[Analysis on cancer incidence and mortality attributed to human papillomavirus infection in China, 2016].

Objective: We aim to evaluate the morbidity and mortality of cancer attributable to human papillomavirus (HPV) infection in China in 2016. Methods: Based on the cancer incidence and mortality rates, national population data, and population attributable fraction (PAF) in China, we calculated the number of incidence and death cases attributed to HPV infection in different areas, age groups, and gender in China in 2016. The standardized incidence and mortality rates for cancer attributed to HPV infection were calculated by using Segi's population. Results: In 2016, a total of 124 772 new cancer cases (6.32 per 100 000) were attributed to HPV infection in China, including 117 118 cases in women and 7 654 cases in men. Of these cancers, cervical cancer was the most common one, followed by anal cancer, oropharyngeal cancer, penile cancer, vaginal cancer, laryngeal cancer, oral cancer, and vulvar cancer. A total of 41 282 (2.03 per 100 000) deaths were attributed to HPV infection, of which 37 417 occurred in women and 3 865 in men. Most deaths were caused by cervical cancer, followed by anal cancer, oropharyngeal cancer, penile cancer, laryngeal cancer, vaginal cancer, oral cancer, and vulvar cancer. The incidence and mortality rates of cervical cancer increased rapidly with age, peaked in age group 50-54 years, then decreased obviously. The morbidity and mortality rates of non-cervical cancer increased with age. The cancer case and death numbers in rural areas (57 089 cases and 19 485 deaths) were lower than those in urban areas (67 683 cases and 21 797 deaths). However, the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of cervical cancer were higher in rural areas than in urban areas. There were no significant differences in ASIR and ASMR of non-cervical cancers between urban areas and rural areas. Conclusions: The incidence of cancers attributed to HPV infection in China was lower than the global average, but the number of incidences accounted largely, furthermore there is an increasing trend of morbidity and mortality. The preventions and controls of cervical cancer and male anal cancer are essential to contain the increases in cancer cases and deaths attributed to HPV infection.

[Time trends of H. pylori infection and related drug use in patients with peptic ulcer bleeding in a hospital in Beijing from 2010 to 2019].

Objective: To explore the time trends of H. pylori infection and related drug use in patients with peptic ulcer bleeding (PUB) in recent ten years. Methods: PUB patients in Peking University Third Hospital from 2010 to 2019 were included. Time trends of H. pylori infection, related drugs (non-steroidal anti-inflammatory drugs, aspirin, antiplatelet drugs, anticoagulant drugs, glucocorticoids) use and non-H. pylori-non-drug ulcer in PUB patients were analyzed. Results: A total of 1 140 PUB patients were included from 2010 to 2019 (including 925 males and 215 females). The age M(Q1,Q3)was 53.5 (33.0, 66.0) years, with 833 patients <65 years old. The positive rates of H. pylori were 79.3%, 75.7%, 73.1%, 71.6%, 77.0%, 70.4%, 69.7%, 63.1%, 51.4%, 50.9%, respectively, showing a decreasing trend (χ²=32.386, P<0.001), and the decreasing trends were significant in different ulcer location, age and gender subgroups(all P<0.05). The proportions of PUB patients using at least one of the above drugs were 23.1%, 28.6%, 34.0%, 39.5%, 33.8%, 35.9%, 28.7%, 39.8%, 40.9%, 41.8%, respectively, showing an increasing trend (χ²=6.857, P=0.009), and the proportions of patients with antiplatelet drugs and anticoagulant drugs history showed increasing trends. The proportions of non-H. pylori-non-drug patients were 12.3%, 22.1%, 14.6%, 13.2%, 7.7%, 13.0%, 16.9%, 18.7%, 22.6% and 20.9%, respectively, showing an increasing trend (χ²=4.808, P=0.028). Accordingly, the proportions of elderly (≥65 years old) patients (χ²=4.608, P=0.032) and large ulcer (≥2 cm) patients (χ²=8.173, P=0.004) showed increasing trends. Conclusion: In the last decade, the positive rate of H. pylori in PUB patients showed a decreasing trend, while the proportions of patients with antiplatelet drugs and anticoagulant drugs history and the proportion of non-H. pylori-non-drug patients showed increasing trends.

