Screening of active components of Ganoderma lucidum and decipher its molecular mechanism to improve learning and memory disorders.

Learning and memory impairment (LMI), a common degenerative central nervous system disease. Recently, more and more studies have shown that Ganoderma lucidum (GL) can improve the symptoms of LMI. The active ingredients in GL and their corresponding targets were screened through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) databases, and the potential LMI targets were searched for through GeneCard (GeneCards Human Gene Database) and DrugBank. Then, we construct a "main active ingredient-target" network and a protein-protein interaction (PPI) network diagram.The GO (Gene Ontology) functional enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotation analysis were performed on the common targets through DAVID (Database for Annotation Visualization and Integrated Discovery) to clarify the potential molecular mechanism of action of active ingredients in GL. The TNF protein was verified by western blot;Twenty one active ingredients in GL and 142 corresponding targets  were screened out, including 59 targets shared with LMI. The 448 biological processes shown by the GO functional annotation results and 55 signal pathways shown by KEGG enrichment analysis were related to the improvement of LMI by GL, among which the correlation of Alzheimer disease pathway is the highest, and TNF was the most important protein; TNF can improve LMI.GL can improve LMI mainly by 10 active ingredients in it, and they may play a role by regulating Alzheimer disease pathway and TNF protein.

RhIII-Catalyzed Direct Heteroarylation of Unactivated C(sp3)-H with N-Heteroaryl Boronates.

Disclosed herein is a rhodium(III)-catalyzed direct heteroarylation reaction between unactivated aliphatic C(sp3)-H bonds in 2-alkylpyridines and heteroaryl organoboron reagents. This catalytic protocol is compatible with various heterocyclic boronates containing ortho- and meta-pyridine, pyrazoles, furan, and quinoline with strong coordination capability. The achievement of this methodology provides an efficient route to build new C(sp3)-heteroaryl bonds.

Long-term outcomes of pelvic exenterations for gynecological malignancies: a single-center retrospective cohort study.

BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.

The Diagnostic Potential of Circulating Autoantibodies to Amyloid-ß in Alzheimer's Disease.

BACKGROUND: The profile of naturally occurring antibodies to amyloid-ß (NAbs-Aß) is altered in patients with Alzheimer's disease (AD). However, the diagnostic potential of NAbs-Aß for AD is not clear yet. OBJECTIVE: This study aims to investigate the diagnostic capacities of NAbs-Aß for AD. METHODS: A total of 40 AD patients and 40 cognitively normal (CN) controls were enrolled in this study. Levels of NAbs-Aß were detected by ELISA. The correlations of NAbs-Aß levels with cognitive function and AD-associated biomarkers were examined by Spearman correlation analysis. Diagnostic abilities of NAbs-Aß were evaluated by the receiver operating characteristic (ROC) curve analyses. The integrative diagnostic models were established by logistic regression models. RESULTS: We found that NAbs-Aß7-18 had the highest diagnostic capability (AUC = 0.72) among all single NAbs-Aß. The combined model (NAbs-Aß7-18, NAbs-Aß19-30, and NAbs-Aß25-36) had a noticeable improvement (AUC = 0.84) in the diagnostic capacity compared with each single NAbs-Aß. CONCLUSION: NAbs-Aßs are promising in the diagnosis of AD. Further investigations are needed to confirm the translational potential of this diagnostic strategy.

A systematic analysis of genotype-phenotype associations with PLA2G6.

BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) can be categorized into infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), neurodegeneration with brain iron accumulation (NBIA), and early-onset parkinsonism (EOP). OBJECTIVES: To determine the genotype-phenotype association in PLAN. METHODS: "PLA2G6" or "PARK14" or "phospholipase A2 group VI" or "iPLA2ß" were searched across MEDLINE from June 23, 1997, to March 1, 2023. A total of 391 patients were identified, and 340 patients of them were finally included in the assessment. RESULTS: The loss of function (LOF) mutation ratios were significantly different (p < 0.001), highest in INAD, followed by NBIA, aNAD, and EOP. Four ensemble scores (i.e., BayesDel, VARITY, ClinPred, and MetaRNN) were assessed to predict the deleteriousness of missense mutations and demonstrated significant differences (p < 0.001). Binary logistic regression analyses demonstrated that LOF mutations were independently associated with brain iron accumulation (p = 0.006) and ataxia (p = 0.025). CONCLUSIONS: LOF or more deleterious missense mutations are more likely to promote the development of serious phenotype of PLAN, and LOF mutations are independently associated with brain iron accumulation and ataxia.

