To investigate the value of serum hydroxybutyrate dehydrogenase (HBDH) level, an isozyme of lactate dehydrogenase, in evaluating the severity of acute pancreatitis (AP).Patients diagnosed with AP from January 2013 to December 2018 were included in this retrospective study. Patients were divided into the normal serum HBDH levels group (n-HBDH group) and the high serum HBDH levels group (h-HBDH group) according to the criteria HBDH ≥ 182 U/L after admission. The demographic parameters, laboratory data and the severity of AP in the two groups were compared. The receiver operating curve (ROC) was used to evaluate the efficacy of serum HBDH in predicting persistent organ failure and systemic inflammatory response syndrome (SIRS).P < 0.001). In addition, the HBDH level was significantly decreased in 110 patients who were re-measured after AP treatment. The serum HBDH levels were positively correlated with Atlanta classification, Ranson score, and BISAP score . ROC analysis showed that a serum HBDH cut-off point of 195.0 U/L had optimal predictive value for the development of persistent organ failure (AUC = 0.778) and 166.5 U/L for the development of SIRS (AUC = 0.724).A total of 260 AP patients were enrolled, including 176 cases in the n-HBDH group and 84 cases in the h-HBDH group. The incidence of SIRS and organ failure in the h-HBDH group were significantly higher than those in n-HBDH group (both The elevated serum HBDH in early stage of AP is closely related to the adverse prognosis of AP patients, which can be used as a potential early biomarker for predicting the severity of AP. Acute pancreatitis (AP) is one of the most common gastrointestinal diseases of hospitalised patients in China, the United States and other countries, and its incidence rate continues to rise globally. The incidence and mortality of AP were estimated to be 33.74 cases per 100,000 person-years and 1.60 deaths per 100,000 person-years, respectively , systemiEarly assessment of the severity of AP is a key factor in determining treatment strategies . At presLactate dehydrogenase (LDH) is a key enzyme in anaerobic glycolysis, catalysing the mutual conversion of lactic acid and pyruvate . The levAt present, LDH has been incorporated into the Ranson scoring system to assess the severity of AP and predict persistent organ failure in AP . WhetherPatients diagnosed with AP from January 2013 to December 2018 in the Department of Gastroenterology, Yangzhou, China, were included in our study. Diagnosis of AP was based on the existence of two or more of the following criteria: (1) typical clinical symptoms with persistent abdominal pain; (2) serum amylase and/or lipase levels higher than three times the normal upper limit; (3) characteristic results of abdominal imaging . ExclusiLaboratory data was obtained from a blood screening test during hospitalisation. Total quantity of HBDH (BIOSINO) was tested by an enzymatic kit by automatic biochemical analyzer (measure absorbance at 340 nm), with a reference value ranged from 72 to 182 U/L. The basic principle is that HBDH catalyses the reduction of α-ketobutyric acid to α- hydroxybutyric acid and catalysed the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to oxidized nicotinamide adenine dinucleotide (NAD+). In order to obtain relevant demographics, physiological variables and disease severity, the electronic medical records and laboratory test results of all patients were checked by an independent doctor. This study was conducted in accordance with the principles of the Helsinki Declaration. Due to the retrospective characteristics of the study from 2013 to 2018, informed consent was waived and the study was approved by the ethics committee of the affiliated hospital of Yangzhou University.According to the Atlanta classification revised in 2012 , AP was 9/L or neutral rod-shaped granulocyte ratio > 10%. In addition, other conditions that may cause the above acute abnormal changes should be excluded [SIRS was defined by the existence of two or more of the following four criteria: (1) temperature > 38 °C or < 36 °C; (2) heart rate > 90 beats/min or hypotension; (3) tachypnoea (> 20 breaths/min) or hyperventilation (PaCO2 < 32 mmHg); (4) Peripheral blood leukocyte count > 12 × 10excluded .P < 0.05 was considered to be a statistically significant difference.All continuous variables were represented as the mean ± standard deviation (SD). Data were analysed with SPSS 16.0 . Independent sample t test and chi-square test were used to compare continuous variables and categorical variables, respectively. Pearson correlation analysis was used to examine the correlation between serum HBDH levels and other laboratory indicators. Receiver operating characteristic (ROCs) curves were applied to assess the sensitivity and specificity of the indicators by GraphPad Prism 5.0 software. A bilateral A total of 842 patients diagnosed with AP from 2013 to 2018 were reviewed in this study, 582 patients were excluded according to the exclusion criteria, and finally 260 AP patients were enrolled. Of them, 176 (67.7%) patients had normal serum HBDH levels, whereas 84 patients (32.3%) had elevated serum HBDH levels.Of all 260 patients, 162 patients (62.3%) were male, and the average age was 51.7 years old. Hypertriglyceridemia was the most common AP etiology (40.4%), followed by biliary diseases (24.2%) and alcohol consumption (14.2%), and other causes accounted for 21.2% of cases. Among these patients, 81 (31.2%) patients suffered from organ failure, and 75 (28.8%) had SIRS, as showed in Table P < 0.001). Moreover, there was a higher proportion of organ failure (52.4% vs. 21.0%) and SIRS (46.4% vs. 20.5%) in the h-HBDH group, as shown in Table P < 0.001). In addition, in the h-HBDH group, patients had higher levels of white blood cell (WBC), percentage of neutrophils (N%), LDH, direct bilirubin (DB), aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT), blood urea nitrogen (BUN), C-reactive protein (CRP) and calcium ion (Ca2+) . Whereas, there was no significant difference in the serum levels of creatinine (Cr) between the two groups, as shown in Table There was no significant difference in terms of age, gender, history of tobacco and alcohol consumption, and underling disease between the n-HBDH and h-HBDH groups. Compared with the n-HBDH group, the incidence of MAP was lower (47.6% vs. 79.0%), whereas the incidence of SAP (14.3% vs. 2.3%) and MSAP (38.1% vs. 18.8%) were higher in the h-HBDH group , N% , LDH , AST , GGT , BUN , triglyceride , cholesterol , glucose , CRP . Whereas, there was no significant correlation between serum HBDH and Ca2+, ALT, CRP, DB, high-density lipoprotein (HDL), and low-density lipoprotein (LDL).To further evaluate the predictive value of HBDH level for AP prognosis, correlation analysis was carried out between the serum HBDH level and other clinical markers . As shown in Table ROC curve analysis was performed to determine the cut-off value of HBDH for predicting AP with persistent organ failure or SIRS. As shown in Fig. AP is a non-infectious inflammatory disease that usually presents as self-limiting. Most AP cases do not require treatment interventions, but some of them suffer organ failure when the inflammatory response is excessive and can lead to a poor prognosis . The durSome studies have pointed out the value of LDH in AP disease assessment. Yin et al. found that the patient’s LDH level can be used as an indicator to assess the severity and prognosis of AP . Cui et Our study focused on the predictive value of serum HBDH in the early assessment of AP. HBDH is an isoenzyme of LDH exhibiting LDH activity. Previous studies have shown that HBDH can be used to assess the severity of systemic lupus erythematosus-associated liver injury diseases, intrahepatic cholestasis of pregnancy and AIDS-related pneumocystis pneumonia –24. All All kinds of inflammatory diseases involve cell injury. Cells injury or necrosis caused by different pathogens releases structurally different LDH isoenzymes, which can regulate the metabolism of lactate and pyruvate, resulting in increased lactate and reduced pyruvate production, and eventually aggravating the inflammation –28. FerrOur study has some limitations worth noting. Firstly, this is a retrospective study that only demonstrated the correlation between HBDH and AP, but could not clarify the specific role of HBDH in the development of AP. Secondly, the study was conducted in a single centre with a relatively small sample size and therefore, future large-scale cohort studies are warranted to confirm the predictive role of HBDH in AP.In conclusion, our results provide evidence that elevated serum HBDH indicates adverse prognosis in AP patients. HBDH can be used as an early marker to distinguish SIRS from organ failure clinically.


