BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Background: To date, consistent data have not been reported on the association between serum amyloid A (SAA) levels and type 2 diabetes mellitus (T2DM). The purpose of this study was to systematically summarize their relationship. Methods: Databases including PubMed, Cochrane Library, Embase, Web of Science, and MEDLINE were searched until August 2021. Cross-sectional and case-control studies were included. Results: Twenty-one studies with 1,780 cases and 2,070 controls were identified. SAA levels were significantly higher in T2DM patients than in healthy groups (standardized mean difference [SMD], 0.68; 95% confidence interval [CI], 0.39 to 0.98). A subgroup analysis showed that the mean age of participants and the continent that participants were from were related to differences in SAA levels between cases and controls. Furthermore, in T2DM patients, SAA levels were positively associated with body mass index (r=0.34; 95% CI, 0.03 to 0.66), triglycerides (r=0.12; 95% CI, 0.01 to 0.24), fasting plasma glucose (r=0.26; 95% CI, 0.07 to 0.45), hemoglobin A1c (r=0.24; 95% CI, 0.16 to 0.33), homeostasis model assessment for insulin resistance (r=0.22; 95% CI, 0.10 to 0.34), C-reactive protein (r=0.77; 95% CI, 0.62 to 0.91), and interleukin-6 (r=0.42; 95% CI, 0.31 to 0.54), but negatively linked with highdensity lipoprotein cholesterol (r=–0.23; 95% CI, –0.44 to –0.03). Conclusion The meta-analysis suggests that high SAA levels may be associated with the presence of T2DM, as well as lipid metabolism homeostasis and the inflammatory response.

Background Tricresyl phosphate (TCP) is mainly used as a flame retardant. Studies have confirmed that it has cytotoxicity and neurotoxicity, but its reproductive toxicity is not clear. Objective To investigate the reproductive toxicity and potential mechanism of TCP subacute exposure on Caenorhabditis elegans. Methods Caenorhabditis elegans were exposed to solvent control and 0.1, 1, 10, 100, and 1000 μg·L⁻¹ TCP respectively for 72 h. Brood size and number of fertilized eggs in the uterus were detected to evaluate reproductive ability. The number of total germline cells and the relative area of gonad arm were measured to evaluate the development of gonads. The body length and body width of Caenorhabditis elegans were detected to evaluate growth and development. The activities of reactive oxygen species (ROS) and superoxide dismutase (SOD) in Caenorhabditis elegans, and the mitochondrial active oxygen metabolism genes (mev-1 and gas-1) of N2 nematodes were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) to evaluate oxidative stress. WS1433 transgenic nematodes and wild-type nematodes N2 were exposed to solvent control or TCP (0.1, 1, 10, 100, and 1000 μg·L⁻¹) respectively. DNA damage in germ cells of WS1433 transgenic nematodes was detected, the relative expressions of DNA damage-related genes (hus-1, clk-2, cep-1, and egl-1) in N2 nematodes were detected by qRT-PCR to evaluate the effect of TCP exposure on genetic damage. Results Compared with the solvent control group (217.00 ± 12.20), the brood size of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (170.80 ± 11.51, 169.60 ± 10.52, P < 0.05). Compared with the solvent control group (18.43 ± 1.69), the number of fertilized eggs of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (13.47 ± 0.81, 11.95 ± 0.90, P < 0.05). Compared with the solvent control group (312.46 ± 77.4), the number of total germline cells of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (281.80 ± 12.98, 273.50 ± 8.53, P < 0.05). Compared with the solvent control group, the relative area of gonads of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased by 13.83% and 17.25% respectively (P<0.05). Compared