Specific antitumor activity and mechanism of protonic bis-phenanthroline / 药学学报

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwise. The incidence rate of HCC is high and is easy to metastasis and recurrence, which seriously affects human health. Traditional chemical drugs have some challenges such as toxicity, side effects, and multidrug resistance, thus it is urgent to find new drugs and effective targets. Here we synthesized a novel chemical, protonic bis-phenanthroline (H-BP), and the antitumor effect was investigated in the study. The results showed that H-BP could selectively inhibit the proliferation of tumor cells and cause HCC apoptosis. And also, in HCC tumor-bearing mice, H-BP could effectively prevent the growth of tumor mass, even completely eliminate the tumor at medium dose (5 mg·kg-1) and high dose (10 mg·kg-1), and meanwhile H-BP has no significant effect on the body weight of mice. The experimental protocol was approved by the Animal Ethics Committee of Southwest University, and the experimental operation was strictly carried out in accordance with the ethical principles of animal use and care. Mechanism studies showed that H-BP induced HCC apoptosis was related to down-regulation the expression of pleomorphic adenoma gene like-2 (PLAGL2), a oncogene transcription factor, resulting in the down-regulation of PLAGL2 downstream proteins hypoxia inducible factor and β-catenin. This study not only introduces the dimerization method to form novel compounds that will provide a new approach for drug design, but also suggests that PLAGL2 may be an effective target in tumor therapy.

Effect of abdominal electrical stimulation combined with high-frequency chest wall oscillation on airway clearance ability for critical ill patients with tracheostomy / 中国康复理论与实践

@#Objective To observe the effect of abdominal electrical stimulation combined with high-frequency chest wall oscillation on airway clearance ability in critical ill patients with tracheostomy. Methods From January to June, 2021, a total of 84 critical ill patients with tracheostomy in the department of Critical Care Medicine, Zhongda Hospital, Southeast University, were randomly divided into control group (n = 28),experimental group A (n = 28) and experimental group B (n = 28). All the groups received routine therapy and early activities; while high-frequency chest wall oscillation was added to experimental group A, and abdominal electrical stimulation combined with high-frequency chest wall oscillation were added to experimental group B, for two weeks. Their involuntary cough peak flow (ICPF), Clinical Pulmonary Infection Score (CPIS), diaphragmatic excursion (DE), diaphragmatic thickness fraction (DTF) and thickness of abdominal muscle (Tab) were measured before and after treatment. Results The improvement of CPIS, ICPF and Tab were better in the experimental group B than in the other two groups (P < 0.05). The improvement of DE and DTF were slightly better in experimental group B, however, there was no significant difference among groups (FDE = 0.514, FDTF = 1.582, P > 0.05). The thickness d-values of rectus abdominis, musculi obliquus internus abdominis and musculus transversus abdominis were positively correlated with the d-value of ICPF in the exprimental group B (r > 0.415, P < 0.05). ICPF was highly negatively correlated with CPIS before treatment for all the patients (r = -0.702, P < 0.001). No adverse events occurred during the intervention period. Conclusion Abdominal electrical stimulation combined with high-frequency chest wall oscillation could improve airway clearance ability in critical ill patients with tracheostomy.

Synthesis and biological activities of three-molecule conjugates with para-aminosalicylic acid as parent nucleus / 药学学报

Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.

Detection of DNA methylation of HYAL2 gene for differentiating malignant from benign thyroid tumors / 南方医科大学学报

OBJECTIVE@#To assess the value of DNA methylation level of HYAL2 gene as a molecular marker for differential diagnosis of malignant and benign thyroid tumors.@*METHODS@#DNA methylation of HYAL2 gene in tissue specimens of 190 patients with papillary thyroid cancer (PTC) and 190 age- and gender-matched patients with benign thyroid tumors was examined by mass spectrometry, and the protein expression of HYAL2 was detected immunohistochemically for another 55 pairs of patients. Logistic regression analysis was performed to calculate the odds ratio (OR) and evaluate the correlation of per 10% reduction in DNA methylation with PTC. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) was calculated to assess the predictive value of alterations in HYAL2 methylation.@*RESULTS@#Hypomethylation of HYAL2_CpG_3 was significantly correlated with early-stage PTC (OR=1.51, P=0.001), even in stage I cancer (OR=1.42, P=0.007). Age-stratified analysis revealed a significantly stronger correlation between increased HYAL2_CpG_ 3 methylation and early-stage PTC in patients below 50 years than in those older than 50 years (OR: 1.89 vs 1.37, P < 0.05); ROC analysis also showed a larger AUC of 0.787 in younger patients. The results of immunohistochemistry showed that patients with PTC had significantly higher protein expressions of HYAL2 than patients with benign tumors.@*CONCLUSION@#The alterations of DNA methylation level of HYAL2 gene is significantly correlated with early-stage PTC, suggesting the value of DNA methylation level as a potential biomarker for differentiation of malignant from benign thyroid tumors.

