Objective: Patients with severe symptomatic aortic stenosis are assessed for coronary artery disease (CAD) prior to transcatheter aortic valve implantation (TAVI) with treatment implications. Invasive coronary angiography (ICA) is the recommended modality but is associated with peri-procedural complications. Integrating machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) into existing TAVI-planning CT protocol may aid exclusion of significant CAD and thus avoiding ICA in selected patients. Materials and Methods: A single-center, retrospective study was conducted, 41 TAVI candidates with both TAVI-planning CT and ICA performed were analyzed. CT datasets were evaluated by a ML-based CT-FFR software. Beta-blocker and nitroglycerin were not administered in these patients. The primary outcome was to identify significant CAD. The diagnostic performance of CT-FFR was compared against ICA. Results: On per-patient level, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were 89%, 94%, 80%, 97% and 93%, respectively. On per-vessel level, the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 75%, 94%, 67%, 96% and 92%, respectively. The area under the receiver operative characteristics curve per individual coronary vessels yielded overall 0.90 (95% confidence interval 85%–95%). ICA may be avoided in up to 80% of patients if CT-FFR results were negative. Conclusion ML-based CT-FFR can provide accurate screening capabilities for significant CAD thus avoiding ICA. Its integration to existing TAVI-planning CT is feasible with the potential of improving the safety and efficiency of pre-TAVI CAD assessment.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis.Metods From January 2018 to December 2021,a multicenter randomized controlled study was per-formed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method.There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of(41.20±5.50)years old;the course of disease ranged from 1 to 14 days with an average of(5.24±1.35)days;they were treated once every other day for 2 weeks.There were 96 patients in control group,including 33 males and 63 females,aged from 26 to 60 years old with an average of(43.35±7.75)years old;the course of disease ranged from 1 to 14 days with an average of(5.86±1.48)days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks.Visual analogue scale(VAS)and Hospital for Surgery Scoring System(HSS)elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2(HSS2)was compared before treatment and the final treatment.Results All patients were followed up for 10 to 14 days with an average of(12±1.6)days.VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment.VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment.HSS of treatment group were signifi-cantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).On the 5th day after treat-ment,the external and internal rotation angles of elbow in treatment group were(66.41±12.69)° and(66.35±13.54)°,while those in control group were(62.08±16.03)° and(61.77±16.35)°.On the 7th day after treatment,the external and internal ro-tation angles of elbow were(69.79±12.64)° and(70.02±13.55)° in treatment group,and(65.28±15.86)° and(65.09± 16.67)° in control group.Elbow joint motion in treatment group was higher than that in control group(P＜0.05).On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were(39.43±15.94)°and(46.68±11.10)° in treatment group,and(38.51±18.49)° and(44.27±13.58)° in control group.On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were(42.52±16.50)° and(49.23±10.96)° in treatment group,and(41.18±20.09)° and(46.64±14.63)° in control group.The motion of wrist joint in treatment group was higher than that in control group(P＜0.05).On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P＜0.05).There was no significant difference in elbow tenderness between two groups at each time point(P＞0.05).Conclusion Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of exter-nal humeral epicondylitis.Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.

Objective:To investigate the effect of pre-treatment plasma Epstein-Barr virus(EBV)DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH).Methods:The clinical characteristics,survival rate,and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study.Patients were divided into three groups,including the EBV DNA-negative group(＜5.0 × 102 copies/ml),lower EBV-DNA loads group(5.0 × 102-8.51 × 104 copies/ml),and higher EBV-DNA loads group(＞8.51 × 104 copies/ml),according to pre-treatment plasma EBV-DNA copy number.Cox regression model was established for screening prognostic factors.Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index(C-index)and calibration curves were calculated to verify model predictive and discriminatory capacity.Results:Among 171 adult sHLH patients,84 patients were not infected with EBV(EBV DNA-negative group),and 87 with EBV(EBV DNA-positive group,48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group).Consistent elevations in the levels of liver enzymes(ALT and AST),LDH,TG,β2-microglobulin and ferritin across the increasing of EBV-DNA load(all P＜0.05),while the levels of fibrinogen decrease(P＜0.001).The median follow-up time was 52 days(range 20-230 days),and 123 patients died.The overall survival(OS)rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group(median OS:40 days vs 118 days,P＜0.001).Higher EBV-DNA loads had worse OS(median OS:24 days vs 45 days vs 118 days,P＜0.0001 for trend)compared to lower EBV-DNA loads and EBV DNA-negative group.Multivariate Cox analysis revealed that higher EBV-DNA loads(P=0.005),fibrinogen≤ 1.5 g/L(P=0.012),ferritin(P=0.041),associated lymphoma(P=0.002),and anti-tumor based strategy(P=0.001)were independent prognostic factors for OS.The C-indexes of 30 day,90 days,365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability.Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women,ferritin＞5 000 μg/L,β2-microglobulin＞7.4 mmol/L and regardless of age,etiologies,HScore points.Conclusion:The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH.The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.

