Relativistic ultrafast electron diffraction at high repetition rates.

The ability to resolve the dynamics of matter on its native temporal and spatial scales constitutes a key challenge and convergent theme across chemistry, biology, and materials science. The last couple of decades have witnessed ultrafast electron diffraction (UED) emerge as one of the forefront techniques with the sensitivity to resolve atomic motions. Increasingly sophisticated UED instruments are being developed that are aimed at increasing the beam brightness in order to observe structural signatures, but so far they have been limited to low average current beams. Here, we present the technical design and capabilities of the HiRES (High Repetition-rate Electron Scattering) instrument, which blends relativistic electrons and high repetition rates to achieve orders of magnitude improvement in average beam current compared to the existing state-of-the-art instruments. The setup utilizes a novel electron source to deliver femtosecond duration electron pulses at up to MHz repetition rates for UED experiments. Instrument response function of sub-500 fs is demonstrated with < 100 fs time resolution targeted in future. We provide example cases of diffraction measurements on solid-state and gas-phase samples, including both micro- and nanodiffraction (featuring 100 nm beam size) modes, which showcase the potential of the instrument for novel UED experiments.

Reaching adults who smoke cigarettes in rural Appalachia: Rationale, design & analysis plan for a mixed-methods study disseminating pharmacy-delivered cessation treatment.

INTRODUCTION: Unlike other U.S. geographical regions, cigarette smoking prevalence remains stagnant in rural Appalachia. One avenue for reaching rural residents with evidence-based smoking cessation treatments could be utilizing community pharmacists. This paper describes the design, rationale, and analysis plan for a mixed-method study that will determine combinations of cessation treatment components that can be integrated within community pharmacies in rural Appalachia. The aim is to quantify the individual and synergistic effects of five highly disseminable and sustainable cessation components in a factorial experiment. METHODS: This sequential, mixed-method research design, based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework, will use a randomized controlled trial with a 25 fully crossed factorial design (32 treatment combinations) to test, alone and in combination, the most effective evidence-based cessation components: (1) QuitAid (yes vs. no) (2) tobacco quit line (yes vs. no) (3) SmokefreeTXT (yes vs. no) (4) combination NRT lozenge + NRT patch (vs. NRT patch alone), and (5) eight weeks of NRT (vs. standard four weeks). RESULTS: Logistic regression will model abstinence at six-months, including indicators for the five treatment factors and all two-way interactions between the treatment factors. Demographic and smoking history variables will be considered to assess potential effect modification. Poisson regression will model quit attempts and percent of adherence to treatment components as secondary outcomes. CONCLUSION: This study will provide foundational evidence on how community pharmacies in medically underserved, rural regions can be leveraged to increase utilization of existing evidence-based tobacco cessation resources for treating tobacco dependence. CLINICAL TRIALS: NCT05660525.

[Efficacy of non-surgical comprehensive treatment for locally advanced hypopharyngeal carcinoma with cervical esophagus invasion].

Objective: To analyze the treatment effects and side effects of non-surgical comprehensive treatment for locally advanced hypopharyngeal carcinoma invading cervical esophagus. Methods: A retrospective analysis was performed on sixty-six patients with locally advanced hypopharyngeal carcinoma invade the esophagus. These patients were treated in the Department of Otolaryngology, Head and Neck Surgery of Chinese People's Liberation Army General Hospital between January 2011 and May 2022, including sixty-five males and one female, aged 43-71 years. Treatment regimen consisted of induction chemotherapy and concurrent chemoradiothrapy and epidermal growth factor receptor (EGFR)-targeted therapy, three of these cases were treated with programmed cell death 1 (PD-1) immunotherapy. The Kaplan-Meier method was used for survival analysis. Side effects were evaluated with the established CTCAE (Common Terminology Criteria for Adverse Events) 5.0 criteria. The factors affecting prognosis were analyzed by Cox multivariate regression analysis. Results: Sixty-four (97.0%, 64/66) patients completed the radiotherapy and chemotherapy plan. The most common grade three side effects were radioactive oropharyngeal mucositis (89.1%, 57/64) and leukopenia (23.4%, 15/64). Five (7.8%, 5/64) patients showed grade three hoarseness; two patients (3.1%, 2/64) suffered from grade three swallowing dysfunction and required feeding tube and intravenous nutrition; the remaining patients(89.1%) retained good vocal and swallowing functions. The overall survival (OS) of all patients was 81.5% after one year, 54.0% after three years, and 39.9% after five years; the progression-free survival (PFS) was 78.3% after one year, 54.9% after three years, and 42.6% after five years; local control rate (LCR) was 80.9% after one year, 62.5% after three years, and 52.0% after five years. T4a patients showed better OS, PFS and LCR than T4b patients, with statistically significant differences (χ2=8.10, 8.27, and 6.64, respectively, all P<0.05). Cox multivariate regression analysis showed that lymph node metastasis was an independent factor affecting prognosis (χ2=10.21, P<0.05). Conclusion: Non-surgical comprehensive treatment can provide with another option of radical treatment for locally advanced hypopharyngeal carcinoma with cervical esophagus invasion, offering the patients higher rate of larynx and esophageal preservation with tolerable side effects.