[Analysis on prevalence and epidemic risk of animal plague in different ecological plague foci in Inner Mongolia Autonomous Region].

The risk of plague epidemics and relapse of various types of plague foci persists in Inner Mongolia Autonomous Region. For Marmota sibirica plague foci, the animal plague has not been found but antibody has been detected positive. Nowadays, Marmota sibirica has been increasing in population and distribution in China. In bordering countries Mongolia and Russia, the animal plague has been continuously prevalent. For Spermophilus dauricus plague foci, the animal plague has been taken place now and then. Compared to the above foci, the animal plague is most prevalent in Meriones unguiculatus plague foci and frequently spread to humans. Due to higher strain virulence and historical disaster in Marmota sibirica plague foci and Spermophilus dauricus plague foci, plague prevention and control should be strengthened on these foci. In addition to routine surveillance, epidemic dynamics need to be further monitored in these two foci, in order to prevent their relapse and spread to humans.

[Comparison of hereditary breast and ovarian cancer syndrome and sporadic ovarian cancer in ovarian cancer BRCA mutations].

Objective: To study the difference between BRCA gene mutations in hereditary breast and ovarian cancer syndrome (HBOC) and in sporadic ovarian cancer (SOC). Methods: This study was for exploratory research, the inclusion criteria were 284 patients with ovarian cancer admitted at Shanxi Provincial Cancer Hospital from November 2018 to December 2019, with high-throughput DNA sequencing including the full coding regions and exon-intron link regions of BRCA1 and BRCA2 gene. Pathogenic mutations in the BRCA gene of patients with ovarian cancer were collected and mutation site analysis was performed to compare phenotypic differences in pathogenic mutations between HBOC syndrome and SOC patients. Results: (1) Of the 284 ovarian cancer patients, seventy-seven had BRCA pathogenic mutations with a mutation rate of 27.1% (77/284), with BRCA1 mutation rate of 19.7% (56/284), BRCA2 gene 6.7% (19/284) and BRCA1/2 common mutation rate of 0.7% (2/284). Of the 284 patients with ovarian cancer, the pathogenic mutation rate in the BRCA gene in HBOC syndrome patients was 43.8% (32/73), which were significantly higher than that in SOC patients [21.3% (45/211); χ²=13.905, P<0.01]. Among BRCA1 gene mutation, the mutation rate in HBOC syndrome was higher than that of SOC [87.5% (28/32) vs 62.2% (28/45)], the BRCA2 gene mutation rate in patients with HBOC syndrome was lower than that in SOC patients [6.2% (2/32) vs 37.8% (17/45)], and there were statistically significant differences (all P<0.05). Two of the 77 patients with pathogenic mutations in the BRCA gene were multisite mutations, including one simultaneous two site mutation, one simultaneous three site mutation. There were 80 mutation sites with frameshift deletion mutations (55.0%, 44/80) and nonsense mutations (31.2%, 25/80). (2) Of the 73 patients with HBOC syndrome, 32 cases had pathogenic mutations in BRCA gene, including 28 cases in BRCA1, mainly in exon 11 and 24 (9 and 7 cases, respectively), and only two cases in BRCA2, both in exon 11; another two had multiple locus mutations. Of the 211 patients with SOC, 45 cases had pathogenic mutants in BRCA gene, including 28 cases in BRCA1, mainly in exon 11 and 24 (15 and 2 cases, respectively), and 17 cases in BRCA2, mainly in exon 11 (11 cases). (3) Thirty-four pathogenic mutation sites in BRCA gene were found newly, twenty of them were located in the BRCA1 gene, including a locus located on the intron 6, 301+1G>A, and the remaining 19 sites were located on the exons, including 283_286delCTTG, 68_69delAG, 132C>T, 514_547+3del37, 742delA, 1126_1129delAATA, 1196delA, 1352_1364del, 1465G>T, 2171delC, 2341G>T, 3359_3363delTTAAT, 4085_4086ins11, 4161_4162delTC, 4165_4166delAG, 4258G>T, 4338_4339del8insAGAA, 4468G>T, and 4783delA; fourteen sites were located in the BRCA2 gene, including a locus located on the intron 7, 631+1G>A, and the remaining 13 sites were located on the exons, including 2648delT, 2914A>T, 2950_2951insG, 4357+1G>A, 5054C>T, 5257A>T, 5291_5292insTC, 5913delT, 3593delA, 6091_6092insA, 6135_6136delTT, 7452delT, 9097_9098insA. A tal of 28 repeat mutations were located in the BRCA1 gene; among them, the site 5470_5477del8 was repeated 6 times, while 3 times in 981_982delAT. Conclusions: Patients with HBOC syndrome have a significantly higher rate of pathogenic mutation in the BRCA gene than that in patients with SOC. BRCA gene pathogenic mutation sites in HBOC syndrome patients occur commonly in exon 11 and 24 of BRCA 1 gene, while SOC patients occur mainly in exon 11 and 24 of BRCA1 gene and exon 11 of BRCA2 gene. The two loci of BRCA1∶5470_5477del8, BRCA1∶981_982delAT may be ancestor mutations in Chinese ovarian cancer patients, and 34 newly discovered pathogenic mutations in the BRCA gene, enriching the BRCA gene mutation spectrum in the Chinese population.