OBJECTIVE: To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve. RESULTS: Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001). CONCLUSION Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.
Humans ; Lymphohistiocytosis, Hemophagocytic ; Clinical Relevance ; ROC Curve ; Sensitivity and Specificity ; Lupus Erythematosus, Systemic

Objective: Dysregulation of gene expression through epigenetic mechanisms may have a vital role in the pathogenesis of schizophrenia (SZ). In this study, we investigated the association of altered methylation patterns with SZ symptoms and early trauma in patients and healthy controls. Methods: The present study was conducted to identify methylation changes in CpG sites in peripheral blood associated with recent-onset (RO) psychosis using methylome-wide analysis. Lifestyle factors, such as smoking, alcohol, exercise, and diet, were controlled. Results: We identified 2,912 differentially methylated CpG sites in patients with RO psychosis compared to controls. Most of the genes associated with the top 20 differentially methylated sites had not been reported in previous methylation studies and were involved in apoptosis, autophagy, axonal growth, neuroinflammation, protein folding, etc. The top 15 significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways included the oxytocin signaling pathway, long-term depression pathway, axon guidance, endometrial cancer, long-term potentiation, mitogen-activated protein kinase signaling pathway, and glutamatergic pathway, among others. In the patient group, significant associations of novel methylated genes with early trauma and psychopathology were observed. Conclusion Our results suggest an association of differential DNA methylation with the pathophysiology of psychosis and early trauma. Blood DNA methylation signatures show promise as biomarkers of future psychosis.

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Dactinomycin/adverse effects* ; Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Methotrexate/therapeutic use* ; Pregnancy ; Retrospective Studies

Objective: To explore the distribution patterns of cardiometabolic diseases (CMD) in elderly patients with colorectal cancer, and provide a reference for the prevention and treatment of cardiovascular metabolic diseases in these patients. Methods: Clinical data of 3 894 elderly patients with colorectal cancer from January 2008 to March 2018 admitted in the Chinese PLA General Hospital were recruited and the incidence rate of CMD was retrospectively analyzed. The influence factors of elderly patients with colorectal cancer combined with CMD were analyzed by multivariate Logistic regression model. Results: The morbidity rate of CMD in elderly patients with colorectal cancer is 33.4% (1 301/3 894), among them, the morbidity rate of the male was 31.9% (768/2 409), and that of the female was 35.9% (533/1 485). There was not significant difference between these two sex (P=0.074). The morbidity rates of CMD in patients of 65-74 years, 75-84 years and ≥85 years were 30.6% (754/2 462), 37.0% (479/1 294) and 49.3% (68/138), respectively, with significant differences (P<0.001). Multiple Logistic regression analysis revealed that female (OR=1.213, 95%CI: 1.056-1.394), age (75-84 years group: OR=1.344, 95%CI: 1.164-1.552; ≥85 years group: OR=2.345, 95%CI: 1.651-3.331) and body mass index (BMI 18.5-24.9 kg/m(2) group: OR=1.319, 95%CI: 1.065-1.638; ≥25 kg/m(2) group: OR=2.041, 95%CI: 1.627-2.561) were independent risk factors for elderly colorectal cancer patients with CMD. Conclusion: The morbidity rate of CMD in elderly patients with colorectal cancer increases with age and it is urgent to strengthen multidisciplinary cooperation and develop reasonable treatment plans to extend the survival and life quality of these patients.
Aged ; Aged, 80 and over ; Cardiovascular Diseases ; China/epidemiology* ; Colorectal Neoplasms ; Female ; Humans ; Male ; Retrospective Studies ; Risk Factors

