Objective:This study examines the application of echocardiography in the prenatal diagnosis of copy number variation (CNV) associated with fetal congenital heart disease (CHD).Methods:A retrospective analysis was conducted on 447 singleton pregnancies from Quanzhou Maternal and Child Care Hospital (Quanzhou Children's Hospital) from January 2019 to August 2022. These individuals underwent echocardiographic assessments suggestive of fetal CHD and subsequently received invasive prenatal diagnoses. Comprehensive karyotype analysis and chromosome microarray analysis (CMA) were performed for each case. The discrepancies in the chromosomal abnormality detection were analyzed between the results produced by CMA and karyotype analysis. Furthermore, differences in the detection of pathogenic copy number variation (pCNV) between the two methods in CHD cases with diverse cardiac phenotypes, including the presence or absence of extracardiac structural malformations, the type, and quantity of cardiac structural anomalies, were explored. Statistical analysis was conducted using the Chi-square test. Results:Compared with conventional karyotype analysis, CMA demonstrated a higher detection rate of fetal chromosomal abnormalities [10.5% (47/447) vs. 20.6% (92/447), χ 2=161.56, P<0.001]. In terms of distinct cardiac phenotypes, CHD cases with extracardiac structural anomalies displayed an escalated pCNV detection rate in comparison to isolated CHD cases [11.4% (45/394) vs. 32.1% (17/53), χ 2=16.68, P<0.001]. Within the cardiac structural anomaly subgroups, increased pCNV detection rates were observed in the septal defect subgroup, conotruncal malformation subgroup, and left ventricular malformation subgroup [18.4%(29/158), 25.9%(7/27), and 25.0%(7/28) vs. 7.6%(16/210); χ 2=9.15, 9.68, and 8.55, respectively, all P<0.05]. The CMA-identified pCNV correlated with CHD included 22q11.2 deletions/duplications in eight cases, 4p16.3 deletions in two cases, 11q23.3 microduplications in two cases, 1q21.1 microdeletions/microduplications in two cases, 4q28.3 microduplications in one case, and 10p15.3 microdeletions in one case. Conclusions:CMA technology exhibited an enhanced ability to detect pCNV in fetuses with CHD. Echocardiography can guide targeted CMA screening, thereby facilitating prenatal genetic assessment of CHD.

Objective:To investigate the application value of metagenomic next-genera-tion sequencing (mNGS) in pathogenic diagnosis of suspected infected severe acute pancreatitis (SAP).Methods:The prospective study was conducted. The clinical data of 25 patients with suspected infected SAP who were admitted to the Xiangya Hospital of Central South University from May to September 2023 were collected. Upper limb venous blood samples of all the patients were collected for both of mNGS and routine pathogen microbial culture. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture; (3) results of peripheral blood pathogen microbial testing and peri-pancreatic effusion microbial culture; (4) testing time and cost. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 25 patients were selected for eligibility. There were 18 males and 7 females, aged 48(40,59)years. The duration of hospital stay of 25 patients was 30(20,50)days. The etiologies of 25 patients included 14 cases of hyperlipidemic pancreatitis, 8 cases of biliary pancreatitis, 1 case of alcohol-induced acute pancreatitis, and 2 cases of pancreatitis caused by other causes. Of the 25 patients, there were 17 cases with infected pancreatic necrosis (IPN) including 7 cases of death, and 8 cases with sterile pancreatic necrosis including no death. (2) Comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture. The positive rates of mNGS and routine pathogen microbial culture in diagnosis of suspected infected SAP were 72.0%(18/25) and 32.0%(8/25), respectively, showing a significant difference between them ( χ2=8.01, P<0.05). The sensitivity and negative predic-tive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 94.1%(16/17), 35.3%(6/17) and 85.7%(6/7), 35.3%(6/17), showing significant differences between them ( χ2=12.88, 5.04, P<0.05). The specificity and positive predictive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 75.0%(6/8), 75.0%(6/8) and 88.9%(16/18), 75.0%(6/8), showing no significant difference between them ( χ2=0, 0.82, P>0.05). (3) Results of peripheral blood pathogen microbial testing and peripancreatic effusion microbial culture. Of the 17 patients with IPN, 36 strains of pathogenic bacteria were detected by mNGS, and 6 strains were detected by routine pathogen microbial culture. There were 16 of 17 patients with IPN showing positive mNGS pathogenic testing, of which 13 cases were consistent with the pathogenic testing results of peri-pancreatic effusion microbial culture, showing a consistency rate of 76.5%(13/17). There were 6 pati-ents with IPN showing positive routine pathogen microbial culture, with a consistency rate of 35.3%(6/17) to peripancreatic effusion microbial culture. (4) Testing time and cost. Testing time of mNGS and routine pathogen microbial culture were (43±17)hours and (111±36)hours, showing a signifi-cant difference between them ( t=9.31, P<0.05). Testing cost of mNGS was (2 267±0)yuan/case, accoun-ting for 1.7% of the hospitalization expenses of (133 759±120 744)yuan/case. Testing cost of routine pathogen microbial culture was (240±0)yuan/case, accounting of 0.2% of the hospitalization expenses. Conclusion:mNGS has important value for early pathogenic diagnosis of suspected infected SAP, and has a high timeliness.