A bimodal burst energy distribution of a repeating fast radio burst source.

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

[A prospective study on the associations between dietary intakes of energy and macronutrients before menarche and age at menarche among girls].

Based on the data from China Health and Nutrition Survey (CHNS), 840 girls aged 6-15 years who had information about menarche and participated in dietary survey at least once within 1-5 years before onset of menarche between 1989 and 2015 were included in the study. The median age at baseline of the 840 participants was 10 (9, 11) years. The median age at menarche of the participants was 13 (12, 14) years. After adjusting for the age of birth, place of residence, body mass index Z-score, physical activity level and annual household income per capita, the average age of menarche was advanced by 0.036 (95%CI: -0.068, -0.004) years for every 10 g increase in daily fat intake before menarche. The average age at menarche was 0.008 (95%CI: -0.014, -0.001) years earlier for every 1% increase in the daily energy supply ratio of fat before menarche.

[Effectiveness of the thermal ablation in the treatment of human papillomavirus infection and cervical intraepithelial neoplasia in Chinese women].

Objective: To evaluate the effectiveness of thermal ablation in the treatment of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) in Chinese women. Methods: The high-risk HPV-positive women aged 20-65 who were detected through a cervical cancer screening project implemented in three rural sites (Etuoke counties in Inner Mongolia, Xiangyuan and Yangcheng counties in Shanxi Province) and one urban site (Shenzhen) in China were included in this prospective study. Follow up evaluation was performed on HPV positive women who underwent thermal ablation (n=166) as well as received no treatment (n=2 716) in cervical cancer screening program. For women with thermal ablation treatment, HPV test and cytology were used for follow-up with the interval of 6 months or longer after treatment. For women without treatment, HPV test was used for annual follow-up. Women with positive results in either of the HPV tests or abnormal cytology were referred for a colposcopy or biopsy if necessary. The HPV clearance rate and the cure rate of CIN were compared between the two groups. Results: A total of 152 women treated with thermal ablation and 2 539 women without treatment reported for follow-up evaluation with the age M(Q1, Q3) of 42 (36, 48) and 47 (41, 54) years old, and the median time to follow-up time of 23.4 (12.4, 24.5) and 23.5 (12.4, 24.0)months, respectively. The HPV clearance rate in women undergoing thermal ablation was significantly higher than that in women with no treatment (73.0% vs 46.1%, P<0.001). The HPV16, HPV52 and HPV58 clearance rates among women receiving thermal ablation were higher than that in women without treatment with the OR (95%CI) of 2.8 (1.3-6.1), 3.2 (1.3-7.9) and 5.8 (2.1-15.6). For women with histologically confirmed CIN at baseline, cure rates were 77.4%(n=72) for thermal ablation. Cure rates of the thermal ablation were 81.0%(n=47) for CIN grade one (CIN1) and 71.4% (n=25) for CIN grade two or worse (CIN2+). Conclusions: Thermal ablation is effective to clear the HPV infection as well as to treat CIN. Particularly for the HPV genotypes with the paramount attributable proportion to cervical cancer and precancerous in China, the HPV clearance rate was significantly higher than that reported in the women without treatment.