Changes of heparin-binding protein in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells and neutrophils / 中华烧伤杂志

Objective: To investigate the changes of heparin-binding protein (HBP) in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells (HUVECs) and neutrophils in vitro. Methods: Prospective observational and experimental research methods were used. Twenty severe burn patients who met the inclusion criteria and were admitted to the Department of Burns and Plastic Surgery of Affiliated Suzhou Hospital of Nanjing Medical University from August to November 2020 were included in severe burn group (12 males and 8 females, aged 44.5 (31.0, 58.0) years). During the same period, 20 healthy volunteers with normal physical examination results in the unit's Physical Examination Center were recruited into healthy control group (13 males and 7 females, aged 39.5 (26.0, 53.0) years). Enzyme-linked immunosorbent assay (ELISA) method was used to detect the protein expression levels of HBP and tissue inhibitor of metalloproteinase 1 (TIMP-1) in plasma of patients within 48 hours after injury in severe burn group and in plasma of volunteers in healthy control group. The correlation between protein expression of HBP and that of TIMP-1 in the plasma in the two groups was analyzed by Pearson correlation analysis. The fourth passage of HUVECs in logarithmic growth phase were used for the experiment. The HUVECs were divided into normal control group with routine culture (the same treatment below) and recombinant HBP (rHBP)-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group with corresponding treatment according to the random number table (the same grouping method below), and the mRNA expression of TIMP-1 in cells was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. The HUVECs were divided into normal control group and rHBP-treated 48 h group with corresponding treatment, and the protein expression of TIMP-1 in the cells was detected by Western blotting. The HUVECs were divided into normal control group, rHBP alone group, aprotinin alone group, and rHBP+aprotinin group treated with the corresponding reagents (with the final molarity of rHBP being 200 nmol/L and the final concentration of aprotinin being 20 μg/mL, respectively), cultured for 48 h, and ELISA was used to detect the protein expression of TIMP-1 in the culture supernatant of cells. The neutrophils were isolated from the peripheral venous blood of the aforementioned 10 healthy volunteers by immunomagnetic bead sorting, and the cells were divided into normal control group, recombinant TIMP-1 (rTIMP-1) alone group, phorbol acetate (PMA) alone group, and rTIMP-1+PMA group treated with corresponding reagents (with the final concentration of rTIMP-1 being 500 ng/mL and the final molarity of PMA being 10 nmol/L, respectively). After being cultured for 1 h, the expression of CD63 protein in cells was detected by immunofluorescence method, the positive expression rate of CD63 protein in cells was detected by flow cytometry, and the protein expression levels of HBP and myeloperoxidase (MPO) in the culture supernatant of cells were detected by ELISA. The normal control group underwent the above-mentioned related tests at appropriate time points. The number of samples was 3 in each group of cell experiment. Data were statistically analyzed with chi-square test, Mann-Whitney U test, Kruskal-Wallis H test, and Tamhane's T2 test. Results: The protein expression levels of HBP and TIMP-1 in the plasma of patients in severe burn group were 404.9 (283.1, 653.2) and 262.1 (240.6, 317.4) ng/mL, respectively, which were both significantly higher than 61.6 (45.0, 68.9) and 81.0 (66.3, 90.0) ng/mL of volunteers in healthy control group (with Z values of -5.41 and -5.21, respectively, P<0.01). The correlation between the protein expression of HBP and that of TIMP-1 in the plasma of volunteers in healthy control group was not strong (P>0.05). The protein expression of HBP was significantly positively correlated with that of TIMP-1 in the plasma of patients in severe burn group (r=0.64, P<0.01). Compared with that in normal control group, the mRNA expression of TIMP-1 in HUVECs was significantly increased in rHBP-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group (with t values of -3.58, -2.25, and -1.26, respectively, P<0.05). Western blotting detection showed that compared with that in normal control group, the protein expression of TIMP-1 in HUVECs in rHBP-treated 48 h group was significantly enhanced. After 48 h of culture, compared with that in normal control group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP alone group was significantly increased (t=9.43, P<0.05), while the protein expression level of TIMP-1 in the culture supernatant of HUVECs didn't change significantly in aprotinin alone group or rHBP+aprotinin group (P>0.05); compared with that in rHBP alone group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP+aprotinin group was significantly decreased (t=4.76, P<0.01). After 1 h of culture, the trend of CD63 protein expression in neutrophils detected by immunofluorescence method and that by flow cytometry were consistent in each group. After 1 h of culture, compared with that in normal control group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1 alone group all had no significant changes (P>0.05), while the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells were all significantly increased in PMA alone group and rTIMP-1+PMA group (with t values of 2.41, 3.82, 5.73, 1.05, 4.16, and 1.08, respectively, P<0.05 or P<0.01); compared with that in PMA alone group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1+PMA group were all significantly decreased (with t values of 5.26, 2.83, and 1.26, respectively, P<0.05 or P<0.01). Conclusions: The expression level of HBP in the plasma of severe burn patients is increased during shock stage. HBP can induce HUVECs to secrete TIMP-1 in vitro, and TIMP-1 can reduce the expression of CD63 molecule in human neutrophils.

