Application of Botulinum Toxin at the Yonsei Point for the Treatment of Gummy Smile: A Randomized Controlled Trial.

BACKGROUND: Demand for less-invasive procedures for treating gummy smile, such as botulinum toxin A injections, has increased substantially over the years. Meanwhile, the optimal injection site for botulinum toxin A injection is debated. The authors aimed to investigate the efficacy of botulinum toxin A injection at the Yonsei point for treating gummy smile. METHODS: In this double-blind, single-site, randomized clinical trial, healthy participants with a gummy smile (anterior gingival exposure of ≥3.0 mm) were enrolled and randomized (1:1 ratio) into two groups. The experimental group was administered 6 U of botulinum toxin A at the Yonsei point (a single-site injection of 3 U to the right Yonsei point and 3 U to the left Yonsei point), and the control group received the same dose in the bilateral levator labii superioris alaeque nasi muscle sites. The patients were assessed at baseline and 4, 12, 24, and 48 weeks after the first injection using a digital vernier caliper. RESULTS: A total of 49 participants were enrolled. Anterior and bilateral posterior gingival exposure were reduced at 4, 12, and 24 weeks ( P ≤ 0.05) and returned to baseline at 48 weeks in both groups; there was no difference between the groups at these time points. The increase in satisfaction among patients was significant, and few adverse events were observed. CONCLUSION: Both the Yonsei point and the levator labii superioris alaeque nasi muscle site can be used as botulinum toxin A injection sites for treating gummy smile. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Clinical outcomes of doxycycline, azithromycin and chloramphenicol for the treatment of patients with severe scrub typhus.

BACKGROUND: Previous studies have evaluated treatment efficacy of various antibiotics for patients with mild-to-moderate scrub typhus (ST). However, the efficacy of different antibiotics for treating severe ST remains uncertain. METHODS: A retrospective study of patients with severe ST was undertaken in China. The treatment efficacy rates of doxycycline, azithromycin and chloramphenicol were compared, using treatment failure and time to defervescence as primary outcomes. RESULTS: In total, 876 patients with severe ST who initially received doxycycline, azithromycin or chloramphenicol were recruited. The treatment failure rate did not differ significantly between patients receiving doxycycline and patients receiving azithromycin (6.0% vs 11.4%; P=0.109). However, a higher treatment failure rate was observed for chloramphenicol compared with doxycycline (14.6% vs 6.0%; P=0.004). No significant difference in time to defervescence was observed between patients receiving doxycycline, azithromycin or chloramphenicol. Further subgroup analysis revealed a higher risk of treatment failure for chloramphenicol compared with doxycycline in patients with acute kidney injury, pneumonia and shock; and a higher risk of treatment failure for azithromycin compared with doxycycline in patients with meningitis. Significant correlation was found between azithromycin resistance and meningitis (P=0.009), and between chloramphenicol resistance and acute respiratory distress syndrome (ARDS) (P<0.001) using Cramer's V correlation coefficient. Multi-variate Cox regression analysis revealed significant associations between time to defervescence and presence of ARDS, shock, myocarditis, meningitis and acute kidney injury. CONCLUSION: Azithromycin and doxycycline were found to have significant therapeutic effects in patients with severe ST. In contast, chloramphenicol was less efficacious for the treatment of these patients.

Decline of onset-to-diagnosis interval and its impacts on clinical outcome of COVID-19 in China: a nation-wide observational study.

BACKGROUND: To quantitatively assess the impact of the onset-to-diagnosis interval (ODI) on severity and death for coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study was conducted based on the data on COVID-19 cases of China over the age of 40 years reported through China's National Notifiable Infectious Disease Surveillance System from February 5, 2020 to October 8, 2020. The impacts of ODI on severe rate (SR) and case fatality rate (CFR) were evaluated at individual and population levels, which was further disaggregated by sex, age and geographic origin. RESULTS: As the rapid decline of ODI from around 40 days in early January to < 3 days in early March, both CFR and SR of COVID-19 largely dropped below 5% in China. After adjusting for age, sex, and region, an effect of ODI on SR was observed with the highest OR of 2.95 (95% CI 2.37‒3.66) at Day 10-11 and attributable fraction (AF) of 29.1% (95% CI 22.2‒36.1%) at Day 8-9. However, little effect of ODI on CFR was observed. Moreover, discrepancy of effect magnitude was found, showing a greater effect from ODI on SR among patients of male sex, younger age, and those cases in Wuhan. CONCLUSION: The ODI was significantly associated with the severity of COVID-19, highlighting the importance of timely diagnosis, especially for patients who were confirmed to gain increased benefit from early diagnosis to some extent.

