N-3 PUFA supplementation alleviates anxiety symptoms by manipulating erythrocyte fatty acid levels in depression.

PURPOSE: Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels. METHODS: A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression. RESULTS: Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ2 = 96.36, p = 0.000). The n-3 index (χ2 = 10.59, p = 0.001), EPA (χ2 = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ2 = 10.71, p = 0.001) were increased, while C22:4n6 (χ2 = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05). CONCLUSION: These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms.

Effect of propranolol on pharmacokinetics of clozapine in schizophrenic patients: a meta-analysis.

PURPOSE: Clozapine is the effective therapy for treatment-refractory schizophrenia. However, the use of clozapine is limited by its adverse effects. As propranolol is frequently used for the prevention and treatment of clozapine-induced tachycardia, we performed a meta-analysis to evaluate the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients. METHODS: We included 16 retrospective studies on the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients, with data from both generic and brand name treatment phases in eight clozapine bioequivalence studies conducted in a single center in China from 2018 to 2022. Review Manager 5.4 was used for meta-analysis of the included studies. RESULTS: The SMDs with 95% CIs of AUC0-12, Cmax,ss, C, and C were calculated to be 0.44 (0.23, 0.64), 0.40 (0.20, 0.61), 0.43 (0.22, 0.63), and 0.44 (0.23, 0.64), respectively. These findings proved that combination with propranolol would increase the systemic exposure of clozapine. T1/2 of clozapine was significantly longer in the presence of propranolol than in the absence of propranolol (SMD = 0.32, 95% CI [0.12, 0.52], p = 0.002). There was no statistically significant difference for T of clozapine in the presence or absence of propranolol (SMD = - 0.05, 95% CI [- 0.25, 0.15], p = 0.63). CONCLUSION: The combination with propranolol could significantly increase systemic exposure and extended T1/2 of clozapine, and thus need to be considered in prescribing decisions.

Association of childhood trauma, social support, cognition, and suicidality in females with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe mental disorder with heavy disease burden. Females with BD are special populations who suffer a lot from childhood trauma, social support, cognitive deficits, and suicidality. In this study, the relationship among childhood trauma, social support, and clinical symptoms of BD was investigated and the risk factors for suicidality were explored in female patients with BD. METHODS: This study included 57 drug-naive female BD patients, 64 female BD patients with long-term medication, and 50 age-matched female healthy controls. Childhood trauma, social support, clinical symptoms, cognition, and suicidality (suicide ideation, suicide plan, suicide attempt, suicide frequency) were measured with scales. RESULTS: Compared with healthy controls, females with BD showed higher levels of childhood trauma and suicidality, and lower levels of social support and cognitive deficits. In the drug-naïve BD group, social support mediated the relationship between childhood trauma and insomnia symptoms (indirect effect: ab = 0.025). In the BD with long-term medication group, mania symptom was associated with suicide plan (OR = 1.127, p = 0.030), childhood trauma was associated with suicide attempt (OR = 1.088, p = 0.018), and years of education (OR = 0.773, p = 0.028), childhood trauma (OR = 1.059, p = 0.009), and delayed memory (OR= 1.091, p= 0.016) was associated with suicide frequency (OR = 1.091, p = 0.016). CONCLUSIONS: This study provides initial evidence that social support partially explains the relationship between childhood trauma and clinical symptoms in females with BD. Additionally, mania symptoms, childhood trauma, and delayed memory were risk factors for suicidality. Interventions providing social support and improving cognitive function may be beneficial for females with BD who are exposed to childhood trauma and with high suicide risk.

Association among abnormal glycolipids, reproductive hormones, and cognitive dysfunction in female patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition. METHODS: A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test). RESULTS: Patients with BD showed significant cognitive impairment (p < 0.05), which was not affected by medication. Triglycerides (TG), luteinizing hormone (LH), and high-density lipoprotein cholesterol (HDL-c) were altered in stable-medicated BD patients. In addition, regression analysis showed that progesterone (PRGE) and prolactin (PRL) were negatively associated with cognitive performance in stable-medicated BD patients. CONCLUSIONS: Female BD patients may have cognitive deficits and abnormal levels of glycolipids and reproductive hormones. And abnormal levels of glycolipids and reproductive hormones may be associated with cognitive dysfunction in female BD patients.

