A large-scale genome-wide association analysis reveals QTL and candidate genes for intramuscular fat content in Duroc pigs.

This study aimed at identifying genomic regions and genes associated with intramuscular fat content (IMF) in Duroc pigs using a weighted single-step GWAS. Data from 3912 pigs, of which 3770 animals were genotyped with GeneSeek Porcine 50K Bead chip, were used for the association analysis. We identified 19 genomic regions that each explained >1% of the additive genetic variance associated with IMF. Notably, a consistent QTL on SSC7 (117.42-117.92 Mb) was confirmed, explaining 3.70% of the additive genetic variance, and two genes, BDKRB2 and ATG2B, were highlighted as promising candidates for IMF. Two QTL (SSC7, 94.19-94.64 Mb; SSC14, 123.25-123.75 Mb), which harbored MED6 and MAP3K9 genes and TCF7L2 gene respectively, were newly identified as associated with IMF. In conclusion, we identified a consistent QTL and additional genomic regions and genes that contributed to the genetic variance of IMF using a large-scale sample size of genotyped pigs and genealogical information.

[Initial findings in chest X-rays as predictors of worsening lung infection in patients with COVID-19: correlation in 265 patients]. / Hallazgos iniciales en la radiografía de tórax como predictores de empeoramiento en la infección pulmonar por SARS-CoV-2. Correlación en 265 pacientes.

Background and aims: We aimed to analyze the relationship between the initial chest X-ray findings in patients with severe acute respiratory syndrome due to infection with SARS-CoV-2 and eventual clinical worsening and to compare three systems of quantifying these findings. Material and methods: This retrospective study reviewed the clinical and radiological evolution of 265 adult patients with COVID-19 attended at our center between March 2020 and April 2020. We recorded data related to patients' comorbidities, hospital stay, and clinical worsening (admission to the ICU, intubation, and death). We used three scoring systems taking into consideration 6 or 8 lung fields (designated 6 A, 6 B, and 8) to quantify lung involvement in each patient's initial abnormal chest X-ray and to classify its severity as mild, moderate, or severe, and we compared these three systems. We also recorded the presence of alveolar opacities and linear opacities (fundamentally linear atelectasis) in the first chest X-ray with pathologic findings. Results: In the χ2 analysis, moderate or severe involvement in the three classification systems correlated with hospital admission (p = 0.009 in 6 A, p = 0.001 in 6 B, and p = 0.001 in 8) and with death (p = 0.02 in 6 A, p = 0.01 in 6 B, and p = 0.006 in 8). In the regression analysis, the most significant associations were 6 B with alveolar involvement (OR 2.3; 95%CI 1.1.-4.7; p = 0.025;) and 8 with alveolar involvement (OR 2.07; 95% CI 1.01.-4.25; p = 0.046). No differences were observed in the ability of the three systems to predict clinical worsening by classifications of involvement in chest X-rays as moderate or severe. Conclusion: Moderate/severe extension in the three chest X-ray scoring systems evaluating the extent of involvement over 6 or 8 lung fields and the finding of alveolar opacities in the first abnormal X-ray correlated with mortality and the rate of hospitalization in the patients studied. No significant difference was found in the predictive ability of the three classification systems proposed.

Protective effect of sonic hedgehog signaling pathway activation on acute myocardial infarction.

To study changes in the sonic hedgehog (Shh) signaling pathway in acute myocardial infarction (AMI) and the protective effect of changes in Shh signaling pathway activity on AMI, specific pathogen-free (SPF) C57BL/6 mice were treated with left anterior descending (LAD) ligation to establish an AMI model. The samples were collected on the 1st, 3rd, 14th, and 21st days after AMI induction. After the operations, the mice were administered the Shh signaling pathway receptor agonist SAG1.3 (5 mg/kg/d) and antagonist SANT-1 (3.3 mg/kg/d) by intraperitoneal injection. The myocardial ischemia model was established by oxygen glucose deprivation (OGD) in vitro. The AMI mouse model and the in vitro OGD-induced myocardial ischemia model were established. The Smo agonist SAG1.3 was used to activate the Shh signaling pathway, thereby reducing the expression of Bcl-2 and Bax. The number of apoptotic cells was reduced. Administration of the antagonist SANT-1 inhibited Shh signaling pathway activity by increasing the expression of Bcl-2 and Bax, and the number of apoptotic cells increased. In conclusion, activation of the Shh signaling pathway improved cardiac functions and myocardial remodeling and reduced the apoptosis of myocardial cells.

[Construction and evaluation of a novel diagnosis pathway for 2019-Corona Virus Disease].