Severe periodontal disease is highly prevalent worldwide, affecting 20% of the population between the ages of 35 and 44 years. The etiological epidemiology in Peru is scarce, even though some studies describe a prevalence of 48.5% of periodontal disease in the general population. Periodontitis is one of the most prevalent oral diseases associated with site-specific changes in the oral microbiota and it has been associated with a socioeconomic state. This study aimed to determine the etiology and resistance profile of bacteria identified in a group of Peruvian patients with periodontal disease.  Six subgingival plaque samples were collected from eight patients with severe periodontitis. Bacterial identification was carried out by an initial culture, PCR amplification, and subsequently DNA sequencing. We evaluated the antibiotic susceptibility by the disk diffusion method. Streptococcus spp.  followed by Rothia spp. , Actinomyces spp. , and Eikenella spp. . The most common species found was Rothia dentocariosa . The antimicrobial susceptibility assay varied according to the species tested; however, among all the isolates evaluated, Actinomyces naeslundii was resistant to penicillin and tetracycline; Eikenella corrodens was resistant to dicloxacillin; and Rothia dentocariosa was resistant to amoxicillin + clavulanic acid and metronidazole but also susceptible to trimethoprim-sulfamethoxazole.  Variable diversity in oral microbiota was identified in each one of the eight patients. The bacterial genus most frequently found was Rothia dentocariosa. Specific antimicrobial therapy is required to improve the treatment outcomes of patients with periodontal disease and avoid antibiotic resistance. The most prevalent periodontal bacterium found in this study was  Oral diseases remain highly prevalent affecting 3.9 billion people worldwide . Oral diPeriodontal disease is a common condition affecting the dental supporting structure. It is classified as gingivitis or periodontitis. Both are inflammatory processes but are distinguished by the presence of alveolar bone involvement in periodontitis . The maiStreptococcus, Peptostreptococcus, Veillonella, and diphtheroid account for more than 80% of healthy oral cavity flora. Vengerfeldt et al. found that the microbial communities that colonize the root canal in antibiotic-naive patients with periodontal disease were Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria, Proteobacteria, Spirochaetes, Tenericutes, and Synergistetes [Periodontitis covers the major plaque‐associated periodontal diseases. It could be classified as necrotizing periodontal disease, periodontitis as manifestation of systemic diseases, and periodontitis (stages and grades) . Periodogistetes .Due to microbial specificity in periodontitis, the use of antibiotics along with surgical management is suitable in certain cases of severe periodontitis or periodontal disease in patients with medical risk factors . NeverthThe present study aimed to screen and assess the antimicrobial susceptibility of periodontopathic bacteria in Peruvian patients with periodontitis, a pilot study.Eight patients diagnosed with periodontitis were included in this study. Six periodontal pocket depths in the range from 4 mm to 8 mm were selected for each patient to collect the total sample. None of the patients received any antibiotic or periodontal treatment prior to sample collection. Also, they did not have any systemic disease and were nonsmoking.The subgingival plaque samples were collected from each patient, following the standard collection protocol as described by Jervoe-Storm et al. . Before This study was approved by the Ethics Committee from Universidad Peruana de Ciencias Aplicadas in Lima, Peru.µL of samples was cultured on Brucella Agar plates , supplemented with 10% sheep blood, vitamin K (1 µg/mL), hemin (5 µg/mL), and kanamycin (50 µg/mL) and incubated at 37°C under anaerobic conditions. The plates were reviewed every 24 hours until bacterial growth was observed.A volume of 200 Specific colonies were selected according to morphological characteristics. PCR was performed by amplifying a universal 16S ribosomal sequence on the studied microorganisms , as previously described . The ampµg (CIP), azithromycin 15 µg (AZM), clindamycin 2 µg (CD), tetracycline 30 µg (TE), dicloxacillin 1 µg (DCX), ampicillin 10 µg (AMP), trimethoprim-sulfamethoxazole 25 µg (SXT), amoxicillin 10 µg (AML), amoxicillin + clavulanic acid 30 µg (20/10) (AUG), and metronidazole 5 µg (MTZ). Susceptibility breakpoints were interpreted according to Clinical and Laboratory Standards Institute (CLSI) breakpoint criteria. Due to the lack of CSLI criteria in some species in this study, such as Rothia spp. and E. corrodens, the categorical interpretations  were carried out following the criteria for Staphylococcus spp. [Bacterial susceptibility was evaluated using the disk diffusion method. The following antimicrobials obtained commercially were evaluated : penicillin 10 U (P), ciprofloxacin 5 id 30 µg /10 (AUG)cus spp. .A total of 6 samples were collected from each of the 8 patients with periodontitis. Six patients (75%) were female, and 2 (25%) were male. The average age of the study population was 51.13 years.Streptococcus spp. , followed by Rothia spp. , Actinomyces spp. , and Eikenella spp.  . In contrast, Eikenella corrodens was found in half of all patients tested (4 isolates) and Actinomyces naeslundii along with Granulicatella adiacens in 3 different patients (3 isolates)  patients with the identification of at least 5 different genera. The most frequent bacterial genus identified in all the samples was 8, 8.3%) . In the solates) .Rothia dentocariosa, Eikenella corrodens, Granulicatella adiacens, and Actinomyces naeslundii. The study found that the antimicrobial susceptibility patterns were very variable according to each microorganism. Rothia dentocariosa showed resistance to metronidazole (MTZ), amoxicillin + clavulanic acid (AUG), and amoxicillin (AML). Meanwhile, Eikenella corrodens was resistant to ciprofloxacin (CIP), azithromycin (AZM), clindamycin (CD), trimethoprim-sulfamethoxazole (SXT), dicloxacillin (DCX), and ampicillin (AMP). Granulicatella adiacens was resistant to ciprofloxacin (CIP), trimethoprim-sulfamethoxazole (SXT), dicloxacillin (DCX), ampicillin (AMP), and metronidazole (MTZ). Finally, Actinomyces naeslundii exhibited resistance to 7 of the 11 antibiotics tested and was susceptible to ciprofloxacin (CIP), dicloxacillin (DCX), amoxicillin + clavulanic acid (AUG), and amoxicillin (AML) (Actinomyces naeslundii was resistant to penicillin (P) and tetracycline (TE) while other bacteria were susceptible to those antibiotics; only Eikenella corrodens was resistant to dicloxacillin (DCX); and only Rothia dentocariosa was resistant to amoxicillin + clavulanic acid (AUG) and metronidazole (MTZ) but also susceptible to trimethoprim-sulfamethoxazole (SXT).Based on the frequency of identification within the study group, we selected 4 different microorganisms to determine their antimicrobial susceptibility: in (AML) . In the Periodontal disease is a diagnosable, treatable, and potentially preventable condition. The prevalence of periodontal disease in Peru is nearly 50%  and it cPorphyromonas gingivalis (seen in chronic periodontitis), Aggregatibacter actinomycetemcomitans (seen in aggressive periodontitis), Bacteroides sp., Treponema sp., Fusobacterium sp., Prevotella sp., Campylobacter sp., and Eikenella [Bacteroides forsythus, Porphyromonas gingivalis, and Treponema denticola. This complex was strongly associated with bleeding on probing; hence, it was categorized as being more closely associated with severe forms of periodontal disease. The second more related complex was labeled with the color orange. It included members of the Fusobacterium nucleatum/periodonticum subspecies, Prevotella nigrescens, Prevotella intermedia, and Peptostreptococcus. The orange complex was associated with the following species: Eubacterium nodatum, Campylobacter rectus, Campylobacter showae, Streptococcus constellatus, and Campylobacter gracilis. The yellow complex was comprised of Streptococcus sanguinis, Streptococcus oralis, Streptococcus mitis, Streptococcus gordonii, and Streptococcus intermedius. The green complex consisted of Eikenella corrodens, Campylobacter concisus, Actinobacillus actinomycetemcomitans serotype A, and three Capnocytophaga species. The A-A complex included Actinomyces naeslundii, Actinomyces odontolyticus, Actinobacillus actinomycetemcomitans serotype B, and Veillonella parvula (purple complex) [The evidence in the literature that supports the etiological role of bacteria in periodontal diseases is overwhelming. Subgingival plaque is a complex microbial ecosystem with more than 800 microbial species of microorganisms. Some of these microbial species have been identified as the causative organisms for periodontal disease under the effect of local and systemic causes , 15. Amoikenella , 24. Thecomplex) .Streptococcus spp., which belongs to the yellow complex and also Rothia spp. (22.9% of the samples). It should be mentioned that Rothia species have previously been described as part of the oral cavity flora in healthy patients [Actinomyces naeslundii was primarily associated with oral plaque but may also be a factor in periodontal disease and opportunistic infections when invading tissues (18.8% of samples), which is part of the A-A complex. The absence of the most common periodontopathogens  could reflect the presence of periodontal disease in the initial stages [The most frequently isolated genus in this study was patients . Actinoml stages ,24.Eikenella corrodens, Granulicatella adiacens and Neisseria spp., but in a lesser proportion  but susceptible to penicillin (P) (Actinomyces naeslundii is a Gram-positive anaerobic bacillus. The isolated Actinomyces naeslundii in our study was susceptible amoxicillin (AML), but also to ciprofloxacin (CIP), dicloxacillin (DCX), and amoxicillin + clavulanic acid (AUG), and it was resistant to other antibiotics assessed. In contrast, Actinomyces spp. are susceptible only to penicillin and amoxicillin [Granulicatella adiacens is a Gram-positive coccus belonging to the family of “nutritional variant streptococci” (NVS). Infective endocarditis due to NVS is rare but is associated with significant mortality and morbidity [Granulicatella adiacens has also been related to septic arthritis and bacterial abscesses [Granulicatella adiacens was susceptible to penicillin (P); however, it was resistant to ampicillin (AMP) , amoxicillin + clavulanic acid (AUG), and amoxicillin (AML)  . Actinomxicillin   and trimethoprim-sulfamethoxazole (SXT), which are commonly used antibiotics in dentistry. Biofilms have significantly high antimicrobial resistance when compared with their free-floating counterparts, which leads to severe concerns in the treatment procedure. Antimicrobial resistance of microorganisms is inherent or arises because of the emergence of resistant strains of bacteria [The antimicrobial susceptibility tests in this study showed that the isolated microorganisms were susceptible to penicillin (P), except for bacteria , 34. A fbacteria . A signiThe results showed that it is an important specific antimicrobial therapy as part of successful periodontitis treatment that also avoids an increase in antibiotic resistance of periodontopathic bacteria responsible for infectious complications, such as endocarditis or other complications associated with oral-hematogenous dissemination. It is relevant to highlight the significance of microbial resistance in antibiotics, thereby meaning it should be used more responsibly to prevent the spread of resistant microbial strains ,35. FurtRothia dentocariosa, which was most prevalent in this study. Actinomyces naeslundii was resistant to most of the antibiotics evaluated.Bacterial species of medical importance were detected in patients with periodontitis, especially


