Aberrant cortical morphology patterns are associated with cognitive impairment in patients with chronic heart failure.

A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r = .476, p < .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF.

Evaluation of drug interactions of Saposhnikoviae Radix and its major components with astragaloside IV and paeoniflorin using in vitro and in vivo experiments.

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed. The pharmacokinetic parameters of SR were determined using noncompartmental analyses CCK-8 assays were used to detect the cytotoxicity of ASIV, PAE, cimifugin (CIM), prim-o-glucosylcimifugin (POG) and their combinations. Moreover, drug transport was studied using MDCK-MDR1 cells. Western blotting was performed to measure the protein expression levels of P-GP and MRP1. Claudin-5, ZO-1, and F-actin expression was determined via immunohistochemical staining of MDCK-MDR1 cells. harmacokinetic studies revealed that, compared with those of Huangqi Chifeng Tang-Saposhnikoviae Radix (HQCFT-SR), the Tmax of ASIV increased by 11.11 %, and the MRT0-t and Tmax of PAE increased by 11.19 % and 20 %, respectively, in the HQCFT group. Transport studies revealed that when ASIV was coincubated with 28 µM CIM or POG, the apparent permeability coefficient (Papp) increased by 71.52 % and 50.33 %, respectively. Coincubation of PAE with 120 µM CIM or POG increased the Papp by 87.62 % and 60.95 %, respectively. Moreover, CIM and POG significantly downregulated P-gp and MRP1 (P < 0.05), inhibited the expression of Claudin-5, ZO-1, and F-actin (P < 0.05), and affected intercellular tight junctions (TJs). In conclusion, our study successfully established a selective, sensitive and reproducible UPLC‒MS/MS analytical method to detect drug‒drug interactions between SR, AR and PR in vivo and in vitro, which is beneficial for enhancing the therapeutic efficacies of AR and PR. Moreover, this study provides a theoretical basis for further research on the use of SR as a drug carrier.

Case report: MOG-IgG-associated encephalitis with Epstein-Barr virus infection and Alzheimer's pathologic change in cerebrospinal fluid.

Immunoglobulin G antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) associated disease is a rare, demyelinated disease in the central nerve system (CNS) predominately involving optic nerve, spinal cord, and brain leading to optic neuritis (ON), transverse myelitis (TM), encephalitis. The phenotype of MOG-IgG-associated encephalitis is similar to acute disseminated encephalomyelitis (ADEM) presenting with seizures, abnormal behavioral and psychological symptoms, and cognitive impairment. A few brain biopsies show multiple sclerosis (MS) pattern histopathology with T cells, macrophages, and complement activation. To date, how MOG-IgG is produced is unknown. Herein, we report a case of a 32-year-old male with MOG-IgG-associated encephalitis presenting MOG-IgG in cerebrospinal fluid (CSF) but seronegative, as well as Epstein-Barr virus (EBV) infection and Alzheimer's pathologic change in CSF (Aß42 = 317 pg/ml, T-Tau = 538 pg/ml, p-Tau =10.09 pg/ml). With a combination treatment of administering intravenous immunoglobulin (0.4 mg/kg/d, 5 days) with a low dose of methylprednisolone (80 mg/d, 5 days) and rituximab (100 mg/week, 3 weeks), the patient recovered significantly after 3 months follow-up. This case provides us with new thoughts into the production of MOG-IgG and the possible pathologic mechanism of MOG-IgG-associated disease (MOG-AD) and simultaneously further confirms the interaction between EBV and changes of CSF biomarkers of Alzheimer's disease (AD).

Nonsyndromic supernumerary teeth in patients in National Taiwan University Children's hospital.