Erythrocyte Membrane Fatty Acid Composition as a Potential Biomarker for Depression.

BACKGROUND: Major depressive disorders is a chronic and severe psychiatric disorder with poor prognosis and quality of life. Abnormal erythrocyte fatty acid (FA) composition in depressed patients were found in our previous study, but the relationship between erythrocyte membrane FA levels and different severity of depressive and anxiety symptoms remains to be explored. METHODS: This cross-sectional study included 139 patients with first-diagnosed, drug-naïve depression and 55 healthy controls whose erythrocyte FA composition was analyzed. Patients with depression were divided into severe depression and mild to moderate depression or depression with severe anxiety and mild to moderate anxiety. Then the differences of FA levels among different groups were analyzed. Finally, the receiver operating characteristic curve analysis was applied to identify potential biomarkers in distinguishing the severity of depressive symptoms. RESULTS: Levels of erythrocyte membrane FAs were elevated among patients with severe depression compared with healthy controls or patients with mild to moderate depression of almost all kinds. While C18:1n9t (elaidic acid), C20:3n6 (eicosatrienoic acid), C20:4n6 (arachidonic acid), C22:5n3 (docosapentaenoic acid), total fatty acids (FAs), and total monounsaturated FAs were elevated in patients with severe anxiety compared with patients with mild to moderate anxiety. Furthermore, the level of arachidonic acid, C22:4n6 (docosatetraenoic acid), elaidic acid, and the combination of all 3 were associated with the severity of depressive symptoms. CONCLUSIONS: The results suggested that erythrocyte membrane FA levels have the potential to be the biological indicator of clinical characteristics for depression, such as depressive symptoms and anxiety. In the future, more research is needed to explore the causal association between FA metabolism and depression.

Risk factors for osteoporosis in chronic schizophrenia on long-term treatment with antipsychotics: a cross-sectional study.

BACKGROUND: Little is known about the laboratory variable risks with bone mineral density (BMD) in patients with schizophrenia. This study was designed to fully investigate the related risk factors for decreased BMD in schizophrenia, as well as evaluate the gender difference of BMD. METHOD: The BMD of the forearm of 211 patients (males/females = 140/71) who met the diagnostic criteria for DSM-5 schizophrenia was measured by dual-energy X-ray absorptiometry. Basic demographic information, clinical assessments, and laboratory variables (regarding nutrition, hormones, metabolism, and inflammatory markers) were comprehensively collected. RESULTS: Among 211 subjects, seventy-four (35%) patients had low BMD. Males had a significantly lower BMD T-score than females (P = 0.002). Multiple regression analyses showed that the independent risks with low BMD were lower folate, glycosylated hemoglobin levels, higher age, serum ferritin, and follicle-stimulating hormone (FSH) levels. In female patients, the BMD was mainly associated with age and serum hormones (FSH and testosterone), while the BMD of male patients was primarily related to age, microelements (serum ferritin and 25-OH-VD), and parathyroid hormone. CONCLUSION: Our study found several meaningful correlations between osteoporosis and schizophrenia, especially regarding laboratory measures, which may provide new clues to identifying or preventing osteoporosis in clinical patients.

Effectiveness and safety of blonanserin in young and middle-aged female patients with schizophrenia: data from a post-marketing surveillance.