Mapping the viruses belonging to the order Bunyavirales in China.

BACKGROUND: Viral pathogens belonging to the order Bunyavirales pose a continuous background threat to global health, but the fact remains that they are usually neglected and their distribution is still ambiguously known. We aim to map the geographical distribution of Bunyavirales viruses and assess the environmental suitability and transmission risk of major Bunyavirales viruses in China. METHODS: We assembled data on all Bunyavirales viruses detected in humans, animals and vectors from multiple sources, to update distribution maps of them across China. In addition, we predicted environmental suitability at the 10 km × 10 km pixel level by applying boosted regression tree models for two important Bunyavirales viruses, including Crimean-Congo hemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV). Based on model-projected risks and air travel volume, the imported risk of RVFV was also estimated from its endemic areas to the cities in China. RESULTS: Here we mapped all 89 species of Bunyavirales viruses in China from January 1951 to June 2021. Nineteen viruses were shown to infect humans, including ten species first reported as human infections. A total of 447,848 cases infected with Bunyavirales viruses were reported, and hantaviruses, Dabie bandavirus and Crimean-Congo hemorrhagic fever virus (CCHFV) had the severest disease burden. Model-predicted maps showed that Xinjiang and southwestern Yunnan had the highest environmental suitability for CCHFV occurrence, mainly related to Hyalomma asiaticum presence, while southern China had the highest environmental suitability for Rift Valley fever virus (RVFV) transmission all year round, mainly driven by livestock density, mean precipitation in the previous month. We further identified three cities including Guangzhou, Beijing and Shanghai, with the highest imported risk of RVFV potentially from Egypt, South Africa, Saudi Arabia and Kenya. CONCLUSIONS: A variety of Bunyavirales viruses are widely distributed in China, and the two major neglected Bunyavirales viruses including CCHFV and RVFV, both have the potential for outbreaks in local areas of China. Our study can help to promote the understanding of risk distribution and disease burden of Bunyavirales viruses in China, and the risk maps of CCHFV and RVFV occurrence are crucial to the targeted surveillance and control, especially in seasons and locations at high risk.

Ecology of Middle East respiratory syndrome coronavirus, 2012-2020: A machine learning modelling analysis.

The ongoing enzootic circulation of the Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East and North Africa is increasingly raising the concern about the possibility of its recombination with other human-adapted coronaviruses, particularly the pandemic SARS-CoV-2. We aim to provide an updated picture about ecological niches of MERS-CoV and associated socio-environmental drivers. Based on 356 confirmed MERS cases with animal contact reported to the WHO and 63 records of animal infections collected from the literature as of 30 May 2020, we assessed ecological niches of MERS-CoV using an ensemble model integrating three machine learning algorithms. With a high predictive accuracy (area under receiver operating characteristic curve = 91.66% in test data), the ensemble model estimated that ecologically suitable areas span over the Middle East, South Asia and the whole North Africa, much wider than the range of reported locally infected MERS cases and test-positive animal samples. Ecological suitability for MERS-CoV was significantly associated with high levels of bareland coverage (relative contribution = 30.06%), population density (7.28%), average temperature (6.48%) and camel density (6.20%). Future surveillance and intervention programs should target the high-risk populations and regions informed by updated quantitative analyses.

Clinical characteristics and risk factors for severe scrub typhus in pediatric and elderly patients.