Background/purpose: A literature review reveals limited data for supernumerary teeth in Taiwan. This study aimed to analyze the characteristics of nonsyndromic supernumerary teeth in patients in the National Taiwan University Children's Hospital. Materials and methods: This retrospective study analyzed the nonsyndromic supernumerary teeth in 1280 patients (710 boys and 570 girls) based on examination of mainly panoramic radiographs and related radiographs. Chi-square test was used for trend analysis. Results: The incidence of nonsyndromic supernumerary teeth was 11.25% (179 supernumerary teeth in 144 of the 1280 patients). There was a male predominance (4.33: 1, P < 0.0001) for our 144 patients. Most supernumerary teeth were single (63.69%), conical-shaped (78.77%), and unerupted (77.09%). Supernumerary teeth also tended to be located in the premaxilla (93.85%), fully developed (51.40%), invertedly oriented (45.25%), sagittally located in a palatal/lingual position (67.60%), and adjacent to the root and root apex of permanent teeth (70.39%). The supernumerary teeth with a normal orientation (64.52%) had a high potential to erupt into the oral cavity, but the majority of the supernumerary teeth with a transverse orientation (97.22%) or an inverted orientation (100%) were unerupted. Conclusion: The nonsyndromic supernumerary teeth occur most commonly in male patients with a male to female ratio of 4.33: 1. The incidence of nonsyndromic supernumerary teeth in our 1280 patients is 11.25%, and the most frequent location of supernumerary teeth is the anterior maxillary region. More than three quarters of supernumerary teeth are conical-shaped or unerupted. Inverted supernumerary teeth are all embedded in the jawbones.

Bruceine D may affect the phenylpropanoid biosynthesis by acting on ADTs thus inhibiting Bidens pilosa L. seed germination.

Bruceine D is a natural quassinoid, which was successfully isolated in our research group from the residue of Brucea javanica (L.) seeds. Our previous research showed that Bruceine D prevented Bidens pilosa L. seed germination by suppressing the activity of key enzymes and the expression levels of key genes involved in the phenylpropanoid biosynthesis pathway. In this study, integrated analyses of non-targeted metabolomic and transcriptomic were performed. A total of 356 different accumulated metabolites (DAMs) were identified, and KEGG pathway analyses revealed that most of these DAMs were involved in phenylpropanoid biosynthesis. The decreased expression of ADTs and content of L-phenylalanine implicates that Bruceine D may suppress the downstream phenylpropanoid biosynthesis pathway by disrupting primary metabolism, that is, the phenylalanine biosynthesis pathway, thus inhibiting the final products, resulting in the interruption of B. pilosa seed germination. These results suggest that Bruceine D may inhibit the B. pilosa seed germination by suppressing phenylpropanoid biosynthesis through acting on ADTs.

Cyperus rotundus L. drives arable soil infertile by changing the structure of soil bacteria in the rhizosphere, using a maize field as an example.

Rhizosphere microorganisms can greatly affect plant growth, especially the plant growth-promoting rhizobacteria (PGPR), which can improve plant root development and growth because they contain various biological functions including nitrogen fixation, phosphate solubilization, and phytosiderophore production. This study demonstrates that Cyperus rotundus L. is capable of developing and forming complex underground reproductive systems at arbitrary burial depths and cutting modes due to its extremely strong multiplication and regeneration ability. With the densities of C. rotundus increasing, the abundance of PGPR, soil enzymes invertase and urease, the nutrient contents of the field soil, and maize quality were impacted. Notably, more abundance of PGPR-most notably, the nitrogen-fixing microorganisms (NFMs) such as Azospirillum, Burkholderia, Mycobacterium, and Rhizobium-enriches in the rhizosphere of C. rotundus than in that of maize. In addition, the activities of soil enzymes invertase (S_SC) and urease (S_SU) were significantly higher in its rhizosphere than in maize, further proving that more NFMs enrich the C. rotundus rhizosphere. The nutrient contents of the field soil of TN, SOM, and SOC were reduced, indicating that the presence of C. rotundus made the soil infertile. Hence, these pieces of evidence indicate that C. rotundus may drive the field soil infertile as reflected by reduced soil nutrients via altering rhizosphere bacteria community structure.

Phase I Targeted Combination Trial of Sorafenib and GW5074 in Patients with Advanced Refractory Solid Tumors.