BACKGROUND: A post-marketing surveillance of blonanserin has been ongoing since September 2018. The aim of this study was to assess the effectiveness and safety of oral blonanserin in Chinese young and middle-aged female patients with schizophrenia in real clinical settings, using the data from the post-marketing surveillance. METHODS: A 12-week, prospective, multi-center, open-label, post-marketing surveillance was conducted. Female patients aged 18-40 years were included in this analysis. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the effectiveness of blonanserin in improving psychiatric symptoms. The incidence of adverse drug reactions (ADRs) such as of extrapyramidal symptoms (EPS), prolactin elevation and the weight gain were used to evaluate the safety profile of blonanserin. RESULTS: A total of 392 patients were included both in the safety and full analysis sets, 311 patients completed the surveillance protocol. The BPRS total score was 48.8 ± 14.11 at the baseline, decreasing to 25.5 ± 7.56 at 12 weeks (P < 0.001, compared with baseline). EPS (20.2%) including akathisia, tremor, dystonia, and parkinsonism were found as the most frequent ADRs. The mean weight gain was 0.27 ± 2.5 kg at 12 weeks from the baseline. Four cases (1%) of prolactin elevation were observed during the period of surveillance. CONCLUSION: Blonanserin significantly improved the symptoms of schizophrenia in female patients aged 18-40 years; the drug was well tolerated and had a low tendency to cause metabolic side effects, including prolactin elevation in these patients. Blonanserin might be a reasonable drug for the treatment of schizophrenia in young and middle-aged female patients.

Safety and effectiveness of oral medium to high dose blonanserin in patients with schizophrenia: subgroup analysis from a prospective, multicenter, post-marketing surveillance study in mainland China.

BACKGROUND: Blonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ). METHODS: A 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions. RESULTS: 364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P < 0.001). When compared with other groups, the median to high dose group achieved significantly more reduction in BPRS score at week 12 (P = 0.004 versus low dose and P = 0.033 versus higher dose). Extrapyramidal symptoms [EPS (46.4%)] were the most common adverse reactions in the medium to high group. The average weight gain during the surveillance was 0.5 ± 2.56 kg and prolactin elevation occurred in 2.2% patients. Most adverse reactions were mild. CONCLUSIONS: BNS at medium to high doses (mean 15.1 mg/d) significantly improved symptoms of SZ and was well-tolerated. Most ADRs were mild, and the likelihood of causing metabolic side effects and prolactin elevations was low. Medium to high dose of BNS is a more potent treatment choice for SZ. TRIAL REGISTRATION NUMBER: ChiCTR2100048734. Date of registration: 2021/07/15 (retrospectively registered).

Ulinastatin inhibits the metastasis of nasopharyngeal carcinoma by involving uPA/uPAR signaling.

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.

LncRNA GAS5 Attenuates Cardiac Electrical Remodeling Induced by Rapid Pacing via the miR-27a-3p/HOXa10 Pathway.

Previous studies indicated long non-coding RNAs (lncRNAs) participated in the pathogenesis of atrial fibrillation (AF). However, little is known about the role of lncRNAs in AF-induced electrical remodeling. This study aimed to investigate the regulatory effect of lncRNA GAS5 (GAS5) on the electrical remodeling of neonatal rat cardiomyocytes (NRCMs) induced by rapid pacing (RP). RNA microarray analysis yielded reduced GAS5 level in NRCMs after RP. RT-qPCR, western blot, and immunofluorescence yielded downregulated levels of Nav1.5, Kv4.2, and Cav1.2 after RP, and whole-cell patch-clamp yielded decreased sodium, potassium, and calcium current. Overexpression of GAS5 attenuated electrical remodeling. Bioinformatics tool prediction analysis and dual luciferase reporter assay confirmed a direct negative regulatory effect for miR-27a-3p on lncRNA-GAS5 and HOXa10. Further analysis demonstrated that either miR-27a-3p overexpression or the knockdown of HOXa10 further downregulated Nav1.5, Kv4.2, and Cav1.2 expression. GAS5 overexpression antagonized such effects in Nav1.5 and Kv4.2 but not in Cav1.2. These results indicate that, in RP-treated NRCMs, GAS5 could restore Nav1.5 and Kv4.2 expression via the miR-27a-3p/HOXa10 pathway. However, the mechanism of GAS5 restoring Cav1.2 level remains unclear. Our study suggested that GAS5 regulated cardiac ion channels via the GAS5/miR-27a-3p/HOXa10 pathway and might be a potential therapeutic target for AF.