African swine fever virus(ASFV)I177L gene deletion vaccine is one of the key directions of African swine fever(ASF)live attenuated vaccine research and development.In order to effec-tively distinguish between the wild-type ASFV strain and the I177L gene-deleted strain,specific primers and probes were designed based on ASFV B646L and I177L genes,respectively.After screening and optimization,a duplex real-time PCR method was developed that can simultaneously detect these two genes.The results showed that ASFV B646L and I177L genes were detected spe-cifically and simultaneously by the method developed without cross-reactions with porcine circovir-us type 2,Seneca virus A,classical swine fever virus,foot-and-mouth disease virus,porcine respira-tory and reproductive syndrome virus.The detection limits of the duplex real-time PCR for recom-binant plasmids pUC57-B646L and pUC57-I177L were 1×103 copies/mL.The intra-and inter-as-say coefficients of variation were less than 4％,respectively.Detection of 122 pork and pork prod-ucts using the duplex real-time PCR developed and the real-time PCR recommended by WOAH showed that the coincidence rates of the two methods for B646L gene detection was 100％with two amplification curves appeared in the positive results of the established methods.The method established in this study can be used for the detection of ASFV I177L gene deletion strains,which provides technical support for ASF surveillance and epidemiological investigation.

Background and Aims:Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis(IPN)patients.However,there is currently a lack of efficient methods for early identification of IPN in clinical settings.This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture(MetaCAP)in the pathogen diagnosis of IPN. Methods:A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024.Blood samples were tested using MetaCAP and conventional pathogen culture.The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods. Results:Due to three cases lacking peritoneal fluid culture results,a total of 26 cases were included in the final analysis.The overall mortality rate was 23.1％(6/26).During hospitalization,9 cases(34.6％)were diagnosed with IPN.The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture(77.8％vs.11.1％,P=0.031;86.7％vs.65.2％,P=0.032),while the differences in specificity(76.5％vs.88.2％,P=0.689)and positive predictive value(63.6％vs.33.3％,P=0.347)between the two methods were not statistically significant.The average detection time for MetaCAP was 33(20-49)h,while microbial culture took 125(45-142)h,with a significant difference(P＜0.001).The average cost for blood MetaCAP testing was 2 500 yuan per case,but it accounted for only 1.19％of the average hospitalization cost. Conclusion:MetaCAP has significant value in the early pathogen diagnosis of IPN,with a shorter detection time,good testing efficacy,and health-economic value,demonstrating a promising clinical application prospect.