Analyses on horizontal scientific research projects from 2015 to 2019 by provincial Center for Disease Control and Prevention in China / 中华医学科研管理杂志

Objective:To analyze the horizontal scientific research projects from 2015 to 2019 by the provincial Centers for Disease Control and Prevention (CDC) in China, and to compare the regional differences, in order to provide the suggestion on the scientific management of CDC.Methods:The horizontal scientific research projects from 2015 to 2019 were retrospectively analyzed by questionnaire survey. Multiple linear regression models were adopted to examine the trend, and variance analyses were used to test the differences in horizontal scientific research projects among the Eastern, Central, and Western regions.Results:From 2015 to 2019, provincial CDC have received RMB 124.3 million of horizontal scientific research project funds totally, of which 51.9% were funded by enterprises, and 86.9% were undertaken by provincial CDC themselves. There were no statistical significance in the change of research project funds obtained by provincial CDC ( F=0.46, P = 0.764) during this period.The number of horizontal scientific research projects undertook or participated by provincial CDC in the Eastern region were more than that of the Central and Western region ( F = 5.85, P = 0.004; F = 5.03, P = 0.008). Conclusions:The horizontal scientific research projects obtained by the provincial CDC remained stable in recent years while distribution was unbalanced in the region areas. It is suggested to innovate the management mode of scientific research projects with strengthening the trans-agency, trans-department and trans-regional cooperation.

Digital technology in repair of soft tissue defect in hand by anterior tibial artery perforator flap / 中华显微外科杂志

Objective:To investigate the clinical value of digital technology in repair of soft tissue defect in hand by anterior tibial artery perforator flap.Methods:From January 2015 to February 2021, 9 patients with soft tissue defects in hand were repaired with anterior tibial artery perforator flap assisted by digital technology in flap design, including 6 males and 3 females aged from 19 to 63 years with a mean age of 33 years. The size of defects varied from 2.0 cm×1.5 cm to 4.0 cm×3.0 cm, with exposed bones or tendons. Preoperative CTA scan of lower limb was performed and three-dimensional image was reconstructed with Mimics 20.0. The anterior tibial artery perforator flap was designed according to the shape and size of the defect, then the resection of flap was digitally simulated. The flap based on the digital design was harvested and the defect was repaired in the operation. The size of flap was 2.5 cm×2.0 cm~4.5 cm×3.5 cm. Outpatient clinic follow-up was performed to evaluate the survival of flaps. Disability of Arm, Shoulder and Hand(DASH) was used for function evaluation.Results:All flaps were harvested successfully and all donor sites were closed directly. After surgery, 8 flaps survived completely. One flap developed venous occlusion that showed partial necrosis of the flap, and it was rescued after exploration and re-anastomosis. The follow-up period ranged from 6 to 21 months, with an average of 13 months. The DASH scores of the affected limb were 2 to 15 points at the last follow-up, with an average of 6.4 points. Mild scar hyperplasia occurred at donor site in 1 case without sensory abnormality.Conclusion:The digital technology is able to accurately locate the perforators by allowing an individualised design of the anterior tibial artery perforator flap. The flap is suitable for repair of small and medium-sized soft tissue defect in hand, and the digital technology has certain value in clinical application.