BACKGROUND: Combination therapy with the administration of GW5074 and sorafenib significantly induced necrotic death in various cancer cells in vivo, as well as prolonging the survival of an animal disease model due to significant suppression of the primary and metastatic lesions. We sought to determine the safety, tolerability, pharmacokinetics, and anti-tumor activity of this co-administration therapy in patients with refractory advanced solid cancers. METHODS: Twelve patients were enrolled. Eligible subjects received different dosages of GW5074 in one of the three dose cohorts (Cohort 1: 750 mg daily, Cohort 2: 1500 mg daily, Cohort 3: 750 mg twice daily) plus 200 mg of sorafenib daily to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) at phase 1. Furthermore, the expression level of phosphorylated DAPKS308 in primary tumor, metastatic tumor, and circulating tumor cells (CTC) were evaluated to investigate the relationship between biomarker and the efficacy profile. RESULTS: Among the 12 enrolled patients in this phase 1 trial, most adverse effects (AE) were grade 1, with two being grade 3. The most frequent AE of all grades were weight loss and hypertension, occurring in 16.7% of participants. Eight patients (66.7%) had the disease controlled by receiving co-administration therapy of GW5074 and sorafenib. GW5074 was found to have poor absorption, as increasing the dosage did not result in a significant increase in the bioavailability of GW5074 in subjects. Furthermore, the expression level of phosphorylated DAPKS308 in tumor and CTCs were correlated with the disease control rate (DCR) and duration of response (DOR). CONCLUSIONS: Co-administration therapy of GW5074 and sorafenib demonstrated a favorable safety profile and showed anti-tumor activity in a variety of tumor types. However, the solubility of GW5074 is not satisfactory. A future phase 2a trial will be carried out using the new salted form that has been proven to be more effective.

Determining programmed cell death ligand 1 expression in circulating tumor cells of patients with clear cell renal cell carcinoma and its correlation with response to programmed cell death protein 1 inhibitors.

OBJECTIVE: There is a great interest in determining whether the expression of the programmed cell death ligand 1 is correlated with the efficacy of immune checkpoint inhibitors in patients with clear cell renal cell carcinoma; however, primary tumor biopsies can only provide limited information. Therefore, we explored the expression of programmed cell death ligand 1 on circulating tumor cells, which is a potential predictor of therapeutic response. METHODS: Circulating tumor cells were isolated from 20 clear cell renal cell carcinoma patients based on cell surface markers targeting clear cell renal cell carcinoma using IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. Programmed cell death ligand 1 expression status and clinical correlations were also analyzed. RESULTS: Before treatment with programmed cell death protein 1 inhibitors, circulating tumor cells were detected in all patients, ranging from 1 to 22 (median 7), with 75% (15/20) of the patients having programmed cell death ligand 1 + circulating tumor cells. Circulating tumor cell programmed cell death ligand 1 expression did not correlate with the immunohistochemical staining of programmed cell death ligand 1 in primary tumors. During treatment with programmed cell death protein 1 inhibitors, the disease control rate was much higher in the patients harboring programmed cell death ligand 1 + circulating tumor cells (73%, 11/15) than others (20%, 1/5). We also found that changes in total circulating tumor cell numbers and programmed cell death ligand 1 + circulating tumor cell counts correlated well with the disease outcome. CONCLUSION: We showed that the presence of programmed cell death ligand 1 + circulating tumor cells before programmed cell death protein 1 inhibition treatment could be a prognosis predictive factor and that the dynamic changes in circulating tumor cell numbers may be used to monitor the therapeutic response. Our study confirms the possibility of programmed cell death ligand 1 + circulating tumor cell detection in clear cell renal cell carcinoma patients' blood samples, which can potentially be used as an individualized immunotherapy molecular biomarker for real-time exploration.

Klf4 methylated by Prmt1 restrains the commitment of primitive endoderm.

The second cell fate decision in the early stage of mammalian embryonic development is pivotal; however, the underlying molecular mechanism is largely unexplored. Here, we report that Prmt1 acts as an important regulator in primitive endoderm (PrE) formation. First, Prmt1 depletion promotes PrE gene expression in mouse embryonic stem cells (ESCs). Single-cell RNA sequencing and flow cytometry assays demonstrated that Prmt1 depletion in mESCs contributes to an emerging cluster, where PrE genes are upregulated significantly. Furthermore, the efficiency of extraembryonic endoderm stem cell induction increased in Prmt1-depleted ESCs. Second, the pluripotency factor Klf4 methylated at Arg396 by Prmt1 is required for recruitment of the repressive mSin3a/HDAC complex to silence PrE genes. Most importantly, an embryonic chimeric assay showed that Prmt1 inhibition and mutated Klf4 at Arg 396 induce the integration of mouse ESCs into the PrE lineage. Therefore, we reveal a regulatory mechanism for cell fate decisions centered on Prmt1-mediated Klf4 methylation.