Objective:To explore the association between child abuse and suicidal ideation in patients with bi-polar disorder.The mediation of self-esteem and depression in this association was also investigated.Methods:A to-tal of 292 patients with bipolar disorder who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were enrolled.Their child abuse,suicidal ideation,self-esteem,depres-sion,and mania were assessed with the Childhood Trauma Questionnaire(CTQ),Beck Scale for Suicide Ideation-Chinese Version(BSICV),Self-Esteem Scale(SES),17-item Hamilton Depression Rating Scale(HAMD-17)and Young Mania Rating Scale(YMRS).The mediating effects were evaluated using PROCESS for SPSS.Results:The BSICV scores were positively associated with the scores of CTQ(r=0.37,P＜0.01)and HAMD-17(r=0.53,P＜0.01)and negatively associated with SES scores(r=-0.50,P＜0.01)in patients with bipolar disorder.Self-esteem and depression played mediating roles between child abuse and suicidal ideation,respectively(95％CI:0.01-0.09,0.01-0.10).Besides,self-esteem and depression sequentially mediated the relationship between child a-buse and suicidal ideation(95％CI:0.02-0.06).Conclusion:Child abuse,low self-esteem,and depression may be related factors of suicidal ideation in patients with bipolar disorder.

Objective:To analyze clinical characteristics and high-frequency ultrasound features of localized scleroderma, and to construct and validate a non-invasive prediction model for staging of skin lesions based on the high-frequency ultrasound features.Methods:Patients with localized scleroderma were retrospectively collected from the Department of Dermatology and Venereology, Second Xiangya Hospital of Central South University from February 1, 2021 to February 28, 2023, and clinical data as well as high-frequency ultrasound and pathologic features of 85 lesions from these patients were analyzed. Lesions were divided into modeling cohort and validation cohort according to the chronological order of patient enrollment. The univariate analysis and multivariable logistic regression models were used to analyze the independent influential factors in the staging of localized scleroderma lesions in the modeling cohort, construct the regression equation, and to build a nomogram prediction model. The Bootstrap validation method was used for internal validation, and the predictive performance of the nomogram model in the modeling cohort and validation cohort was further evaluated by the calibration curve and receiver operating characteristic (ROC) curve.Results:In the modeling cohort, 60 patients with localized scleroderma, including 16 males and 44 females, were enrolled, with the age [ M ( Q1, Q3) ] being 22.0 (10.0, 39.2) years, and there were 28 lesions in the oedematous phase and 32 lesions in the fibrotic and atrophic phase; in the validation cohort, 25 patients with localized scleroderma, including 8 males and 17 females, were enrolled, with the age being 18.0 (7.0, 30.0) years, and there were 9 lesions in the oedematous phase and 16 lesions in the fibrotic and atrophic phase. Univariate analysis in the modeling cohort showed no significant differences in the age and gender of patients or the location of lesions between the oedematous phase group and the fibrotic and atrophic phase group (all P > 0.05) ; compared with the oedematous phase group, the fibrotic and atrophic phase group showed an increased proportion of patients with disease duration ≥ 2 years (20/32 cases vs. 10/28 cases, χ2 = 4.29, P = 0.038), decreased thicknesses of the subcutaneous fat layer in skin lesions (1.4 [0.0, 26.0] mm vs. 1.8 [0.1, 14.3] mm, Z = -2.14, P = 0.032), increased decrements in the subcutaneous fat layer thickness in the lesional sites compared with non-lesional control sites (1.8 [0.5, 11.0] vs. 0.3 [-1.9, 8.0] mm, Z = -4.72, P < 0.001), increased ratios of the lesional elasticity values to control elasticity values (2.9 [1.8, 6.9] vs. 1.8 [1.1, 5.9], Z = -4.34, P < 0.001), and increased ultrasound-based lesional activity scores (5.0 [3.0, 8.0] points vs. 3.0 [0.0, 5.0] points, Z = -4.76, P < 0.001). Multivariable logistic stepwise regression analysis showed that the disease duration ≥ 2 years ( P = 0.032), increased ratios of the lesional elasticity values to control elasticity values ( P = 0.019), increased ultrasound-based lesional activity scores ( P = 0.013), and increased decrements in the subcutaneous fat layer thickness in the lesions compared with the controls ( P = 0.013) helped to confirm localized scleroderma lesions in the fibrotic and atrophic phase. Based on the results of regression analysis, a total of 4 factors were included in the nomogram prediction model, including the disease duration, the decrement in the subcutaneous fat layer thickness in lesions compared with controls, the ratio of the lesional elasticity values to control elasticity values, and the ultrasound-based lesional activity score; additionally, the constructed logistic regression model formula for predicting the probability (p) of skin lesions in fibrotic and atrophic phase was "ln (p/[1 - p]) = -9.595 + 2.204 × the disease duration + 0.784 × the decrement in the subcutaneous fat layer thickness in the lesions compared with the controls (mm) + 0.887 × the ratio of the lesional elasticity values to control elasticity values + 1.374 × the ultrasound-based lesional activity score". The calibration curve showed a good predictive performance of the model through the Bootstrap validation method, and the ROC curve demonstrated good discrimination and accuracy (modeling cohort: area under the curve = 0.936, 95% CI: 0.879 - 0.994; validation cohort: area under the curve = 0.889, 95% CI: 0.748 - 1.000) . Conclusions:High-frequency ultrasound could provide essential details for staging the localized scleroderma lesions. Based on the disease duration, subcutaneous fat layer thickness, skin elasticity values, and ultrasound-based lesional activity scores, the constructed prediction model could predict the stages of localized scleroderma lesions with excellent discrimination, accuracy, and predictive performance.