Etiological and phylogenetic analysis of hand, foot and mouth disease in Qujing city, Yunnan Province, 2020 / 中华微生物学和免疫学杂志

Objective:To analyze the etiological distribution and phylogenetic characteristics of hand, foot and mouth disease (HFMD) in Qujing city of Yunnan Province in 2020.Methods:Stool samples were collected from HFMD cases in Qujing city in 2020 and virus RNA was extracted directly from treated stool suspensions. Virus VP4 gene sequences were firstly amplified using MD91/OL68-1 primer pairs and sequenced, then the virus serotypes were determined by BLAST search on the GenBank. Virus entire VP1 gene sequences were amplified and sequenced. Virus serotypes were identified online using Enterovirus Genotyping Tool Version 0.1. Sequences of reference virus genotypes/sub-genotypes were downloaded according to references. Phylogenetic trees were constructed by MEGA5.2 software and the genetic characteristics were analyzed.Results:A total of 47 strains of enteroviruses (EVs) were detected with a detection rate of 10.22% (47/460). The detected viruses were coxsackievirus A4 (CVA4, 0.65%, 3/460), CVA6 (7.83%, 36/460), CVA10 (0.87%, 4/460) and CVA16 (0.87%, 4/460). All were enterovirus species A (EVA), while other group viruses were not detected. The predominant virus was CVA6, accounting for 7.83% (36/460). EVA71 was not detected. CVA4 strains of C2 and C4 subgenotypes were co-circulating strains in Qujing city. CVA6 subgenotype D3a and CVA16 subgenotype B1a were also circulated in Qujing city. All CVA10 strains were in a separate lineage.Conclusions:Similar to the previous situation in China, the detection rates of EVA71 and CVA16 were very low, even zero. This study showed that CVA6 was the predominant virus, indicating a HFMD outbreak caused by CVA6 in Qujing city in 2020. The phylogenetic analysis showed CVA10 isolates belonged to a separate lineage, which might be unique to Qujing city. Laboratory and molecular epidemiological surveillance of non-EVA71 and non-CVA16 viruses, especially CVA6 and CVA10 should be strengthened in the future.

The effects of transtracheal pressure on the utility of speaking valves in critically ill patients after tracheostomy / 中华物理医学与康复杂志

Objective:To analyze the effect of transtracheal pressure (TTP) on the application of a speaking valve in critically ill patients after tracheostomy.Methods:A retrospective analysis was conducted of 50 patients wearing a speaking valve after tracheostomy. Patients who had been wearing a speaking valve for 30min or more were the tolerance group, while those with less than 30min were the intolerance group. Transtracheal pressure was monitored during resting breathing, forced expiration and speaking. Linear regression models were evaluated to isolate the factors best predicting tolerance. The changes in respiratory muscle contraction before and after wearing a speaking valvs were evaluated using ultrasound. The patients′ satisfaction with wearing a speaking valve was also recorded.Results:TTP during speaking significantly predicted tolerance. The baseline values of diaphragmatic thickening fraction and physical functioning also positively predicted tolerance. Acute physiology and chronic health (APACHE II) score was a significant negative predictor. After wearing the speaking valve, the average contraction of the rectus abdominis, external oblique, internal oblique and transverse abdominis muscles increased significantly. Both groups expressed high satisfaction with the speaking valves.Conclusions:Transtracheal pressure during speaking can help predict the tolerance for wearing a speaking valve among critically ill patients after a tracheostomy. Baseline diaphragmatic thickening fraction, physical functioning and APACHE II score can predict the duration of speaking valve tolerance.