A systemic review and meta-analysis were conducted to investigate the diagnostic ability for staging and impact on management of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (MRI) in patients with pancreatic ductal adenocarcinoma. A comprehensive search was performed in four databases to retrieve studies of pancreatic ductal adenocarcinoma patients that have reported the diagnostic ability of FDG PET/CT and PET/MRI for detecting metastasis and the proportion of patients whose management was changed by its results. The sensitivity and specificity for detecting metastasis and the proportion of patients with management changes were pooled using a random-effects model. A total of 10 studies were included. The pooled sensitivity and specificity for detecting lymph node metastasis were 0.55 and 0.94, respectively, while the pooled sensitivity and specificity for detecting distant metastasis were 0.80 and 1.00, respectively. The areas under the summarized receiver operating characteristic curves for detecting lymph node and distant metastasis were 0.88 and 0.92, respectively. The pooled proportion of patients with management changes was 19%. FDG PET/CT and PET/MRI showed high diagnostic accuracy for detecting lymph node and distant metastasis in pancreatic ductal adenocarcinoma patients, and the use of these imaging tools led to management changes in a significant portion of these patients. Pancreatic cancer is notorious for its extremely poor prognosis . A previIn addition to anatomical imaging examinations, positron emission tomography (PET) imaging using F-18 fluorodeoxyglucose (FDG), a radiotracer preferentially taken up by malignant cells, is currently used for the evaluation of pancreatic cancer . In prevIn the present study, we systematically reviewed the available literature and performed a meta-analysis to investigate the diagnostic ability of staging FDG PET/CT and PET/MRI for detecting lymph node and distant metastasis in patients with pancreatic ductal adenocarcinoma. We also conducted a meta-analysis of the impact of staging FDG PET/CT and PET/MRI on management in those patients.The methodological approach of this meta-analysis complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) of Diagnostic Test Accuracy Studies . All proA systematic literature search was performed in four different bibliographic databases  for all studies published from 1 January 2000 to 6 November 2019 using combinations of the following keywords: “pancreatic neoplasm” or “pancreas tumor” or “pancreas cancer” or “pancreas carcinoma” or “pancreas adenocarcinoma” or “pancreas malignancy” AND “positron emission tomography” or “PET” or “PET/CT” or “PET-CT” or “PET/MRI” or “PET-MRI” AND “staging” or “stage” or “diagnosis” or “detect” or “metastasis” AND “diagnostic accuracy” or “sensitivity” or “specificity” or “receiver operating characteristic” or “ROC curve” or “area under the curve” or “AUC” or “added value” or “diagnostic yield” or “predict” or “accuracy”. No language restriction was applied for the literature search. In addition, reference lists of retrieved studies were also screened to avoid missing eligible studies.All relevant literature underwent evaluation for eligibility according to inclusion criteria based on the patient/intervention/comparator/outcome/study (PICOS) approach , as follThe following information was extracted from each of the included studies: the first author, publication year, country, study design, number and characteristics  of patients, details of the intervention techniques , reference standard, and outcomes. The methodological quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool . The QUAThe primary outcome of this meta-analysis was the diagnostic accuracies of FDG PET/CT and PET/MRI for detecting lymph node metastasis (N staging) and distant metastasis (M staging) in patients with pancreatic cancer. The secondary outcome was the impact of FDG PET/CT and PET/MRI on patient management, as assessed by calculating the proportion of patients whose therapeutic plan was changed due to the PET/CT or PET/MRI findings.2 statistic was used to assess the heterogeneity among the included studies. An I2 value lies from 0% to 100%, with a value of >50% suggesting substantial heterogeneity [2 > 50%, subgroup analyses were further performed to investigate the sources of heterogeneity; investigated subgroups were country (Asia vs. non-Asia), study design (prospective vs. retrospective), and analytical method of PET images . Publication bias was assessed using Deek’s funnel plot and Egger’s test. All statistical analyses were performed using Stata software version 15.0 .With the data extracted from the included studies, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) in detecting lymph node metastasis and distant metastasis were calculated by using a bivariate meta-analysis method with a random-effects model. Furthermore, summarized receiver operating characteristic (SROC) curves were generated for evaluating the diagnostic abilities of PET/CT and PET/MRI using the calculated area under the curves (AUC). The proportion of patients with management changes was calculated for each study, and the results were meta-analytically pooled using a random-effects model. The Iogeneity . In metaThe process of study selection is depicted in The characteristics of the 10 enrolled studies are shown in The methodological quality assessment of the included studies is shown in Six studies with a total of 357 patients with pancreatic ductal adenocarcinoma were included in the meta-analysis of using FDG PET/CT and PET/MRI for diagnosing lymph node metastasis ,23,24,26Seven studies with a total of 296 patients provided data regarding the diagnostic ability of FDG PET/CT and PET/MRI for detecting distant metastasis ,23,25,26Six studies with a total of 650 patients assessed the proportions of patients who underwent management changes following FDG PET/CT staging and compared it to that of conventional staging ,13,14,15Among the six studies, two prospective studies have evaluated the cost-effectiveness of PET/CT in staging of pancreatic cancer ,15. In ap < 0.001; I2 = 77.1; 95% CI: 58.8–95.4%; p < 0.001; I2 = 87.5; 95% CI: 79.7–95.4%; p < 0.001; I2 = 96.3; 95% CI: 91.1–98.7%; p = 0.08; I2 = 49.1%; 95% CI: 2.0–96.1%; p = 0.05; I2 = 52.9%; 95% CI: 12.7–93.1%; 2 statistic. No significant publication bias was shown for all meta-analyses in the current study . Meanwhile, all analyzed factors failed to explain the heterogeneity in the specificity for detecting lymph node and distant metastasis. In subgroup analysis of the proportion of subjects who underwent management changes, studies in non-Asian countries, with a prospective study design, and with qualitative analytical methods revealed higher proportions of patients with management changes following PET/CT  than those in Asian countries, with a retrospective design, and with quantitative analytical methods .Subgroup analyses was performed based on the country, study design, and the analytical method of each study . For theIn patients with pancreatic cancer, contrast-enhanced CT is the preferred primary imaging modality for the initial evaluation . AdditioIn previous meta-analyses of studies of pancreatic cancer patients, the sensitivity and specificity of FDG PET and PET/CT were 32–67% and 75–81%, respectively, for identifying lymph node metastasis and 57–67% and 96–100%, respectively, for distant metastasis ,34. SincOur meta-analyses found substantial heterogeneity across the included studies. Notably, in subgroup analyses performed to investigate the source of this heterogeneity, the method of analyzing PET images was found to be a significant factor for heterogeneity in all meta-analyses. Qualitative analysis is subjective and known to be dependent on the clinical experience of the reader, which might lead to significant inter-reader discrepancies ,37,38. HThe present analysis had several limitations that need to be addressed. First, the number of studies included in this meta-analysis was relatively small, and most of the included studies were retrospectively performed (7 out of 10 studies) or single-center studies (9 out of 10 studies). Further studies are necessary which include a large number of prospective and multi-center studies. Second, the definition of a positive lesion on PET/CT, as well as reference standards, varied among the included studies which could affect the accuracy of the results. Third, due to insufficient information regarding the stages of those patients who underwent management changes following PET/CT, the pooled proportion of patients with management changes could not be stratified by initial stage. However, given this limitation, our results could support the clinical use of PET/CT in pancreatic cancer irrespective of the initial stage. Fourth, the definition of changes in patient management following PET/CT staging might differ among the enrolled studies. Furthermore, although the diagnostic performance of PET/MRI was similar to that of PET/CT, because only a single study evaluated the diagnostic performance of PET/MRI , we coulIn the present meta-analysis, FDG PET/CT and PET/MRI showed high specificity for detecting lymph node metastasis and high sensitivity and specificity for identifying distant metastasis in patients with pancreatic ductal adenocarcinoma. Furthermore, FDG PET/CT and PET/MRI had a significant impact on the management of pancreatic ductal adenocarcinoma, with our results showing a pooled proportion of 19% of patients who underwent management changes following imaging. Based on our results, FDG PET/CT and PET/MRI would be considered to be one of the routine imaging examinations used in the staging work-up of pancreatic cancer. However, because of the relatively small number of included studies with substantial heterogeneity among them, further prospective studies with larger populations are needed to further elucidate our results.


