Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages

SARS-CoV-2 variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding working mechanisms and developing therapeutic agents. In this study, we characterized previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-EM structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

EGFR mutation, expression of PD-L1/Ki-67 and their correlation with clinical features in elderly NSCLC patients / 中华检验医学杂志

Objective:To investigate the mutation of epidermal growth factor receptor (EGFR), the expression of programmed death ligand 1 (PD-L1), cell proliferation-associated antigen (Ki-67) in elderly patients with non-small cell lung cancer (NSCLC), and their correlation with clinical feature such as gender, histological type and TNM stage.Methods:The tissue samples of 340 elderly NSCLC patients with definite histopathological diagnosis were collected from January 2020 to December 2020 in Huadong Hospital Affiliated to Fudan University, including 195 males and 145 females, age between 68.9±6.0 years. Patients were grouped according to clinical features such as gender, histological type and TNM stage. The expression of EGFR mutation, PD-L1 and Ki-67 were detected by Super-ARMS and immunohistochemistry. The correlation between tnem and clinical features was statistically analyzed, and the correlation between EGFR mutation and PD-L1/Ki-67 expression was further analyzed separately.Results:In elderly NSCLC patients′ tissues, the positive rate of EGFR mutation was 48.53% (165/340). L858R and 19del mutations were the most common types, which were 56.36% (93/165), 30.30% (50/165) respectively. The mutation rate of EGFR was higher in women, lung adenocarcinoma, well-differentiated, and low-stage patients, which were 65.52% (95/145), 53.77% (164/305), 56.75% (143/252), 52.53% (135/257) respectively. In addition, the positive rate of PD-L1 expression was higher in elderly patients with non-adenocarcinoma lung cancer and poorly differentiated adenocarcinoma, which were 37.14% (13/35), 24.53% (13/53) respectively. The negative rate of PD-L1 expression was higher in elderly patients with NSCLC in stage Ⅰ+Ⅱ, no lymph node metastasis and weakly positive Ki-67, which were 89.11% (229/257), 87.63% (248/283), 94.71% (197/208) respectively. Correlation analysis showed that EGFR mutation was negatively correlated with the expression of PD-L1 and Ki-67 (PD-L1: r=-0.22, P<0.001; Ki-67: r=-0.32, P<0.001). Conclusion:There is a negatively correlation between EGFR mutation and the expression of PD-L1 and Ki-67 in elderly NSCLC, suggesting that the combined detection of EGFR mutation and PD-L1 expression could provide the basis for precise targeted therapy for elderly NSCLC patients.

Potential diagnostic and therapeutic targets and anti-tumor mechanisms of Neddylation pathway in digestive system tumors / 中华检验医学杂志

Neddylation,a novel post-translational modification of proteins, is overactivated in digestive system tumors and can be used as a potential anti-tumor molecular target. Targeting Neddylation pathway plays an anti-tumor role by inducing cell cycle arrest, apoptosis, senescence and autophagy of digestive system tumor cells, as well as enhancing the sensitivity of digestive system tumor cells to the radiotherapy and chemotherapy. Targeting Neddylation pathway and its inhibnitor MLN4924 can act as poential targets against digestive system tumors.