Objective: To construct and evaluate a diagnosis pathway (Xiangya pathway) for Corona Virus Disease 2019 (COVID-19). Methods: Consecutive subjects aged ≥12 years old who were screened for COVID-19 were included in Xiangya Hospital of Central South University from January 23 to February 3, 2020, and the subjects were further divided into the inception cohort and the validation cohort. The gender, age, onset time of disease of the subjects were recorded. The information of epidemiological history, fever, and the declined blood lymphocytes were collected as clinical indicators, CT scan was used to evaluate the possibility of COVID-19 and range of lung involvement. According to the current Chinese national standards, throat swabs of suspected cases were collected and the nucleic acid of COVID-19 was detected by reverse transcription-polymerase chain reaction (RT-PCR). The Xiangya pathway was constructed with multi-indexes, compared with clinical indicators, CT results and Chinese national standards, their effectiveness of detecting confirmed cases were verified in the inception and validation cohort. Results: A total of 382 consecutive adults who was screened for COVID-19 were included, and 261 cases were in the inception cohort and 121 cases were in the validation cohort. Among the 382 cases, 192 were males (50.3%) and 190 were females (49.7%), with a median age of 35 years (range: 15-92 years). There were 183 cases (47.9%) with epidemiological history, 275 cases (72.0%) with fever, 212 cases (55.5%) with decreased peripheral blood lymphocytes, 114 cases (29.8%) with positive CT findings, 43 cases (11.3%) with positive CT-COVID-19, and 30 cases (7.9%) with positive virus nucleic acid by throat swab. Compared with clinical indicators, the sensitivity and specificity of CT were 0.950 and 0.704, respectively. The accuracy of CT to make a definite diagnosis was higher than that of epidemiological history, fever, and declined blood lymphocyte count (0.809 vs 0.660, 0.532, 0.596, P=0.001, 0.002, 0.003, respectively). The sensitivity of this pathway and the pathway recommended by the Health Commission of China were both high (all were 1.000), while the specificity and accuracy of the Xiangya pathway were higher than the one recommended by the Health Commission (0.872 vs 0.765, 0.778 vs 0.592, both P<0.001). The CT-COVID-19 reduced the missed diagnosis rate caused by false negative of nucleic acid test (31 vs 64), with difference rate of 51.6%, and the positive rate of nucleic acid test was 64.5% (20/31). In validation cohort, the specificity and accuracy of the Xiangya pathway was 0.967, the positive rate of nucleic acid test was 76.9%(10/13). Conclusions: The Xiangya pathway can predict the nucleic acid test results of COVID-19, and can be applied as a reliable strategy to screen patients with suspected COVID-19 among people aged ≥12 years in areas other than Hubei during the epidemic period of COVID-19. The cohort size needs to be increased for further validation.

[Mechanisms of fosfomycin resistance of extended-spectrum ß-lactamases-producing Escherichia coli and Klebsiella pneumoniae].

Objective: To study the in vitro activity of fosfomycin to extended-spectrum ß-lactamases (ESBLs)-producing Escherichia coli and Klebsiella pneumoniae and to explore the mechanisms of fosfomycin resistance. Methods: A total of 1 052 ESBLs-producing E. coli(ESBL-EC) and K. pneumoniae(ESBL-KP) isolates were collected from bloodstream infections of 28 hospitals of 22 provinces and municipalities, which were stored by our laboratory.Minimum inhibitory concentrations (MICs) of fosfomycin against these clinical isolates were determined by agar dilution methods according to the Clinical and Laboratory Standards Institute (CLSI)(2015). The genes related to fosfomycin resistance were confirmed by Polymerase Chain Reaction (PCR) and sequencing. Results: The susceptibility rates of ESBL-EC and ESBL-KP isolates to fosfomycin were 91.3% (818/896) and 91.7% (143/156), respectively. A total of 91 fosfomycin-non-susceptible isolates were detected, of which 73 (80.2%) isolates carried fosA3 genes.Amongst 18 fosA3-negative isolates, 16 isolates were detected to have chromosomal mutations or insertion inactivation, while the rest two isolates had not been detected any resistant mechanisms. Conclusions: Fosfomycin shows great in vitro antimicrobial activity to ESBL-EC and ESBL-KP. The primary mechanism of fosfomycin-non-susceptible isolates is fosA3 gene.Chromosomal mutations may also involve in the fosfomycin resistance.

Diabetes incidence and prevalence in Hong Kong, China during 2006-2014.