The concept and preliminary practice of precise flap surgery based on CTA / 中华骨科杂志

Objective:To introduce the concept and procedure of CTA guided precision flap surgery and report the preliminary clinical application.Methods:The theory of CTA guided precision flap surgery is: based on CTA high-throughput data, comprehensively evaluate the wound and potential donor sites, and select the best plan for wound repair. This article reviews 177 patients treated under the guidance of CTA guided precision flap surgery from August 2014 to December 2018. Among them, 131 were males and 46 were females; they were 7-72 years old, with an average age of 39.5 years. The tissue defects were: 74 cases of foot and ankle, 64 cases of wrist, 15 cases of calf, 11 cases of forearm and upper arm, 7 cases of thigh and perineum, 5 cases of face and neck, and 1 case of abdomen. The size of the defect was 2 cm×1 cm to 65 cm×50 cm. The recipient and donor sites were assessed based on CTA guided precision flap surgery, then choose the optimal flap to repair the defect. The flap types, outcomes and complications were recorded. The visual analogue scale (VAS), British Medical Research Council sensory rating scale, and revascularization assessments of digital replantation standard by Hand Surgery Branch of Chinese Medical Association was used to assess clinical results.Results:All flaps were uneventfully harvested as planned according to the CTA guided precision flap surgery concept.A total number of 181 flaps were harvested, including 125 free flaps and 56 pedicled flaps. The flap area rangedfrom 4 cm×3 cm to 40 cm×8 cm. After surgery, 165 cases were survival completely, 7 cases were total necrosis, 9 cases were partial necrosis. A total of 174 cases of flaps survived. The mean follow-up was 9.2 months (range, 6-60 months). After surgery 53 flaps were bulky, and 7 cases with other complications.At the last follow-up, only 6 patients had mild pain, the VAS score was 1-3. The sensation of the flaps recovered partially. According to the British Medical Research Council sensory rating scale: 68 cases were grade S2 and 106 cases were grade S3. According to the revascularization assessments of digital replantation standard by Hand Surgery Branch of Chinese Medical Association, 171 cases were excellent and 3 cases were good.Conclusion:The concept of precision flap surgery based on CTA can effectively guide flap surgery and achieve precise wound repair.

Agreement of manual, semi-automatic, and automatic measurements in measuring diameters and volumes of solid pulmonary nodules / 中华放射学杂志

Objective:To assess the agreement of manual measurement, semi-automatic measurement based on computer-aided diagnosis (CAD), and automatic measurement based on artificial intelligence (AI) in measuring diameters and volumes of solid pulmonary nodules.Methods:The clinical and low dose CT (LDCT) data of 165 participants in lung cancer screening of Sichuan Cancer Hospital from July 2018 to April 2020 were retrospectively analyzed. The largest nodule of each participant was selected to analyze, and its diameter and volume were measured by one junior and one senior radiologist using manual measurement, semi-automatic measurement based on CAD, and automatic measurement based on AI. Referring to Lung CT imaging reporting and data system (Lung-RADS, version 1.1), all nodules were classified into Lung-RADS 2, 3, 4A, 4B, 4X categories and low and high risk groups according to the diameter and volume measured by different measurement methods. Repeated-measures analysis of variance and paired t-test were used to compare the differences in the diameter and volume of lung nodules measured by different methods. The consistency of the three methods in measuring nodule diameter and volume was assessed by the correlation coefficient (ICC). Linear weighted Kappa coefficient was applied to assess the consistency of different measurement methods in Lung-RADS classification results; simple Kappa coefficient was applied to assess the consistency of different methods in high and low risk grouping results. Results:Difference in the diameters of pulmonary nodules measured by manual measurement, semi-automatic measurement based on CAD, and automatic measurement based on AI was statistically significant [(14.9±6.3) mm, (17.0±6.7) mm, (15.0±5.7) mm, F=88.39, P<0.001], and the pairwise comparisons showed that there was significant difference between semi-automatic measurement based on CAD and manual measurement method ( t=10.97, P<0.001), semi-automatic measurement based on CAD and automatic measurement based on AI ( t=10.07, P<0.001), but no significant difference between manual measurement method and automatic measurement based on AI method ( t=1.04, P=0.301). There was no significant difference in the measurement of pulmonary nodule volumes between the semi-automatic measurement and the automatic measurement method based on AI ( Z=0.70, P=0.482). The consistency of pulmonary nodules diameter measured by different measurement methods was high (ICC>0.75), and the consistency of semi-automatic and automatic measurement of lung nodule volume was high (ICC=0.927). The consistency of three methods for lung-RADS classification and high-and low-risk grouping according to nodule diameter was good (Kappa>0.80). The agreements between the semi-automatic measurement and the automatic measurement method for Lung-RADS classification and high-and low-risk grouping according to nodule volume were good (Kappa>0.80). Conclusion:In terms of diameter measurement of solid pulmonary nodules, automatic measurement based on AI is more consistent with manual measurement than semi-automatic measurement based on CAD. The agreement between automatic measurement and semi-automatic measurement is high in terms of volume measurement.