Detection of circulating tumor cells as therapeutic markers in patients with penile squamous cell carcinoma: A preliminary study.

BACKGROUND: This study aimed to investigate the presence of circulating tumor cells (CTCs) in patients with penile squamous cell carcinoma (PSCC). METHODS: CTCs were isolated from 14 patients with PSCC, 6 patients with balanoposthitis, and 6 healthy individuals. CTCs were enriched based on cell surface markers and filtered through the IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. RESULTS: CTCs were found in all PSCC blood samples but not in balanoposthitis samples and samples from healthy individuals. Immunofluorescence studies confirmed the tumor origin. When the patients with PSCC were stratified according to metastatic inguinal lymph node status, a statistically significant difference was observed in the number of detected CTCs. CONCLUSION: Our study showed that CTCs in PSCC may represent a valuable marker for differentiating PSCC from other tumors. Based on the correlation with some clinical parameters, CTC analysis is possibly relevant for noninvasive monitoring of disease progression and prognosis. The results also suggested a potential role of CTCs in preventing overtreatment, such as inguinal lymph node dissection.

[Research Progress on the Application of Artificial Intelligence in Rehabilitation Medicine in China].

The development of science and technology and the increasing demand of rehabilitation have driven the integration between artificial intelligence and rehabilitation medicine.In this study,statistical methods,document visualization tools,and other analysis methods were used in the Citespace software to analyze China's research status of artificial intelligence in the field of rehabilitation medicine with the key words of co-occurrence,emergence,and clustering.The relevant research hot spots were then classified and expounded.The results demonstrated that the current hot spots of artificial intelligence related to rehabilitation medicine included robots,brain-computer interfaces,human-computer interaction,and motor imagery.According to the clustering of key words and literature analysis,the five themes of artificial intelligence in rehabilitation medicine were determined as robot,brain-computer interface,intelligent rehabilitation training system,human-computer interaction,and assisted diagnosis and remote rehabilitation.Robotics and human-computer interaction would still be the research hot spots in the long future,and brain-computer interfaces,motor imagery,and remote rehabilitation would be new ones.This study analyzed the current hot spots,predicted the development trends,discussed the limitations,and proposed suggestions,aiming to provide reference for other scholars focusing on the application of artificial intelligence in rehabilitation medicine.

Effects of robot-assisted versus hand-assisted nephroureterectomy on circulating tumor cells for upper urinary tract urothelial carcinoma.

To compare perioperative circulating tumor cells (CTC) in primary upper tract urothelial carcinoma (UTUC) patients who underwent hand-assisted retroperitoneoscopic nephroureterectomy (HANU) or robotic-assisted nephroureterectomy (RANU). A total of 29 patients received RANU (n = 10) or HANU (n = 19). Peripheral blood samples were collected before, 24 h after surgery (POh24) and on postoperative day 28 (POD28). The demographic and pathologic data are similar in both groups. RANU had a longer operative time (p = 0.031), less bleeding volume (p = 0.004), and comparable pain sore (p = 0.169). The mean CTC numbers before surgery (2.4 vs. 2.3, p = 0.482), POh24 (2.4 vs. 1.9, p = 0.668) and POD28 (0.5 vs. 0.6, p = 0.280) were not significant different among groups. The amount of CTCs in both groups decreased and reached similar level on POD28. No significant difference of overall and intravesical recurrence rate between the two approaches. In comparison to RANU, more surgical manipulation does not affect tumor cell translocation into the bloodstream in UTUC patients who received HANU. However, a longer follow-up would be needed for the final comparison of tumor recurrence.

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction.