BACKGROUND: Scrub typhus (ST) is a life-threatening infectious disease if appropriate treatment is unavailable. Large discrepancy of clinical severity of ST patients was reported among age groups, and the underlying risk factors for severe disease are unclear. METHODS: Clinical and epidemiological data of ST patients were collected in 55 surveillance hospitals located in Guangzhou City, China, from 2012 to 2018. Severe prognosis and related factors were determined and compared between pediatric and elderly patients. RESULTS: A total of 2,074 ST patients including 209 pediatric patients and 1,865 elderly patients were included, with a comparable disease severity rate of 11.0% (95% CI 7.1%-16.1%) and 10.3% (95% CI 9.0%-11.8%). Different frequencies of clinical characteristics including lymphadenopathy, skin rash, enlarged tonsils, etc. were observed between pediatric and elderly patients. Presence of peripheral edema and decreased hemoglobin were the most important predictors of severe illness in pediatric patients with adjusted ORs by 38.99 (9.96-152.67, p<0.001) and 13.22 (1.54-113.50, p = 0.019), respectively, while presence of dyspnea and increased total bilirubin were the potential determinants of severe disease in elderly patients with adjusted ORs by 11.69 (7.33-18.64, p<0.001) and 3.17 (1.97-5.11, p<0.001), respectively. Compared with pediatric patients, elderly patients were more likely to receive doxycycline (64.8% v.s 9.9%, p<0.001), while less likely to receive azithromycin therapy (5.0% v.s 41.1%, p<0.001). CONCLUSION: The disease severity rate is comparable between pediatric and elderly ST patients, while different clinical features and laboratory indicators were associated with development of severe complications for pediatric and elderly patients, which is helpful for diagnosis and progress assessment of disease for ST patients.

Etiological and epidemiological features of acute respiratory infections in China.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.

Epidemiology and evolution of Middle East respiratory syndrome coronavirus, 2012-2020.

BACKGROUND: The ongoing transmission of the Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East and its expansion to other regions are raising concerns of a potential pandemic. An in-depth analysis about both population and molecular epidemiology of this pathogen is needed. METHODS: MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports, supplemented by other reliable sources. Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models, respectively. Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV. RESULTS: A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7% (95% CI: 30.9‒34.6%). Saudi Arabia accounted for 83.6% of the cases. Age of ≥ 65 years old, underlying conditions and ≥ 5 days delay in diagnosis were independent risk factors for death. However, a history of animal contact was associated with a higher risk (adjusted OR = 2.97, 95% CI: 1.10-7.98) among female cases < 65 years but with a lower risk (adjusted OR = 0.31, 95% CI: 0.18-0.51) among male cases ≥ 65 years old. Diffusion of the disease was fastest from its origin in Saudi Arabia to the east, and was primarily driven by the transportation network. The most recent sub-clade C5.1 (since 2013) was associated with non-synonymous mutations and a higher mortality rate. Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV. CONCLUSIONS: MERS-CoV remains primarily locally transmitted in the Middle East, with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases. Animal contact is associated with a higher risk of death, but the association differs by age and sex. Transportation network is the leading driver for the spatial diffusion of the disease. These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic.

Association between fatality rate of COVID-19 and selenium deficiency in China.

BACKGROUND: COVID-19 has impacted populations around the world, with the fatality rate varying dramatically across countries. Selenium, as one of the important micronutrients implicated in viral infections, was suggested to play roles. METHODS: An ecological study was performed to assess the association between the COVID-19 related fatality and the selenium content both from crops and topsoil, in China. RESULTS: Totally, 14,045 COVID-19 cases were reported from 147 cities during 8 December 2019-13 December 2020 were included. Based on selenium content in crops, the case fatality rates (CFRs) gradually increased from 1.17% in non-selenium-deficient areas, to 1.28% in moderate-selenium-deficient areas, and further to 3.16% in severe-selenium-deficient areas (P = 0.002). Based on selenium content in topsoil, the CFRs gradually increased from 0.76% in non-selenium-deficient areas, to 1.70% in moderate-selenium-deficient areas, and further to 1.85% in severe-selenium-deficient areas (P < 0.001). The zero-inflated negative binomial regression model showed a significantly higher fatality risk in cities with severe-selenium-deficient selenium content in crops than non-selenium-deficient cities, with incidence rate ratio (IRR) of 3.88 (95% CIs: 1.21-12.52), which was further confirmed by regression fitting the association between CFR of COVID-19 and selenium content in topsoil, with the IRR of 2.38 (95% CIs: 1.14-4.98) for moderate-selenium-deficient cities and 3.06 (1.49-6.27) for severe-selenium-deficient cities. CONCLUSIONS: Regional selenium deficiency might be related to an increased CFR of COVID-19. Future studies are needed to explore the associations between selenium status and disease outcome at individual-level.

Epidemiological parameters of COVID-19 and its implication for infectivity among patients in China, 1 January to 11 February 2020.

BackgroundThe natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic.AimOur objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period.MethodsWe estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period.ResultsThe median incubation period was 7.2 (95% confidence interval (CI): 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission.ConclusionThe high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.