[Characteristics and diversity of infectious diarrheal caused by various pathogens].

Objective: To understand the characteristics and differences of diarrhea-related symptoms caused by different pathogens, and the clinical features of various pathogens causing diarrhea. Methods: Etiology surveillance program was conducted among 20 provinces of China from 2010 to 2016. The acute diarrhea outpatients were collected from clinics or hospitals. A questionnaire was used to survey demographics and clinical features. VFeces samples were taken for laboratory detection of 22 common diarrhea pathogens, to detect and analyze the clinical symptom pattern characteristics of the patient's. Results: A total of 38 950 outpatients were enrolled from 20 provinces of China. The positive rates of Rotavirus and Norovirus were the highest among the five diarrhea-causing viruses (Rotavirus: 18.29%, Norovirus: 13.06%). In the isolation and culture of 17 diarrhea-causing bacterial, Escherichia coli showed the highest positive rates (6.25%). The clinical features of bacterial diarrhea and viral diarrhea were mainly reflected in the results of fecal traits and routine examination, but pathogenic Vibrio infection was similar to viral diarrhea. Conclusion: Infectious diarrhea presents different characteristics due to various symptoms which can provide a basis for clinical diagnosis.

[The application of amodified scalp retractor in the craniotomy for intracranial aneurysms].

Objective: To investigate the application of a modified scalp retractor in the craniotomy for intracranial aneurysms withlateral supraorbital approach. Methods: From January 2019 to April 2020, a total of 32 patients with anterior circulation aneurysms clipping by superior lateral orbital approach were selected from Beijing Tiantan Hospital and Peking University International Hospital. The subjects were randomly divided into the traditional scalp retractor group and the modified scalp retractor group utilizing a random number table, with 16 patients in each group. The number of intraoperative retractor adjustment, incision length, postoperative scalp necrosis rate, postoperative wound healing grade, postoperative neurosurgical satisfaction score and patients' satisfaction score for incision were compared between the two groups. Results: The number of retractor adjustment in the modified scalp retractors group was significantly less than that in the traditional scalp retractor group (10.1±2.2 vs 14.2±3.6, P<0.05) . Incision length was also significantly shorter than that of the conventional scalp retractor group ( (10.1±1.0) cm vs (13.9±0.9) cm, P<0.05) .Neurosurgeons were significantly more satisfied with modified scalp retractors than the traditional scalp retractors (8.1±0.9 vs 6.0±0.9, P<0.05). There was no significant difference in postoperative scalp necrosis rate between two groups (P>0.05). Conclusion: The modified scalp retractor group is superior to the traditional scalp retractor group in the craniotomy for intracranial aneurysms with later supraorbital approach, with shorter in cision, less retractor adjustment and shorter surgical time.

Circ-RPL15/miR-146b-3p/VEGFA feedback loop is responsible for triggering proliferation and migration in glioma.