Huangqi Chifeng Tang (HQCFT), a traditional Chinese formula of three herbs, has been used to treat cerebral infarction (CI). Saposhnikoviae Radix (SR) was designed as a guiding drug for HQCFT to improve its angiogenic and anti-inflammatory effects. In this study, TTC staining was used to detect the area of CI. H&E staining was used to detect the histopathologic changes in the cerebral tissue. Western blotting was performed to detect the protein expression of NLRP3, caspase 1, IL-1ß, IL-6, TNF-α, MMP-9, VEGF, and VEGFR2 in cerebral tissue. Immunohistochemistry was used to detect the protein expression of MMP-9, VEGF, and VEGFR2. The contents of HIF-1α, NLRP3, caspase 1, IL-1ß, IL-6, and TNF-α in the serum were determined by ELISA. Our study showed that HQCFT and HQCFT-SR could improve the pathological condition and reduce the infarcted area of the brain tissue in a rat model. In addition, HQCFT and HQCFT-SR significantly decreased the expression levels and serum contents of NLRP3, caspase 1, IL-1ß, IL-6, and TNF-α; increased the expression levels of the VEGF and VEGFR2 proteins; and obviously reduced the serum content of HIF-1α. Importantly, the cytokines in brain tissue and serum from the HQCFT group exhibited better efficacy than those from the HQCFT-SR group. HQCFT exerted significant angiogenic and anti-inflammatory effects in rats subjected to middle cerebral artery occlusion (MCAO); these effects can be attributed to the guiding and enhancing effect of SR.

Programmed Cell Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor of Treatment Response in Patients with Urothelial Carcinoma.

Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma (UC). Therefore, this study evaluated the relationship between PD-L1 expression in circulating tumor cells (CTCs) and treatment response to PD-L1 inhibitors using blood samples collected from patients with UC (n = 23). Subsequently, PD-L1 expression and its clinical correlation were analyzed. All patients had CTCs before PD-L1 inhibitory treatment, of which 15 had PD-L1-positive CTCs. However, PD-L1-positive expression in CTCs was not correlated with PD-L1 expression in tumor biopsy samples. Patients with PD-L1-positive CTCs had better disease control (DC) rates than those without PD-L1-positive CTCs. Moreover, changes in the proportion of PD-L1-positive CTCs were associated with disease outcomes. Furthermore, the PD-L1-positive CTC count in 9 of 11 patients who achieved DC had significantly decreased (p = 0.01). In four patients with progressive disease, this was higher or did not change. PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Hence, PD-L1-positive CTCs could be employed as a real-time molecular biomarker for individualized immunotherapy.

Rectal Dose Is the Other Dosimetric Factor in Addition to Small Bowel for Prediction of Acute Diarrhea during Postoperative Whole-Pelvic Intensity-Modulated Radiotherapy in Gynecologic Patients.

We studied the association of rectal dose with acute diarrhea in patients with gynecologic malignancies undergoing whole-pelvic (WP) intensity-modulated radiotherapy (IMRT). From June 2006 to April 2019, 108 patients with previous hysterectomy who underwent WP IMRT were enrolled in this cohort study. WP irradiation of 39.6-45 Gy/22-25 fractions was initially delivered to the patients. Common Terminology Criteria for Adverse Events (CTCAE) version 3 was used to evaluate acute diarrhea during radiotherapy. Small bowel volume at different levels of isodose curves (Vn%) and mean rectal dose (MRD) were measured for statistical analysis. The multivariate analysis showed that the MRD ≥ 32.75 Gy (p = 0.005) and small bowel volume of 100% prescribed (V100%) ≥ 60 mL (p = 0.008) were independent factors of Grade 2 or higher diarrhea. The cumulative incidence of Grade 2 or higher diarrhea at 39.6 Gy were 70.5%, 42.2%, and 15.0% (p < 0.001) in patients with both high (V100% ≥ 60 mL and MRD ≥ 32.75 Gy), either high, and both low volume-dose factors, respectively. Strict constraints for the rectum/small bowel or image-guided radiotherapy to reduce these doses are suggested.

Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via a Network Pharmacology Approach.

OBJECTIVE: To investigate the shared mechanisms of scutellarin in angina pectoris (AP) and ischemic stroke (IS) treatment. METHODS: A network pharmacology approach was used to detect the potential mechanisms of scutellarin in AP and IS treatment by target prediction, protein-protein interaction (PPI) data collection, network construction, network analysis, and enrichment analysis. Furthermore, molecular docking simulation was employed to analyze the interaction between scutellarin and core targets. RESULTS: Two networks were established, including a disease-target network and a PPI network of scutellarin targets against AP and IS. Network analysis showed that 14 targets, namely, AKT1, VEGFA, JUN, ALB, MTOR, ESR1, MAPK8, HSP90AA1, NOS3, SERPINE1, FGA, F2, FOXO3, and STAT1, might be the therapeutic targets of scutellarin in AP and IS. Among them, NOS3 and F2 were recognized as the core targets. Additionally, molecular docking simulation confifirmed that scutellarin exhibited a relatively high potential for binding to the active sites of NOS3 and F2. Furthermore, enrichment analysis indicated that scutellarin might exert a therapeutic role in both AP and IS by regulating several important pathways, such as coagulation cascades, mitogen-activated protein kinase (MAPK) signaling pathway, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, Toll-like receptor signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, forkhead box O (FoxO) signaling pathway, tumor necrosis factor (TNF) signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, insulin resistance, and estrogen signaling pathway. CONCLUSIONS: The shared underlying mechanisms of scutellarin on AP and IS treatment might be strongly associated with its vasorelaxant, anticoagulant, anti-inflammatory, and antioxidative effects as well as its effect on improving lipid metabolism.