Objective: To investigate the relationship between nutritional risk status and clinical outcome in children with tuberculous meningitis (TBM). Methods: The clinical data (basic information, clinical symptoms and laboratory test results) of 112 patients with TBM, who were admitted to Department of Pediatric Infectious Diseases of West China Second Hospital of Sichuan University,from January 2013 to December 2020 were retrospectively analyzed. The patients were divided into the nutritional risk group and the non-nutritional risk group according to the assessment of the nutritional risk by the STRONGkids Scale. The variables of basic information, clinical symptoms and laboratory test measurements etc. were compared between the two groups by using Student t test, Rank sum test or Chi-square test. Multivariate Logistic regression analysis were used to analyze nutritional risk factors. Results: Among 112 patient with TBM, 55 were males and 57 females. There were 62 cases in the nutritional risk group and 50 cases in the non-nutritional risk group. The proportion of cases with nutritional risk was 55.4% (62/112). Patients in the nutritional risk who lived in rural areas, had symptoms of brain nerve damage, convulsions, emaciation and anorexia, with a diagnosis time of ≥21 days, and the level of cerebrospinal fluid (CSF) protein were all higher than those in the non-nutritional risk group ((50 cases (80.6%) vs. 32 cases (64.0%), 20 cases (32.3%) vs.8 cases (16.0%), 33 cases (53.2%) vs. 15 cases (30.0%), 30 cases (48.4%) vs. 2 cases (4.0%), 59 cases (95.2%) vs. 1 case (2.0%),41 cases (66.1%) vs.18 cases (36.0%), 1 406 (1 079, 2 068) vs. 929 (683, 1 208) mg/L, χ²=3.91, 3.90, 6.10, 26.72, 98.58, 10.08, Z=4.35, all P<0.05). The levels of serum albumin,hemoglobin,lymphocyte count, white blood cell count, and CSF glucose were significantly lower in patients with nutritional risk ((36±5) vs. (41±4) g/L, (110±17) vs. (122±14) g/L, 1.4 (1.0, 2.0)vs. 2.3 (1.6, 3.8)×10⁹/L, 7.8 (6.3, 10.0)×10⁹ vs. 10.0 (8.3, 12.8)×10⁹/L, 1.0 (0.8, 1.6) vs. 2.1 (1.3, 2.5) mmol/L, t=-6.15, -4.22, Z=-4.86, -3.92, -4.16, all P<0.05).Increased levels of serum albumin (OR=0.812, 95%CI:0.705-0.935, P=0.004) and lymphocyte count (OR=0.609, 95%CI:0.383-0.970, P=0.037) may reduce the nutritional risk of children with TBM; while convulsions (OR=3.853, 95%CI:1.116-13.308, P=0.033) and increased level of CSF protein (OR=1.001,95%CI:1.000-1.002, P=0.015) may increase the nutritional risk of children with TBM. Similarly, the rate of complications and drug-induced liver injury was higher in the nutritional risk group (47 cases (75.8%) vs. 15 cases(30.0%), 31 cases (50.0%) vs.8 cases (16.0%), χ²=23.50, 14.10, all P<0.05). Moreover, the length of hospital stay was also longer in the nutritional risk group ((27±13) vs. (18±7) d, t=4.38, P<0.05). Conclusions: Children with TBM have a high incidence of nutritional risk. Convulsive, the level of serum albumin, the level of lymphocyte count and CSF protein may affect the nutritional risk of children with TBM. The nutritional risk group has a high incidence of complications and heavy economic burden.It is necessary to carry out nutritional screening and nutritional support for children with TBM as early as possible.
Female ; Humans ; Leukocyte Count ; Male ; Nutrition Assessment ; Nutritional Status ; Retrospective Studies ; Tuberculosis, Meningeal/diagnosis*