[Study on the correlation between ceramic and chronic obstructive pulmonary disease in Foshan City].

Objective: To study the correlation between ceramic and chronic obstructive pulmonary disease (COPD), and explore its related risk factors. Methods: In January 2021, five representative ceramic enterprises were selected from Chancheng District, Nanhai District, Gaoming District and Sanshui District of Foshan City. The ceramic workers who came to Chancheng Hospital of Foshan First People's Hospital for physical examination from January to October 2021 were selected as the research objects, and 525 people were included. Conduct questionnaire survey and pulmonary function test. Logistic regresion was performed to analyze the influencing facters of COPD among ceramic workers. Results: The subjects were (38.51±1.25) years old, 328 males and 197 females, and the detection rate of COPD was 9.52% (50/525). The incidence of respiratory symptoms such as dyspnea, chronic cough, wheezing and chest tightness, the detection rates of abnormal lung age, abnormal lung function and COPD in males were higher than those in females (P<0.05). The logistic regression analysis showed that male, age, working years, smoking status and family history of COPD were the risk factors for COPD among ceramic workers (P<0.05) . Conclusion: The ceramic workers are the high risk population of COPD. We should do a good job in health education, and do a regular physical examination to find the changes of lung function in time, and prevent the occurrence of COPD as soon as possible.

[Immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants: A phase â ¢ clinical trial study].

Objective: To evaluate the immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants under 2 years old. Methods: From March 2017 to June 2018, 1 932 healthy infants in Biyang County, Henan Province, who were not vaccinated with meningococcal meningitis vaccine and whose axillary temperature was ≤37.0 ℃, were recruited as participants. The 3 months and 6-11 months old infants were allocated to the experiment group and the control group in a ratio of 1∶1. Infants aged 12-23 months were allocated to the 1-dose group, the 2-dose group and the control group in a ratio of 1∶1∶1, with 276 infants in each group. The infants in the experiment group were intramuscularly injected with freeze-dried group A+C meningococcal polysaccharide conjugate vaccine to be evaluated, and infants in the control group received intramuscular injection of commercially available freeze-dried group A+C meningococcal conjugate vaccine. The venous blood of infants was collected 30 days before the first dose and after the last dose of inoculation, and the antibody seroconversion of each group was determined and compared. Results: The completion rate of immunogenicity study was 95.2% (1 839/1 932). Before inoculation, there was no statistical difference in the geometric mean titer and positive rate of group A+C antibodies between the experiment group and the control group in 3 months and 6-11 months old infants (all P values >0.05). The geometric mean titers and positive rate of group A antibodies in the 1-dose group were higher than those in the control group (all P values <0.05), but there was no statistical difference between the 2-dose group and the control group (all P values >0.05) in infants aged 12-23 months. After inoculation, the differences (95%CI) in the positive conversion rate of group A+C antibodies between the experiment group and the control group were -0.12% (-6.01%-5.77%) and 0.82% (-4.23%-5.86%) in the 3 months old infants. At the age of 6-11 months, the differences were 6.75% (1.71%-11.79%) and -4.32% (-8.73%-0.08%), respectively. At the age of 12-23 months, the differences were 1.02% (-3.80%-5.83%) and -4.40% (-7.79%- -1.01%) in the 2-dose group and -7.22% (-12.90%- -1.54%) and -18.61% (-23.75%- -13.46%) in the 1-dose group, respectively. The geometric mean titers of group A+C antibodies in the 3 months old infants were 48.50 and 63.12, respectively, which had no significant difference from the control group (43.02 and 57.99, respectively) (both P values <0.05). The geometric mean titers of group A+C antibodies in the 6-11 months and 12-23 months old infants were 84.09 and 92.51 (2-dose group), which were higher than those in the corresponding control group (43.10 and 61.83, respectively) (all P values <0.001). Conclusion: Group A+C meningococcal conjugate vaccine has good immunogenicity in infants under 2 years old.