(D620N) VPS35 causes the impairment of Wnt/ß-catenin signaling cascade and mitochondrial dysfunction in a PARK17 knockin mouse model.

Patients with familial type 17 of Parkinson's disease (PARK17) manifest autosomal dominant pattern and late-onset parkinsonian syndromes. Heterozygous (D620N) mutation of vacuolar protein sorting 35 (VPS35) is genetic cause of PARK17. We prepared heterozygous VPS35D620N/+ knockin mouse, which is an ideal animal model of (D620N) VPS35-induced autosomal dominant PARK17. Late-onset loss of substantia nigra pars compacta (SNpc) dopaminergic (DAergic) neurons and motor deficits of Parkinson's disease were found in 16-month-old VPS35D620N/+ mice. Normal function of VPS35-containing retromer is needed for activity of Wnt/ß-catenin cascade, which participates in protection and survival of SNpc DAergic neurons. It was hypothesized that (D620N) VPS35 mutation causes the malfunction of VPS35 and resulting impaired activity of Wnt/ß-catenin pathway. Protein levels of Wnt1 and nuclear ß-catenin were reduced in SN of 16-month-old VPS35D620N/+ knockin mice. Downregulated protein expression of survivin, which is a target gene of nuclear ß-catenin, and upregulated protein levels of active caspase-8 and active caspase-9 were observed in SN of VPS35D620N/+ mice at age of 16 months. VPS35 is involved in controlling morphology and function of mitochondria. Impaired function of VPS35 caused by (D620N) mutation could lead to abnormal morphology and malfunction of mitochondria. A significant decrease in mitochondrial size and resulting mitochondrial fragmentation was found in tyrosine hydroxylase-positive and neuromelanin-positive SNpc DAergic neurons of 16-month-old VPS35D620N/+ mice. Mitochondrial complex I activity or complex IV activity was reduced in SN of 16-month-old VPS35D620N/+ mice. Increased level of mitochondrial ROS and oxidative stress were found in SN of 16-month-old VPS35D620N/+ mice. Levels of cytosolic cytochrome c and active caspase-3 were increased in SN of VPS35D620N/+ mice aged 16 months. Our results suggest that PARK17 mutant (D620N) VPS35 impairs activity of Wnt/ß-catenin signaling pathway and causes abnormal morphology and dysfunction of mitochondria, which could lead to neurodegeneration of SNpc DAergic cells.

Psychometric testing of the support and control in birth scale.

BACKGROUND: The Support and Control in Birth (SCIB) scale primarily measures the perceived support and control of expectant mothers during childbirth, thereby obtaining an understanding of their birth experiences. The advantages of this scale are its good reliability and validity and that it consolidates birth support and control. However, a Chinese version of the scale has yet to be developed. Therefore, this study sought to evaluate the validity and reliability of a Chinese version of the Support and Control in Birth Scale (C-SCIB). METHODS: A total of 228 postpartum women participated in this study. The C-SCIB scale was developed through a translation and back translation, followed by an evaluation of its content validity by a group of experts. Cronbach's α internal consistency and test-retest reliability were used to test the reliability of the scale. In addition, criterion-related validity (predictive validity and concurrent validity) and construct validity were used to test the validity of the scale. RESULTS: The C-SCIB scale showed good results in terms of the item-level and scale-level content validity indices. The Cronbach's α internal consistency was 0.81, and its test-retest reliability was 0.96. The confirmatory factor analysis results showed the overall goodness-of-fit was parsimony fit indices. The predictive validity analysis showed a significant positive correlation between the C-SCIB scale and the Questionnaire Measuring Attitudes About Labor and Delivery (r = 0.31, p < 0.01). Furthermore, the concurrent validity analysis showed a significant and moderate correlation between the C-SCIB and the Bryanton Adaptation of the Nursing Support in Labor Questionnaire (r = 0.49, p < 0.01) as well as the Labor Agentry Scale (r = 0.51, p < 0.01). CONCLUSION: The C-SCIB scale was proven to have good reliability and validity, and thus can be used to measure the degree of support and the locus of control perceived by expectant women during labor.