AIMS: To estimate recent secular changes in the incidence and prevalence of diabetes and pre-diabetes among Hong Kong Chinese adults, and thus show possible future trends for developing mainland China. METHODS: Based on a complete census of the public sector health records of 6.4 million people from 2006 to 2014, diabetes cases were ascertained using different methods including the World Health Organization (WHO) 2011 guidelines (HbA1c , fasting plasma glucose and glucose tolerance test), American Diabetes Association (ADA) 2015 guidelines (plus random plasma glucose), and additionally recorded diagnosis codes and medication dispensation. Pre-diabetes was defined using ADA 2015 guidelines. RESULTS: We identified 697 201 people with diabetes (54.2% were incident cases); and 1 229 731 people with diabetes or pre-diabetes. In 2014, the overall incidence of diabetes was 9.46 per 1000 person-years [95% confidence interval (CI): 9.38 to 9.54], and overall prevalence was 10.29% (95% CI: 10.27% to 10.32%). Incidence of diabetes decreased significantly from 2007 to 2014 (quadratic trend, P < 0.001). From 2006 to 2014, the prevalence of diabetes increased significantly in both sexes and across all age groups (quadratic trend, P < 0.001). The overall incidence of pre-diabetes in 2014 was 18.88 per 1000 person-years (95% CI: 18.76 to 18.99), and the overall prevalence of pre-diabetes was 8.90% (95% CI: 8.87% to 8.92%). CONCLUSIONS: Similar to other developed western and Asian populations, diabetes (and pre-diabetes) incidence in Hong Kong Chinese appeared to have stabilized and there have been small declines during the period of observation. Ageing and survivorship will likely drive a continued increase in the prevalence of diabetes and pre-diabetes, albeit with a decelerating growth rate if past trends persist.

Abrp, a new gene, confers reduced susceptibility to tetracycline, glycylcine, chloramphenicol and fosfomycin classes in Acinetobacter baumannii.

Acinetobacter baumannii, a non-fermenting gram-negative coccobacillus, is a major pathogen responsible for a variety of healthcare-associated infections, including pneumonia, urinary tract and bloodstream infections. Moreover, A. baumannii is associated with alarming increases in drug resistance rates to almost all available antibiotics leaving limited treatment options. Here, we characterize the biological functions of a novel gene, abrp, which encodes a peptidase C13 family. We demonstrate that the abrp is associated with decreased susceptibility to tetracycline, minocycline, doxycycline, tigecycline, chloramphenicol and fosfomycin. Deletion of abrp was able to increase cell membrane permeability and display slower cell growth rate. Results from the present study show that abrp plays an important role in conferring reduced susceptibility to different classes of antibiotics and cell growth in A. baumannii. The change of antibiotic sensitivities may result from modifications to the cell membrane permeability of A. baumannii.

[The activity of moxalactam against Enterobacteriaceae and anaerobia in vitro].

OBJECTIVE: To observe the antibacterial activity of moxalactam against Enterobacteriaceae bacteria and anaerobic bacteria in vitro, and to compare with other antibacterial drugs, for providing experimental basis for the clinical application of moxalactam. METHODS: Minimum inhibitory concentrations (MICs) of moxalactam and other antibacterial agents against 491 Enterobacteriaceae spp. and anaerobic spp.collecting from clinical settings were determined by agar dilution methods and E-test strips according to the Clinical and Laboratory Standards Institute (CLSI)(2014). RESULTS: Moxalactam showed great antibacterial activity to Enterobacteriaceae spp., including ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp., with the MIC(50), MIC(90), and susceptibility rates of 0.25-4 mg/L, 0.5-8 mg/L, and >90%, respectively. The susceptibility rates of Enterobacteriaceae with ESBLs-producing or non-ESBLs-producing to imipenem and meropenem were both higher than 90%. The susceptibility rates of ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp.to piperacillin/tazobactam and cefoperazone/sulbactam were 90%, 68%, 53% and 76%, 66%, 76.6%, respectively, while the susceptibility rates of non-ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp.were all more than 95%. The susceptibility rates of Enterobacter spp. and other Enterobacter to piperacillin/tazobactam were 80%, 80%and that to cefoperazone/sulbactam were 80%, 76.7%, respectively.The MICs range of moxalactam on anaerobic spp.was from ≤0.064 to >256 mg/L, while MIC(50) was 2 mg/L and MIC(90) was 64 mg/L. CONCLUSIONS: Moxalactam showed well activity against ESBLs-producing and non-ESBLs-producing Enterobacteriaceae and anaerobia.

[KAP research and intervention effects of health education on prevention and control of occupational diseases in occupational groups in Jinzhou, China].