with the solvent control group [(1058.10±80.12) μm, (78.21±14.69) μm], the body length and body width of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (P<0.05). Compared with the solvent control group, the relative fluorescence intensity of ROS in nematodes in the 10, 100, and 1000 μg·L⁻¹ TCP groups increased significantly (107.60%±1.02%, 105.90%±1.40%, and 106.40%±1.85%, respectively, P<0.05), and the activities of SOD were reduced (by 20.66%, 15.88%, and 16.44%, respectively, P<0.05). Compared with the solvent control group (1.3±1.3), the number of DNA-damaged germ cells of WS1433 nematodes in the 100 and 1000 μg·L⁻¹ TCP groups increased significantly (2.4±0.3, 2.7±0.3, P<0.05); the expressions of mev-1 and gas-1 genes in N2 nematodes in the 10, 100 and 1000 μg·L⁻¹ TCP groups decreased significantly (P<0.05); the expressions of hus-1 in the 0.1-1000 μg·L⁻¹ TCP groups significantly increased (P<0.05); the expressions of clk-2 and egl-1 in the 100 and 1000 μg·L⁻¹ TCP groups increased significantly (P<0.05); the expressions of cep-1 in the 1, 10, and 100 μg·L⁻¹ TCP groups increased significantly (P<0.05). Conclusion TCP may cause reproductive damage to nematodes through oxidative stress and germ cell DNA damage.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the endoscopic modality of choice for the treatment of biliary and pancreatic diseases. However, patients with cirrhosis, particularly those with decompensated cirrhosis, are believed to be at increased risk for complications associated with ERCP. There is a paucity of literature describing the outcomes of ERCP for patients with cirrhosis. This study aimed to investigate the outcomes of ERCP for cirrhosis patients, especially adverse events, and evaluated its safety and efficacy. METHODS: We performed a multicenter, retrospective study of all patients at Beijing Friendship Hospital affiliated to Capital Medical University, Xijing Hospital affiliated to Air Force Military Medical University, Beijing Youan Hospital affiliated to Capital Medical University, and the Fifth Medical Center of the People's Liberation Army General Hospital from June 2003 to August 2019. The adverse events of inpatient ERCP for patients with ( n  = 182) and without liver cirrhosis (controls; n  = 385) were compared. RESULTS: A total of 567 patients underwent ERCP between January 2003 and December 2019 were enrolled in this study. Compared to patients without cirrhosis, patients with cirrhosis were at higher risk for postoperative complications (odds ratio [OR], 4.172; 95% confidence interval [CI], 1.232-7.031; P  < 0.001) such as postoperative pancreatitis (OR, 2.026; 95% CI, 1.002-4.378; P  = 0.001) and cholangitis (OR, 3.903; 95% CI, 1.001-10.038; P  = 0.036). The main indications for ERCP for patients with cirrhosis in this study included choledocholithiasis (101 cases; 55.5%), benign bile duct strictures (46 cases; 25.3%), and malignant bile duct strictures (28 cases; 15.4%). Among them, 23 patients (12.6%) underwent balloon dilation and 79 patients (43.4%) underwent sphincterotomy. Of the patients with cirrhosis, delayed bleeding occurred in ten patients (5.5%), postoperative pancreatitis occurred in 80 patients (44.0%), and postoperative cholangitis occurred in 25 patients (13.7%). An additional multivariate analysis showed that the total bilirubin (TBIL) level (OR, 4.58; 95% CI, 2.37-6.70) and Child-Pugh score of C (OR, 3.11; 95% CI, 1.04-5.37) were risk factors for postoperative complications in patients with cirrhosis. CONCLUSIONS Compared with the general population of patients undergoing ERCP, patients with cirrhosis were more prone to postoperative pancreatitis and cholangitis. TBIL levels and Child-Pugh scores were risk factors for postoperative complications in patients with cirrhosis.