Characterization of an Ecdysteroid-Regulated 16 kDa Protein Gene in Chinese Oak Silkworm, Antheraea pernyi (Lepidoptera: Saturniidae).

A large number of ecdysteroid-regulated 16 kDa proteins (ESR16s) of insects have been isolated and annotated in GenBank; however, knowledge on insect ESR16s remain limited. In the present study, we characterized an ecdysteroid-regulated 16 kDa protein gene isolated in Chinese oak silkworm, Antheraea pernyi Guérin-Méneville ('ApESR16' in the following), an important silk-producing and edible insect. The obtained cDNA sequence of ApESR16 is 1,049 bp, harboring an open reading frame of 441 bp that encodes a polypeptide of 146 amino acids. CD-search revealed that ApESR16 contains the putative cholesterol/lipid binding sites on conserved domain Npc2_like (Niemann-Pick type C-2) belonging to the MD-2-related lipid-recognition superfamily. Sequence comparison revealed that ApESR16 exhibits 51-57% identity to ESR16s of lepidopteran insects, 36-41% identity to ESR16 or NPC2a of nonlepidopteran insects, and 28-32% identity to NPC2a of vertebrates, indicating a high sequence divergence during the evolution of animals. Phylogenetic analysis found that the used sequences were divided into two groups corresponding to vertebrates and invertebrates, and the used insect sequences were also well clustered according to their families. The A. pernyi ESR16 mRNA is expressed during all four developmental stages and in all tested tissues. Injection of 20-hydroxyecdysone (20-E) into A. pernyi diapausing pupae triggering diapause termination induced upregulation of ESR16 mRNA compared to the diapausing pupae, with the highest expression level at day 2 in the ovaries but day 12 in the fat body. Our results suggested that ApESR16 might be a diapause-related gene and plays a vital role in the pupal diapause of A. pernyi.

A Bayesian Network Meta-Analysis for Identifying the Optimal Taxane-Based Chemotherapy Regimens for Treating Gastric Cancer.

Background: Several taxane-based chemotherapy regimens are effective in the treatment of gastric cancer; nevertheless, their comparative efficacy and safety remain disputed. This network meta-analysis (NMA) was designed to compare the efficacy and safety of different taxane-based chemotherapy regimens against gastric cancer. Methods: A comprehensive search was conducted to identify all relevant randomized controlled trials (RCTs) in multiple electronic databases. A Bayesian NMA was performed to combine the direct and indirect evidence and estimate the comparative efficacy and safety of different taxane-based chemotherapy regimens simultaneously by utilizing WinBUGS 1.4.3 and Stata 13.1 software. The efficacy outcomes included overall survival rate (OS), progression-free survival (PFS), and overall response rate (ORR), and the safety outcomes were adverse reactions (ADRs), namely, neutropenia, leucopenia, vomiting, and fatigue. Results: A total of 37 RCTs were identified involving 7,178 patients with gastric cancer, and 10 taxane-based chemotherapy regimens (RT, T, TC, TCF, TF, TO, TOF, mTCF, mTF, and mTOF) were collected in gastric cancer therapy. According to the results of cluster analysis, compared with other taxane-based chemotherapy regimens, the regimens of TOF, mTCF, and TF were associated with the most favorable clinical efficacy in improving OS, PFS, and ORR. On the other hand, the regimens of T and mTF had the potential to be the most tolerable and acceptable therapeutic alternative in terms of ADRs. Conclusions: The current NMA provides the evidence that the combination of taxanes (paclitaxel or docetaxel) and fluorouracil is associated with the most preferable and beneficial option for patients with gastric cancer, although additional results from multicenter trials and high-quality studies will be pivotal for supporting our findings.