[The risk of incident gastric cancer for populations with different precancerous gastric lesions: a prospective follow-up study].

Objective: To provide evidence for optimizing the screening strategy for gastric cancer (GC), we evaluated the risk of incident GC for individuals with different precancerous gastric lesions in a prospective cohort study. Methods: Based on the National Upper Gastrointestinal Cancer Early Detection Program launched in Linqu, Shandong, a high-risk area of gastric cancer in China, we included a total of 14 087 subjects diagnosed with different gastric lesions stages by endoscopic screening from 2012 to 2018. Study subjects were prospectively followed up until December 31, 2019. The incidence of GC during the follow-up was ascertained by repeated endoscopic examinations, cancer, death registry reports, and active follow-up of study subjects and was confirmed by reviewing medical records extracted from the hospital information management system. The Poisson regression model was applied to calculate the relative risk (RR) and 95%CI for GC occurrence among subjects with different gastric lesions. Results: Among 14 087 subjects with different gastric lesions as determined by their first endoscopic examination in 2012-2018, 7 608 (54.00%) had a global diagnosis of superficial gastritis (SG), 2 848 (20.22%) had chronic atrophic gastritis (CAG), 3 103 (22.03%) had intestinal metaplasia (IM), and 520 (3.69%) had low-grade intestinal neoplasia (LGIN). During the follow-up, 109 subjects were diagnosed with GC, including 63 with high-grade intestinal neoplasia (HGIN) and 46 with invasive GC. Compared to subjects having normal gastric mucosa or SG, those with CAG (RR=3.85, 95%CI: 2.04-7.28), IM (RR=5.18, 95%CI: 2.79-9.60), and LGIN (RR=19.08, 95%CI: 9.97-36.53) had significantly increased risk of progression to GC. Individuals with these gastric lesions had an elevated risk of developing HGIN and invasive GC. For subjects with LGIN, the RR was 22.96 (95%CI: 9.71-54.27) for developing HGIN and 14.64 (95%CI: 5.37-39.93) for developing invasive GC. Subgroup analyses found that all age group subjects with LGIN diagnosed during the initial endoscopic examination had a significantly increased risk of developing the GC. Conclusions: Our large-scale prospective study on a high-risk area of GC showed that most residents aged 40-69 years had gastric lesions of different stages. Subjects with more advanced gastric lesions had a significantly increased risk of progression to GC.

Pandemic realism as the indispensable political precondition for global disease eradication.

This article examines the politico-scientific mechanism, which leads nations to declare an epidemic or a pandemic finished, irrespective of the actual epidemiological situation at a given time. A historical comparison is made with the famous behavior of Emperor Justinian I (482-565 CE) during the plague pandemic named after him (part of the first plague pandemic). Finally, a reference to the importance of the multidisciplinary study of the history of medicine and the intersection between pandemics and wars is made.

Antigen-specific depletion of CD4+ T cells by CAR T cells reveals distinct roles of higher- and lower-affinity TCRs during autoimmunity.

Both higher- and lower-affinity self-reactive CD4+ T cells are expanded in autoimmunity; however, their individual contribution to disease remains unclear. We addressed this question using peptide-MHCII chimeric antigen receptor (pMHCII-CAR) T cells to specifically deplete peptide-reactive T cells in mice. Integration of improvements in CAR engineering with TCR repertoire analysis was critical for interrogating in vivo the role of TCR affinity in autoimmunity. Our original MOG35-55 pMHCII-CAR, which targeted only higher-affinity TCRs, could prevent the induction of experimental autoimmune encephalomyelitis (EAE). However, pMHCII-CAR enhancements to pMHCII stability, as well as increased survivability via overexpression of a dominant-negative Fas, were required to target lower-affinity MOG-specific T cells and reverse ongoing clinical EAE. Thus, these data suggest a model in which higher-affinity autoreactive T cells are required to provide the "activation energy" for initiating neuroinflammatory injury, but lower-affinity cells are sufficient to maintain ongoing disease.