Mechanisms of Ersi Decoction on Rheumatoid Arthritis Rats Induced by Bovine Type Ⅱ Collagen-solution / 中国实验方剂学杂志

ObjectiveTo observe that effect of Ersi decoction on rats with rheumatoid arthritis （RA） induced by using the complete Freund's adjuvant emulsion containing bovine type Ⅱ collagenand and elucidate underlying menchanisms involving to inhibit inflammation and joint synovial angiogenesis. MethodThe rat model of RA was established by immune induction with complete Freund's adjuvant emulsion containing bovine type Ⅱ collagen. All male SD rats were randomly divided into blank group， RA model group， methotrexate group（1.0 mg·kg-1）， and low-， medium- and high-dose group（30，15，7.0 g·kg-1·d-1）of Ersi decoction， with 8 rats in each group. Except the blank group， rats in the methotrexate group and Ersi decoction groups were given corresponding doses of methotrexate and Ersi decoction after establishment of RA induced by strengthen immunity，respectively，and those in the model group and blank group received normal saline of equivalent volume，once a day for 28 days. After the administration， the degree of joint swelling of rats in each group was analyzed by joint swelling volume and index. The small animal ultrasound imaging system was used to detect the score and area of synovial hyperplasia of knee joint in right lower limb of rats and hematoxylin-eosin（HE）staining to observe the histomorphological changes in joint synovium of rats. The levels of tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） were measured by enzyme-linked immunosorbent assay（ELISA）. Immunohistochemistry was employed to analyze the expression of CD31 and vascular endothelial growth factor receptor 2（VEGFR2） in in joint synovium. ResultCompared with the blank group， the model group demonstrated significant increase in joint swelling volume and index， inflammatory cytokines including TNF-α and IL-1β in serum， the score and area of synovial hyperplasia of knee joint in right lower limb， obvious pathological changes in the synovium and the expression of CD31 and VEGFR2 in joint synovium. Medium and high-dose Ersi decoction significantly alleviated the pathological changes of synovium tissue， attenuated joint swelling volume and index and decreased the expression of CD31 and VEGFR2 in joint synovium as compared with the model group. Moreover， high-dose Ersi decoction showed significantly lower levels of TNF-α and IL-1β in serum， and the score and area of synovial hyperplasia of knee joint in right lower limb. But medium-dose Ersi decoction only showed lower levels of TNF-α and area of synovial hyperplasia of knee joint. ConclusionErsi decoction could reduce synovial inflammation and hyperplasia through inhibiting synovial angiogenesis in rats with RA induced by bovine type Ⅱ collagen for achieving the effect of reducing RA joint damage， which provides an important reference for anti-RA of Ersi decoction in clinical application.

A Bibliometric Analysis and Visualization of Current Research Trends in Chinese Medicine for Osteosarcoma / 中国结合医学杂志

BACKGROUND@#To illustrate the research framework, overall knowledge structure, and development trends of Chinese medicine (CM) treatment for osteosarcoma (OS) by using a bibliometric analysis and newly developed visualization tools.@*METHODS@#Research datasets were acquired from the Web of Science (WOS) database from January 1, 1980 to September 30, 2019. VOS viewer and Citespace software was used to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution of institutes, distribution of journals, citation and H-index status, co-authorship status, research hotspots and co-citation status were analyzed.@*RESULTS@#A total of 223 publications in the WOS database met the requirement. The number of published articles showed a rise but the citation frequency and the H-index of China were relatively low. The cooperation between the countries, institutes and authors were relatively weak. Most publications were basic researches. Most of the previous researches focused on basic mechanisms of CM in treating OS, and therapy and improvement of dosage form may become a frontier in this research field.@*CONCLUSIONS@#Compared with other fields, the field of CM treatment for osteosarcome is still in infancy. The distribution of researches is imbalanced and cooperation between countries, institutions and authors remains to be strengthened. Furthermore, basic research occupies an absolute dominant position, and the exploration of the molecular mechanism of CM in preventing and treating OS may become a key point in the future.