OBJECTIVE: This study aims to elucidate the role of circ-RPL15 in the progression of glioma. PATIENTS AND METHODS: Circ-RPL15 levels in glioma tissues and normal brain tissues were detected. Subcellular distribution of circ-RPL15 was examined. The binding between miR-146b-3p and circ-RPL15 was verified by Luciferase assay. Potential targets of miR-146b-3p were further determined. The influences of the circ-RPL15/miR-146b-3p/VEGFA feedback loop on proliferative and migratory abilities in T98G and U251 cells were detected by cell counting kit-8 (CCK-8) and transwell assay, respectively. RESULTS: Circ-RPL15 and VEGFA were upregulated in glioma tissues than normal ones, whereas miR-146b-3p was downregulated. Circ-RPL15 was mainly distributed in the cytoplasm. The interaction in the circ-RPL15/miR-146b-3p/VEGFA feedback loop was indicated by Luciferase assay, and it markedly promoted proliferative and migratory abilities in glioma. CONCLUSIONS: Circ-RPL15 triggers proliferative and migratory potentials in glioma by competitively binding miR-146b-3p and thus upregulates VEGFA.

Diagnostic accuracy of computed tomography colonography in patients at high risk for colorectal cancer: a meta-analysis.

AIM: The aim was to explore the diagnostic value of computed tomographic colonography (CTC) compared with conventional colonoscopy in individuals at high risk for colorectal cancer. METHOD: PubMed, Embase, the Cochrane Library and the Web of Science were searched by two independent reviewers for potentially eligible studies published up to 31 October 2018 that were based on a per-patient analysis. stata, meta-disc and revman were used to perform this meta-analysis. A random-effect model was used, and a subgroup analysis was conducted to explore the sources of heterogeneity. RESULTS: A total of 14 full-text articles, involving 3578 patients, were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and the area under the summary receiver operating characteristic curve of CTC for detecting polyps ≥ 6 mm were 0.87 (95% CI 0.83-0.90), 0.90 (95% CI 0.86-0.93), 9.08 (95% CI 6.28-13.13), 0.14 (95% CI 0.11-0.18) and 0.94 (95% CI 0.92-0.96), respectively. For polyps ≥ 10 mm, the pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of CTC were 0.91 (95% CI 0.86-0.94), 0.98 (95% CI 0.95-0.99), 40.36 (95% CI 19.16-85.03), 0.90 (95% CI 0.06-0.14) and 0.98 (95% CI 0.96-0.99), respectively. CONCLUSION: In this meta-analysis, CTC had high diagnostic accuracy for detecting polyps ≥ 6 mm and ≥ 10 mm in patients at high risk of developing colorectal cancer and it had a higher sensitivity and specificity for detecting polyps ≥ 10 mm than polyps ≥ 6 mm. However, the results should be used cautiously due to the significant heterogeneity.

[The association of pre-pregnancy body mass and weight gain during pregnancy with macrosomia: a cohort study].

Objective: To examine the association of pre-pregnancy body mass and weight gain during pregnancy with macrosomia. Methods: From January 2015 to December 2015, a total of 20 477 pregnant women were recruited by probabilistic proportional scale sampling with simple randomization in Sichuan, Yunnan and Guizhou Provinces. Basic information of pregnant women, weight gain during pregnancy and weight of newborn were collected. A multiple logistic regression model was used to assess the association between the pre-pregnancy body mass and gestational weight gain indicators with macrosomia. Results: 20 321 mother-infant were included in the final analysis. 20 321 pregnant women were (30.09±4.10) years old and delivered at (39.20±1.29) weeks, among which 12 341 (60.73%) cases were cesarean delivery. The birth weight of 20 321 infants were (3 292.26±431.67) grams, and 970 (4.77%) were macrosomia. The multiple logistic regression model showed that after adjusting for the age of women, compared to the normal weight group in the pre-pregnancy, the overweight and obesity group elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.69-2.35) and 4.05 (95%CI: 3.05-5.39), respectively. After adjusting for the age, the pre-pregnancy BMI, delivery weeks, delivery mode and infant's gender, compared to the weight-gain appropriate group, higher weight gain rate in the mid-pregnancy and excessive total gestational weight gain elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.66-2.39) and 1.80 (95%CI: 1.55-2.08), respectively. Conclusion: The overweight before pregnancy, obesity before pregnancy, the rate of weight gain in the second trimester and the high total weight gain during pregnancy could increase the risk of macrosomia.