The role of the protein tyrosine phosphatase SHP2 in ossification.

SHP2, encoded by the PTPN11 gene, participates in multiple cell functions including cell proliferation, movement, and differentiation. PTPN11 loss-of-function and gain-of-function mutations are both associated with diseases, such as Noonan syndrome, whose manifestations include bone defects, suggesting a crucial role for SHP2 in the skeleton. However, the exact mechanisms by which SHP2 regulates bone development remain unclear. This review focuses on the current understanding of the regulation of SHP2 and highlights the vital roles of SHP2 in skeletal development, especially its roles in ossification. Overall, a better understanding of the functions of SHP2 in ossification will provide a new avenue to treat-related skeletal diseases.

An Enterprise Service Demand Classification Method Based on One-Dimensional Convolutional Neural Network with Cross-Entropy Loss and Enterprise Portrait.

To address the diverse needs of enterprise users and the cold-start issue of recommendation system, this paper proposes a quality-service demand classification method-1D-CNN-CrossEntorpyLoss, based on cross-entropy loss and one-dimensional convolutional neural network (1D-CNN) with the comprehensive enterprise quality portrait labels. The main idea of 1D-CNN-CrossEntorpyLoss is to use cross-entropy to minimize the loss of 1D-CNN model and enhance the performance of the enterprise quality-service demand classification. The transaction data of the enterprise quality-service platform are selected as the data source. Finally, the performance of 1D-CNN-CrossEntorpyLoss is compared with XGBoost, SVM, and logistic regression models. From the experimental results, it can be found that 1D-CNN-CrossEntorpyLoss has the best classification results with an accuracy of 72.44%. In addition, compared to the results without the enterprise-quality portrait, the enterprise-quality portrait improves the accuracy and recall of 1D-CNN-CrossEntorpyLoss model. It is also verified that the enterprise-quality portrait can further improve the classification ability of enterprise quality-service demand, and 1D-CNN-CrossEntorpyLoss is better than other classification methods, which can improve the precision service of the comprehensive quality service platform for MSMEs.

Intense d-p Hybridization in Nb3 O15 Tripolymer Induced the Largest Second Harmonic Generation Response and Birefringence in Germanates.

We herein report two asymmetric germanate crystals, KNbGe3 O9 and K3 Nb3 Ge2 O13 , with different structures and optical properties derived from divergent polymerized forms of GeO4 and NbO6 groups. Remarkably, K3 Nb3 Ge2 O13 achieved a rare combination of the strongest second harmonic generation (SHG) response of 17.5×KDP @ 1064 nm and the largest birefringence of 0.196 @ 546 nm in germanates. It features unique [Nb3 O12 ]∞ tubular chains constructed by circular Nb3 O15 tripolymers. Theoretical calculations reveal that the d-p interactions in the Nb3 O15 group are responsible for outstanding optical properties. This work emphasizes the significance of the polymerizable functional units in obtaining high-performance nonlinear optical (NLO) crystals.

PBRM1 deficiency oncogenic addiction is associated with activated AKT-mTOR signalling and aerobic glycolysis in clear cell renal cell carcinoma cells.

The PBRM1 (PB1) gene which encodes the specific subunit BAF180 of the PBAF SWI/SNF complex, is highly mutated (~ 40%) in clear cell renal cell carcinoma (ccRCC). However, its functions and impact on cell signalling are still not fully understood. Aerobic glycolysis, also known as the 'Warburg Effect', is a hallmark of cancer, whether PB1 is involved in this metabolic shift in clear cell renal cell carcinoma remains unclear. Here, with established stable knockdown PB1 cell lines, we performed functional assays to access the effects on 786-O and SN12C cells. Based on the RNA-seq data, we selected some genes encoding key glycolytic enzymes, including PFKP, ENO1, PKM and LDHA, and examined the expression levels. The AKT-mTOR signalling pathway activity and expression of HIF1α were also analysed. Our data demonstrate that PB1 deficiency promotes the proliferation, migration, Xenograft growth of 786-O and SN12C cells. Notably, knockdown of PB1 activates AKT-mTOR signalling and increases the expression of key glycolytic enzymes at both mRNA and protein levels. Furthermore, we provide evidence that deficient PB1 and hypoxic conditions exert a synergistic effect on HIF 1α expression and lactate production. Thus, our study provides novel insights into the roles of tumour suppressor PB1 and suggests that the AKT-mTOR signalling pathway, as well as glycolysis, is a potential drug target for ccRCC patients with deficient PB1.