Social net work analysis of referral of stroke inpatients in Changsha / 中华医院管理杂志

Objective:To analyze the current status of referral of stroke inpatients and explore the characteristics of the referral network in Changsha, for the reference to improve and promote the hierarchical medical system of stroke.Methods:Data of the inpatient medical record of stroke patients and the annual reports of medical institutions in Changsha in 2018 were collected from the health statistics network direct reporting system of Health Commission of Hunan province, for analysis of the referrals of inpatients in different medical institutions. Social network analysis was adopted to analyze the density, centrality and K-core of the referral network of stroke inpatients.Results:A total of 82 medical institutions for stroke inpatients were included with 2 859 referrals of patients. Most of the referrals were made between tertiary hospitals(1 515), especially within hospitals of a stroke alliance(1 123). The density of referral network was 0.613.Tertiary hospitals were in the center of the network, the entry points of secondary hospitals were in the center of the network and primary medical institutions were located at peripheral positions. Most of the tertiary hospitals in the 15-core(14, 72.68%), 12 of them were the units of Hunan Stroke Alliance.Conclusions:Tertiary hospitals played an important role in the region, secondary hospitals were able to receive patients referred by tertiary hospitals, but few patients were transferred to primary care institutions; The primary medical institutions failed to play due roles in the referral network. The establishment of stroke alliances could promote the cooperation of hospitals in the alliance, but the division of labor and cooperation among different levels of medical institutions in the region needed to be further optimized.

Antibody Cocktail Exhibits Broad Neutralization against SARS-CoV-2 and SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446 -S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, F61 and H121 exhibited efficient neutralizing activity against variants B.1.1.7 and B.1.351, those showed immune escape. Efficient neutralization of F61 and H121 against multiple mutations within RBD revealed a broad neutralizing activity against SARS-CoV-2 variants, which mitigated the risk of viral escape. Our findings defined the basis of therapeutic cocktails of F61 and H121 with broad neutralization and delivered a guideline for the current and future vaccine design, therapeutic antibody development, and antigen diagnosis of SARS-CoV-2 and its novel variants.

Research on the anti-lung cancer effects of targeted Neddylation modifying pathway and its inhibitor MLN4924 and its mechanism / 国际肿瘤学杂志

Neddylation is overactivated in lung cancer, which promotes the development of lung cancer by activating its downstream CRL ubiquitin ligase and promoting the CRL tumor-suppressor protein substrate degradation. MLN4924, a small molecule inhibitor of Neddylation, plays an anti-lung cancer role by inducing cell cycle arrest, apoptosis and senescence. Furthermore, targeting the key enzymes of Neddylation and their substrates, Cullin family proteins, can inhibit the development of lung cancer.

Progress of cell death induced by Neddylation modification pathway inhibitor MLN4924 / 肿瘤研究与临床

Protein ubiquitin-like modification of Neddylation is an important post-translational modification mode of protein to widely regulate cell cycle, growth, development and other biological processes. Recent studies have found that MLN4924, small molecule inhibitor of Neddylation modification, has a significant anti-tumor effect, which can inhibit the tumor growth by inducing cell cycle arrest, senescence and apoptosis, and inhibiting tumor angiogenesis. This paper reviews the related mechanism research of cell programmed death induced by Neddylation modification pathway inhibitor MLN4924.

Establishment, evaluation, and determination of saliva glucose concentration by ion chromatography / 中华内分泌外科杂志

Objective:To establish an analytical method for measuring the concentration of glucose in saliva by ion chromatography.Methods:The proteins in saliva were removed by thermal denaturation method, CarboPac PA20 (3×30 mm) was used as a protective column and CarboPac PA20 (3×150 mm) was used as an analytical column for ion chromatography analysis. Gradient elution was carried out with A: ultra-pure water, B: 250 mmol/L NaOH solution and C: 500 mmol/L NaAc solution. Pulsed ampere detector was used for detection.Results:This method had a good linear relationship in the range of 0.04 to 0.12 mg/L, with a linear relation coefficient of 0.9967. The detection limit of glucose was 2 μg/L, the mean value of the relative standard deviation (RSD) of the repeatability measurement was 0.75%, and the average spike recovery was 103.07%.Conclusion:This method is simple, sensitive, accurate and stable, and can be used for the determination of glucose concentration in saliva.