OBJECTIVE: To investigate the current status of knowledge, attitude, and practice (KAP)on the prevention and control of occupational diseases in occupational groups in Jinzhou, China, and to evaluate the intervention effects of health education. METHODS: Using the cluster random sampling method, 1000 workers who underwent occupational health examination in Jinzhou Center for Disease Control and Prevention from September 2014 to April 2015 were enrolled in this study. They were equally and randomly divided into intervention group and control group. The intervention group received health education for 6 months through bulletin board, promotion materials, expert lecture, Q&A session, and other relevant educational events. The questionnaire survey was performed before and after intervention. The control group received the questionnaire survey but not the health education. RESULTS: The overall awareness rate of prevention and control knowledge was 75.34% in 990 workers in Jinzhou, China. After the intervention, the intervention group had a significantly higher awareness rate of prevention and control knowledge than the control group (89.87%~98.86% vs 71.25%~80.82%, P<0.05); the intervention group had a significantly higher attitude accuracy for" whether occupational health examination is necessary or not" and " is willing to received the training on occupational health knowledge" than the control group(χ(2)=57.857, P<0.05; χ(2)=70.683, P<0.05); and the intervention group had a significantly higher rate of correct behavior for" whether help the business management personnel to carry out the prevention and control of occupational diseases or not" and"whether actively understand the occupational hazards of job" (χ(2)=102.186, P<0.05; χ(2)=91.159, P<0.05). CONCLUSION: Health education can significantly increase the awareness rate of prevention and control knowledge on occupational diseases in occupational groups in Jinzhou, China. However, the more structured and longterm comprehensive intervention is necessary for improving their attitude and behavior.

Knockdown of Pim-3 suppresses the tumorigenicity of glioblastoma by regulating cell cycle and apoptosis.

Products of the Pim (the proviral integration site for the Moloney murine leukemia virus) family of proto—oncogenes possess serine/threonine kinase activity and belong to the Ca2+/calmodulin—dependent protein kinase group. Pim—3, a member of the Pim family is closely linked to the development of a variety of tumors. However, the role of Pim—3 in human glioblastoma remains unknown. In this study, we elucidated the role of Pim—3 in the growth and apoptosis of glioblastoma cells. Western blotting was used for determination of protein levels, and shRNA was used for Pim—3 knockdown. The MTT assay was used to evaluate cell proliferation and flow cytometry was used to determine cell cycle status and the number of apoptotic cells. A mouse xenograft model was established by injecting nude mice with Pim—3—depleted glioblastoma cells in order to determine tumor growth in vivo. We demonstrated that Pim—3 was highly expressed in human glioblastoma cell lines. We also found that knockdown of Pim—3 by specific shRNA slowed decreased proliferation, induced cell cycle arrest in the G0/G1 phase, and increased apoptosis in glioblastoma cells. Pim—3 knockdown potently inhibited the growth of subcutaneously implanted glioblastoma cells in vivo. We further revealed that Pim—3 knockdown induced growth inhibition by reducing the levels of the anti—apoptotic protein Bcl—xl and cell cycle regulatory proteins, including cyclin D1 and Cdc25C, and increasing the levels of the pro—apoptotic protein Bax.

First Report of Foxtail Millet Seedling Damping-Off Caused by Binucleate Rhizoctonia AG-A in China.