Cell-Free Extracts from Human Fat Tissue with a Hyaluronan-Based Hydrogel Attenuate Inflammation in a Spinal Cord Injury Model through M2 Microglia/Microphage Polarization.

Treatment for spinal cord injuries (SCIs) is often ineffective because SCIs result in a loss of nerve tissue, glial scar formation, local ischemia and secondary inflammation. The current promising strategy for SCI is the combination of bioactive materials and cytokines. Bioactive materials support the injured spinal cord, stabilize the morphology, and avoid excessive inflammatory responses. Fat extract (FE) is a cell-free liquid component containing a variety of cytokines extracted from human fat tissue using mechanical methods. In this research, a biocompatible HAMC (hyaluronan and methylcellulose) loaded with FE is used to treat a model of spinal cord contusion in mice. The composite not only inhibits death of neuro- and vascular cells and leads to the preservation of neural and vascular structure, but also modulates the inflammatory phenotype of macrophages in the locally injured region. Specifically, FE promotes the polarization of macrophages from an inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. During the screening of the involved pathways, it is corroborated that activation of the STAT6/Arg-1 signaling pathway is involved in macrophage M2 polarization. In summary, FE is a promising treatment for SCI, as it is easy to obtain, nonimmunogenic, and effective.

The Relationship Between Preoperative Cervical Sagittal Balance and Clinical Outcome of Acute Traumatic Central Cord Syndrome.

OBJECTIVE: To explore the sagittal radiological parameters related to clinical recovery of patients with acute traumatic central cord syndrome (ATCCS) and determine the diagnostic value of related variables. METHODS: A retrospective review was performed of 104 patients with ATCCS. Six cervical sagittal balance parameters were collected: Cobb angle, T1 slope, neck tilt, thoracic inlet angle (TIA), C2-C7 sagittal vertex axis, T1 slope - C2-C7 Cobb angle. The patients were assigned to an ideal improvement group and poor improvement group according to their recovery rate. Receiver operating characteristic curve and area under the curve were used to evaluate the significant results of logistic regression and the optimal diagnostic value. RESULTS: Preoperative and postoperative Japanese Orthopaedic Association scores indicated a good recovery after surgical intervention. Radiological findings revealed that neck tilt and TIA were risk factors for poor neurological improvement of patients with ATCCS. Area under the curve (95% confidence interval) values of neck tilt and TIA were 0.763 (0.660-0.866) and 0.749 (0.643-0.855), and cutoff values were 39.1° and 65.6°, respectively. CONCLUSIONS: Lower neck tilt and TIA are risk factors for poor outcomes in patients with ATCCS after surgery. Neck tilt <39° and TIA <66° had significant diagnostic value for poor prognosis.

The Relationship Between Preoperative Cervical Sagittal Balance and Clinical Outcome of Patients With Hirayama Disease Treated With Anterior Cervical Discectomy and Fusion.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is a common surgical method used to treat patients with Hirayama disease. And sagittal balance indexes have been revealed to be predictors of clinical outcomes in patients with cervical diseases, but their relationships with ACDF-treated Hirayama disease outcomes remain unknown. The purpose of this study is to evaluate the relationship of preoperative cervical sagittal balance indexes and clinical outcomes in ACDF-treated Hirayama disease patients. METHODS: Eighty patients with Hirayama disease treated by ACDF were reviewed retrospectively. Six cervical sagittal balance parameters were collected including Cobb angle, T1 slope, C1-7 sagittal vertical axis (SVA), C2-7 SVA, center of gravity of the head (CGH)-C7 SVA, range of motion. The recovery outcomes of the patients were divided into 2 groups by Odom score and the differences in recovery between the 2 groups were confirmed by electromyography. The correlation between imaging parameters and postoperative outcome was evaluated with logistic regression. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the significant result of logistic regression and the optimal diagnostic value. RESULTS: Only 2 parameters, Cobb angle and CGH-C7 SVA, showed statistical correlation with the postoperative outcome assessment by logistic regression. AUC of Cobb angle and CGH-C7 SVA were 0.559 and 0.702 respectively. The optimal predictive threshold was 1.50° and 5.40 mm, respectively. CONCLUSION: A larger Cobb angle and smaller CGH-C7 SVA seemed to correlate with a better postoperative outcome. These 2 factors could be used to predict the outcome of surgical treatment of Hirayama disease preoperatively.