Household Secondary Attack Rate of COVID-19 and Associated Determinants.

BACKGROUND: As of April 2, 2020, the global reported number of COVID-19 cases has crossed over 1 million with more than 55,000 deaths. The household transmissibility of SARS-CoV-2, the causative pathogen, remains elusive. METHODS: Based on a comprehensive contact-tracing dataset from Guangzhou, we estimated both the population-level effective reproductive number and individual-level secondary attack rate (SAR) in the household setting. We assessed age effects on transmissibility and the infectivity of COVID-19 cases during their incubation period. RESULTS: A total of 195 unrelated clusters with 212 primary cases, 137 nonprimary (secondary or tertiary) cases and 1938 uninfected close contacts were traced. We estimated the household SAR to be 13.8% (95% CI: 11.1-17.0%) if household contacts are defined as all close relatives and 19.3% (95% CI: 15.5-23.9%) if household contacts only include those at the same residential address as the cases, assuming a mean incubation period of 4 days and a maximum infectious period of 13 days. The odds of infection among children (<20 years old) was only 0.26 (95% CI: 0.13-0.54) times of that among the elderly (≥60 years old). There was no gender difference in the risk of infection. COVID-19 cases were at least as infectious during their incubation period as during their illness. On average, a COVID-19 case infected 0.48 (95% CI: 0.39-0.58) close contacts. Had isolation not been implemented, this number increases to 0.62 (95% CI: 0.51-0.75). The effective reproductive number in Guangzhou dropped from above 1 to below 0.5 in about 1 week. CONCLUSION: SARS-CoV-2 is more transmissible in households than SARS-CoV and MERS-CoV, and the elderly ≥60 years old are the most vulnerable to household transmission. Case finding and isolation alone may be inadequate to contain the pandemic and need to be used in conjunction with heightened restriction of human movement as implemented in Guangzhou.

Household secondary attack rate of COVID-19 and associated determinants in Guangzhou, China: a retrospective cohort study.

BACKGROUND: As of June 8, 2020, the global reported number of COVID-19 cases had reached more than 7 million with over 400 000 deaths. The household transmissibility of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains unclear. We aimed to estimate the secondary attack rate of SARS-CoV-2 among household and non-household close contacts in Guangzhou, China, using a statistical transmission model. METHODS: In this retrospective cohort study, we used a comprehensive contact tracing dataset from the Guangzhou Center for Disease Control and Prevention to estimate the secondary attack rate of COVID-19 (defined as the probability that an infected individual will transmit the disease to a susceptible individual) among household and non-household contacts, using a statistical transmission model. We considered two alternative definitions of household contacts in the analysis: individuals who were either family members or close relatives, such as parents and parents-in-law, regardless of residential address, and individuals living at the same address regardless of relationship. We assessed the demographic determinants of transmissibility and the infectivity of COVID-19 cases during their incubation period. FINDINGS: Between Jan 7, 2020, and Feb 18, 2020, we traced 195 unrelated close contact groups (215 primary cases, 134 secondary or tertiary cases, and 1964 uninfected close contacts). By identifying households from these groups, assuming a mean incubation period of 5 days, a maximum infectious period of 13 days, and no case isolation, the estimated secondary attack rate among household contacts was 12·4% (95% CI 9·8-15·4) when household contacts were defined on the basis of close relatives and 17·1% (13·3-21·8) when household contacts were defined on the basis of residential address. Compared with the oldest age group (≥60 years), the risk of household infection was lower in the youngest age group (<20 years; odds ratio [OR] 0·23 [95% CI 0·11-0·46]) and among adults aged 20-59 years (OR 0·64 [95% CI 0·43-0·97]). Our results suggest greater infectivity during the incubation period than during the symptomatic period, although differences were not statistically significant (OR 0·61 [95% CI 0·27-1·38]). The estimated local reproductive number (R) based on observed contact frequencies of primary cases was 0·5 (95% CI 0·41-0·62) in Guangzhou. The projected local R, had there been no isolation of cases or quarantine of their contacts, was 0·6 (95% CI 0·49-0·74) when household was defined on the basis of close relatives. INTERPRETATION: SARS-CoV-2 is more transmissible in households than SARS-CoV and Middle East respiratory syndrome coronavirus. Older individuals (aged ≥60 years) are the most susceptible to household transmission of SARS-CoV-2. In addition to case finding and isolation, timely tracing and quarantine of close contacts should be implemented to prevent onward transmission during the viral incubation period. FUNDING: US National Institutes of Health, Science and Technology Plan Project of Guangzhou, Project for Key Medicine Discipline Construction of Guangzhou Municipality, Key Research and Development Program of China.