Objective:To investigate the expressions of MUC1, MUC4, MUC5AC and MUC16 in patients with first diagnosis of dry eye and their correlation with dry eye symptoms and signs.Methods:A cross-sectional study was conducted.Sixty-nine dry eye patients (69 eyes) as dry eye group and 40 normal volunteers (40 eyes) as normal control group were recruited in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Puotuo District Center Hospital from December 2016 to May 2018.Symptoms were evaluated by Chinese dry eye questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-Life Score Questionnaire (DEQS). Signs were assessed by tear film breakup time (TBUT), keratoconjunctival fluorescein sodium staining, and Schirmer I test.Conjunctival cells were collected by conjunctival impression cytology.The expression levels of MUC1, MUC4, MUC5AC and MUC16 mRNA in the two groups were determined by real-time fluorescence quantitative PCR.The correlation between the mRNA levels of conjunctival mucins and dry eye symptoms and signs were analyzed by Spearman correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Puotuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from each subject before any medical examination.Results:The expression levels of MUC1 and MUC16 mRNA in dry eye patients were 3.277(0.568, 5.790) and 1.815(1.048, 3.694), which were higher than 1.055(0.550, 2.010) and 1.024(0.541, 1.965) in normal control group (Z=819.00, P=0.008; Z=861.00, P=0.002). According to OSDI scores, MUC1 was mainly increased to 3.277(1.161, 6.226) in mild to moderate (12-32 points) dry eye patients (Z=9.04, P=0.029), and MUC16 was mainly increased to 1.968(1.074, 3.726) in severe (>32 points) dry eye patients (Z=12.24, P=0.007). MUC1 expression was positively correlated with TBUT, and was negatively correlated with corneal staining scoring and keratoconjunctival staining scoring ( r s=0.270, P=0.025; r s=-0.331, P=0.006; r s=-0.325, P=0.007). MUC16 expression was positively correlated with TBUT, and was negatively correlated with blurred vision scoring, symptom exacerbation scoring during reading, impact scoring of driving at night, impact scoring of computer and impact scoring of TV use ( r s=0.249, P=0.039; r s=-0.359, P=0.047; r s=-0.370, P=0.034; r s=-0.558, P=0.016; r s=-0.498, P=0.006; rs=-0.515, P=0.002). Conclusions:The gene expressions of MUC1 and MUC16 are higher in conjunctiva of dry eye patients.MUC1 mRNA expression is related to patients' signs.MUC16 mRNA expression is related to the quality of life of patients.