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2.

BACKGROUND: The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. METHODS: We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds. RESULTS: We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2. CONCLUSION: This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

Evaluation of nuclear PGAM2 value in hepatocellular carcinoma prognosis.

Phosphoglycerate mutase (PGAM) is a critical enzyme in glycolysis. PGAM2 is abundant in several types of tissues and malignant tumours. However, there is limited information regarding their clinicopathological significance in dysplastic nodules and hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of PGAM2 as a new biomarker for HCC. The PGAM2 expression level was evaluated by immunohistochemistry in liver cirrhosis (n = 10), low-grade dysplastic nodules (n = 15), high-grade dysplastic nodules (n = 15) and HCCs (n = 20) and 178 pairs of HCC and adjacent peritumoral liver tissues. We selected X-tile software for counting cut-point based on the outcomes for prognosis analysis, and used Kaplan-Meier analysis and Cox regression analysis can assess the prognosis of clinicopathologic parameters. Nuclear PGAM2 was significantly overexpressed in peritumoral liver tissues compared with HCC tissues (P = 0.0010). Kaplan-Meier analyses of 178 HCC samples revealed that nuclear PGAM2's high expression level, but not cytoplasmic PGAM2, was significantly related to good overall survival rate (OS). In addition, univariate and multivariate Cox analyses indicated nuclear PGAM2 expression could be regarded as valuable predictors for OS in HCC. PGAM2 was highly expressed in HCC tissues than liver cirrhosis tissues, and nuclear PGAM2's high expression might demonstrate HCC patients have poor postoperative results. Thus, nuclear PGAM2 can be regarded as valuable predictors for OS in HCC patients after surgery.

Risk factors for left atrial thrombus or spontaneous echo contrast in non-valvular atrial fibrillation patients with low CHA2DS2-VASc score.

OBJECTIVE: Risk factors of left atrial thrombus (LAT) or spontaneous echo contrast (LASEC) in non-valvular atrial fibrillation (NVAF) had been reported. However, information in the subgroup of NVAF patients with low CHA2DS2-VASc scores was limited. Here, we evaluated the risk factors of LAT/LASEC in NVAF patients with low CHA2DS2-VASc scores. METHODS: Transesophageal echocardiography (TEE) file of NVAF patients with low CHA2DS2-VASc scores was reviewed (between June 2009 and Feb 2019) in this retrospective observational study. Binary logistic regression analysis was performed to identify risk factors other than the CHA2DS2-VASc score. Propensity score matching (PSM) was used to further evaluate independent risk markers for LAT/LASEC. The newly discovered factors were added to the CHA2DS2-VASc score, and receiver operating characteristic analysis was used to evaluate the ability of the model to predict LAT/LASEC. RESULTS: TEE files of 3056 NVAF patients with low CHA2DS2-VASc scores were reviewed. Regression analysis revealed elevated fibrinogen and enlarged left atrium (LA) were risk factors for LAT/LASEC. Further PSM analysis confirmed that elevated fibrinogen and enlarged LA were independent risk factors for LAT/LASEC. After including fibrinogen and left atrial diameter (LAD), the CHA2DS2-VASc score was more accurate for LAT/LASEC prediction in NVAF patients with low CHA2DS2-VASc scores (area under the curve difference is 0.241, 95% confidence interval (CI) 0.188-0.294, Z = 8.890, P < 0.0001). CONCLUSIONS: Elevated fibrinogen and enlarged LA were independent risk factors for LAT/LASEC in NVAF patients with low CHA2DS2-VASc scores. Taking fibrinogen and LAD into consideration may help improve LAT/LASEC risk evaluation, which warrants further validation studies.