Foxtail millet (Setaria italica) is an important food and fodder grain crop in China. In June 2013, foxtail millet seedlings of cultivar Jigu19 showing symptoms of damping-off were observed with about 30% incidence in Handan, Hebei Province. Infected plants showed pale brown lesions on the stems and brown discoloration of the roots, which later turned into root rot. As a consequence, infected seedlings wilted and died prematurely. Segments of the diseased root tissue (5 mm long) were washed with sterile water, disinfected with 0.5% NaOCl for 2 min, rinsed with sterile water, placed on potato dextrose agar (PDA), and incubated at 25°C in the dark. Three isolates were obtained and designated HD-1, HD-3, and HD-5. Morphological characteristics of the three isolates were similar with white colonies bearing large amounts of floccose aerial hyphae and no production of sclerotia after 14 days. Hyphal cells were stained with DAPI and all the three isolates were binucleate. Total genomic DNA was extracted from the mycelial mat using CTAB (4). The rDNA internal transcribed spacer (ITS) region was amplified using the universal primer pair ITS1 and ITS4 (1). PCR amplicons were purified and sequenced. A BLASTn search revealed that the resulting sequences (GenBank Accession Nos. KM017960, KM017961, and KM017962 for HD-1, HD-3, and HD-5, respectively) shared 99% identity with other Ceratobasidium sp. AG-A isolates (JX913824, FJ440197). In addition, sequence identity of HD-1, HD-3, and HD-5 with each other was 99.8%, 99.7%, and 99.8%, respectively. Thus, the isolates were identified as Ceratobasidium sp. AG-A, i.e., binucleate Rhizoctonia (BNR) AG-A. Pathogenicity tests were conducted by placing autoclaved wheat seeds, each colonized with Rhizoctonia isolates at inoculum density of 25 propagules per gram (ppg), on the surface of a sterilized mix of soil, sand, and nutrient soil (1:1:1, v/v/v) in pots (3). Each pot contained five healthy seedlings of the foxtail millet cultivar Yugu 1, and every seedling was inoculated by placing three colonized wheat seeds under the sheath of foxtail millet at the 2- or 3-leaf stage; non-inoculated sterilized wheat seeds were used as a control. Plants were incubated at 25°C with 14 h light and 10 h dark in a growth room for 10 days, and then assessed for disease. Damping-off symptoms similar to those in the field appeared on inoculated plants; control plants were asymptomatic. BNR Rhizoctonia were re-isolated from diseased plants and confirmed to be AG-A based on morphological characteristics and rDNA-ITS sequence. BNR AG-A has been reported in China as a pathogen of Chinese mustard, Chinese cabbage, potato, and sugar beet, but there are no previous reports of its presence on foxtail millet. R. solani AG-1 and AG-4 are usually regarded as pathogenic to foxtail millet (2). To our knowledge, this is the first report of BNR AG-A causing foxtail millet damping-off in China. We found binucleate Rhizoctonia AG-A, the anamorph of Ceratobasidium sp., can infect foxtail millet at seeding stage, which may cause serious losses of the crop. Therefore, we should pay particular attention to it when considering seeding disease control and breeding disease resistance varieties of foxtail millet in the future. References: (1) K. de la Cerda et al. Plant Dis. 91:791, 2007. (2) W. D. Gao. Acta Phytopathologica Sinica. 17:247, 1987. (3) M. J. Lehtonen et al. Plant Pathol. 57:141, 2008. (4) M. G. Murray and W. F Thompson. Nucleic Acids Res. 8:4321, 1980.

First Report of Sheath Blight Caused by Waitea circinata Affecting Foxtail Millet (Setaria italica) in China.

Foxtail millet (Setaria italica) is planted widely in northern China, especially in Hebei, Shanxi, Shandong, and Henan provinces. Although several diseases reduce production of this important crop species, sheath blight is considered one of the important diseases of foxtail millet in China. Sheath blight is caused by a soil-borne pathogen and is difficult to control. Epidemics are most common at the late growth stage of foxtail millet. In August 2013, an outbreak was recorded in Shijiazhuang city, Hebei, with an incidence of about 60%. Typical disease symptoms consisted of large, irregular lesions with reddish-brown margin and as the disease progressed, the plants lodge. Three representative sheath fragments (each 1 cm long) were collected from diseased plants during that outbreak. The samples were disinfected with 0.5% (v/v) sodium hypochlorite, rinsed with sterile water, placed on a water agar plate, and then incubated at 26°C in the dark for two days. After the hyphae appeared, ~3-mm-long hyphal tips from typical colonies were excised and transferred to potato dextrose agar (PDA) plates. Three isolates were obtained and all showed typical features of Rhizoctonia-like fungus. Each isolate occupied its whole plate within 5 days of incubation at 26°C in the dark, and abundant aerial mycelia were produced. The color of all colonies was first orange, turning a salmon color when the mycelia matured. Orange sclerotia appeared after 2 weeks of incubation. The nuclei were stained with DAPI (2-(4-amidinophenyl)-1H-indole-6-carboxamidine) and observed under a fluorescent microscope. The hyphal cells were multinucleate and the mycelia branched at a right angle. For molecular identification of the pathogen, mycelia of each isolate were cultured in potato dextrose broth at 26°C for a week, and genomic DNA was extracted from mycelia and used as a template for PCR amplification. The primers set of ITS1 and ITS4 was used for amplification of rDNA-ITS from these isolates and the amplified rDNA-ITS regions of all isolates (GenBank Accession Nos. KJ765700, KJ765701, and KJ765702, respectively) were 99% identical to other Waitea circinata deposited in GenBank (1,2). To further confirm the pathogenicity of the isolates, freshly collected PDA plugs were inoculated on the lower leaf blades of 8-week-old seedlings of the foxtail millet variety Yugu 1. PDA plugs without the isolate were used as a negative control. Five plants were used for each isolate and negative control. After inoculation, pots were placed together in a moist chamber at 26°C. No symptoms developed on the control plants, while obvious lesions appeared on the sheaths of tested plants at 5 days post inoculation and later the plants were lodging. The fungus was re-isolated from diseased plants and confirmed to be W. circinata based on morphological characteristics and sequence analysis as previously described, completing Koch's postulates. Further, on the basis of morphological tests, pathogenicity assays, and molecular analyses, the pathogen of foxtail millet sheath blight was identified as W. circinata (4). Although Rhizoctonia solani AG-1, AG-4 has been reported in earlier studies as the pathogen causing foxtail millet sheath blight, there has been no previous report of the disease caused by W. circinata (3). To our knowledge, this is the first report of foxtail millet sheath blight caused by W. circinata in China. With the spread of high millet plant density and fertilizer application, this disease may become a major threat to foxtail millet; therefore, W. circinata should be taken into account when designing measures for disease control in foxtail millet. References: (2) K. A. de la Cerda et al. Plant Dis. 91:791, 2007. (1) M. Fiers et al. Eur. J. Plant. Pathol. 128:353, 2010. (4) W. D. Gao. Acta Phytopathol. Sinica 17:247, 1987. (3) T. Toda et al. Plant Dis. 89:536, 2005.