Development of an improved virus plaque assay based on avicel / 生物工程学报

Avicel is made of a mixture of microcrystalline cellulose (MCC) and carboxymethyl cellulose (CMC), and used for virus plaque assay. The avicel in common use is produced by FMC Biopolymer. Due to the relatively fixed proportion of MCC and CMC, avicel in common use is not suitable for plaque determination experiment of all types of viruses. In this study, we evaluated the effect of avicel made of different proportions of MCC and CMC on virus plaque assay, and developed an improved avicel virus plaque assay featured with simple and convenient operation, good practicability and high stability. To generate avicel overlays with different proportions of MCC and CMC, twelve different 2×avicel solutions were prepared. Their overall viscosity and bottom viscosity were measured to evaluate the ease of operation. The results showed that most of the 2×avicel solutions (except the 4.8% MCC+1.4% CMC and 4.8% MCC+1.0% CMC group) were easy to absorb and prepare nutrient overlap than 2×CMC solution. In order to find the best scheme to detect the titer of porcine epidemic diarrhea virus (PEDV), these avicel overlay solutions with different proportion of MCC and CMC were used as a replacement in the standard plaque assay. By comparing the size, clarity, stability and titer accuracy of virus plaque, we identified that 0.6% MCC and 0.7% CMC was the most preferable composition of avicel overlay for PEDV plaque assay. In conclusion, we developed an improved virus plaque assay based on avicel, which may facilitate the research of virus etiology, antiviral drugs and vaccines.

Influential factors of psychological state and their correlation with nutritional risk in patients undergoing thoracic tumor radiotherapy / 中国基层医药

Objective:To investigate the prevalence of anxiety and depression in patients undergoing thoracic tumor radiotherapy, preliminarily evaluate the nutritional risk of patients, and analyze the possible influential factors of anxiety and depression and their correlation with nutritional risk, providing a theoretical basis for further formulating a personalized psychological nursing plan for patients undergoing thoracic tumor radiotherapy.Methods:A total of 121 patients who underwent thoracic tumor radiotherapy between April 2019 and March 2020 in Cancer Hospital of The University of Chinese Academy of Sciences were selected for this study. We evaluated patients' psychological statuses using the Hospital Anxiety and Depression Scale and patients' nutritional risk using the Nutrition Risk Screening. We performed univariate analysis, unconditional logistic regression analysis, and contingency analysis to analyze the factors that affected the psychological status of patients undergoing thoracic tumor radiotherapy and correlate patients' psychological status with nutritional risk.Results:Among 121 patients, 99 (81.8%) patients undergoing thoracic tumor radiotherapy would develop or had developed anxiety, and 42 (34.7%) patients were at the boundary of depression or had depression. Correlation analysis revealed that nutritional risk was correlated with the prevalence of anxiety and depression. Logistic regression analysis showed that surgery, first radiotherapy, and nutritional risk were the factors that affected the prevalence of anxiety. Marital status, location of tumors, surgery, first radiotherapy, and nutritional risk affected the prevalence of depression.Conclusion:Patients undergoing thoracic tumor radiotherapy have serious psychological problems. Nutritional risk is positively correlated with the prevalence of anxiety and depression. Surgery and first radiotherapy are the factors that affect the prevalence of anxiety and depression.

Curriculum design and implementation of teaching in experimental genetic engineering blended course under the principle of learning-centered teaching / 生物工程学报

Teaching in experiments of biology is important for the cultivation of life science talents. In view of the rapid development of life science and the increasing demand for research-oriented talent training, teaching in experiments of biology should set up a variety of learning outcomes: to train experimental skill, to cultivate students' experimental design and operation abilities, and to improve students' scientific thinking and innovative consciousness. We have carried out an educational reform on experimental genetic engineering blended course. In this paper, we introduced our methods of organizing online materials, the curriculum design of the blended course, the implementation details, and a preliminary analysis of teaching effects. We found that experimental genetic engineering blended course could support students' active learning and a learning-centered teaching model. Moreover, it could facilitate students' achievement of improving experimental skills, cultivating a rigorous scientific attitude, professional research quality and academic innovation ability.

Recent Trends in Sedentary Behaviors among Chinese Children According to Demographic and Social Characteristics / 生物医学与环境科学（英文）

Objective@#This study aims to explore trends in sedentary behavior among Chinese children aged 6-17 years per demographic and social characteristics.@*Methods@#A total of 4,341 children aged 6-17 years who participated in the @*Results@#From 2004 to 2015, sedentary time among children aged 6-17 years increased from 23.9 ± 0.6 h/week to 25.7 ± 0.6 h/week ( @*Conclusions@#Sedentary time among Chinese children aged 6-17 years showed an upward trend from 2004 to 2015, especially among children residing in rural areas and regions with low urbanization levels.