Meatballs are a processed product of animal origin that is consumed cooked, usually with chicken, beef, or pork as the main ingredient. Unfortunately, some unscrupulous sellers in Indonesia may adulterate this product with rat meat to decrease production costs. Rat meat in any food is a critical public health issue and is prohibited under Indonesian food safety laws, as well as within Muslim communities. This study aimed to test the sensitivity of the polymerase chain reaction (PCR) method in the detection of rat meat contained in processed, cooked beef meatballs.Beef meatballs were formulated with different concentrations of rat meat. Molecular detection of adulteration was initiated by DNA extraction of each cooked meatball formulation followed by PCR using a specific primer for mitochondrial DNA Cytochrome b gene of rat, which primer sequences, i.e., forward primer: 5’CATGGGGACGAGGACTATACTATG ’3 and reverse primer: 5’GTAGTCCCAATGTAAGGGATAGCTG’3.Our study showed that the PCR method is sensitive in detecting 5% or greater rat meat adulteration of cooked beef meatballs.The PCR method can be used to detect most rat meat adulteration of cooked beef meatballs and offers a sensitive and effective means to protect food safety and religious requirements in Indonesia. Animal protein is an important substance for human health as it contains amino acids that increase the body’s metabolism and energy . AccordiMeatballs are a very popular food in all classes of Indonesian society, partly due to their cheap cost and availability. The basic ingredients include beef, chicken, or pork , but havet al. [et al. [et al. [et al. [The adulteration of meatballs with rat meat also breaches Indonesian food laws ,4. Howevet al. , PCR-bas [et al. , multipl [et al. , or empl [et al. .Hence, this study aimed to evaluate the sensitivity of the conventional PCR method in the detection of rat meat adulteration of cooked beef meatballs.The approval from the Institutional Animal Ethics Committee to carry out this study was not required as no live animals were used. The rat meat was collected from other studies with ethics approval as part of carcass disposal. This use of the carcass aligns with the reduction principle of the 3 R’s .Beef meatballs using minced sirloin were formulated in the laboratory using the following concentrations of minced rat meat: P0 (0% rat meat – negative control) 0 g rat meat/20 g beef; P1 (1.25% rat meat) 0.25 g rat meat/19.75 g beef; P2: (2.5% rat meat) 0.5 g rat meat/19.5 g beef; P3 (5% rat meat) 1 g rat meat/19 g beef; P4 (10% rat meat) 2 g rat meat/18 g beef; P5 (15% rat meat) 3 g rat meat/17 g beef; P6 (20% rat meat) 4 g rat meat/16 g beef; P7 (25% rat meat) 5 g rat meat/15 g beef, and P+ (100% rat meat – positive control) 20 g rat meat/0 g beef). The formulated beef meatballs were then soaked in boiling water until cooked and ready for further testing.Deoxyribonucleic acid (DNA) isolation was done using the Purelink DNA Mini Kit according to the manufacturer’s procedure with a slight modification ,12. Two ris/borate/EDTA for 10 min. The gel was visualized using UV transillumination and recorded on a digital camera FE-270 with a 7.1-megapixel lens. Positive results were indicated by the presence of PCR product in 188 base pair (bp) position.The PCR program was carried out in 25 μl reaction mix containing 5 μl DNA template (200 ng/μl), 18 μl PCR SuperMix 2×, and 2 μl (20 pmol/μl) of each primer F: 5-CATGTGGGACGAGGACTATACTATG-3 and R: 5-GTAGTCCCAATGTAAGGGATAGCTG-3 . The PCRmtDNA) cytochrome b (cyt-b) gene in rat meat using specific primers that showed a positive result, which is characterized by PCR product 188 base pair (bp)  .The result of the PCR analysis in The data in The data in Meatballs are a very popular traditional dish in Indonesia, partly due to their cheap cost and availability. The basic ingredients include beef, chicken, or pork, but some studies have found instances of food fraud, in which the advertised meat is, in fact, a mixture of other kinds of meat . Beef isharam or forbidden for Muslims, who make up 87.18 % of Indonesia’s population [Adulteration means that substances have been added to food that changes its composition and impact its nutritional value  and socipulation .et al. [cyt-b of each mtDNA of each species. The forward primer amplified the conserved DNA sequence of the different species of the mitochondrial gene, while reverse primers were designed on the specific species of DNA sequences [et al. [cyt-b of mtDNA.The PCR method is a backbone of molecular technology and has been used worldwide to identify adulteration of meat products due to its sensitivity and accuracy. Older methods using the identification of lipids and proteins are considered unreliable due to biochemical changes during processing and cooking. These problems prompted scientists to consider the potential of DNA testing in food safety . The PCRet al.  from Japequences . Srihant [et al.  from Indcyt-b is known as one part of the cytochrome that involves the genetic transport of mitochondria. The cyt-b contains eight helical transmembranes connected by intramembranous or extramembranous domains. The cyt-b is encoded by mtDNA, which is commonly used to determine the phylogenetic relationships among organisms due to its sequence variability. It is also considered to be most useful in determining the relationships between families and genera. Furthermore, some comparative studies involving cyt-b have been used in new classification schemes and to assign newly described species or genus, as well as to gain a deeper understanding of evolutionary relationships [Hence, ionships .cyt-b gene from rat meat at various levels of adulteration. The beef meatballs adulterated with rat meat were detected to as low as 5% concentration of rat meat, over 10 PCR repetitions. Furthermore, the PCR also appears to be accurate at the lower concentrations of 1.25% and 2.5% rat meat, as these were not detected in any of the PCR runs. Our study also confirmed that the PCR method was successful in detecting rat meat adulteration in products that had undergone processing and cooking. Thus, our results support the superiority of the conventional PCR method to detect rat meat adulteration of cooked beef meatballs on the basis of its sensitivity, efficiency, especially for high scales of production and accuracy. Of course, the success of this method also depends on several factors, including specific primary use, good reagent, sample storage, and no DNAse contamination [In addition, in our study, the conventional PCR method with a specific primer has been successfully used to amplify mination ,19.Furthermore, additional confirmation of PCR products can be obtained by the sequencing of DNA amplicons, restriction fragment length polymorphism analysis (PCR-RFLP), and real-time PCR and single-strand conformation polymorphism analysis (PCR-SSCP). The techniques used to obtain the product include amplified fragment length polymorphism analysis (AFLP), analysis of inter-simple sequence repeat polymorphism, analysis of short tandem repeat polymorphisms, and amplification of multiple templates during a single PCR reaction (Multiplex PCR) .et al. [Escherichia coli O157:H7.Random amplified polymorphic DNA (RAPD) was the first PCR-based technique and is currently the simplest one. Randomly chosen short primers (about 10 bp) are used to amplify DNA in the genome. This method makes it possible to obtain a larger number of products by reproducing unspecified fragments of template DNA , as wellet al.  in identThe PCR method is a very useful tool to improve food safety and security in Indonesia by providing authorities with a sensitive and cost-effective means to detect 5% or greater rat meat adulteration of cooked beef meatballs. This is also very important to Indonesia’s Muslim majority as rat meat is haram or forbidden.GYS, ISW, and INW conceived and designed the experiments. GYS performed the PCR. All authors read and approved the final manuscript.


To verify the protective effect of phosphocreatine on myocardium in an ischemic model and the possible mechanism of action. n = 10 in each group. Sham operation group: the coronary artery was not blocked and observed for 120 minutes. The ischemia/reperfusion (I/R) group was given ischemia for 30 minutes and ischemia reperfusion for 90 minutes. Phosphocreatine (PCr) group: after 30 minutes of ischemia, the rats were intraperitoneally injected with PCr (200 mg/kg) for 90 minutes. The animal groups of myocardial ischemia/reperfusion model in vitro were the same as those in vivo. The heart was removed by thoracotomy and washed immediately in H-K buffer solution. Then, the heart was installed on the Langendorff instrument. The concentration of PCr perfusion fluid in the PCr group was 10 mmol/L. The changes in coronary blood flow in isolated myocardium were recorded. The heart rate and electrocardiogram were recorded by RM6240BT. At the end of the experiment, myocardial pathological sections and Cx43 immunofluorescence staining were made, and the contents of malondialdehyde (MDA) in myocardial tissue were detected.  The model of myocardial ischemia/reperfusion (I/R) was established by the ligation balloon method. 30 SD rats were randomly divided into three groups,  Phosphocreatinine treatment improved the myocardial ischemia model, performance in electrocardiogram (ECG) changes (ST segment apparent), and histological changes . At the same time, MDA decreased, while coronary blood flow and Cx43 expression significantly improved.  Phosphocreatine can improve the electrocardiogram and restore histologic changes in ischemic myocardium and coronary blood flow. The postulated mechanism is by inhibiting the generation of free oxygen radicals and restoring the expression of Cx43 protein. More people have died because of cardiovascular diseases (CVD) than any other diseases in the world . IschemiSeveral studies have reported that testicular ischemia/reperfusion incremented the oxidative stress and decreased the level of “antioxidant enzymes” , 14. TheThere are multiple mechanisms that have been proposed to underlie the pathology, including oxidative damage , 17, eneExogenous phosphocreatine (PCr), an ATP buffer, is a high-energy phosphate admixture and has been shown to play a protective role in I/R-injured myocardial tissue , 21. How60 healthy male SD rats weighing 240–280 g were acquired from Slac Laboratory Animal Co. Ltd. . The laboratory animal license number is SCXK (FUJIAN)-2007–0001. The experiment obtained the necessary approval from the Animal Ethics Committee of Xiamen University. With a relative humidity of 55 ± 5% in a pathogen-free facility, the animals were kept under standard laboratory conditions at 22 ± 2°C. All procedures were in accordance with the Institutional Animal Care and Use Committee (IACUC) guidelines and the Laboratory animals guidelines for ethical review of welfare (GB/T 35892–2018).2PO4, 1.2 mmol/L CaCl2, 1.2 mmol/L MgSO4, 25 mmol/L sodium acetate, and 11 mmol/L glucose, pH 7.4. In the experiment, a mixture of 95% O2 and 5% CO2 was used. Ringer solution composition was 6.5 g NaCl, 0.12 g CaCl2, 0.14 g KCl, 0.10 g Na2HPO4·12H2O, 0.20 g NaHCO3, and 2.00 g glucose, in 1.0 L distilled water. Other reagents employed were either domestic or imported analytical reagents.Sodium creatine phosphate (PCr), number 922-32-7, was obtained from the Dalian Meilun Biotechnology Co., Ltd. MDA Kits, no. A003-2, were obtained from the Nanjing Jiancheng Bio Co. . Antibodies of connexin 43 (Cx43), no. C6219, were obtained from Sigma Bio Co. . Krebs-Henseleit fluid (k-h fluid) was composed at a ratio of 120 mmol/L NaCl, 1.2 mmol/L KHMultichannel biological signal acquisition instrument  and multichannel biological signal acquisition and processing system (version 3.0) were used. A small animal ventilator, number HX-101E, , was used. A Heart Langendorff irrigation device  was used. A visible spectrophotometer (number V-1100D) and MAPADA were also used to assess absorbance.The model of myocardial ischemia reperfusion was established by ligating the left anterior descending (LAD) coronary artery and releasing the ligation line , 23. Then = 10 in each group. The control group (sham operation group): the coronary artery was not blocked and observed for 120 minutes. The ischemia/reperfusion (I/R) group was given ischemia for 30 minutes and ischemia reperfusion for 90 minutes. The creatine phosphate (PCr) group: after 30 minutes of ischemia, the rats were intraperitoneally injected with 200 mg/kg PCr (the concentration of PCr was 40 mg/ml) and then given ischemia reperfusion for 90 minutes. The heart rate and electrocardiogram were recorded by RM6240BT. In the experiment, purple cyanosis and electrocardiogram II lead ST elevation in the anterior wall of the left ventricle developed into myocardial ischemia.30 SD rats were randomly divided into three groups, The animal groups of the myocardial I/R model in vitro were the same as those in vivo. The heart was removed by thoracotomy and washed immediately in H-K buffer solution . Then, tSpecimens from different models were examined. All specimens were implanted in OCT and frozen according to routine histological methods . Slices For detection of MDA, manufacturer instructions were followed. Briefly, to assess the effect of PCr on oxidative stress, the MDA concentration (nmol/mg) was determined using the thiobarbital acid (TBA) method.t-tests, while the remaining data were assessed by one-way analysis of variance (ANOVA). A P value < 0.05 was recognized to be statistically significant; P < 0.01 and P < 0.001 indicated highly significant differences. All analyses were performed using Graph Pad Prism 5®  software.All data are presented as the mean ± standard deviation (SD). Electrocardiography parameters were compared using paired R, and T waves all increased. After ischemia, ST elevation and QT elongation were significantly different from those of the blank control (P < 0.001), demonstrating that the myocardial ischemia was obvious after the ligation of the left anterior descending branch. After 10 min of reperfusion, the ST segment height and the QT segment both declined, which proved that the reperfusion was successful. After PCr treatment, the ST segment decreased and the QT segment returned to normal levels. Compared with the control group, there was no statistically significant difference (P > 0.05) observed, indicating that PCr exerted a good therapeutic effect on myocardial ischemia. At the same time, in the PCr group, the changes in ST segment, ventricular tachycardia (VT), and ventricular fibrillation (VF) were significantly lower than those of the ischemia/reperfusion group. P, T, and R waves and the QT interval were significantly smaller than the ischemia/reperfusion group, while the heart rate decreased to a normal level. The results are shown in Ischemia immediately induced a progressive increase in ST height and prolongation of the QT segment, and the amplitude of P,  P < 0.00, demonstThe histologic changes induced immediately after 90 min of reperfusion were evaluated through hematoxylin and eosin staining. Compared to normal myocardial tissue , myocardial changes were noted immediately after 30 min ischemia. These included coagulation and necrosis, cardiomyocyte disorganization, stromal edema (★), hemorrhage, and increased infiltration of inflammatory cells (◀) . With the application of PCr, cardiomyocyte necrosis decreased, inflammatory cell infiltration decreased, and there was a relief of myocardial edema . These data indicated that PCr was able to improve the pathologic damage inflicted upon heart tissue due to myocardial ischemia. The results are shown in In order to indirectly estimate the contractile capacity of cardiomyocytes after 30 min ischemia, coronary blood flow was assessed once every five minutes using a cylinder to collect blood at the end of the reperfusion period. As shown in P < 0.001), while the MDA was significantly decreased compared with the I/R group (P < 0.001) but did not return to control levels.As shown in R group was significantly decreased, and the fluorescence intensity increased after PCr treatment. The results are shown in To analyze the distribution of Cx43, heart tissue was labeled with Cx43 antibody and DAPI. In the control group, the nucleus was clearly stained with DAPI, and Cx43 was strongly expressed in the cell membrane Figures . In contIschemic heart disease (IHD) still represents a large burden on individuals and health care resources worldwide. With the recent advances in cardiovascular research, IHD continues to be associated with both high morbidity and mortality globally . IHD pat2+ overload, and mitochondrial permeability transition pore (mPTP) opening. From the regulation of the inflammatory-immune response and the energy and metabolism in mitochondria to the epigenetic modification of chromatin, more and more novel molecular targets for MIRI and cardioprotection are being identified [This coupled comorbidity of pathological ischemia and therapeutic reinjury of infarcted myocardium, namely, myocardial ischemia/reperfusion injury (MIRI), is particularly refractory to treatment , 29. Traentified .Furthermore, reperfusion therapy promotes the rapid recovery of blood flow to the myocardial ischemic zone but can result in further complications including diminished cardiac contractile and electrical conductivity function, and irreversible tissue necrosis . TherefoAs a crucial energy substrate, PCr has a dual function of both storing and transporting ATP in energy metabolism. Exogenous PCr adds energy directly to the cell through the PCr/CK system . The phaR waves and the QT interval were significantly smaller than in the ischemia/reperfusion group, while the heart rate dropped to normal levels.In order to check the protective effect of PCr on the myocardium of ischemic reperfusion injury, models of acute ischemia/reperfusion injury in rats were established to certify ECG and histopathological changes. There is evidence available to demonstrate the efficiency of ECG changes in the diagnosis of acute myocardial ischemia/reperfusion injury . In our In addition to I/R, the inflammatory response can exacerbate myocardial injury , 36. MyoAcute ischemia reperfusion myocardial injury may include mechanisms associated with mitochondrial damage and consequent energy metabolic disorders, calcium overload, excitatory amino acid (EAAs) nerve toxicity, the accumulation of oxygen free radicals, and other inflammatory reactions. Among these mechanisms, oxidative stress injury is an important mechanism, which is also a currently researched activity. In the human body, the level of ROS and antioxidant compounds are in equilibrium as the overproduction of ROS results in oxidative stress. Oxidative stress could be originated from the perturbation in the balance of prooxidant and antioxidant agents in which the human body would not be capable of eliminating the excessive amount of ROS from the body . Used toRecently, the protective mechanism of PCr for myocardial ischemia reperfusion has been extensively researched. As the main connecting protein of cardiomyocytes, Cx43 provides a structural basis for the maintenance of the electrical physiological pulsation of the cardiomyocyte , 40. To For the first time, this study found that PCr may exert its effect on the myocardium by affecting the expression of Cx43. However, the exact mechanism of action needs further elucidation through future research.Our study showed that PCr could be used to treat and improve myocardial ischemia in a model of ischemia/reperfusion injury. The ST segment in the ECG and necrotic myocardial cells decreased, inflammatory cell infiltration decreased, myocardial interstitial edema decreased, and coronary blood flow was restored. One possible mechanism is through inhibition of the generation of oxygen free radicals and to protect the expression of Cx43 protein, thus restoring normal function to the myocardium.


Yunnanopilia longistaminea, an endemic species in southwest China, is presented in this study. The total genome size of Y. longistaminea was 148,503 bp in length, with a typical quadripartite structure including a pair of inverted repeat  regions separated by a large single copy  region and a small single copy  region. The all GC content was 37.3%. The genome contains 117 genes, including 72 protein-coding genes, 37 tRNA genes, and 8 rRNA genes, 13 genes contain a single intron, and 3 genes have two introns. Further, a maximum-likelihood (ML) phylogenetic tree results that Y. longistaminea was closely related to the genera of Champereia manillana.The complete chloroplast genome sequence of  Yunnanopilia longistaminea is a tropical evergreen woody plant belongs to the genus Opiliaceae in the family Yunnanopilia which mainly distributed in southwest China . The Total DNA samples (YL 1-3) was extracted with Magnetic beads plant genomic DNA preps Kit  and kept at the Key Laboratory for Forest Genetic and Tree Improvement and Propagation in Universities of Yunnan Province, Southwest Forestry University, Kunming, China. Total DNA was used the Illumina Hiseq X platform to sequenced. Approximately 5.73 GB of raw data were genomic paired-end library of 150 bp length. Then, the raw data were used to assemble the complete Cp genome made by the software of GetOrganelle , and then manually confirmed by comparison with the homologues Champereia manillana. The CpDNA sequence of Y. longistaminea was submitted to GenBank (accession number: MN444856).Leaf samples of Y. longistaminea is 148,503 bp in size, which comprising a large single copy (LSC) region with a size of 84,547 bp, a small single copy (SSC) region of with a size of 7805 bp, separated by a pair of inverted repeats of 28,075 bp. The GC content of all Y. longistaminea Cp genome is 37.3%, while the GC contant of LSC was 35.2%, and the corresponding values of SSC and IR regions are 27.8% and 41.9%, respectively. A total of 117 function genes are contained in the chloroplast genome of Y. longistaminea, including 72 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. 5 protein-coding genes, 8 tRNA genes, and all of rRNA genes were duplicated in IR regions. Among these function genes, 13 genes  have a single intron and three genes  contain two introns.The complete Cp genome of Y. longistaminea, maximum-likelihood (ML) phylogenetic tree was reconstructed within the family of Santalales with fully sequenced chloroplast genomes, 16 complete chloroplast genome of Santalales were obtained from GenBank, the plastomes of Viscum coloratum in the family of Santalales were used as out-group. The chloroplast genome sequences of Santalales were aligned using MAFFT version 7 software (Katoh and Standley Santalales. The ML method for phylogenetic was reconstructed by using RA × ML version 8 programme with 1000 bootstrap replicates which based on TVM + F + I + G4 model (Stamatakis Y. longistaminea was closely related to Champereia manillana (Y. longistaminea will provide useful information for phylogenetic studies and genomic resources available of Opiliaceae species.To determine the phylogenetic location of anillana . Moreove


The renin-angiotensin system plays a very critical role in hypertension, diabetes, and kidney and heart diseases. The blockade of the renin-angiotensin system results in the prevention of progression of renal and cardiac damage. There have been controversial hypotheses raised regarding the safety of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in COVID-19 (coronavirus disease 2019). We present the case series of four patients  with confirmed COVID-19, presenting with respiratory symptoms and acute kidney injury, who have been on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been implicated as the gateway for viral entry into the human cell in causing the infection. The factors contributing to acute kidney injury are diuretics, iodinated contrast administration, hemodynamic instability apart from ACE inhibitors, and angiotensin receptor blockers. The ACE inhibitors and ARBs were stopped in these patients due to acute kidney injury. We also discussed the role of ACE2 and the renin-angiotensin system (RAS) blockade in patients with COVID-19 infection along with pathogenesis. The severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) has resulted in mortality worldwide and has been declared a global pandemic. The United States has the highest number of positively tested cases in the world, and the virus has been spreading relentlessly. The lung is the main organ affected by COVID-19 resulting in respiratory failure, but there is also the involvement of other organs like the heart, kidney, and gastrointestinal tract. The patients who tend to have severe disease or need intensive care unit (ICU) admission have multiorgan involvement. Membrane-bound angiotensin-converting enzyme 2 (ACE 2) has been implicated as the gateway for viral entry into the human cell in causing the infection [The renin-angiotensin system (RAS) plays a very critical role in hypertension, diabetes, and kidney and heart diseases. The blockade of RAS results in the prevention of progression of renal and cardiac damage. The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) needs to be elucidated in COVID-19. There have been controversial hypotheses raised regarding the safety of ACEIs/ARBs in COVID-19 [A 49-year-old male presented to the emergency room with complaints of cough and shortness of breath started getting worse for one week. Associated symptoms included fever, chills, and generalized body aches. The patient was found to be hypoxic in the emergency room, requiring oxygen via a nasal cannula. Past medical history was significant for type 2 diabetes mellitus, hypertension, dyslipidemia, depression, and gastroesophageal reflux disease. The patient had a 28-pack-year smoking history and quit smoking four years ago. The patient denied any chest pain, orthopnea, paroxysmal nocturnal dyspnea, or swelling of his extremities. The patient denied any recent travel history. His home medications included metformin 1000 mg by mouth twice a day, hydrochlorothiazide 25 mg by mouth daily, amlodipine 10 mg by mouth daily, duloxetine 60 mg by mouth daily, atorvastatin 40 mg by mouth daily, lisinopril 40 mg by mouth daily, and aspirin 81 mg by mouth daily. The patient had no significant family history.Initial vital signs showed a blood pressure of 132/89 mmHg, heart rate of 88 beats per minute (bpm), oxygen saturation of 80% on room air, which improved to 89% on a 5 L nasal cannula, respiratory rate of 30 breaths/min, and temperature of 99.1°F. Physical examination revealed an unkempt obese male with mild tachypnea and coarse breath sounds bilaterally. The rest of the physical examination was within normal limits.3. Liver function tests were