[A survey on the application of online and offline blended teaching in microendodontics].

Objective: To evaluate the effect of online and offline blended teaching in microendodontics, attempting to promote the widespread application of blended teaching mode in Operative Dentistry and Endodontics. Methods: A questionnaire survey was carried out among 865 trainees who attended the blended teaching in microendodontics combined the online theory curriculum and offline practice training from April 6 to 28 in 2022, organized by Department of Operative Dentistry and Endodontics, Hospital of Stomatotogy, Sun Yat-sen University. The content of questionnaire included trainees' basic information as well as their perspectives and expectations on the teaching mode. Data was analyzed by SPSS 24.0 and Chi-square test was used for enumeration data. Results: A total of 855 trainees participated in the valid survey with the effective recall rate of 98.8% (855/865), 50.3% (430/855) of which were young people in 18-30 years old. Their working period ranged from 0.5 to 40 years. Physicians and physician assistants occupied 40.9% (350/855) and 32.9% (281/855), respectively. And the intermediate and senior titles accounted for 26.2% (224/855). The proportion of trainees who had used and never used dental operative microscope (DOM) were 70.5% (603/855) and 29.5% (252/855), respectively. The blended teaching in microendodontics was universally approved by the trainees, which showed more superiority in the improvement of learning efficiency and interest, comprehension of knowledge as well as practical ability, etc., compared to the traditional offline teaching. For the current stomatology education, trainees were inclined to choose the blended teaching mode combining online theory curriculum and offline practice training, whereas 41.3% (353/855) and 39.6% (339/855) of trainees agreed that the teaching effectiveness was likely influenced by the condition and frequency of the offline training, respectively. Besides, significant differences were detected in the question about the factors affecting the blended teaching effectiveness of microendodontics between the trainees who had used and not used DOM (χ²=13.37, P=0.004). Conclusions: The application of online and offline blended teaching in microendodontics was affirmed to have some advantages, and it should be considered that the discrepancy in the level of expertise among trainees probably influenced the teaching effectiveness, which may promote the quality and effect of teaching, the spread and sharing of microendodontics, and provide experience and reference for the practice teaching of Operative Dentistry and Endodontics.

Assessment of surrogate models for flood inundation: The physics-guided LSG model vs. state-of-the-art machine learning models.

Hydrodynamic models can accurately simulate flood inundation but are limited by their high computational demand that scales non-linearly with model complexity, resolution, and domain size. Therefore, it is often not feasible to use high-resolution hydrodynamic models for real-time flood predictions or when a large number of predictions are needed for probabilistic flood design. Computationally efficient surrogate models have been developed to address this issue. The recently developed Low-fidelity, Spatial analysis, and Gaussian Process Learning (LSG) model has shown strong performance in both computational efficiency and simulation accuracy. The LSG model is a physics-guided surrogate model that simulates flood inundation by first using an extremely coarse and simplified (i.e. low-fidelity) hydrodynamic model to provide an initial estimate of flood inundation. Then, the low-fidelity estimate is upskilled via Empirical Orthogonal Functions (EOF) analysis and Sparse Gaussian Process models to provide accurate high-resolution predictions. Despite the promising results achieved thus far, the LSG model has not been benchmarked against other surrogate models. Such a comparison is needed to fully understand the value of the LSG model and to provide guidance for future research efforts in flood inundation simulation. This study compares the LSG model to four state-of-the-art surrogate flood inundation models. The surrogate models are assessed for their ability to simulate the temporal and spatial evolution of flood inundation for events both within and beyond the range used for model training. The models are evaluated for three distinct case studies in Australia and the United Kingdom. The LSG model is found to be superior in accuracy for both flood extent and water depth, including when applied to flood events outside the range of training data used, while achieving high computational efficiency. In addition, the low-fidelity model is found to play a crucial role in achieving the overall superior performance of the LSG model.

