning of infectious diseases in major countries and regions / 中华流行病学杂志

The COVID-19 pandemic is yet another reminder that the threat of infectious disease has never really gone away. As the cornerstone of preventing and controlling infectious diseases, effective surveillance and early warning are of great significance in understanding the outbreak and epidemic of specific infectious diseases and putting forward effective prevention and control measures. Therefore, we must continue strengthening the construction of infectious disease surveillance and early warning system. We reviewed the surveillance and early warning practices of infectious diseases in major countries and regions, then discussed the development direction in the field of surveillance and early warning of infectious diseases to provide the reference for strengthening the construction and capacity of infectious disease surveillance and early warning system in China.

Chlamydia muridarum respiratory infection induces macrophage infiltration and polarization toward M1 phenotype / 中华微生物学和免疫学杂志

Objective:To investigate the infiltration and polarization of macrophages in mice during Chlamydia muridarum ( Cm) respiratory infection. Methods:C57BL/6 mice were intranasally infected with 1×10 3 inclusion-forming units (IFU) of Cm to establish the mouse model of Cm respiratory tract infection. The percentages of CD45 + F4/80 + cells and the macrophages expressing CD86, major histocompatibility complex Ⅱ (MHC), inducible nitric oxide synthase (iNOS) and CD206 were detected by flow cytometry. Expression of iNOS, CD206 and CCL2 at mRNA level was detected by real-time quantitative PCR. Results:Cm respiratory tract infection induced the increase of macrophages in mouse lung tissues. Compared with uninfected group, CD45 + F4/80 + macrophages were increased significantly from day 3 and reached the peak on day 7 after Cm infection. Moreover, the expression of CD86, MHCⅡ and CCL2 was increased, and the macrophages were polarized to M1 phenotype. However, the expression of M2 macrophage marker CD206 was decreased gradually. Further studies showed that iNOS expression, the indicator of M1 macrophage activation, was increased after Cm infection and reached to the top on day 7. Conclusions:Cm respiratory infection could induce the infiltration of macrophages in lung tissues and promote the polarization of macrophages to M1 phenotype.

Preliminary exploration of the relationship between the serum anti-Müllerian hormone and the related clinical factors / 中华核医学与分子影像杂志

Objective:To explore the relationship between serum anti-Müllerian hormone (AMH) level and related clinical factors in healthy females, and establish and validate equation of correlation between age and serum AMH level for healthy females.Methods:From March 2015 to December 2016, a total of 602 females who measured serum AMH level in Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University were retrospectively enrolled. All cases had relatively complete clinical data, and were divided into healthy group (484 cases, 20-52 years) and case group (118 cases, 20-42 years; patients with menstrual disorders). Relationships between serum AMH level and estradiol (E2), tesosterone (T), follicle stimulating hormone (FSH), luetinizing hormone (LH), body mass index (BMI) of healthy group were analyzed by Spearman rank correlation. Kruskal-Wallis rank sum test was used to analyze the relationship between history of gestation and serum AMH level. Serum AMH level of health group was processed to establish predictive equation for serum AMH level. Internal ( n=27) and external ( n=37) validation group were chosen from healthy females with serum AMH level measured to validate the equation, and signed rank test was used to analyze the data. Difference between serum AMH level in case group and healthy group with corresponding age was explored by independent-sample t test. Results:Serum AMH levels were positively correlated with E2 and T ( rs values: 0.263, 0.334, both P<0.001), and negatively correlated with FSH, LH, BMI ( rs values: from -0.515 to -0.110, all P<0.005). Predictive equation was established as LogAMH=-1.208+ 0.1×age-0.000 042×age 3 ( R2=0.735, P<0.001). No statistically significant difference was found between real serum AMH levels and calculated serum AMH levels in the internal and external validation groups ( z values: -1.62 and -1.52, both P>0.05). Females in case group ( n=118) and control group ( n=446) were divided into two sub-groups respectively (<35 years and ≥35 years), and serum AMH levels of case group were lower than those of control group with corresponding age ( t values: 18.64, 11.70, both P<0.001). Conclusions:In healthy females, serum AMH level is related to some clinical data. The equation between serum AMH level and age established in the study may provide reference for clinical diagnosis and treatment.