within normal limits. Lactic acid was slightly elevated at 1.7 mmol/L. The rest of the laboratory data are summarized in Laboratory data revealed normal hemoglobin at 13.9 g/dL and platelet count of 220K/mmThe patient's clinical course was complicated by transferring to the intensive care unit due to worsening hypoxic respiratory failure requiring high flow oxygen. He was subsequently intubated. The patient was started on treatment for possible community-acquired pneumonia with ceftriaxone 1 g intravenously daily and azithromycin 500 mg once followed by 250 mg by mouth daily. The patient was also started on lopinavir and ritonavir as per protocol at that time.His clinical course was also complicated by worsening renal function with the increased blood urea nitrogen to 21 mg/dL and serum creatinine to 2.2 mg/dL. The patient's lisinopril and hydrochlorothiazide were held, and he was started on 0.9% normal saline intravenously. His urine analysis was significant for 2+ protein and no RBC casts. The patient complement levels were within normal limits. Testing for hepatitis B, hepatitis C, and HIV screen was all negative. Serum protein electrophoresis did not reveal any monoclonal protein. His COVID-19 testing returned positive. The patient's urine output subsequently continued to drop, and hence he was started on dialysis due to volume overload and hyperkalemia in the setting of acute respiratory distress syndrome type. The patient is currently receiving dialysis three times a week, and his antibiotic coverage was expanded to pulse-dose vancomycin and cefepime. The patient remains intubated and ventilated in the intensive care unit.A 48-year-old female was admitted with worsening shortness of breath for two days after attending a funeral where some people have tested positive for COVID-19. The patient complained of dry cough but denied any chest pain, orthopnea, or paroxysmal nocturnal dyspnea. The patient denied any nausea, vomiting, or diarrhea. Her past medical history was significant for hypertension, dyslipidemia, and hypothyroidism. Her surgical history was positive for thyroidectomy in 2001. The patient denied any history of smoking or illicit drug use. Her home medications included rosuvastatin 20 mg by mouth daily, hydrochlorothiazide/losartan 25–100 mg by mouth daily, amlodipine 10 mg by mouth daily, levothyroxine 150 mcg by mouth daily, and aspirin 81 mg by mouth daily.Initial vital signs were a blood pressure of 132/56 mmHg, heart rate of 109 bpm, respiratory rate of 22 breaths/min, oxygen saturation of 80% on room air, which improved to 90% on 5 L of oxygen via a nasal cannula, and temperature of 101°F. Her physical examination was significant for morbidly obese female in mild acute distress with decreased breath sounds and positive rales bilaterally. The rest of the physical examination was unremarkable.3. Liver function testing was within normal limits. The rest of the laboratory data are summarized in 2 of 58 mmHg, PCO2 of 63 mmHg, and oxygen saturation of 83% on a high flow nasal cannula at 40 liters. Influenza A and B testing was negative. Chest X-ray PA and lateral showed cardiomegaly and pulmonary edema. The patient's nasopharyngeal swab was sent for COVID-19 testing, and she was placed in appropriate isolation.Laboratory testing: CBC was significant for hemoglobin of 12 g/dL and platelet count of 160K/mmThe patient was initially admitted to the medical floor, and subsequently, her oxygen requirements escalated to high flow oxygen and venti mask and she was subsequently transferred to the intensive care unit for worsening hypercapnic hypoxic respiratory failure requiring intubation and ventilation. The patient was started on intravenous Lasix 80 mg every 8 hours and was also started on hydroxychloroquine 200 mg twice a day and azithromycin 500 mg once followed by 250 mg daily for five days as per protocol. The patient's creatinine continued to increase to 3.65 mg/dL, and blood urea nitrogen increased to 92 mg/dL over three days. Lisinopril and hydrochlorothiazide were held since admission, and later Lasix was also held. Her urine analysis was negative for any protein or RBC casts. The patient is currently being monitored without any requirement for dialysis at present.A 64-year-old female was admitted with complaints of cough and shortness of breath getting worse over one week. She also had fever, nausea, vomiting, and diarrhea. The patient also complained of decreased appetite. Her cough was productive with greenish sputum. The patient denied any chest pain, orthopnea, paroxysmal nocturnal dyspnea, or pedal edema. The patient denied any history of recent travel. The patient's past medical history was significant for type 2 diabetes mellitus, hypertension, dyslipidemia, and seasonal allergies. The patient denied any history of smoking or illicit drug use. The patient's home medications included metformin 750 mg by mouth twice a day, spironolactone 25 mg by mouth daily, amlodipine 10 mg by mouth daily, and azilsartan 80 mg by mouth daily.Initial vital signs showed a blood pressure of 132/89 mmHg, heart rate of 88 bpm, respiratory rate of 30 breaths/min, temperature of 100.1°F, and oxygen saturation of 82% on room air, which improved to 89% on 5 L of oxygen via a nasal cannula. Her physical examination revealed an obese female with mild respiratory distress. Her respiratory examination revealed coarse breath sounds bilaterally. The rest of her physical examination was unremarkable.3. Liver function tests were within normal limits. The rest of the laboratory data are summarized in Laboratory testing: the patient's initial CBC revealed anemia with hemoglobin 9.5 g/dL and platelet count 121K/mmThe patient was admitted to the medical floor initially but later transferred to the intensive care unit due to hypoxic respiratory failure requiring high flow oxygen. The patient was also started on lopinavir and ritonavir per protocol at that time. The patient's clinical course continued to get worse with continued worsening of renal function with an increase in creatinine from 1.1 mg/dL to 1.7 mg/dL and then to 6.9 mg/dL for the next 3-4 days. The patient was treated with IV fluids and intravenous bicarbonate. Her medications, azilsartan and spironolactone, were discontinued because of hypotension and worsening renal function. Urine analysis was negative for protein or RBC casts. Testing for hepatitis B and C and HIV screening were negative. Testing for antinuclear antibody, anti-neutrophilic cytoplasmic antibody, and anti-glomerular basement membrane antibodies was either negative or within normal limits. Complement levels, including C3 and C4, were 65 mg/dL and 8 mg/dL, respectively, which were low. Serum protein electrophoresis revealed no M spike.The patient's COVID-19 testing came back as positive. Her urine output dropped to 5–10 milliliters/hour. The patient developed acute respiratory distress syndrome with fluid overload and was started on Lasix 80 mg IV every 8 hours and was also placed in a prone position. The patient failed medical management and was started on dialysis due to oliguric renal failure. Despite the above efforts, the patient's clinical condition continued to deteriorate with hypoxia and hypotension, which persisted despite being maximized on four vasopressors. The family decided to opt for comfort measures only, and the patient, unfortunately, died 11 days after the presentation.2, and temperature of 95.8°F. Physical examination revealed an obese patient who was intubated and sedated. Respiratory examination revealed coarse breath sounds bilaterally.A 77-year-old African American male presented with a chief complaint of dry cough, shortness of breath, and fever for one week. The patient was encephalopathic on presentation and went into cardiac arrest, received 1 round of cardiopulmonary resuscitation, and was able to achieve the return of spontaneous circulation. He was then placed on the hypothermic protocol. The patient was also hypotensive, requiring norepinephrine. The patient's past medical history was significant for type 2 diabetes mellitus, hypertension, dyslipidemia, and hypothyroidism. The patient has no travel history, but the wife reported a concern that he might have encountered a person who was sick. The patient has no history of smoking or illicit drug use. His home medications were pioglitazone 30 mg by mouth daily, olmesartan 40 mg by mouth daily, levothyroxine 100 mcg by mouth daily, glimepiride 4 mg by mouth daily, fenofibrate 160 mg by mouth daily, aspirin 81 mg by mouth daily, and sitagliptin 100 mg by mouth daily. His vital signs were a blood pressure of 102/66 mmHg, heart rate of 92 bpm, respiratory rate of 26 breaths per minute, oxygen saturation of 89% on 100% FiO3. The rest of the laboratory data are summarized in His laboratory examination was significant for hemoglobin 14.1 g/dL and platelet count 306K/mmAll antihypertensives and hypoglycemics were held, including olmesartan. The patient was treated with aggressive IV fluid resuscitation along with IV bicarbonate. The patient was administered insulin therapy for hyperglycemia.The patient's vasopressor requirement continued to increase due to hypotension. His renal failure continued to get worse. Dialysis was considered but was not done due to hemodynamic instability, and the patient was able to urinate. Due to persistent hypotension despite the use of vasopressors and continued hypoxia despite intubation and ventilation, after discussion with the family, the family chose to opt for do not resuscitate (DNR) and comfort care only. The patient died immediately after extubation.We presented the case series of four patients who were on angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs) with COVID-19 infection and acute renal failure. We summarize the findings, including patient characteristics, comorbidities, presenting symptoms, types of ACE inhibitors, or ARB use, including diuretic use at home as well as in the hospital, whether the patient had a computed tomography with IV contrast, dialysis initiation in hospital, and outcome of the patients in SARS-CoV-2 utilizes ACE2 and type 2 transmembrane serine proteases (TMPRSS 2) to enter the human cell , which cAngiotensin-converting enzyme 2 (ACE2) is a zinc metalloprotease discovered in 2000 and has substantial homology with human angiotensin-converting enzymes (ACEs) . The mRNACE2 is expressed in the proximal tubular cells significantly compared to other components in the kidney . In kidnHypertension, diabetes, and cardiovascular disease are the common comorbidities associated with COVID-19 . ACEI anAngiotensin II causes inflammation, fibrosis, and edema through AT1R, and the absence of ACE2 causes the unrestricted activity of Ang II, which results in acute severe respiratory distress syndrome (ARDS). ACE2/Ang-(1–7)/Mas axis has an inhibitory effect on the signaling pathways of inflammation, fibrinogenesis, and cellular proliferation . The netIncreased cardiac ACE2 gene expression and cardiac ACE2 activity were seen in Lewis rats after selective use of lisinopril or losartan, whereas the combination resulted in elevated cardiac ACE2 but not cardiac ACE2 mRNA . In adulIn a study of 79 patients that evaluated plasma ACE2 activity and long-term cardiovascular outcomes in patients with obstructive coronary artery disease (CAD), the ACE2 levels did not vary with age and the use of ACE1/ARBs did not alter the levels . This stKuba et al., in a mouse model, showed that the RAS blockade attenuated the lung injury in SARS-CoV . In a reFang et al. hypothesized that the use of ACE2 modulation medications in hypertensive and diabetic patients increased the risk of developing severe COVID-19 infection . Many inThe understanding of COVID-19 and its pathogenesis sheds light on the potential targets for the treatment: development of spike subunit 1 protein-based vaccine, inhibiting viral spike protein priming proteases, through the serine protease inhibitor camostat mesylate, blocking ACE2 receptors to inhibit the viral interaction with ACE2 ; solubleNCT04287686) [NCT04311177) [NCT04312009) [There are currently few clinical trials underway to analyze ACE2 and RAAS blockade, a potential target for COVID-19: recombinant human angiotensin-converting enzyme 2 (rhACE2) as a treatment for patients with COVID-19 (4287686) , losarta4311177) , and los4312009) .The incidence of AKI in patients infected with COVID-19 is around 3–15% as per recently published studies from China , 28. TheAKI is associated with increased mortality in patients infected with COVID-19. The incidence of AKI was 23% in 101 patients reported by Shi et al., who died from COVID-19 infection . ElevateIn the above case series, all the patients developed acute kidney injury, but other factors were contributing to acute kidney injury like diuretics, iodinated contrast administration, hemodynamic instability apart from ACE inhibitors, and angiotensin receptor blockers. The ACE inhibitors and ARBs were stopped in these patients due to acute kidney injury.There is no established evidence that suggests that the use of ACEIs/ARBs is associated with the COVID-19 or can potentiate the severe infection. Preclinical and clinical studies have shown beneficial evidence in viral pneumonia. The patients must follow the healthcare provider's advice before changing the medications. The medical professionals should follow the guidance of the national and international societies.