Decline in Cancer Diagnoses during the 'Zero COVID' Policy in Hong Kong: Indirect Spillover Impact of the COVID-19 Pandemic.

AIMS: Despite a largely successful 'zero COVID' policy in 2020, the COVID-19 pandemic disrupted routine cancer services in the city of Hong Kong. The aims of this study were to examine the trends in cancer incidence before and during the COVID-19 pandemic and estimate missed cancer diagnoses. MATERIALS AND METHODS: We used population-based data from the Hong Kong Cancer Registry 1983-2020 to examine the trends of age- and sex-standardised cancer incidence before and during the COVID-19 pandemic. We applied: (i) the annual average percentage change (AAPC) calculated using the Joinpoint regression model and (ii) the autoregressive integrated moving average (ARIMA) model to forecast cancer incidence rates in 2020. Missed cancer diagnoses in 2020 were estimated by comparing forecasted incidence rates to reported rates. A subgroup analysis was conducted by sex, age and cancer site. RESULTS: The cancer incidence in Hong Kong declined by 4.4% from 2019 to 2020 (male 8.1%; female 1.1%) compared with the long-term AAPC of 0.5% from 2005 to 2019 (95% confidence interval 0.3, 0.7). The gap between the reported and forecasted incidence for 2020 ranged from 5.1 to 5.7% (male 8.5%, 9.8%; female 2.3%, 3.5%). We estimated 1525-1596 missed cancer diagnoses (ARIMA estimate -98, 3148; AAPC 514, 1729) in 2020. Most missed diagnoses were in males (ARIMA 1361 [327, 2394]; AAPC 1401 [1353, 1460]), with an estimated 479-557 missed cases of colorectal cancer (ARIMA 112, 837; AAPC 518, 597) and 256-352 missed cases of prostate cancer (AAPC 231, 280; ARIMA 110, 594). CONCLUSION: The incidence of new cancer diagnoses declined in 2020 contrary to the long-term increase over the previous decades. Significantly lower diagnoses than expected were observed in males, particularly for colorectal and prostate cancers. Fewer reported cancer cases indicate missed diagnoses and could lead to delayed treatment that could impact future health outcomes.

Unusual Instance of Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Confined to a Colonic Polyp.

Extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT) commonly affects the gastrointestinal (GI) tract but rarely occurs within the colon. Colonic EMZL is a rare diagnosis accounting for 2.5% of EMZL and less than 0.5% of colon cancers. We present a unique case of asymptomatic colonic EMZL diagnosed on a routine surveillance colonoscopy. The lymphoma was confined to a single colonic polyp presenting endoscopically as a sessile polypoid lesion at the recto-sigmoid junction. The patient was successfully treated with polypectomy with no recurrence of the disease.

An Atypical Presentation of an Uncommon Malignancy: Plasmablastic Lymphoma Presenting As Recurrent Scrotal Abscesses.

Plasmablastic lymphoma (PBL) is a rare and extremely diagnostically challenging entity. We report a unique case of PBL in an adult male with a history of recurrent scrotal abscesses who presented with progressively worsening scrotal pain, swelling, and drainage. Pelvic CT demonstrated a large scrotal abscess with external draining tracts with foci of air. Surgical debridement revealed necrotic tissue throughout the abscess cavity, abscess wall, and scrotal skin. Immunohistochemical analysis of the scrotal skin specimen uncovered diffuse proliferation of plasmacytoid cells with immunoblastic features that stained positive for CD138, CD38, IRF4/MUM1, CD45, lambda restriction, and Epstein-Barr encoded RNA in situ hybridization (EBER-ISH) with high Ki-67 proliferation index greater than 90%. Taken together, these findings confirmed a diagnosis of PBL. Treatment with six cycles of infusional etoposide, prednisolone, vincristine, cyclophosphamide, and hydroxydaunorubicin (EPOCH-like regimen) was administered with subsequent positron emission tomography (PET)/CT confirmation of complete response. There was no clinical evidence of lymphoma recurrence at the time of follow-up six months later. Our case exemplifies the growing diversity of ways in which PBL may manifest and underscores the importance of a clinician's familiarity with this entity and its well-defined risk factor of immunosuppression.

Gamma-Delta Large Granular Lymphocytic Leukemia: A Diagnostic Dilemma.

We report an initial diagnostic dilemma case of a 60-year-old male who presented with worsening hemolytic anemia, thrombocytopenia, and acute kidney injury requiring hemodialysis. His presentation was initially suspected to be secondary to thrombotic thrombocytopenic purpura (TTP) and he was treated with intravenous immunoglobulin (IVIG) and plasmapheresis. Despite treatment, he failed to improve during his admission leading to further workup revealing gamma-delta T-cell large granular lymphocytic (γδ T-LGL) leukemia. In this paper, we will discuss the features, workup, and treatment of this rare malignancy.