Abnormal Upregulation of Cardiovascular Disease Biomarker PLA2G7 Induced by Proinflammatory Macrophages in COVID-19 patients

BACKGROUNDCoronavirus disease 2019 (COVID-19) triggers distinct patterns of pneumonia progression with multiorgan disease, calling for cell- and/or tissue-type specific host injury markers. METHODSAn integrated hypothesis-free single biomarker analysis framework was performed on nasal swabs (n = 484) from patients with COVID-19 in GSE152075. The origin of candidate biomarker was assessed in single-cell RNA data (GSE145926). The candidate biomarker was validated in a cross-sectional cohort (n = 564) at both nucleotide and protein levels. RESULTSPhospholipase A2 group VII (PLA2G7) was identified as a candidate biomarker in COVID-19. PLA2G7 was predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, PLA2G7 was found in patients with COVID-19 and pneumonia, especially in severe pneumonia, rather than patients suffered mild H1N1 influenza infection. Up to 100% positive rates of PLA2G7 were positively correlated with not only viral loads in patients with COVID-19 but also severity of pneumonia in non-COVID-19 patients. Although Ct values of PLA2G7 in severe pneumonia was significantly lower than that in moderate pneumonia (P = 7.2e-11), no differences were observed in moderate pneumonia with COVID-19 between severe pneumonia without COVID-19 (P = 0.81). Serum protein levels of PLA2G7, also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), were further found to be elevated and beyond the upper limit of normal in patients with COVID-19, especially among the re-positive patients. CONCLUSIONSWe firstly identified and validated PLA2G7, a biomarker for cardiovascular diseases (CVDs), was abnormally enhanced in COVID-19 patients at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in COVID-19 patients. PLA2G7 could be a hallmark of COVID-19 for monitoring disease progress and therapeutic response. FUNDINGThis study was supported by grants from China Mega-Projects for Infectious Disease (2018ZX10711001), National Natural Science Foundation of China (82041023).

Clinical application of circulating tumor cells in the diagnosis and treatment of urothelial carcinoma / 中华检验医学杂志

Objective:To study the correlation between circulating tumor cells (CTC) and the degree of pathological invasion, recurrence and metastasis of urothelial carcinoma, and so to explore the clinical value of CTC detection in bladder cancer.Methods:A total of 142 patients with urothelial carcinoma in Huadong Hospital Affiliated to Fudan University were enrolled as cancer group from July 2016 to January 2018. According to the degree of tumor invasion, cancer group was divided into the non-muscle-invasive group (49 cases) and the muscle-invasive group(93 cases). In addition, 52 patients with benign urinary tract lesions admitted were selected as the benign group and 56 patients with non-urinary tract diseases and non-tumor as the control group. A total of 3.2 ml of venous anticoagulant blood from each subject was collected. CTC was enriched by negative enrichment using the magnetic beads coated with monoclonal antibody Cluster 45 of differentiation (CD45) to capture and remove white blood cells, and identified by chromosome 8 probe(CEP8) fluorescence in situ hybridization (FISH) technique. CD45-/4′,6′-diamidino-2-phenylindole+/CEP8>2(CD45-/DAPI+/CEP8>2) cells were judged as CTC. SPSS22.0 statistical software was used for statistical analysis.Results:≥2 CTCs/3.2 ml in blood was set as cutoff value. CTC positive rates in bladder cancer group, benign group and control group were 70.42%(100/142), 28.85%(15/52) and 8.93%(5/56), respectively, and there was a significant difference (χ 2=70.496, P=0.000). There was a statistically difference ( U=2 863.5, P=0.011) in the mean count of CTC(2 CTCs/3.2 ml vs 4 CTCs/3.2 ml) between the two groups. The proportion of≥5 CTCs/3.2 ml in the muscle-invasive group was 40.86% (38/93), which was significantly higher than that in the non-muscle-invasive group, 18.37% (9/49) (χ 2=7.330, P=0.007). Cystoscope follow-up of 65 patients treated with transurethral resection of the bladder tumor showed that the recurrence and metastasis rate in patients with≥5 CTCs/3.2 ml was as high as 47.62% (10/21), compared with 11.36% (5/44) of patients with<5 CTCs/3.2 ml (χ 2=10.530, P=0.001). Among 59 patients undergoing radical cystectomy, no significant difference was found in tumor diameter >3 cm, positive surgical margins and positive lymph nodes among all groups according to CTC negative or positive and CTC number ( P>0.05). But the recurrence and metastasis rate of patients with ≥5 CTCs/3.2 ml (59.10%) was significantly higher than that of patients with <5 CTCs/3.2 ml (6/30)(χ 2=8.364, P=0.004). Conclusion:The number of CTC increased with the deepening of tumor invasion; Tumor recurrence and metastasis increased significantly in the patients with ≥5/3.2 ml CTCs in blood.