Muscle-derived stem cells in silk fibroin hydrogels promotes muscle regeneration and angiogenesis in sheep models: an experimental study.

OBJECTIVE: Silk fibroin (SF) hydrogels are of high interest in tissue engineering. However, angiogenesis is one of the major challenges in tissue regeneration and repair. In this study, we present a simple and effective method to develop a 1,2-Dimyristoyl-sn-glycero-3-phosphorylglycerol sodium salt (DMPG)-SF hydrogel. The SF hydrogels had no immunogenicity and approached natural tissues. MATERIALS AND METHODS: The SF scaffolds were first prepared from Bombyx mori silkworms and DMPG. The SF scaffold was seeded with muscle-derived stem cells derived from sheep embryo and implanted in the tibialis anterior muscle of mature sheep. Gelation time, H&E staining, and histochemistry were conducted and observed. The suitability of the hydrogels for 3D cell culture was assessed by living cell stain CM-Dil. RESULTS: The results showed that the SF hydrogels resembled the mechanical properties of natural soft tissues better. The results of H&E staining and histochemistry revealed that the degradation rate showed an S-type change, and muscle regeneration and angiogenesis were clearly visible. Adverse effects were not observed in the sheep models. CONCLUSIONS: DMPG-induced SF hydrogels can be successfully used for in situ cell encapsulation. It provides promising opportunities in biomedical applications, such as in tissue engineering and regeneration.

[Urine proteomics signatures associated with alcohol drinking among residents attending the National Upper Gastrointestinal Cancer Early Detection Program in Linqu, Shandong province].

The liquid chromatography tandem mass spectrometry was used to detect the urinary proteomics of 223 residents aged 40-69 years old who participated in the National Upper Gastrointestinal Cancer Early Detection Program in Linqu County, Shandong Province from November 22 to December 7, 2018, and analyze the alcohol consumption related proteomic profiles and individual urinary protein. There were significant differences in urinary protein profiles between alcohol consumption group and non-alcohol consumption group. The expression of 26 urinary proteins was up-regulated and 20 urinary proteins were down-regulated in alcohol consumption group (P<0.05). The differentially expressed proteins had enzyme inhibitor activity and phospholipid binding function, and mainly enriched in pathways involving proximal tubule bicarbonate regeneration, complement and coagulation cascade, and cholesterol metabolism. The protein expressions of complement factor I (CFI), angiotensin converting enzyme 2 (ACE2) and protein C inhibitor (SERPINA5) were positively correlated with daily alcohol consumption.

[Deep learning-based dental plaque detection on permanent teeth and the influenced factors].

Objective: To develop an artificial intelligence system for detecting dental plaque on permanent teeth and find the influenced factors. Methods: Photos of the labial or buccal surfaces of the permanent teeth were taken by using an intraoral camera (1 280×960 pixels; TPC Ligang, Shenzhen, China) before and after applying the plaque-disclosing agent (Cimedical, Japan) in 25 volunteers [12 males, 13 femals, aged (23±3) years] recruided in accordance with the inclusion criteria from the students of Peking University School of Stomatology from October 2018 to June 2019. A total of 549 groups of photos were captured and then divided into a training dataset containing 440 groups of photos and a test dataset including 109 groups of photos. The scopes of teeth and dental plaque on photos were labeled using LabelMe (Windows 3.2.1, MIT, U S A). A DeepLab based deep learning system was designed for the intelligent detection of dental plaque on permanent teeth. The mean intersection over union (MIoU) was employed to indicate the detection accuracy. Matlab (Windows R2017a, MathWorks, U S A) was used to extract the plaque edge line of 109 groups of photos and to calculate the number of pixels for the measurement of the complexity of the plaque edge line. The percentage of dental plaque area was calculated. Multivariate linear regression was used to explore whether tooth site, plaque percentage, number of plaque edge line pixels and lens light spot location would influence the detection accuracy, of which P<0.05 was considered statistically significant. Results: The MIoU of the permanent tooth model was 0.700±0.191 when 440 photos were used for training and 109 photos were used for testing. In the regression model of significance test (P<0.05), the percentage of plaque and the number of pixels on the edge of plaque had significant influence on the accuracy of dental plaque detection. The standardized coefficient of the number of pixels of the plaque edge line is -0.289, and the standardized coefficient of the percentage of plaque is -0.551. Conclusions: In the present study, an artificial intelligence system was built to detect dental plaque area on tooth photos collected by family intraoral camera. The system showed the ability to detect the dental plaque of permanent teeth. The more complex the marginal line of dental plaque and higher the percentage of dental plaque are, the lower the accuracy of plaque recognition is.