[A preliminary study on the construction and application of the smart classroom teaching mode in endodontics].

Objective: To evaluate the application effect of smart classroom teaching mode in undergraduate teaching of endodontics. Methods: Through micro-lecture and massive open online course which were closely integrated with clinical practice and frontier advances, we build a new smart classroom teaching mode of endodontics relying on information technology such as the medical education cloud APP platform. The mode was applied to the undergraduate teaching of grade 2017 (110 students) and grade 2018 (107 students) in 2020 and 2021 respectively (experimental group). The theoretical examination was conducted for the grade 2016 (control group, 111 students applied traditional teaching methods) in 2019, and for two experimental grades in 2020 and 2021 respectively. A questionnaire survey was conducted for the 2018 undergraduates to investigate the experience of the smart classroom teaching mode, and the application effect of the smart classroom teaching mode was evaluated by comparing the offline theoretical test scores of grades 2016, 2017 and 2018. Results: The results of the questionnaire showed that students in grade 2018 recognized the overall form of smart classroom teaching mode, and 75.2% (79/105) of the students satisfied with the teaching process, considering that it could enhance learning interest and enthusiasm, improve self-learning ability, facilitate the understanding and memory of knowledge points, as well as increase the extension and expansion of professional knowledge. Thirty-seven point one percent (39/105) of the students thought that smart classroom teaching mode was not conducive to the interaction between teachers and students and couldn't improve learning efficiency. Comparing the final theoretical examination scores of students in three years, it was found that the average scores of 2021 (78.79±9.88) and 2020 (76.45±8.33) were significantly higher than that of 2019 (67.67±10.58) (t=6.77, P<0.001; t=8.51, P<0.001). The average score in 2021 was higher than that in 2020, although the difference was not significant (t=1.79, P=0.223). Conclusions: The application of smart classroom mode improved the teaching effect of endodontics, which is worthy of further promotion to provide a positive reference in improving the educating effects of oral medicine.

Perinatal versus adult loss of ULK1 and ULK2 distinctly influences cardiac autophagy and function.

Impairments in macroautophagy/autophagy, which degrades dysfunctional organelles as well as long-lived and aggregate proteins, are associated with several cardiomyopathies; however, the regulation of cardiac autophagy remains insufficiently understood. In this regard, ULK1 and ULK2 are thought to play primarily redundant roles in autophagy initiation, but whether their function is developmentally determined, potentially having an impact on cardiac integrity and function remains unknown. Here, we demonstrate that perinatal loss of ULK1 or ULK2 in cardiomyocytes (cU1-KO and cU2-KO mice, respectively) enhances basal autophagy without altering autophagy machinery content while preserving cardiac function. This increased basal autophagy is dependent on the remaining ULK protein given that perinatal loss of both ULK1 and ULK2 in cU1/2-DKO mice impaired autophagy causing age-related cardiomyopathy and reduced survival. Conversely, adult loss of cardiac ULK1, but not of ULK2 (i.e., icU1-KO and icU2-KO mice, respectively), led to a rapidly developing cardiomyopathy, heart failure and early death. icU1-KO mice had impaired autophagy with robust deficits in mitochondrial respiration and ATP synthesis. Trehalose ameliorated autophagy impairments in icU1-KO hearts but did not delay cardiac dysfunction suggesting that ULK1 plays other critical, autophagy-independent, functions in the adult heart. Collectively, these results indicate that cardiac ULK1 and ULK2 are functionally redundant in the developing heart, while ULK1 assumes a more unique, prominent role in the adult heart.Abbreviations: ATG4: autophagy related 4, cysteine peptidase; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG9: autophagy related 9; ATG13: autophagy related 13; CYCS: Cytochrome C; DNM1L, dynamin 1-like; MAP1LC3A: microtubule-associated protein 1 light chain 3 alpha; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MFN1: mitofusin 1; MFN2: mitofusin 2; MT-CO1: mitochondrially encoded cytochrome c oxidase I; MYH: myosin, heavy polypeptide; NBR1: NBR1 autophagy cargo receptor; NDUFA9: NADH:ubiquinone oxidoreductase subunit A9; OPA1: OPA1, mitochondrial dynamin like GTPase; PPARGC1A, peroxisome proliferator activated receptor, gamma, coactivator 1 alpha; SDHA: succinate dehydrogenase complex, subunit A, flavoprotein (Fp); SQSTM1: sequestosome 1; ULK1: unc-51 like kinase 1; ULK2: unc-51 like kinase 2; UQCRC1: ubiquinol-cytochrome c reductase core protein 1.