Objective:To analyze the clinical manifestations and signs of the first diagnosed dry eye patients, and to explore the concordance between the Chinese dry eye diagnostic criteria and the Asian dry eye diagnostic criteria.Methods:A cross-sectional multicenter study was conducted.One hundred and forty-one eyes of 141 patients who were diagnosed as dry eye for the first time were included in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Putuo District Center Hospital from December 2016 to May 2018.All patients completed the Chinese Dry Eye Questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) to evaluate the symptoms of dry eye.Tear film breakup time (BUT), keratoconjunctival fluorescein staining, meibomian gland morphology and function examination, and Schirmer Ⅰ test were performed to evaluate dry eye signs and the association between dry eye symptoms and signs.The eyes were divided into corneal staining positive and negative group according to the presence or absence of corneal fluorescein staining, and the dry eye symptoms of the two groups were assessed by the three questionnaires.The eyes were divided into tear-deficient dry eye, evaporative dry eye, mixed dry eye and abnormal tear dynamics dry eye to compare the difference of dry eye signs among the groups.This study adhered to the Declaration of Helsinki.The study protocol complied with Chinese regulations and rules on clinical trial research and was approved by Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Putuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from patients before entering the cohort.Results:The total score of Chinese Dry Eye Questionnaire, OSDI questionnaire and DEQS questionnaire was 12.00(7.00, 16.00), 25.00(17.50, 36.93) and 32.02(15.77, 52.34), respectively.It was found that 130 eyes (92.2%) had dryness, and 109 eyes (77.3%) had ocular fatigue and 108 eyes (76.6%) had foreign body sensation.Dryness, foreign body sensation, photophobia and poor vision were weakly positively correlated with corneal staining ( r=0.177、0.297、0.172, all at P<0.05). Pain, photophobia and poor vision were negatively correlated with tear secretion ( r=-0.178, -0.197, -0.174; all at P<0.05). It was found that 43.3% of dry eye patients had used visual display terminals.Among the 141 eyes, 75 eyes (53.2%) were with over evaporation dry eye, 43 eyes (30.5%) with mixed dry eye, 18 eyes (12.8%) with aqueous-deficient dry eye and 3 eyes (2.1%) with abnormal tear dynamics dry eyes. Conclusions:Initial diagnosis of dry eye patients is mainly mild to moderate.Dry eye signs and symptoms are correlated.Over evaporation dry eye is the most common type of dry eye.The concordance between the Chinese dry eye diagnostic criteria and the Asian Dry Eye Society diagnostic criteria reaches 97.2%.

Psoriatic arthritis is a chronic systemic autoimmune disease, characterized by psoriasis skin lesions and inflammation of the spine and joint. It has complicated clinical manifestations and individual variations. Nearly half of the patients will have joints erosion in two years, which is crippling. The severity of the skin and joint disease frequently do not correlate with each other. Currently, the understanding of the disease is insufficient in China with the lack of standardized diagnosis and treatment. Therefore, researchers from the Chinese Rheumatology Association formulated this specification based on the diagnosis and management experience together with guidelines at home and abroad. The specification summarizes the present situation of domestic diagnosis and treatment, aiming to standardize the diagnosis process and treatment protocols of psoriatic arthritis. Furthermore, it can reduce misdiagnosis and missed diagnosis, as well as improve the prognosis.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics and differential diagnosis of primary skull base chondrosarcoma.Methods:Nine cases of primary skull base chondrosarcoma were collected at the First Affiliated Hospital of Fujian Medical University, from January 2006 to June 2019, reviewed for the clinical and radiologic data and morphologic features, immunophenotype and molecular characteristics.Results:Among all the 9 cases, six were male, three were frmale, with average age 47 years, and median age 47 years; five cases were WHO gradeⅠ, and four were WHO grade Ⅱ. Microscopically, the tumor showed lobulated growth pattern with low-medium cellularity within a chondroid or mucoid background. The tumor cells showed mild-moderate atypia, with binucleated forms, and mitosis was rare or occasional. Immunohistochemistry (IHC) showed tumor cells were positive for S-100 protein, vimentin, SOX-9 and D2-40, and negative for Brachyury, CK, EMA and CK8/18; the Ki-67 index was low (1% to 5%). Molecular analysis showed IDH1 R132C mutation in four cases.Conclusions:Skull base chondrosarcoma is a rare cartilaginous malignant tumor with a good prognosis. Its characteristic morphologies, combined with IHC and molecular detection are helpful for the differential diagnosis.