The complete mitochondrial genome of Sarcophaga tuberosa (Diptera: Sarcophagidae).

Sarcophaga tuberosa has certain sanitary and epidemiological significance and takes proteins from decaying matter. In this study, we first sequenced and analyzed the complete mitochondrial genome (mitogenome) of S. tuberosa. The length of mitogenome was 15,173 bp, consisting of A (39.5%), G (9.4%), T (37.0%), and C (14.1%), and the order and orientation of genes were identical with that from the mittogenomes of flesh flies previously reported. Phylogenetic analyses showed that S. tuberosa was clustered separately, but which was closed to the species of Sarcophaga portschinskyi. This study provided better support for further understanding of phylogenetic relationships and enriched the mitogenome database of flesh flies.

The complete mitochondrial genome of Sarcophaga brevicornis (Diptera: Sarcophagidae).

Sarcophaga brevicornis (Diptera: Sarcophagidae) was of utmost forensic importance due to their wide distribution, ubiquitous, and synanthropic nature. The complete mitochondrial genome (mitogenome) of S. brevicornis was first sequenced and assembled in this study. The length of circular mitogenome was 15,152 bp, which showed in a typical arthropod genome, including 13 protein-coding genes (13 PCGs), two ribosomal RNA (two rRNA) genes, 22 transfer RNA (22 tRNA) genes, and an AT-rich region. Its nucleotide composition was A 39.0%, C 12.7%, G 10.6%, and T 37.7%. Furthermore, phylogenetic relationships of S. brevicornis and the published sarcophagid species were evaluated based on 13 PCGs. The results indicated that S. brevicornis was clearly separated from the other sarcophagid species, but it was closed to the species of Sarcophaga similis. This study provided a significant database reference for genetic structure and phylogenetic analysis of Sarcophagidae.

Methods of packaging lentivirus library for CRISPR/cas9 -based screening / 中华实验和临床病毒学杂志

Objective@#To obtain the optimum of lentiviral library packaging based on CRISPR/cas9 (Clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein 9).@*Methods@#Reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence antibody (IFA) and enzyme linked immunosorbent assay (ELISA) were used to detect the lentivirus titers in condition of different ratio of packaging plasmids, different addition of lipofectamine 3000 reagent and different time points post-transfection. Then, high-throughput sequencing was performed to evaluate the representation and distribution of single guide (sg)RNAs in the library.@*Results@#The lentivirus titer was the highest when the molar ratio of psPAX2∶pMD2.0G∶Lentivirus library was 2∶1∶1, and the optimum addition of Lipofectamine 3000 reagent was 10 μl, while the result of ELISA were correspondent to that of RT-PCR. The IFA result showed that the lentivirus titer was the highest at 60 h post-transfecion. The coverage of sgRNAs in the lentivirus library packaged with the optimum we obtained was 99.3%, and the read counts of sgRNAs was observed in a normal distribution.@*Conclusions@#The optimal lentivirus library packaging was obtained, and this can provide basis for CRISPR/cas9-based screening.