The trend of clinical and pathological characteristics and surgical treatment in patients with spinal metastases: A multicenter retrospective study / 中华骨科杂志

Objective:To retrospectively analyze the patients with spinal metastases who received surgical intervention and summarize the evolution of their clinical and pathological characteristics and surgical methods.Methods:The data of 703 patients with spinal metastases from January 2007 to December 2018 were collected retrospectively. There were 395 males (56.19%, 395/703) and 308 females (43.81%, 308/703) with an average age of 58.14±11.46 years (range 13-84 years). According to the degree of invasion and thoroughness of tumor resection, the surgical methods could be divided into minimally invasive surgery, decompression surgery, separation surgery, piecemeal resection and total en-bloc spondylectomy surgery. The operative methods were minimally invasive surgery in 89 cases (12.66%), decompression surgery in 96 cases (13.66%), separation surgery in 303 cases (43.10%), piecemeal resection in 182 cases (25.89%) and total en-bloc spondylectomy in 33 cases (4.69%). To analyze the trend of the clinical, pathological types and surgical treatment of patients with spinal metastases over the years, and determine the relevant factors affecting the decision-making of surgical methods by multivariate logistic regression.Results:The ratio of male to female was 1.28:1. 39.54% (278/703) of patients with single-segment involvement in 703 patients, 24.04% (169/703) of patients with double-segment metastasis and 36.42% (256/703) of patients with multi-segment metastasis. The most common type of primary tumor was lung cancer (34.57%, 243/703), followed by breast cancer (8.25%, 58/703), myeloma (8.11%, 57/703), gastrointestinal tumor (6.82%, 48/703) and renal malignant tumor (6.40%, 45/703). From 2007 to 2018, there was no significant difference in the percentage change of different age, gender and primary tumor source composition (age: χ 2=14.01, P=0.233; gender: χ 2=35.73, P=0.341; primary tumor: χ 2=120.09, P=0.074). The percentage of patients with sacrococcygeal metastasis decreased from 20.00% in 2008 to 1.89% in 2017 and the difference was statistically significant (χ 2=8.09, P=0.005). The percentage of patients with multi-level metastasis increased from 26.67% in 2008 to 52.83% in 2017, and the difference was statistically significant (χ 2=7.23, P=0.007). The percentage of patients with minimally invasive surgery decreased from 25.00% in 2007 to 5.88% in 2018, and the percentage of patients with segmented resection decreased from 53.33% in 2008 to 10.29% in 2018. The proportion of the two surgical methods showed a significant downward trend, and the differences were statistically significant (minimally invasive surgery: χ 2=1.46, P=0.026; segmented resection surgery: χ 2=19.56, P<0.001). The percentage of patients undergoing separation surgery increased from 13.33% in 2008 to 64.71% in 2018, and the proportion of patients undergoing total en-bloc spondylectomy increased from 0 in 2007 to 10.29% in 2018. Both surgical methods showed a significant growth trend and the differences were statistically significant (separation surgery: χ 2=27.09, P<0.001; χ 2=4.16, P=0.042). Multivariate Logistic regression analysis showed that age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score were independent factors influencing surgical decision-making ( P<0.05). Conclusion:With different time and age, the invasiveness and thoroughness of surgery are increasing, which shows that the percentage of patients who underwent separation surgery and to-tal en-bloc spondylectomy is significantly increasing. Age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score are independent factors affecting surgical decision-making.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported / 中华肿瘤杂志

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

Therapeutic Effect of Buyang Huanwutang on Diabetic Peripheral Neuropathy and Dosage of Astragalus in Prescription： Based on SIRT1/p53-mediated Apoptosis / 中国实验方剂学杂志