Background and objectives: To investigate the serum procalcitonin (PCT) levels among patients with rheumatoid arthritis (RA) without active infection compared with healthy controls and to understand the relationship of PCT with RA disease activity, and treatment received by patients. Materials and Methods: Patients aged 20 years and above with clinician-confirmed diagnosis of RA and healthy volunteers were included during regular outpatient visits, and those with active infection symptoms and signs were excluded. RA disease activity was measured using the Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (DAS28-ESR). Medications received by the patients were also recorded. Results: A total of 623 patients with RA and 87 healthy subjects were recruited in this study. The mean PCT were significantly higher in patients with RA (6.90 ± 11.81 × 10−3 ng/mL) compared with healthy controls (1.70 ± 6.12 × 10−3 ng/mL) (p < 0.001) and the difference remained statistically significant after adjusting for age and sex. In addition, multiple linear regression analysis showed that a lower rank-transformed PCT serum level was significantly correlated with the use of biologics (p = 0.017) and a high DAS28-ESR score (p = 0.028) in patients with RA. Conclusion: Patients with RA have a significantly higher serum PCT levels compared with healthy controls. The use of biologics and an active RA disease activity were associated with a lower level of PCT in patients with RA. Further investigation is required to determine the optimal cutoff value of PCT among patients with RA and its association with disease activity and biologic usage. Rheumatoid arthritis (RA) is a common inflammatory arthritis, affecting 0.5–1% of the general population worldwide. Patients with RA are often treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or biologic DMARDs, putting them in a relatively immunocompromised status.RA patients are at increased risk of infection, but infection is difficult to identify in RA because infection and inflammation can appear very similar. Moreover, it is critical for rheumatologists to differentiate the process of infection or inflammation in a timely fashion, especially when they are presented with toxic signs and high inflammatory markers in order to use antibiotic prescription or escalation of immunosuppressive treatment. Thus, the development of an accurate diagnostic tool is imperative to aid clinicians to promptly make critical decisions.During the past 20 years, many studies have been conducted in critical illness settings, suggesting that serum procalcitonin (PCT) is a specific marker for detection of bacterial infection ,2,3. StuPrevious studies have evaluated PCT application among autoimmune and autoinflammatory diseases, and have shown good sensitivity and specificity for the diagnosis of systemic bacterial infection ,8. A fewAll participants signed informed consent under a study protocol approved by the institutional review board of Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation . The study was carried out in accordance with the Declaration of Helsinki. The blood sample was collected together in our earlier study . In brieSerum samples were collected and stored at −80 °C. Procalcitonin were measured using enzyme-linked immunosorbent assay by a commercially available kit  according to the manufacturer’s protocol.t-test or Mann–Whitney U test was used for the comparison of normally or non-normally distributed variables, respectively. Chi-square test was used for the comparison of categorical variables. As PCT was not normally distributed, we rank transformed the values of PCT and then used the ranks as the dependent variable in conventional simple and multiple linear regression analysis to determine the associations of PCT with different clinical parameters in patients with RA. All statistical analyses were performed using IBM SPSS, version 24.0 . A value of p < 0.05 was considered statistically significant.Data were presented as mean with standard deviation or median with interquartile range, as appropriate. Student’s A total of 623 patients with RA and 87 healthy subjects were recruited in this study, and the demographic data are shown in −3 ng/mL) compared with the controls , p < 0.001 (p < 0.001).The median PCT were significantly higher in RA patients  0.00–10.56 × 10 < 0.001 . After a−3 ng/mL) had low serum PCT levels compared to those did not used biologics .We performed additional subgroup analysis of serum PCT levels in patients with RA by sex, biologics usage, and RA disease activity measured by DAS28-ESR . We founp = 0.012) and DAS28-ESR (p = 0.016), but not age, sex, disease duration, CRP, csDMARD, and comorbidities, were found to be significantly and inversely correlated with serum PCT levels in patients with RA (p = 0.017) and DAS28-ESR (p = 0.028).We further investigated the correlations of rank-transformed PCT levels with different clinical parameters in patients with RA. The use of biologics . Secondly, controls and especially patients with RA might have mild infection that did not detect during enrollment by the physician. Finally, the results of CRP, ESR, and comorbidities of the heathy controls were not available.Patients with RA have a significantly higher PCT compared with healthy controls. The more severe disease activity and use of biologics in patients with RA was associated with a decrease in the serum level of PCT. Further investigation is required to determine the optimal cutoff value of PCT among patients with RA and the association of disease activity and biologics usage.