Clinical application of circulating tumor cells in the diagnosis of prostate cancer / 中华检验医学杂志

Objective To evaluate the diagnostic value of circulating tumor cells(CTCs) in prostate cancer (Pca) through studying the relationship between CTCs and Gleason scores and pathological TNM stage in Pca patients. Methods A total of 238 patients including 161 Pca patients as cancer group, 35 male patients with benign prostatic diseases as benign group and 42 male with non-prostate disease as control group, who were treated in our hospital from July 2016 to January 2018,were enrolled. Venous blood of every patient was collected and CTCs were enriched and identified by immunocytochemistry CD45 capturing leukocyte and fluorescence in situ hybridization with chromosome 8 (CEP8-FISH). Cells displaying CD45-/DAPI+/CEP8>2 were characterized as CTCs. One-way ANOVA was used to exam the correlations of the number of CTCs with Gleason scores and pathological TNM stage. Results CTCs ≥2 were detected in 74.53％(120/161) of Pca patients and 20.00％(7/35)of benign prostatic diseases patients and 7.14％(3/42)of control group (χ2=79.605,P<0.05). In group Gleason scores 6, the numbers of CTCs were 2.00 ± 2.42, the ratios of CTCs≥5 and tetraploid were 13.33％ (2/15)and 26.67％(4/15) respectively. In 7 scores group, the results were 3.14±2.68,17.72％(14/79) and 34.18％(27/79)respectively;In 8 scores group, the results were 3.57 ± 2.70, 33.33％(7/21)and 42.86％ (9/21)respectively; In 9 scores group, these three results were 4.65±4.41, 43.48％(20/46) and 45.65％(21/46)respectively. The numbers of CTCs in the≤pT2b (20), pT2c(27), pT3a(19), pT3b(16)and≥pT4(12) groups were 2.25±2.45, 3.56±2.79, 4.05±3.47, 4.69±2.12 and 5.17±3.21 respectively. The ratios of CTCs≥5 were 25.00％(5/20), 25.93％(7/27), 26.32％(5/19), 50.00％(8/16) and 58.33％ (7/12)respectively. The proportions of tetraploid were 20.00％(4/20), 25.93％ (7/27), 31.58％(6/19), 50.00％(8/16) and 58.33％(7/12) respectively. There were significant differences between CTC and Gleason scores (F=3.200, P<0.05)and pathological stage (F=2.673, P<0.05). The ratios of CTCs≥5 increased with the increase of Gleason scores (χ2=11.592, P<0.05). Conclusions The detection of CTCs could be used for the differential diagnosis of Pca and benign prostatic disease. There were notable correlations between the numbers of CTCs and Gleason scores and pathological stage in Pca patients, especially between CTCs≥5 and Gleason scores.

Epidemiological characteristics of tick borne encephalitis in China, 2014 / 中华实验和临床病毒学杂志

Objective@#To analyze the epidemiological characteristics and distribution characteristics of tick-borne encephalitis in China in 2014, and to provide scientific basis for formulating specific prevention and control measures.@*Methods@#The epidemic data were obtained from the "infectious disease report information management system" , using Excel 2016, GIS and other software to summarize and analyze the cases of tick borne encephalitis (TBE) reported, using the number of cases, incidence, composition ratio and other indicators to analyze and describe the TBE epidemiological characteristics in China in 2014.@*Results@#In 2014, a total of 322 cases of TBE were reported in 9 provinces in China, with an annual incidence of 0.024/100, 000 and 1 death of patient. The provinces with high number of cases were Jilin province, Inner mongolia autonomous region and Heilongjiang province, and the number of cases in the other six provinces is no more than two. TBE was distributed in spring and summer, and it is concentrated in May to July. The age of the affected population was mostly concentrated in 40-49 years old, the male-female ratio was 1.6∶1 (198/124), and the patients were dominantly farmers, household and unemployed workers, and forestry workers, they accounted for 49.40% (159/322), 26.40% (85/322) and 18.60% (60/322) of the national TBE cases respectively. The three hospitals that reported the most TBE cases in 2014 were Inner mongolia forestry general hospital, Jiangyuan People′s hospital of Baishan city, Jilin province and Mudanjiang forestry central hospital of Heilongjiang province. The number of reported cases in these three hospitals accounted for 68.6% of the whole country. The laboratory diagnosis rate of Inner mongolia forestry general hospital was the highest (91.9%).@*Conclusions@#In 2014, the incidence of TBE in China has continued to rise compared with the previous two years. The geographical focus is mainly on the forest areas of Daxing′anling, Xiaoxing′anling and Changbai Mountain.