ObjectiveTo explore the neuroprotective effect of Buyang Huanwutang （BYHW） on diabetic peripheral neuropathy （DPN） rats by regulating SIRT1/p53 pathway and to clarify the mechanism and the dosage of astragalus in the prescription. MethodA total of 90 SD rats were randomized into control group， DPN group， DPN + BYHW containing 120 g Astragalus （at 15 g·kg-1·d-1） （BYHW120 group）， DPN + BYHW containing 60 g Astragalus （at 8.75 g·kg-1·d-1） （BYHW60 group）， DPN + BYHW containing 30 g Astragalus （at 5.625 g·kg-1·d-1） （BYHW30 group）， and DPN + α-lipoic acid （at 60 mg·kg-1·d-1） （ALA group）. Standard diet was given to rats in the control group and high-carbohydrate/high-fat diet and streptozotocin （ip） were used to induce diabetes in rats in other groups. The administration lasted 12 weeks. After the intervention， mechanical pain threshold and nerve conduction velocity were detected. The L4-5 dorsal root ganglions were stained with haematoxylin-eosin （HE） and toluidine blue to observe the pathological changes， and the apoptosis of nerve cells was detected by terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling （TUNEL） assay. Cleaved cysteinyl aspartate-specific proteinase-3 （Caspase-3）， and the main proteins in the SIRT1/p53 pathway， such as silencing information regulator 2 related enzyme 1 （SIRT1）， acetyl-p53， dynamin-related protein 1 （Drp1）， Bcl-2 associated X protein （Bax）， and B-cell lymphoma-2 （Bcl-2）， were detected by immunohistochemistry and Western blot. ResultCompared with the control group， the DPN group presented increase in blood glucose （P<0.01）， decrease in nerve conduction velocity and mechanical pain threshold （P<0.01）， rise of the percentage of positive cells （TUNEL assay， the same below） and the expression of cleaved Caspase-3 （P<0.01）， drop in the expression of SIRT1 （P<0.01）， and elevation of acetyl-p53， Drp1， and Bax/Bcl-2 ratio （P<0.01）. Cleaved Caspase-3， acetyl-p53， Drp1， and Bax/Bcl-2 ratio in each administration group decreased as compared with those in the DPN group （P<0.01）. Nerve conduction velocity， mechanical pain threshold （P<0.05， P<0.01）， and the percentage of positive cells （P<0.05， P<0.01） increased in the administration groups as compared with those in the DPN group except for the BYHW30 group， and BYHW120 group and ALA group showed the increase in SIRT1 （P<0.05， P<0.01）. Nerve conduction velocity， mechanical pain threshold， and SIRT1 expression were lower （P<0.05， P<0.01） and expression of cleaved Caspase-3 was higher （P<0.01） in the BYHW60 and BYHW30 groups than in the BYHW120 group. The percentage of positive cells and the expression of acetyl-p53 were higher in the BYHW30 group than in the BYHW120 group （P<0.01）. ConclusionBYHW inhibits apoptosis and exerts therapeutic effect on DPN by regulating the SIRT1/p53 pathway. The therapeutic effect is related to the dosage of Astragalus in the prescription. BYHW containing 120 g Astragalus suppresses p53-dependent apoptosis more significantly than Buyang Huanwutang containing 60 g and 30 g of Astragalus.

Herbal Textual Research on Violae Herba in Famous Classical Formulas / 中国实验方剂学杂志

By referring to the relevant ancient herbal literature， medical records and prescription books， the textual research of Violae Herba has been conducted to verify the name， origin， producing area， quality evaluation and processing method changes. The results showed that the name of Zihua Diding originated from its flower color and plant morphological characteristics. The primitive plant of Violae Herba is Viola genus of Violaceae， V. yedoensis， as stipulated in the 2020 edition of Chinese Pharmacopoeia， has been the mainstream in past dynasties of China. Violae Herba is mainly wild， and it is widely distributed throughout the country. Since modern times， the quality of Violae Herba is better with integrity， green color and yellow root. There are few records on the harvesting and processing methods of Violae Herba in ancient times， most of which are directly used after drying. It is suggested that the collection and processing methods of Violae Herba in the famous classical formulas can be implemented in accordance with the provisions of the 2020 edition of Chinese Pharmacopoeia.

Research progress on ocular lesions of Stevens-Johnson syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

Stevens-Johnson syndrome(SJS)refers to a type of adverse reactions of the skin and mucosa mainly caused by drug allergy, which can be life-threatening in serious cases. For SJS survivors, ocular damage are accepted as the most severe complications. In recent years, because of the extensive research of its genetic susceptibility and immune pathogenesis, varied susceptibility genes which are involved in the ocular complications of SJS have been discovered. However, further efforts are still needed to clarify relevant mechanisms due to the high ethnicity and drug specificity. Ocular lesions of SJS are prone to be neglected in the early stage, and patients often receive ophthalmic treatment after a severe visual loss. Especially in China, the ocular surface of most patients has already been seriously damaged when they went to the ophthalmology department, while existing treatments achieve unsatisfactory results in improving visual acuity. Therefore, recent research progress is reviewed in this article on etiology and treatment of SJS ocular lesions, in order to raise clinicians' awareness of ocular complications, and provide references for the diagnosis and treatment of diseases and research in related fields.

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke / 医学前沿

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.

Plant Pharmacophylogeny: Review and Future Directions / 中国结合医学杂志

Medicinal plants have provided numerous medicinal active ingredients for thousands of years and these ingredients have been used in Chinese medicine (CM) and traditional pharmacologies worldwide. Recently, the exploitation and utilisation of medicinal plant resources has increased significantly. The results of the studies have led to the identification of many active components, such as steroidal alkaloids, saponins, terpenoids, and glycosides, in various medicinal plants with different evolutionary levels. Moreover, research on the chemical classification, molecular phylogeny, and pharmacological activity of medicinal plants is increasing in popularity. Pharmacophylogeny is an interdisciplinary topic that studies the correlation between plant phylogeny, chemical composition, and curative effects (pharmacological activity and the traditional curative effect) of medicinal plants. In addition, it provides the basic tools to enable research and development of CM resources. This literature review, based on the genetic relationship between phytogroup and species, highlights the formation process, research content, applications, and future directions of pharmacophylogeny.