Humans ; Cholangiopancreatography, Endoscopic Retrograde/adverse effects* ; Retrospective Studies ; Constriction, Pathologic ; Risk Factors ; Liver Cirrhosis/complications* ; Pancreatitis/etiology* ; Postoperative Complications/epidemiology* ; Cholangitis

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Objective:To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) for patients with liver cirrhosis combined with biliopancreatic diseases.Methods:Data of 99 patients with liver cirrhosis combined with biliopancreatic diseases who received ERCP at Xijing Digestive Hospital from November 2008 to December 2017 for the first time were retrospectively studied. Success rate of ERCP and incidence of complications were analyzed.Results:The 99 cases of liver cirrhosis were mainly caused by hepatitis B virus infection (40.4%, 40/99) and unknown reasons (30.3%, 30/99), and the mean model for end-stage liver disease score was 15.4±5.3. The common bile duct stones and bile duct stricture were the most common biliopancreatic diseases, accounting for 49.5% (49/99) and 33.3% (33/99), respectively. The success rate of ERCP was 100.0%(99/99). The total postoperative complication incidence was 14.1% (14/99), among which liver cirrhosis-related complications was 3.0% (3/99); ERCP-related complications was 11.1% (11/99), including 9.1% (9/99) biliary tract infection, and 2.0% (2/99) delayed bleeding. No post-ERCP pancreatitis, perforation or death occurred.Conclusion:ERCP is safe and effective for liver cirrhosis combined with biliopancreatic diseases.

OBJECTIVE: To develop and validate radiomics models based on non-enhanced magnetic resonance (MR) imaging for differentiating chondrosarcoma from enchondroma. METHODS: We retrospectively evaluated a total of 68 patients (including 27 with chondrosarcoma and 41 with enchondroma), who were randomly divided into training group (=46) and validation group (=22). Radiomics features were extracted from TWI and TWI-FS sequences of the whole tumor by two radiologists independently and selected by Low Variance, Univariate feature selection, and least absolute shrinkage and selection operator (LASSO). Radiomics models were constructed by multivariate logistic regression analysis based on the features from TWI and TWI-FS sequences. The receiver-operating characteristics (ROC) curve and intraclass correlation coefficient (ICC) analyses of the radiomics models and conventional MR imaging were performed to determine their diagnostic accuracy. RESULTS: The ICC value for interreader agreement of the radiomics features ranged from 0.779 to 0.923, which indicated good agreement. Ten and 11 features were selected from the TWI and TWI-FS sequences to construct radiomics models, respectively. The areas under the curve (AUCs) of TWI and TWI-FS models were 0.990 and 0.925 in training group and 0.915 and 0.855 in the validation group, respectively, showing no significant differences between the two sequence-based models (>0.05). In all the cases, the AUCs of the two radiomics models based on TWI and TWI-FS sequences and conventional MR imaging were 0.955, 0.901 and 0.569, respectively, demonstrating a significantly higher diagnostic accuracy of the two sequence-based radiomics models than conventional MR imaging (<0.01). CONCLUSIONS The radiomics models based on TWI and TWI-FS non-enhanced MR imaging can be used for the differentiation of chondrosarcoma from enchondroma.
Chondroma ; Chondrosarcoma ; Humans ; Magnetic Resonance Imaging ; ROC Curve ; Retrospective Studies

Objective Early evaluate the feasibility and reproducibility of sorafenib-targeted therapy for hepatocellular carcinoma by RECIST1.1, mRECIST and three-dimensional volume measurement. Methods Seventy patients with pathology or typical imaging findings confirmed as hepatocellular carcinoma along with the sorafenib-targeted treatment for more than 2 months between October 2004 to April 2017 in the Fifth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. Patients underwent chest, abdominal and pelvic CT scans and enhanced scans before and after 2 weeks of sorafenib treatment. Two physicians used RECIST 1.1, mRECIST, and volume measurement criteria to evaluate the efficacy of treatment. According to their averaged results, the patients were divided into two groups (control group and non-control group). Kaplan-Meier survival analysis was used to compare the prognostic values between different response evaluation criterias for early predicting the efficacy of sorafenib-targeted therapy in advanced hepatocellular carcinoma. Kappa test was used to