[The surveillance of Yersiniosis among children in central area of Beijing from 2011 to 2018].

Objective: To illuminate the epidemic characteristics of Yersiniosis among children in the central city of Beijing and the accuracy of current clinical diagnosis towards Yersiniosis. Methods: Etiological surveillance of diarrheal patients, a total of 3 493 cases, was performed in a children hospital in central area of Beijing from 2011 to 2018 continuously. Collected the epidemiological and clinical information of the cases, analyzed the clinical and etiological diagnosis for Yersiniosis and bacterial dysentery and compared the distribution of Yersiniosis cases with the different symptoms. Results: A total of 3 493 acute diarrhea cases distributed from the age of 6 months to 13 years old, M (P(25), P(75)) was 1.50 (0.75, 3.17) years old. The 28 cases were isolated Yersinia enterocolitica (isolation rate of 0.80%) and they could be diagnosed as Yersiniosis by etiology. The isolation peaked in May and February. A total of 85.71% (24/28) of Yersiniosis cases were under 5-year old. The children of 3-4 age group had the highest isolation rate (1.52%) while the rate (0.18%) of 0-1 age group was the lowest (P=0.025). The Yersinia enteroclitica isolation rates of diarrheal patients with the symptoms including mucus feces, fever, white blood cell (WBC) and red blood cell (RBC) in feces were higher than the patients without these symptoms (P>0.05). The 9 of 28 Yersiniosis cases by etiology diagnosis were clinical diagnosed as bacillary dysentery. Conclusion: The infants and young children under 5-year old were the main population of Yersiniosis adolescent patients under 14-year old. The typical symptoms characterized with mucus stool, fever, WBC and RBC by routine microscopic examination. The preliminary clinical diagnosis of Yersiniosis is easily confused with bacterial dysentery.

[Interpretation for diagnosis of Yersiniosis].

Yersiniosis is one of the "other infectious diarrhea" of the notifiable infectious diseases and also an important food-borne disease. However, it lacked the basis or standard for diagnosis. The Chinese Preventive Medicine Association coordinated experienced researchers from National Institute for Communicable Disease Control and Prevention, China CDC and other institutes to produce the group standard entitled "Diagnosis of Yersiniosis" (T/CPMA 005-2019). Based on the principle of "legality, scientificity, advancement, and feasibility" , the standard gives a clear definition for Yerisiniosis, stipulates diagnosis basis, principles and main differential diagnosis and provides two informative appendixes for epidemiological and clinical characteristics and a normative appendix for laboratory detection. The standard provides accurate basis and methods of Yersiniosis diagnosis for hospitals and CDCs at all levels in China. It will solve the problems that Yersiniosis cannot be clearly diagnosed for clinical cases and in the outbreaks.

[Epidemiological and pathogenic features of a bacillary dysentery outbreak in a boarding school caused by Shigella sonneri].

Objective: To investigate the etiologic and epidemiologic features of an infectious diarrhea outbreak in a boarding school in Fuyang city, Anhui province. Methods: Traceability hypothesis of this study was tested according to the epidemiological characteristics of the cases. Feces, anal swabs, water samples and food residues related to the patients and chefs were collected for pathogen isolation and detection. Biochemical identification, virulence gene detection, drug susceptibility test, PFGE and multilocus sequence typing were performed. Results: The incidence rate (3.41%) of different dormitory buildings within the water supply area by shallow wells was higher than that (0.98%) of the deep wells, with statistical significance (χ(2)=17.215, P<0.001). Sixteen strains belonged to the Shigella Sonneri family were isolated from the patient's samples, and all carrying the ipaH gene. Seven strains belonged to sen and ial genes. Set1 gene that did not appear in all the 16 strains were highly resistant to ampicillin, tetracycline, compound xinnomine, cefazoline, cefotaxime, gentamicin, naphthidinic acid and streptomycin, including 9 strains to doxycycline. The pulse field pattern of the 16 strains of Shigella sonneri appeared the same, with the ST type as ST152. Conclusion: When combined data from the etiological and epidemiological investigation, it was confirmed that Shigella sonneri was the pathogen of this outbreak, and water from the shallow wells might be responsible for the source of infection.