Inhibitory effect of andrographolide on angiogenesis induced by the supernatant from cultured tumor cells / 中南大学学报(医学版)

To determine the effect of andrographolide (Andro) on angiogenesis of human umbilical vein endothelial cells (HUVECs).
 Methods: HUVECs were treated with different concentrations of Andro and the cell viability was detected with Cell Counting Kit-8 (CCK-8). HUVECs were treated with half lethal dose (IC50) of Andro. Matrigel was used to make capillary formation of HUVECs and the effect of Andro on capillary formation was evaluated by calculating the percentage of capillary formation. Moreover, the effects of Andro and the supernatant from cultured A549 tumor cells on capillary formation were evaluated by calculating the percentage of capillary formation. The effect of Andro on the expression of matrix metalloproteinase-9 (MMP-9) was determined with Western blot.
 Results: The cell viability of HUVECs decreased with the increase of Andro concentrations. IC50 was 20 μmol/L. The capillary formation of HUVECs was inhibited when treated with 20 μmol/L Andro for 24 hours. Moreover, Andro was able to antagonize the promotion of the capillary formation induced by the supernatant from cultured tumor cells. Andro could suppress the expression of MMP-9 and antagonize the capillary formation.
 Conclusion: Andro inhibits the capillary formation of HUVECs and can antagonize the promotion of angiogenesis induced by the supernatant from cultured tumor cells.

Application of matrix-assisted laser desorption/ionization-time of flight mass spectrometry for the ;identification of Helicobacter pylori / 中华检验医学杂志

Objective To optimize the pre-treatment method before detecting Helicobacter pylori ( H.pylori ) by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry ( MALDI-TOF MS) and evaluate the ability of the Superspectra by MALDI-TOF MS for identifying clinical isolated H.pylori strains.Methods H.pylori were isolated from 469 biopsy samples of gastric mucosa collected from January 2015 to July 2016 in Huadong Hospital affiliated to Fudan University , 16 s rRNA sequencing were then performed to validate the strains.Then 91 isolated H.pylori strains were used for the subsequent MALDI-TOF analysis.The effect of pre-treatment of 50%isopropanol, formic acid and acetonitrile (1∶1), 70%formic acid were compared before H.pylori detecting by MALDI-TOF MS.40 out of 91 clinical H.pylori strains were detected by MALDI-TOF MS and the spectra were randomly assigned to 4 groups including 5, 10, 20, 30 spectra, each group had 3 repeats.Then 4 groups with different amount of spectra were used for creating Superspectra with SARAMIS Premium software , respectively.The remaining 51 H.pylori strains including 306 spectra were used for validating the identification rate of the Superspectra.Results With the use of 70%formic acid, the greater number of ion signals and higher relative intensity of the main peaks were observed than other pre-treatment reagents.The identification rate of Superspectra created by 30 strains group was the highest ( 90.2%).Among the 306 spectra, 46.1% of them achieved highly reliable identification , 22.2% achieved lower degree of reliable identification , and 31.7% of them achieved “no identification”.Conclusions The study optimized the pre-treatment method before H.pylori detecting by MALDI-TOF MS.The Superspectra was created with the good ability to rapidly identify clinical isolated H.pylori strains.

Digitalization of information resources in domestic TCM / 中华医学图书情报杂志

After the following aspects of information resources digitalization in domestic TCM were described, in-cluding different types and contents of digital information resources, effectively developed ancient book resources, expanded team construction, and strengthened cooperation between departments. Measures were put forward for the digitalization of information resources in domestic TCM according to the existed problems, such as insufficient de-velopment, lack of audiovisual products, and low accessibility of TCM information resources.