Post-hepatectomy liver failure prediction and prevention: Development of a nomogram containing postoperative anticoagulants as a risk factor.

INTRODUCTION AND OBJECTIVES: Posthepatectomy liver failure (PHLF) is a serious complication after hepatectomy, and its effective methods for preoperative prediction are lacking. Here, we aim to identify predictive factors and build a nomogram to evaluate patients' risk of developing PHLF. PATIENTS AND METHODS: A retrospective review of a training cohort, including 199 patients who underwent hepatectomy at the Shanghai Eastern Hepatobiliary Surgery Hospital, was conducted. Independent risk variables for PHLF were identified using multivariate analysis of perioperative variables, and a nomogram was used to build a predictive model. To test the predictive power, a prospective study in which a validation cohort of 71 patients was evaluated using the nomogram. The prognostic value of this nomogram was evaluated by the C-index. RESULTS: Independent risk variables for PHLF were identified from perioperative variables. In multivariate analysis of the training cohort, tumor number, Pringle maneuver, blood loss, preoperative platelet count, postoperative ascites and use of anticoagulant medications were determined to be key risk factors for the development of PHLF, and they were selected for inclusion in our nomogram. The nomogram showed a 0.911 C-index for the training cohort. In the validation cohort, the nomogram also showed good prognostic value for predicting PHLF. The validation cohort was used with similarly successful results to evaluate risk in two previously published study models with calculated C-indexes of 0.718 and 0.711. CONCLUSION: Our study establishes for the first time a novel nomogram that can be used to identify patients at risk of developing PHLF.

Mg2In3Si2P7: A Quaternary Diamond-like Phosphide Infrared Nonlinear Optical Material Derived from ZnGeP2.

Balancing the second-harmonic generation (SHG) coefficient, band gap, and birefringence is a vital but addressable challenge for designing infrared nonlinear optical materials. By applying a "rigidity-flexibility coupling" strategy, a quaternary diamond-like phosphide, Mg2In3Si2P7, with wurtzite-type superstructure was successfully designed and synthesized. Remarkably, it achieved the rare coexistence of giant second-harmonic generation (2 × ZnGeP2 and 7.1 × AgGaS2), suitable band gap (2.21 eV), moderate birefringence (0.107), and wide IR transparent range (0.56-16.4 µm). First-principles calculations revealed that the giant SHG response and large birefringence can be attributed to the synergy of arrangement-aligned [InP4] and [SiP4] tetrahedra. This work not only opens a new avenue for designing advanced infrared nonlinear optical materials but also may spur more explorations on quaternary diamond-like pnictides.

Early genetic screening uncovered a high prevalence of thalassemia among 18 309 neonates in Guizhou, China.

Thalassemia is a common monogenic disease in southwestern China, especially in Guizhou province. In this study, 18 309 neonates were examined for thalassemia. The thalassemia carrier rate was 12.90%, which is associated with geographical regions, with carrier frequencies significantly differing between regions (p < 0.0001). The carrier rates for α-thalassemia and ß-thalassemia were 8.91% and 3.36%, respectively. There are 22 genotypes identified among 1632 α-thalassemia cases, and 18 genotypes detected among 615 ß-thalassemia cases. The birthrates of individuals with intermediate thalassemia and ß-thalassemia major were 0.153% and 0.055%, respectively. Methodologically, NGS-Gap-PCR is superior to traditional detection methods, with 65 more cases detected by NGS-Gap-PCR. Since thalassemia-rich genotypes were highly prevalent in this region, early detection of thalassemia carriers would be meaningful for genetic counseling and prevention/treatment of thalassemia. NGS-Gap-PCR provides a powerful tool for neonate genetic testing and clinical diagnosis of thalassemia, especially in high-prevalence regions.