Accelerated bone formation by biphasic calcium phosphate with a novel sub-micron surface topography.

Osteoinductive calcium phosphate (CaP) bone grafts have equivalent performance to autografts in repairing critical-size bone defects. The osteoinductive potential of CaP is linked to the size of the surface topographical features. In the present study, two novel biphasic calcium phosphate (BCP) bone grafts were synthesised with either sub-micron- (BCP<µm) or micron-scale (BCPµm) needle-shaped surface topography and compared to dimensionally similar tricalcium phosphate (TCP) with grain-shaped surface structures (TCP<µm and TCPµm). To clarify the possible function of the surface morphology (needle-like vs. grain-like) in initiating bone formation, the four CaP test materials were physicochemically characterised and implanted for 12 weeks in the dorsal muscle of beagles. The sub-micron needle-shaped topography of BCP<µm triggered earlier bone formation (3-6 weeks) as compared to the grain-shaped surface topography of TCP<µm, which formed bone at 6-9 weeks. After 12 weeks, the amount of induced bone formation in both materials was equivalent, based on histomorphometry. The micron-sized needle-shaped surface topography of BCPµm led to limited formation of new bone tissue, whereas its counterpart, TCPµm with grain-shaped surface topography, failed to trigger de novo bone formation. The relative strength of the parameters affecting CaP-driven bone induction was as follows: surface feature size > surface feature morphology > substrate chemistry. BCP materials with needle-shaped sub-micron surface topography gave rise to accelerated bone formation and slower rate of resorption than a comparable TCP. These characteristics may be translated to improve bone healing in orthotopic defects.

[The effect of AmpD on the expression of AmpC ß-lactamase and the regulation mechanisms of ß-N-acetylglucosaminidase in Yersinia enterocolitica].

Objective: In this study, we analyze the regulation mechanisms of the expression of ampD in AmpC ß-lactamase and the regulation mechanism of ß-N-acetylglucosaminidase (NagZ) in Yersinia enterocolitica. Methods: We construct the mutation strains of Yersinia enterocolitica AmpD (AmpD1-3) gene (ampD1-3), Low-Molecular-Mass Penicillin-Binding Proteins (LMM PBPs) gene (pbp4, pbp5a, pbp5b, pbp7), NagZ gene (nagZ), and ampR gene by deleting and complementing genes, and induce them by cefoxitin. We determined the activity of AmpC ß-lactamase activity (U) of mutant strains (basal level and induce level) by using cephalothiophene hydrolysis method, the promoter activity of AmpC ß-lactamase ((relative light unit (RLU)) was detected by the luxCDABEreporter system, and the activity of ß-N-acetylglucosaminidase (nmol/L) was determined by by using 4-nitrophenyl N-acetyl-ß-D-glucosaminide as the chromogenic substrate. Results: AmpD1 (Basal level: (3.29±1.58) U; Induced level: (4.08±1.75) U) was the most potent one. The YEΔ5b, YEΔ4Δ5b, YEΔ5aΔ5b and YEΔ5bΔ7 of ampC promoter activity increase significantly, whichYEΔ4Δ5b is the highest one (Basal level: (106 903.16±61 910.61) RLU; Induced level: (205 427.45±45 352.17) RLU). The YEΔ4Δ5bΔ7 of ampC promoter activity is the highest among triple mutant strain (Basal level: (304 108.04±99 274.53) RLU; Induced level: (531 440.21±68 891.02) RLU). Quadruple deletion strain YEΔ4Δ5aΔ5bΔ7 have the highest ampC promoter activity (Basal level: (1 013 810.99±260 955.96) RLU; Induced level: (1 230 214.59±205 526.79) RLU). After the deletion of nagZ gene, there is no significant change in ß-lactamase activity of YEΔD1D2D3ΔZ, while ß-lactamase activity of YEΔ4Δ5aΔ5bΔ7ΔZ shows a significant decrease (Basal level: (0.30±0.20) U; Induced level: (0.29±0.21) U), which basically drops to the wild strain level. Conclusion: This is the first report of ampC multi-step upregulation mechanism driven by three AmpD homologues in Yersinia enterocolitica. The AmpC regulation mode with the function of single PBP4, PBP5a or PBP7 is relatively low, which work in coordination with PBP5b. Yersinia enterocolitica have both NagZ-depend and NagZ-independent mechanisms for ß-lactamase expression.