[Screening of biomarkers in exhaled breath of mice exposed to benzene].

Objective: To screen the biomarkers in the exhaled breath of mice exposed to benzene by using exhaled breath online analysis system. Methods: Thirty 8-week-old male C57BL/6 mice were randomly divided into six groups (0, 3, 32, 324, 648, and 1 296 mg/m3) and treated with benzene vapour for 28 days. At the end of the exposure, the peripheral blood cell counts and blood glutathione (GSH) were detected. The content of malondialdehyde (MDA) in HL60 cells treated by mice plasma was examined. Exhaled breath data from mice were collected by Secondary electrospray ionization source high resolution mass spectrometry (SESI-HRMS). Targeted analysis underlying benzene metabolites and oxidative stress metabolites was performed to screen the biomarkers in exhaled breath. Results: After benzene exposure, the number of peripheral blood cells was decreased in different degrees, particularly in the white blood cells (WBC) number. The WBC in 32 and 324 mg/m3 groups was declined by 27.76% and 52.87%, respectively compared to that in control group (P<0.05). Meanwhile, compared with the control group, the GSH content of peripheral blood cells from 324 mg/m3 group decreased by 13.16% (P<0.05). In addition, MDA content was increased by 18.11% in HL60 cells treated with plasma from 324 mg/m3 group mice (P<0.05). The phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid (t,t-MA) in the exhaled gas of mice could be used as biomarkers for benzene exposure (R2>0.8, P<0.001). The peak intensity of five small molecular metabolites related to oxidative stress (ω-carboxylic fatty acid C5H10O3, ω-carboxylic fatty acid C6H12O3, glutamate, cysteine and MDA) increased with the increase of benzene concentration (P<0.05), which was negatively correlated with WBC decline (P<0.001), suggesting that these molecules mignt be used as biomarkers of benzene-induced toxicity. Conclusions: Phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid (t,t-MA) in exhaled breath of mice could be used as biomarkers for benzene exposure; ω-carboxylic fatty acid C5H10O3, ω-carboxylic fatty acid C6H12O3, glutamate, cysteine and MDA might be used as markers of benzene-induced toxicity.

[Random survival forest: applying machine learning algorithm in survival analysis of biomedical data].

Traditional survival methods have a wide application in the field of biomedical research. However, applying traditional survival methods requires data to meet a set of special assumptions while the Random Survival Forest model can overcome this inconvenience. Herein, we used the clinical data of Primary Biliary Cholangitis (PBC) from Mayo Clinic to introduce and demonstrate Random Survival Forest model from mathematical principles, model building, practical example and attentions, aiming to provide a novel method for doing survival analysis.

[Surgical treatment of primary liver cancer:a report of 10 966 cases].