Meteorological conditions and nonpharmaceutical interventions jointly determined local transmissibility of COVID-19 in 41 Chinese cities: A retrospective observational study.

BACKGROUND: Before effective vaccines become widely available, sufficient understanding of the impacts of climate, human movement and non-pharmaceutical interventions on the transmissibility of COVID-19 is needed but still lacking. METHODS: We collected by crowdsourcing a database of 11 003 COVID-19 cases from 305 cities outside Hubei Province from December 31, 2019 to April 27, 2020. We estimated the daily effective reproduction numbers (Rt ) of COVID-19 in 41 cities where the crowdsourced case data are comparable to the official surveillance data. The impacts of meteorological variables, human movement indices and nonpharmaceutical emergency responses on Rt were evaluated with generalized estimation equation models. FINDINGS: The median Rt was 0•46 (IQR: 0•37-0•87) in the northern cities, higher than 0•20 (IQR: 0•09-0•52) in the southern cities (p=0•004). A higher local transmissibility of COVID-19 was associated with a low temperature, a relative humidity near 70-75%, and higher intracity and intercity human movement. An increase in temperature from 0℃ to 20℃ would reduce Rt by 30% (95 CI 10-46%). A further increase to 30℃ would result in another 17% (95% CI 5-27%) reduction. An increase in relative humidity from 40% to 75% would raise the transmissibility by 47% (95% CI 9-97%), but a further increase to 90% would reduce the transmissibility by 12% (95% CI 4-19%). The decrease in intracity human movement as a part of the highest-level emergency response in China reduced the transmissibility by 36% (95% CI 27-44%), compared to 5% (95% CI 1-9%) for restricting intercity transport. Other nonpharmaceutical interventions further reduced Rt by 39% (95% CI 31-47%). INTERPRETATION: Climate can affect the transmission of COVID-19 where effective interventions are implemented. Restrictions on intracity human movement may be needed in places where other nonpharmaceutical interventions are unable to mitigate local transmission. FUNDING: China Mega-Project on Infectious Disease Prevention; U.S. National Institutes of Health and National Science Foundation.

Unveiling tropospheric ozone by the traditional atmospheric model and machine learning, and their comparison:A case study in hangzhou, China.

Tropospheric ozone in the surface air has become the primary atmospheric pollutant in Hangzhou, China, in recent years. Previous analysis is not enough to decode it for better regulation. Therefore, we use the traditional atmospheric model, Weather Research and Forecasting coupled with Community Multi-scale Air Quality (WRF-CMAQ), and machine learning models, Extreme Learning Machine (ELM), Multi-layer Perceptron (MLP), Random Forest (RF) and Recurrent Neural Network (RNN) to analyze and predict the ozone in the surface air in Hangzhou, China, using meteorology and air pollutants as input. We firstly quantitatively demonstrate that the dew-point deficit, instead of temperature and relative humidity, is the predominant meteorological factor in shaping tropospheric ozone. Urban heat island, daily direct solar radiation time, wind speed and wind direction play trivial role in impacting tropospheric ozone. NO2 is the primary influential factors both for hourly ozone and daily O3-8 h due to the titration effect. The most environmental-friendly way to mitigate the ozone pollution is to lower the volatile organic compounds (VOCs) with the highest ozone formation potentials. We deduce that the tropospheric ozone formation process tends to be not only non-linear but also non-smooth. Compared with the traditional atmospheric models, machine learning, whose characteristics are rapid convergence, short calculating time, adaptation of forecasting episodes, small program memory, higher accuracy and less cost, is able to predict tropospheric ozone more accurately.

Prevalence, histologic and clinical characteristics of heterotopic gastric mucosa in Chinese patients.