Maiden outbreak of chikungunya in Dongguan city, Guangdong province, China: epidemiological characteristics.

BACKGROUND: This study was conducted to identify epidemiological characteristics of the first documented CHIK fever outbreak in China and evaluate the effect of the preventive measures taken. METHODOLOGY/PRINCIPAL FINDINGS: From September 1 to October 29, 2010, China's first documented outbreak of CHIK fever occurred in the Xincun community of Wanjiang District of Dongguan city, Guangdong province; 253 case-patients were recorded, of which 129 were laboratory confirmed, with an attack rate of 1%. Before September 18(th) the number of CHIK fever cases remained relatively low in the Xincun community; from September 19(th) onwards, the number of cases increased drastically, with an outbreak peak on October 4(th). Cases were distributed across nine small village groups in the Xincun community, with an attack rate of 0-12% at the village level. The household attack rates ranged between 20% and 100%. No significant difference was found in the attack rate between males and females. There was a significant difference in the attack rate in different age groups (chi-square=18.35, p=0.005); highest in patients aged 60 years or older and the lowest in patients aged under 10. The major clinical characteristics of patients are fever (100%), joint pain (79%) and rash (54%). Phylogenetic analysis of the E1 gene on the five earliest confirmed cases showed that the strains of CHIKV isolated from their sera were highly homologous (up to 99%) with isogeneic strains isolated in Thailand in 2009. After control measures were taken, including killing adult mosquitoes and cleaning breeding habitats of Aedes mosquitoes, the Breteau index and Mosq-ovitrap index decreased rapidly, and the outbreak ended on October 29. CONCLUSION/SIGNIFICANCE: The infection source of the outbreak was imported. Cases showed obvious temporal, spatial, and population aggregation during the outbreak. Comprehensive control measures based on reducing the density of Aedes mosquitoes were effective in controlling the epidemic.

The effects of mycophenolate mofetil on immunologic compromise in rats with severe acute pancreatitis / 中华急诊医学杂志

Objective To observe the modulatory effects of NF-κB on dynamic changes of TNF-α、IL-1β and ICAM-1 in rats with severe acute pancreatitis (SAP),and to assess the effects of pretreatment with mycophenolate mofetil (MMF) on them.Methods A total of 104 male Wistar rats were randomly divided into normal group,sham operation group,SAP group and MMF group.(1) In normal group,rats had just an incision on abdomen wall and sutured (n =8) ; (2) In sham operation group,rats underwent laparotomy with flipping over the pancreas and gendy striking five times by using blunt instrument and abdomen was closed (n =32); (3) In SAP group,SAP in rats was induced by the retrograde injection of sodium taurocholate (STC) into the pancreatic duct (n =32) ; (4) In MMF group,MMF (250mg/kg)was injected intraperitoneally one hours after injection of STC (n =32).Rats were saerificed by abdominalaorta exsanguination separately at intervals of 3,6,12 and 24 h after modeling of pancreatitis.Histologic score of pancreatic tissue was assessed,and serum amylase (AMS) and serum C-reactive protein (CRP)were measured by automatic biochemical detector.The serum levels of inflammatory cyctokines (TNF-α,1L-1β and 1CAM-1 ) were measured by using ELISA,and expression of NF-κB mRNA in pancreatic tissue was measured by using quantitative PCR.Results Compared with sham operation group,histologic score of pancreatic tissue,serum amylase,TNF-α、IL-1β and ICAM-1 in SAP group were increased significantly (P ＜ 0.05 ).Pretreatment with MMF obviously deceased histologic score,and the serum levels of amylase,TNF-α,IL-1β and ICAM-1 and the expression of NF-κB mRNA were higher than those in SAP group in early stage (P ＜0.05 ).Conclusions Cytokines play an important role in early stage of SAP.MMF could attenuate the severity of inflammatory response through inhibiting cellular immunity and modulating the proinflammatory cytokines produced.