Objective: To summarize the experience of surgical treatment of primary liver cancer. Methods: The clinical data of 10 966 surgically managed cases with primary liver cancer, from January 1986 to December 2019 at Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The life table method was used to calculate the survival rate and postoperative recurrence rate. Log-rank test was used to compare the survival process of different groups, and the Cox regression model was used for multivariate analysis. In addition, 2 884 cases of hepatocellular carcinoma(HCC) with more detailed follow-up data from 2009 to 2019 were selected for survival analysis. Among 2 549 patients treated with hepatectomy, there were 2 107 males and 442 females, with an age of (56.6±11.1) years (range: 20 to 86 years). Among 335 patients treated with liver transplantation, there were 292 males and 43 females, with an age of (51.0±9.7) years (range: 21 to 73 years). The outcomes of hepatectomy versus liver transplantation, anatomic versus non-anatomic hepatectomy were compared, respectively. Results: Of the 10 966 patients with primary liver cancer, 10 331 patients underwent hepatectomy and 635 patients underwent liver transplantation. Patients with liver resection were categorized into three groups: 1986－1995(712 cases), 1996－2008(3 988 cases), 2009‒2019(5 631 cases). The 5-year overall survival rate was 32.9% in the first group(1986－1995). The 5-year overall survival rate of resected primary liver cancer was 51.7% in the third group(2009-2019), among which the 5-year overal survival rates of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed liver cancer were 57.4%, 26.6% and 50.6%, respectively. Further analysis was performed on 2 549 HCC patients with primary hepatectomy. The 1-, 3-, 5-, and 10-year overall survival rates were 88.1%, 71.9%, 60.0%, and 41.0%, respectively, and the perioperative mortality rate was 1.0%. Two hundred and forty-seven HCC patients underwent primary liver transplantation, with 1-, 3-, 5-, and 10-year overall survival rates of 84.0%, 64.8%, 61.9%, and 57.6%, respectively. Eighty-eight HCC patients underwent salvage liver transplantation, with the 1-, 3-, 5-, and 10-year overall survival rates of 86.8%, 65.2%, 52.5%, and 52.5%, respectively. There was no significant difference in survival rates between the two groups with liver transplantation (P>0.05). Comparing the overall survival rates and recurrence rates of primary hepatectomy (2 549 cases) with primary liver transplantation (247 cases), the 1-, 3-, 5-, and 10-year overall survival rates in patients within Milan criteria treated with hepatectomy and transplantation were 96.3%, 87.1%, 76.9%, 54.7%, and 95.4%, 79.4%, 77.4%, 71.7%, respectively (P=0.754). The 1-, 3-, 5-year recurrence rates were 16.3%, 35.9%, 47.6% and 8.1%, 11.7%, 13.9%, respectively(P<0.01). The 1-, 3-, 5-, 10-year overall survival rates in patients with no large vessels invasion beyond the Milan criteria treated with liver resection and transplantation were 87.2%, 65.9%, 53.0%, 33.0% and 87.6%, 71.8%, 71.8%, 69.3%, respectively(P=0.003); the 1-, 3-, 5-year recurrence rate were 39.2%, 57.8%, 69.7% and 29.7%, 36.7%, 36.7%, respectively (P<0.01). The 1-, 3-, 5-, and 10-year overall survival rates in patients with large vessels invasion treated with liver resection and transplantation were 62.1%, 36.1%, 22.2%, 15.0% and 62.9%, 31.8%,19.9%, 0, respectively (P=0.387); the 1-, 3-, 5-year recurrence rates were 61.5%, 74.7%, 80.8% and 59.7%, 82.9%, 87.2%, respectively(P=0.909). Independent prognostic factors for both overall survival and recurrence-free survival rates of HCC patients treated with liver resection included gender, neoadjuvant therapy, symptoms, AST, intraoperative or postoperative blood transfusion, tumor number, tumor size, cirrhosis, macrovascular invasion, microvascular invasion, and pathological differentiation. Propensity score matching analysis of 443 pairs further showed that there was no significant difference in overall survival rate between anatomical liver resection and non-anatomical liver resection(P=0.895), but the recurrence rate of non-anatomical liver resection was higher than that of anatomical liver resection(P=0.035). Conclusions: In the past decade, the overall survival rate of HCC undergoing surgical treatment is significantly higher than before. For HCC patients with good liver function reservation, surgical resection can be performed first, and salvage liver transplantation can be performed after recurrence. The effect of salvage liver transplantation is comparable to that of primary liver transplantation. As for the choice of liver resection approaches, non-anatomical resection can reserve more liver tissue and can be selected as long as the negative margin is guaranteed.

Breed difference and regulatory role of CRTC3 in porcine intramuscular adipocyte.