Exosome-Transported circRNA_0000253 Competitively Adsorbs MicroRNA-141-5p and Increases IDD.

The pathogenesis of intervertebral disc degeneration (IDD) is complex, and a better understanding of IDD pathogenesis may provide a better method for the treatment of IDD. Exosomes are 40-100 nm nanosized vesicles that are released from many cell types into the extracellular space. We speculated that exosome-transported circular RNAs (circRNAs) could regulate IDD. Exosomes from different degenerative grades were isolated and added to nucleus pulposus cells (NPCs), and indicators of proliferation and apoptosis were detected. Based on the previous circRNA microarray results, the top 10 circRNAs were selected. PCR was performed to determine the circRNA with the maximum upregulation. Competing endogenous RNA (ceRNA) analysis was carried out, and the sponged microRNA (miRNA) was identified. Further functional verification of the selected circRNA was carried out in vivo and in vitro. NPCs of different degenerative grades secreted exosomes, which could regulate IDD. circRNA_0000253 was selected as having the maximum upregulation in degenerative NPC exosomes. ceRNA analysis showed that circRNA_0000253 could adsorb miRNA-141-5p to downregulate SIRT1. circRNA_0000253 was confirmed to increase IDD by adsorbing miRNA-141-5p and downregulating SIRT1 in vivo and in vitro. Exosomal circRNA_0000253 owns the maximum upregulation in degenerative NPC exosomes and could promote IDD by adsorbing miRNA-141-5p and downregulating SIRT1.

[Decreased expression of CatSper1 in the sperm of varicocele rats and protective effect of L-carnitine].

OBJECTIVE: To investigate the expression of the sperm-specific cation channel (CatSper1) in the epididymal sperm of varicocele (VC) rats and the effect of L-carnitine (LC) on the CatSper1 level. METHODS: Seventy male rats were equally randomized into groups A (normal control), B (VC model control), C (VC treated with normal saline), D (VC treated with low-dose LC), E (VC treated with medium-dose LC), F (VC treated with high-dose LC), and G (VC treated by prolonged medication of high-dose LC). The VC model was established by partial ligation of the left renal vein. At 12 weeks after modeling, the model rats in group C were treated intragastrically with normal saline at 1 ml/kg/d, those in groups D, E and F with LC at 0.05, 0.1 and 0.2 g/kg/d respectively, all for 5 consecutive weeks, and those in group G with LC at 0.2 g/kg/d for 7 successive weeks. Then, all the animals were sacrificed and their epididymides harvested for obtainment of the semen parameters by computer-assisted semen analysis (CASA) and determination of the mRNA and protein expressions of CatSper1 in the sperm by RT-PCR and Western blot. RESULTS: Compared with the rats in group A, those in group B showed significantly decreased percentage of grade a+b sperm (P < 0.01), sperm viability (P < 0.01), sperm concentration (P < 0.01) and expressions of CatSper1 mRNA (1.44 ± 0.67 vs 0.71 ± 0.38, P < 0.01) and protein (1.87 ± 0.67 vs 0.84 ± 0.42, P < 0.01). In comparison with the animals in group C, those in the four LC intervention groups exhibited a markedly increased percentage of grade a+b sperm, sperm viability and mRNA and protein expressions of CatSper1, even more remarkably in groups F and G (P < 0.01). No statistically significant difference, however, was observed in sperm concentration between group C and the LC intervention groups (P > 0.05), nor in the mRNA and protein expressions of CatSper1 between groups F and G. CONCLUSIONS: The expression of CatSper1 is decreased in the epididymal sperm of varicocele rats, and L-carnitine can increase the sperm viability, percentage of grade a+b sperm and CatSper1 expression of the rats.