TLR4) is known to play a critical role in regulating the immune and inflammatory processes. To date, the relationship between genetic variation of TLR4 and AAD is far from clear. The purpose of our study was to illustrate the relevance of TLR4 polymorphisms with the susceptibility to AAD.  Inflammation may be involved in the pathogenesis of acute aortic dissection (AAD). Toll-like receptor 4 (TLR4 polymorphisms (rs10759932 in the promoter and rs11536889 in the 3′-untranslated region) were determined by the KASP method. Clinical parameters were acquired from subjects' medical records, and serum TLR4 levels were collected from our previously published data.  A total of 222 AAD patients and 222 controls were enrolled in this study. Frequency distributions of P = 0.036; recessive model: OR = 0.439, 95%CI = 0.196‐0.984, P = 0.045) and subgroup analyses stratified by sex. The GC genotype and dominant model of rs11536889 conferred a significantly higher risk of AAD compared with GG genotype in female subjects . In addition, a significant interaction between the rs11536889 recessive model and dyslipidemia was observed for an increased risk of AAD  after the adjustment for potential clinical covariates. We also used the false-positive report probability (FPRP) analysis to validate the significant results. Furthermore, rs11536889 polymorphism could affect the maximal aortic diameters of AAD (P = 0.037), while AAD patients carrying CC genotype of rs10759932 showed lower serum TLR4 levels than TT genotype carriers (P = 0.043).  We found that rs10759932 polymorphism was associated with a reduced risk of AAD in the overall population (CC vs. TT: OR = 0.393, 95%CI = 0.164‐0.939, TLR4 polymorphisms and AAD susceptibility in a Chinese Han population, which may have some implications for understanding the role of TLR4 in the pathophysiology of AAD. Our findings provide evidence for the association between  Acute aortic dissection (AAD) is the most life-threatening macrovascular disorder with high mortality, characterized by intimal tear and surging of blood into the medial layer of the aorta , 2. The TLR4), located on chromosome 9q32-q33, is not only the key pattern-recognition receptor in immune-inflammatory reactions but also the initiation protein in this signal transduction pathway [TLR4-mediated signaling has emerged in maintaining aortic homeostasis and establishing the aorta alterations  and their complications [TLR4 could evocate inflammatory cell infiltration, production of proinflammatory mediators, endothelial dysfunction, smooth muscle cell apoptosis, and aortic media degradation, which were closely related to aortic inflammation, remodeling, and dissection [TLR4 expression was independently associated with the risk of AAD, and there was a positive relationship between serum TLR4 and circulating CRP [TLR4 seem to be modulated by genetic variations, principally single nucleotide polymorphisms (SNPs), which may change the ligand binding and balance between pro- and anti-inflammatory cytokines, thereby regulating the progression of various diseases [TLR4 gene may have effects on TLR4 activity and thus modify the signaling of immune and subsequent inflammatory responses, which in turn may affect AAD risk. Some evidences have exhibited that TLR4 polymorphisms were closely associated with the risk of infection [TLR4-mediated metalloproteinase pathways could obviously impact the risk of sporadic thoracic aortic aneurysm [TLR4 polymorphisms are relevant to the susceptibility of AAD.Toll-like receptor 4 , and there were 172 patients under surgical treatment. Excluding criteria incorporated the subjects with coronary heart diseases, congenital cardiovascular defects, severe vascular stenosis, autoimmune diseases, severe organ failure, infectious diseases, hematological system diseases, or malignant tumors. Patients with certain genetic syndromes, such as Marfan syndrome and Ehlers-Danlos syndrome, or traumatic aneurysms were also excluded from the study. A 5 mL fasting venous blood sample was obtained from each subject for DNA isolation. The study was approved by the Ethics Committee of the First Hospital of China Medical University . Written informed consent was obtained from each participant.2. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg and/or use of antihypertensive medications. Diabetes was defined as fasting plasma glucose (FPG) ≥ 7 mmol/L (126 mg/dL) and/or under antidiabetic treatment. Dyslipidemia was defined as total cholesterol (TC) ≥ 6.22 mmol/L (240 mg/dL), or triglyceride (TG) ≥ 2.26 mmol/L (200 mg/dL), or high-density lipoprotein cholesterol (HDL‐C) < 1.03 mmol/L (40 mg/dL), or low-density lipoprotein cholesterol (LDL‐C) ≥ 4.14 mmol/L (160 mg/dL) and/or under taking hypolipidemic drugs.The demographic data and clinical related information were collected from participants' medical records. And maximal aortic diameters of AAD subjects were assessed by CTA. Smoking was defined as having smoked at least one cigarette per day for more than one year. Drinking was defined as having consumed at least one alcoholic drink a day for a minimum period of six months. Body mass index (BMI) was computed as weight in kilograms divided by the square of height in meters. Obesity was defined as BMI ≥ 28 kg/mTLR4 [http://www.HapMap.org) and Haploview software 4.2 (http://www.broadinstitute.org/mpg/haploview) to select the tag-SNPs, which should fit the following criteria: minor allele frequency (MAF) > 0.05 in Chinese Han population, low linkage disequilibrium (r2 < 0.8), and Hardy-Weinberg equilibrium (HWE) > 0.05. Then, potential functions of tag-SNPs were predicted with SNPinfo Web Server (https://snpinfo.niehs.nih.gov/). Accordingly, rs10759932 in the promoter region and rs11536889 in the 3′-untranslated region (3′-UTR) of TLR4, which could separately modify the function of transcription factor binding sites and miRNA binding sites, were chosen in this study.A two-step approach was adopted to identify tag-SNPs in TLR4 . BrieflyA routine phenol-chloroform method was utilized to extract genomic DNA from each blood clot. All samples were randomly placed on the 384-well plates and blinded for disease status. SNPs were genotyped by Baygene Biotechnology Company Limited  with the KASP method using the SNPLine platform . Genotyping quality was assessed by repeated detection of 10% randomly selected samples, yielding a 100% concordance.TLR4 levels were involved in further genotype and TLR4 gene expression correlation analysis.Based on our previously published data , a totalχ2) test. Differences of baseline characteristics between AAD patients and controls were compared by the independent-sample t-test or χ2 test as appropriate. Comparisons of continuous variables among different genotype groups were performed with one-way ANOVA. The association of SNPs with AAD risk was estimated by calculating odds ratios (ORs) and their 95% confidence intervals (CIs) using multivariate logistic regression after adjusting the potential confounding factors. The log-likelihood ratio test was performed to evaluate the SNP-environment interaction by comparing the model that only involved the main effects with the full model also containing the interaction term. The Bonferroni correction was used to adjust P values for multiple tests as needed. Moreover, the false-positive report probability (FPRP) was calculated to verify the significant results at different prior probability levels. First, we used the software NCSS-PASS version 11.0.7 (USA) to test the statistical power of each association. Then, the FPRP values were figured out by following the published instructions, and only the significant result with FPRP < 0.5 was regarded as a noteworthy finding [P < 0.05 was considered statistically significant. In addition, the dominant and recessive genetic models were defined as heterozygote+homozygote variant vs. homozygote wild and homozygote variant vs. heterozygote+homozygote wild, respectively.All the data analyses were conducted with SPSS 17.0 software . HWE for studied SNPs in each group was evaluated with the chi-square ( finding . A two-sP > 0.05). After adjusting age, sex, obesity, smoking, drinking, hypertension, diabetes, and dyslipidemia, the rs10759932 CC genotype and recessive model were associated with a decreased risk of AAD with corresponding ORs of 0.393  and 0.439 , respectively. The overall genetic effects for rs11536889 related to AAD were not observed.The genotype distributions of rs10759932 and rs11536889 in each group are summarized in TLR4 polymorphisms and AAD risk in specific subgroups, we further conducted stratified analyses on the basis of age and sex, as shown in P = 0.026), and the heterozygote TC and dominant model conferred a decreased risk of AAD in female subjects . As for rs11536889, its GC genotype and dominant model were significantly correlated with an increased risk of AAD in female subjects with OR values of 3.382 and 3.043 , respectively, compared with GG genotype.To explore the correlation between TLR4 polymorphisms and environmental factors on the risk of AAD was examined. A combined genotype including the dominant and recessive genetic models of TLR4 SNPs was used for interaction analysis. Pinteraction = 0.038, OR = 15.229), after the adjustment for age, sex, obesity, smoking, drinking, hypertension, and diabetes. However, there were no significant interactions between rs10759932 and risk factors in AAD susceptibility.The interaction effect between TLR4 rs11536889 polymorphism remained noteworthy at the prior probability of 0.25 or 0.1  (TLR4 levels than those with TT genotype for TLR4 rs10759932 (P = 0.043) (Larger aortic diameters were observed in rs11536889 CC genotype carriers when compared to GG genotype carriers (= 0.037) . In addi= 0.043) .TLR4 polymorphisms and AAD susceptibility. The current study is the first report to identify the significance of TLR4 rs10759932 and rs11536889 polymorphisms and their interactions with environmental factors in the risk of AAD, as well as their associations with AAD-related clinical parameters and serum TLR4 levels.To our knowledge, no investigation has focused on the association between TLR4 is considered a useful marker for evaluating local inflammatory reaction and has attracted particular interest because of its important function in mediating vascular remodeling and injury [TLR4 functional regions might cause a dysfunction of TLR4 molecule and interfere with the host immunity and inflammation response, contributing to the risk of various diseases. The SNP rs10759932 locates in the promoter region of the TLR4 gene and may regulate the TLR4 expression level by influencing the binding affinity of transcription factors [TLR4 3′-UTR, where a genetic change can influence mRNA stability and translation efficiency [TLR4 rs11536889 G allele, but not the C allele, inhibited luciferase activity triggered by LPS or IL-6 possibly by binding to miRNAs in posttranscriptional regulation [TLR4 rs11536889 CC genotype or C allele was correlated with an increased risk of coronary artery disease [TLR4 rs10759932 and rs11536889 could be genetic biomarkers and potential therapeutic targets for AAD.AAD is one of the severe and major health issues of aortic disease known to be caused by inflammation, which could destroy the aortic structure and eventually lead to the aortic wall dissection and rupture . TLR4 isd injury , 17. As  factors . The T t factors , 30. Simficiency , 31. A l disease , gastric disease , and hep disease . In thisTLR4 rs10759932 and rs11536889 polymorphism with obesity, smoking, drinking, hypertension, and dyslipidemia in the risk of AAD. Only the effect between the rs11536889 recessive model and dyslipidemia was observed to relate to an increased risk of AAD with an OR value of 15.229 after adjusting the potential confounders. Abnormal blood lipid composition has been demonstrated to play a key role in the occurrence and development of aortic dissection [TLR4 signaling pathway and influence the function of TLR4 [TLR4 activation and contribute to the increased TLR4 expression [AAD is a complex trait, and its susceptibility may be enhanced by a combined effect of genetic background and environmental exposure . We furtssection . Moreove of TLR4 . Recent pression , 39. OurTLR4 can induce the production and secretion of proinflammatory cytokine, while AAD is frequently accompanied by a systemic inflammatory response and severe coagulopathies, which may be provoked by acute aortic injury and reflected in an increment in serum levels of WBC count, CRP, and D-dimer [TLR4 rs10759932 or rs11536889 polymorphism with serum WBC, CRP, and D-dimer levels, AAD patients with rs11536889 CC genotype displayed larger aortic diameters compared to those with GG genotype. Furtherly, our genotype-phenotype analysis suggested that the CC genotype of rs10759932 linked with AAD susceptibility contributed to lower serum TLR4 levels than the TT genotype. Thus, we speculate that rs10759932 polymorphism could have a protective effect on AAD risk by downregulating the expression of TLR4. However, further molecular experiments should be carried out to verify our results.Activation of  D-dimer , 40, 41. D-dimer . InteresSeveral limitations existed in the current study. First, because of the fact that AAD was a rare vascular disease, our sample size was relatively small, especially for stratification and interaction analyses, so further replication and validation in larger and different populations were required. Second, there were some missing data in demographic and clinical parameters. In addition, our investigation was a genetic association study and lacked in vitro functional confirmation tests. Therefore, a series of experiments were needed to identify the potential molecular mechanisms of the significant SNPs in the future.TLR4 rs10759932 was a protective factor whereas rs11536889 was a risk factor for AAD in a Chinese Han population, and these genetic correlations were independent of the classical cardiovascular risk factors. And the interaction between rs11536889 recessive model and dyslipidemia could enhance the susceptibility to AAD. Furthermore, rs11536889 had a significant impact on AAD size, and rs10759932 was in an evident association with serum TLR4 expression levels. Our findings may provide context for the better understanding of genetic features of AAD and thus facilitate the improvement of diagnostic and therapeutic approaches for AAD patients.In summary, our data demonstrated that