The cAMP responsive element binding protein (CREB)-regulated transcription coactivator 3 (CRTC3) is a member of the CRTC protein family and plays an important role in energy metabolism. The aim of this study was to determine if the expression of porcine CRTC3 is related to intramuscular fat (IMF) deposition and meat quality in Heigai pigs (a local fatty breed in China) and Duroc × Landrace × Yorkshire (DLY) pigs (a lean crossbred pig widely cultured in China). In addition, the effect of ectopic expression of CRTC3 on gene expression in porcine IMF adipocytes was also examined. Our results showed that Heigai pigs had lower lean percentage, thicker back fat thickness and smaller loin muscle area than DLY pigs. Compared with DLY pigs, Heigai pigs had higher marbling scores, better meat color and higher IMF contents and triglyceride concentrations. Higher levels of oxidative metabolic enzyme and expression of the slow oxidative muscle fiber-related genes were observed in longissimus dorsi muscle and psoas major muscle (P < 0.05) from Heigai pigs. Notably, CRTC3 and adipocyte-specific marker genes were highly expressed in muscle tissues of Heigai pigs. The expression of lipolysis-related genes ATGL and HSL were lower in Heigai muscles. Moreover, forced expression of CRTC3 promoted lipid accumulation and increased the expression of PPARγ, C/EBPα, leptin and FABP4 (P < 0.05), whereas it decreased the expression of ATGL and HSL in IMF adipocytes. These results suggest that CRTC3 expression is associated with lipid accumulation and IMF deposition in pigs.

[Value of index of microcirculatory resistance for early prediction of periprocedural myocardial microcirculatory injury after percutaneous coronary intervention in patients with coronary heart disease].

Objective: To explore the value of index of microcirculatory resistance (IMR) for early prediction of periprocedural myocardial injury (PMI) in patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) after PCI. Methods: It was a prospective study. One hundred and sixty-four patients who had single coronary lesion were consecutively enrolled from May 2014 to December 2017 at Nanjing Hospital affiliated to Nanjing Medical University. According to clinical manifestation, patients were divided into SAP group (n=81) and ACS group (n=83). IMR was determined by thermal dilution with pressure guide wire. Basic clinical characteristics, coronary angiographic results, PCI procedural details, IMR after PCI, ΔIMR (IMR=post-PCI-IMR pre-PCI), levels of myocardial biomarkers before and after PCI were compared between the two groups. Multivariate logistic regression was used to analyze the relation of PMI with IMR and ΔIMR, and the predictive ability was evaluated by receiver operating characteristic (ROC). Results: The levels of total cholesterol and low density lipoprotein cholesterol were significantly higher in ACS group than in SAP group (P<0.05), other clinical data at baseline were similar between the two groups (P>0.05). Quantitative coronary angiography (QCA) results and PCI related data were also similar between the two groups before PCI (P>0.05). Values of mean transit time (Tmn) of intracoronary injection with room temperature saline, post-PCI IMR and ΔIMR were significantly higher in ACS group than in SAP group after PCI (P<0.05). Plasma creatine kinase isoenzyme-MB difference (ΔCK-MB) (ΔCK-MB=CK-MB post-PCI-CK-MB pre-PCI) and cardiac troponin-I (cTnI) difference (ΔcTnI=cTnI post-PCI-cTnI pre-PCI) were significantly larger in ACS group than in SAP group (P<0.05). Multivariate logistic regression analysis showed that coronary artery disease (CHD) type (SAP and ACS) (OR=1.301, 95%CI 1.083-1.562), age (OR=1.007, 95%CI 1.000-1.013), ΔIMR (OR=1.009, 95%CI 1.000-1.017) and post-PCI IMR (OR=1.008, 95%CI 1.001-1.014) were independent predictors of PMI (P<0.05). The area under the ROC curve (AUC) of ΔIMR was 0.763 to predict PMI (P<0.05), the optimum cut-off value of ΔIMR was 5.485 with 70.0% sensitivity and 77.4% specificity. ΔIMR was positively correlated with ΔcTnI (r=0.592, P<0.05). Conclusions: ΔIMR serves as an early predictor of PMI in CHD patients after PCI. As compared with SAP patients, ACS patients are more likely to develop PMI.

ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges.

ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed responses by Zbtb32-/- mice or bone marrow chimeras against a panel of chronic and acute challenges. Mixed bone marrow chimeras were established in which all B cells were derived from either Zbtb32-/- mice or control littermates. Chronic infection of Zbtb32-/- chimeras with murine cytomegalovirus led to nearly 20-fold higher antigen-specific IgG2b levels relative to controls by week 9 post-infection, despite similar viral loads. In contrast, IgA responses and specificities in the intestine, where memory B cells are repeatedly stimulated by commensal bacteria, were similar between Zbtb32-/- mice and control littermates. Finally, an infection and heterologous booster vaccination model revealed no role for ZBTB32 in restraining primary or recall antibody responses against influenza viruses. Thus, ZBTB32 does not limit recall responses to a number of physiological acute challenges, but does restrict antibody levels during chronic viral infections that periodically engage memory B cells. This restriction might selectively prevent recall responses against chronic infections from progressively overwhelming other antibody specificities.