assess the efficacy response consistency in intra-group and inter-group. Results Based on mRECIST and RECIST 1.1 measurements, the control group included 34 cases, and the non-control group included 36 cases. Based on semi-automatic volume measurement, the control group included 38 cases, and the non-control group included 32 cases. Before the treatment with sorafenib, the RECIST 1.1 and mRECIST methods were used. There was a high degree of consistency between the two doctors (Kappa values were 0.79 and 0.71, respectively), and the semi-automatic volume measurement method was extremely consistent (Kappa value was 0.90); the consistency in intra-observer by three different methods was extremely high (Kappa values were 0.91, 0.85, 0.97, respectively). After the treatment with sorafenib, the consistency between the two radiologists using RECIST 1.1 measurement was high (Kappa value was 0.65), the consistency of mRECIST measurement was moderate (Kappa value was 0.52), and the consistency of tumor volume measurement was extremely high (Kappa The value was 0.83), the consistency in intra-observer using the above three methods was high or very high (Kappa values were 0.86, 0.74, 0.90, respectively). The RECIST 1.1 and mRECIST measurements were less sensitive in early evaluation of sorafenib-targeted treatment, and there was no significant difference between the control group and the non-control group (P=0.578 and 0.613) while the semi-automatic volumetric measurement was sensitive (P=0.004). Conclusion Semi-automated three-dimensional volume measurement which has better intra-and inter-group consistency and reproducibility can reflect the efficacy of sorafenib-targeted therapy for hepatocellular carcinoma in early stage.

Objective To evaluate the diagnostic value of related contrast material(Rel.CM)of the dual-energy CT (DECT) virtual noncalcium (VNCa) for detecting acute traumatic bone marrow edema in knee joint.Methods A total of 17 patients(18 knees)with definite trauma history and knee joint disorders were prospectively enrolled. Conventional CT, VNCa and MRI images were obtained by MRI and DECT scan. Each knee was divided into 12 regions, respectively, to observe the performance of MRI and VNCa images. The diagnostic efficacy of different Rel. CM values (1.25, 1.45, 1.75) was analyzed for the knee traumatic bone marrow edema,select the best Rel.CM value.And the CT values of bone marrow and bone marrow damage were measured on VNCa of the optimal Rel. CM parameters. Using ROC to evaluate the efficacy of VNCa in different Rel.CM values for diagnosing traumatic bone marrow edema,the difference of CT value between bone marrow lesion and bone marrow in normal region of bone marrow was obtained by using rank sum test. Results DECT and MRI were performed in 17 patients (18 knees). Eighteen knees were divided into 216 areas.MRI showed 94 areas of bone marrow edema,including 35 in distal portion of femur, 59 in proximal tibia. Rel.CM values of 1.25, 1.45, 1.75 of the VNCa map were used to diagnose traumatic bone marrow edema in the knee with the area under the ROC curve of 0.643, 0.871, 0.656, respectively. Rel.CM with 1.45 VNCa diagram was the most accurate. The CT values of the bone marrow edema region and the normal region were -64.3(-20.6 to-90.8)HU,-93.4(-70.5 to-120.7)HU, respectively, on the VNCa graph with the optimal Rel.CM parameters (1.45) (Z=-8.270, P<0.05). Conclusions The VNCa image with a Rel.CM value of 1.45 has a better diagnostic performance for traumatic bone marrow edema in knee joint. CT value measurement in VNCa image can be used for quantitative analysis of traumatic bone marrow edema.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma. Its pathological type mainly includes dif-fuse large B cell lymphoma. In MRI images, the condition is usually manifested as solitary deep lesions in brain parenchyma, with vari-ous forms of reinforcement. To date, chemotherapy based on high-dose methotrexate administration is the first-line therapy of PCNSL. Combined radiotherapy and chemotherapy can prolong the overall survival of patients. However, this approach simultaneously causes higher incidence of neurotoxicity. High-dose chemotherapy followed by autologous stem cell transplantation is recommended for re-current and refractory PCNSL. Temozolomide and rituximab can be used as treatment options because of their low toxicity and good tolerance. The prognosis of PCNSL depends on several factors, such as serum LDH concentration, age, ECOG/KPS score、cerebro-spi-nal fluid (CSF) protein concentration and tumor location.