AIM: To determine the prevalence, demographic, clinical and histopathologic features of heterotopic gastric mucosa (HGM) in Chinese patients. METHODS: Patients referred to three endoscopy units were enrolled in this study. The macroscopic characteristics of HGM were documented. Biopsies were obtained and observed using hematoxylin and eosin staining. Helicobacter pylori colonization was examined by Whartin-Starry staining. RESULTS: HGM was observed in 420 Chinese patients, yielding a prevalence of 0.4%. The majority of patients had a single patch (300/420; 71.4%), while the remainder had two (84/420; 20%) or multiple patches (36/420; 8.6%). The size of the patches and the distance from the patch to the frontal incisor teeth varied significantly. The large majority of HGM patches were flat (393/420; 93.6%), whereas the remaining patches were slightly elevated. The primary histological characteristic was fundic-type (216/420; 51.4%) within the HGM patch, and antral- (43/420; 10.2%) and transitional-type (65/420; 15.5%) mucosa were also observed. The prevalence of intestinal metaplasia was 3.1% (13/420) and the prevalence of dysplasia was 1.4% (6/420), indicating the necessity for endoscopic follow-up in patients with HGM. Esophageal and extraesophageal complaints were also observed in patients with HGM. Dysphagia and epigastric discomfort (odds ratios: 6.836 and 115.826, respectively; Ps < 0.05) were independent risk factors for HGM. CONCLUSION: Clinical complaints should be considered to improve the detection rate of HMG. The prevalence of intestinal metaplasia and dysplasia also indicates a need for endoscopic follow-up.

Co-transduction of ribosomal protein L23 enhances the therapeutic efficacy of adenoviral-mediated p53 gene transfer in human gastric cancer.

Induction of murine double minute 2 (MDM2) expression is thought to be a determinant of resistance to p53 gene therapy for cancer. Previous studies have revealed that ribosomal protein L23 (RPL23) inhibits MDM2-mediated p53 degradation through direct binding to MDM2. In addition, ectopically expressed RPL23 was reported to interact with MDM2 in both the nucleus and cytoplasm, by which RPL23 indirectly inhibited MDM2-p53 binding. Based on the known molecular properties of the RPL23 protein, it was speculated that co-transduction of RPL23 may protect wild­type p53 protein from MDM2-mediated inactivation and, thus, improve the effect of delivering therapeutic exogenous p53. To test this hypothesis, we constructed a bicistronic adenoviral vector expressing both the RPL23 and p53 genes (Ad-RPL23/p53) and compared its tumor-suppressor activity in human gastric cancer with that of a single gene vector for p53 (Ad-p53). In the in vivo and in vitro experiments, we observed that treatment with Ad-RPL23/p53 resulted in a stronger antitumor response compared to that obtained using Ad-p53. Moreover, the antitumor response of the bicistronic adenovirus was obtained not only in MGC803 cells (endogenous mutant p53) but also in MKN45 cells (endogenous wild­type p53) which were initially resistant to p53 gene transfer, indicating that co-transduction of RPL23 also expanded the utility of p53 gene therapy. Furthermore, in an orthotopic nude mouse model of human gastric cancer, we found that the survival benefit was greater after Ad-RPL23/p53 treatment than after Ad-p53. Taken together, the data presented here demonstrate that co-transduction of RPL23 enhances the therapeutic efficacy of adenoviral-mediated p53 gene transfer in models of human gastric cancer and support the use of this strategy for cancer treatment.

MiR-26a regulates cell cycle and anoikis of human esophageal adenocarcinoma cells through Rb1-E2F1 signaling pathway.

Resistance to anoikis, the subtype of apoptosis induced by lack of matrix adhesion, contributes to malignant transformation and development of metastasis. MicroRNAs play key regulatory roles in tumorigenesis and metastasis. In this study, we described that miR-26a, which is usually downregulated in tumor cells, is involved in the acquisition of anoikis-resistance of human esophageal adenocarcinoma (EA) cells. Results of qRT-PCR in clinical samples showed that downregulated miR-26a expression is related to tumorigenesis and metastasis of EA. In vitro experiments determined that miR-26a directly participates in the regulation of cell cycle and anoikis of human EA OE33 cells. Further, we identified that Rb1 is the direct functional target of miR-26a, and revealed that the reduction of miR-26a expression leads to increased Rb1 protein level and thus inhibits the function of E2F1, by which it influences the phenotypes of cell cycle and anoikis. The findings we reported here presented the evidence that miR-26a may be involved in regulation of anoikis-resistance of EA cells. Targeting miR-26a may provide a novel strategy to inhibit metastasis.