[KLF3 regulates the movement, migration and invasion of breast cancer cells through STAT3].

Objective: To observe the effect of KLF3 on the expression of STAT3 in breast cancer cells, and to explore the potential mechanism of KLF3 affecting the movement, migration and invasion of breast cancer cells. Methods: Firstly, the expression of STAT3 was detected by Western blot, real-time fluorescent quantitative PCR, luciferase reporter system and chromatin immunoprecipitation in breast cancer cells. Secondly, the STAT3 promoter mutant was constructed. The plasmid further confirmed the effect of KLF3 on the activity of STAT3 promoter; the cell scratching test and Transwell method were used to detect the ability of cell movement, migration and invasion. Finally, animal experiments were conducted to verify the effect of knockdown of KLF3 on tumor metastasis in animals. Results: In breast cancer cells, knockdown of KLF3 promoted STAT3 protein expression. The mRNA level of STAT3 was increased by (3.58±0.65) fold after knockdown of KLF3 in MDA-MB-231 cells, while the mRNA level of STAT3 was increased by (2.28±0.19) fold after KLF3 knockdown in MCF-7 cells (P<0.001). KLF3 boundto the promoter region of STAT3. The transcriptional activity of STAT3 increased by (2.47±0.87) fold after knockdown of KLF3 in MDA-MB-231 cells, while the transcriptional activity of STAT3 increased by (2.63±0.65) fold after KLF3 knockdown in MCF-7 cells, P<0.01. KLF3 knockdown inhibitedthe movement,migrate and invade of breast cancer cells. Based on this, silence STAT3 partially reversed the function of KLF3. Knockdown of KLF3 promotedtumor metastasis in mice. Conclusions: KLF3 knockdown can promote the transcriptional activity of STAT3, which promotes the protein expression of the latter. KLF3 can affect the movement, migration and invasion of breast cancer cells through STAT3. KLF3 may be a potential target for the treatment of metastatic breast cancer.

[Twoyear outcomes and the influence factors of indirect pulp treatment in primary teeth: a retrospective study].

OBJECTIVE: To evaluate the outcomes and to find out the influence factors of indirect pulp treatment in primary teeth. METHODS: Children who received indirect pulp treatment in primary teeth in the Department of Pediatric Dentistry in Peking University School and Hospital of Stomatology from August, 2014 to September, 2016 were collected in the Electronic Medical Record Database of Peking University School and Hospital of Stomatology, via the database for scientific research provided by the corporation of Kaientai. The children selected as the subjects of this study were followed up over 1.5 years, and they were under 9 years old if in the group of primary molars while the children in the group of primary anterior teeth were under 4 and a half years old. Those children who were not reviewed regularly or didn't have complete medical records were removed. Basic information, the relevant medical records and radiographic records of those children were collected. All teeth were examined clinically and classified into 2 outcomes, teeth in group H were regarded as succeeded, and teeth in group P were regarded as failed. Survival analysis was applied. The survival rate and survival time of the deciduous teeth calculated. Multivariate analysis was performed by using Cox proportional hazard model. RESULTS: One hundred and six children were finally included, aged from 1.6 to 8.8 years, with the mean age of (5.0±1.7) years. 168 primary teeth (122 primary molars, 46 primary anterior teeth) were included, and the average follow up time was (729±244) days. Thirty-five primary teeth (23 primary molars, 12 primary anterior teeth) failed upon clinical or radiographic examinations by September, 2018. The cumulative survival probability of half a year, one year, one year and a half, two years, two and a half years for the indirect pulp treatment was 93.5%, 92.9%, 87.5%, 82.7%, and 75.5% through the KaplanMeier method, respectively. Through the analysis of Cox proportional hazard model, in primary molars, the survival probability tended to be lower when the number of tooth surface affected by caries was greater (OR=1.709, P<0.05). Compared with primary molars, the survival probability of primary anterior teeth was lower, but the difference was not significant. CONCLUSION: Complying the current instructions in our department, the cumulative survival probability of two and a half years after the indirect pulp treatment in primary teeth was 75.5%. In primary molars, the survival probability tended to be lower when the number of tooth surfaces affected by caries increased.