Physical Activity and Sedentary Behaviors among Chinese Children: Recent Trends and Correlates / 生物医学与环境科学（英文）

Objective@#This study was aimed at examining the trends and correlates of physical activity (PA) and sedentary behaviors among Chinese children.@*Methods@#A total of 4,341 subjects (6,936 observations) aged 6-17 years who participated in the China Health and Nutrition Survey (2004-2015) were included. Of the subjects, 41% participated in the survey twice or more. Random-effects ordinal regression models and repeated-measures mixed-effects models were used to examine the PA trends. Quantile regression models were applied to examine the factors influencing PA and sedentary behaviors.@*Results@#From 2004 to 2015, the prevalence of physical inactivity among Chinese children aged 6-17 years increased by 5.5% [odds ratio ( @*Conclusions@#A declining PA trend among Chinese children aged 6-17 years was observed from 2004 to 2015, and certain subgroups and geographical areas are at higher risk of physical inactivity.

Repair of defects in dorsal of wrist and hand with posterior interosseous artery propeller flap: a report of 9 cases / 中华显微外科杂志

Objective:To investigate the preliminary clinical effect of posterior interosseous artery propeller flap in the repair of dorsal of wrist and hand wounds.Methods:From March, 2015 to December, 2019, 9 cases of dorsal of wrist and hand wounds were repaired with posterior interosseous artery propeller flap, including 6 cases of dorsal hand defect and 3 cases of dorsal wrist defect. Defect area: 6 cm × 4 cm-3 cm × 3 cm; There were 3 cases of metacarpal fracture, 1 case of phalangeal fracture and 1 case of tendon rupture. According to the size and shape of the wound, the posterior interosseous artery propeller flap was designed to transfer and repair the soft tissue defect wound. The size of the flap: 20 cm × 5 cm-12 cm × 3 cm, the size of posterior interosseous artery propeller flap was recorded and the surgical characteristics were summarized; The survival of the flap, donor and recipient complications were observed and followed-up.Results:All flaps were cut smoothly and the donor areas were sutured directly. The flap survived completely in 8 cases and partial necrosis in 1 case; One case complicated with wound infection. The follow-up ranged from 6 to 31 months, with an average of 14 months. The texture and shape of the flap were good; The last DASH score was 3-18, with an average of 9.3; There were 2 cases of mild scar hyperplasia in the donor area and 1 case of mild scar hyperplasia at the edge of the flap.Conclusion:Posterior interosseous artery propeller flap may be an effective method to repair small and medium-sized wounds of dorsal of wrist and hand.

Molecular characteristics of Escherichia coli strains producing Shiga toxin 2e subtype from different sources / 中华微生物学和免疫学杂志

Objective:To understand the molecular characteristics of Escherichia coli producing Shiga toxin 2e subtype isolated from different sources in China. Methods:Three human-derived, 13 animal-derived and eight food-derived stx2e-positive Escherichia coli strains which were isolated during 2012 to 2018 were analyzed by antimicrobial susceptibility testing and whole genome sequencing. The stx subtype, serotype, multi-locus sequence type, virulence genes and antimicrobial resistance genes of each strain were determined by whole genome sequences. The phylogenetic relationship and genetic composition of Shiga-toxin prophage were explored. Results:Twenty-four stx2e-STEC strains were typed into 19 O∶H serotypes and 19 sequence types (STs). Each strain carried at least one kind of antimicrobial resistance gene and 19 out of 24 strains were resistant to at least one kind of antimicrobials. Three human-derived strains were heterogenous in serotypes and STs, but there were several animal and food-derived strains shared the same serotype or ST with human strains and showed close relationship in the phylogenetic analysis. The sequences of stx2e among all strains were highly conserved (similarity >99.7%), but there were significant differences in the size and the gene composition of Shiga toxin prophage genome. Conclusions:This is report about the characteristics of rare human-derived Stx2e-STEC strains in China. Comparing human isolates with animal-and food-derived strains, it indicates that Stx2e-STEC strains are highly genetic diversity and have the potential to infect humans.