[Etiology of bacterial diarrhea in large cities, mid-sized/small cities and rural areas of China].

Objective: To understand the etiological characteristics of bacterial diarrhea in different areas, including large cities, mid-sized/small cities and rural area, in China. Methods: A cross-sectional surveillance was conducted in 17 provinces of China from 2010 to 2014. The acute diarrhea outpatients were selected from clinics or hospitals in large cities, mid-sized/small cities, including rural-urban fringe zones, and rural areas. The demographical and clinical characteristics of the patients were collected by using questionnaire, and stool samples were taken from them for laboratory detection of 17 kinds of bacteria. The differences in pathogen positive rates (PPR) and pathogen spectrum across the cases from three-type areas were compared. The different infection risk in different cases were analyzed with unconditional logistic regression model. Results: In our study, we enrolled 9 253 cases from large cities, 5 138 cases from rural areas and 13 683 cases from midsized/small cites. The pathogen with largest differences in infection rate across the three-type areas was Shigella (S.) flexneri (rural area: 5.81%, mid-sized/small city: 2.78%, large city: 0.46%), followed by Aeromonas (A.) hydrophila (rural area: 2.14%, mid-sized/small city: 0.96%, large city: 0.48%). Compared with cases in large cities, the cases in mid-sized/small cities and rural areas had higher infection risks for S. flexneri (mid-sized/small city: OR=6.481, 95%CI: 4.666-9.002, rural area: OR=11.304, 95%CI: 8.018-15.938) and A. hydrophila (mid-sized/small city: OR=1.992, 95%CI:1.401-2.832, rural area: OR=4.083, 95%CI: 2.833-5.884). The constituent ratio of diarrheagenic Escherichia coli and Salmonella increased with the urbanization development, while the ratios of Shigella and A. hydrophila had an opposite trend. S. sonnei (60.00%) was the predominant serogroup of Shigella in urban infections, while S. flexneri (77.37%) was the predominant serogroup in rural infections. Conclusion: The differences in pathogen spectrum of bacterial diarrhea were obvious across large cities, mid-sized/small cities and rural areas in China, especially the differences in the infection rates of S. flexneri and A. hydrophila.

[Antinociceptive efficacy of QO-58 in the monosodium lodoacetate rat model for osteoarthritis pain].

Objective: To determine the effects of QO-58 on pain behavior associated with monosodium iodoacetate (MIA)-induced OA. Methods: The OA model was established with an intra-articular injection of 3 mg/50 MIA through the right patellar ligament. Then the model rats were treated with 50 mg/kg QO-58 by intraperitoneal injection, and pain-related behaviors were assessed by single administration and multiple administrations of QO-58. Results: Single adminstration of QO-58 increased the mechanical threshold and prolonged the withdrawal latency of OA pain with the antinociceptive effect occurring at 6 h and 10 h. Compound QO-58 was administered intraperitoneally once a day from day 10 to 14. QO-58 significantly increased the mechanical threshold and prolonged the withdrawal latency of OA rats at 12 and 14 days. Conclusion: QO-58 showed antinociceptive effects for OA pain in the MIA model after pain development. QO-58 may be an alternative therapeutic treatment for OA.