The combination of procalcitonin and C-reactive protein or presepsin alone improves the accuracy of diagnosis of neonatal sepsis: a meta-analysis and systematic review.

BACKGROUND: Sepsis is an important cause of neonatal morbidity and mortality; therefore, the early diagnosis of neonatal sepsis is essential. METHOD: Our aim was to compare the diagnostic accuracy of procalcitonin (PCT), C-reactive protein (CRP), procalcitonin combined with C-reactive protein (PCT + CRP) and presepsin in the diagnosis of neonatal sepsis. We searched seven databases to identify studies that met the inclusion criteria. Two independent reviewers performed data extraction. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under curve (AUC), and corresponding 95% credible interval (95% CI) were calculated by true positive (TP), false positive (FP), false negative (FN), and true negative (TN) classification using a bivariate regression model in STATA 14.0 software. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, and corresponding 95% CI were the primary outcomes. Secondary outcomes included the sensitivity and specificity in multiple subgroup analyses. RESULTS: A total of 28 studies enrolling 2661 patients were included in our meta-analysis. The pooled sensitivity of CRP (0.71 (0.63, 0.78)) was weaker than that of PCT (0.85 (0.79, 0.89)), PCT + CRP (0.91 (0.84, 0.95)) and presepsin (0.94 (0.80, 0.99)) and the pooled NLR of presepsin (0.06 (0.02, 0.23)) and PCT + CRP (0.10 (0.05, 0.19)) were less than CRP (0.33 (0.26, 0.42)), and the AUC for presepsin (0.99 (0.98, 1.00)) was greater than PCT + CRP (0.96 (0.93, 0.97)), CRP (0.85 (0.82, 0.88)) and PCT (0.91 (0.89, 0.94)). The results of the subgroup analysis showed that 0.5-2 ng/mL may be the appropriate cutoff interval for PCT. A cut-off value > 10 mg/L for CRP had high sensitivity and specificity. CONCLUSIONS: The combination of PCT and CRP or presepsin alone improves the accuracy of diagnosis of neonatal sepsis. However, further studies are required to confirm these findings.

One-stage coclear implantation via a facial recess approach in children with otitis media with effusion.

OBJECTIVE: To investigate surgical indications, operative techniques, complications and auditory and speech rehabilitation for cochlear implant (CI) in children with otitis media with effusion (OME). MATERIAL AND METHODS: This is a retrospective review of records of 24children with bilateral profound sensorineural hearing loss and OME who were implanted during January 2011 to November 2014 in the Department of Otorhinolaryngology and Head and Neck Surgery at the PLA Hospital, using one-stage implantation via the facial recess approach and round window insertion. The incus was removed in 8 cases during the implantation procedure. Local infiltration of dexamethasone and adrenaline in the middle ear was also performed. Postoperative complications were examined. Preoperative and postoperative questionnaires including Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR), and the Meaningful Auditory Integration Scale (MAIS) were collected. RESULTS: All electrodes were implanted successfully without any immediate or delayed complications. Inflammatory changes of middle ear mucosa with effusion were noted in all implanted ears. The scores of post-implant CAP and SIR increased significantly in all 24 cases (t = -25.95 and -14.09, respectively for CAP and SIR, p < 0.05). CONCLUSIONS: One-stage CI via the facial recess approach with round window insertion is safe and effective in cochlear implant candidates with OME, as seen in the 24 children in our study who achieved improved auditory performance and speech intelligibility after CI.

Predicting a novel pathogenicity island in Helicobacter pylori by genomic barcoding.

AIM: To apply a new, integrated technique for visualizing bacterial genomes to identify novel pathogenicity islands in Helicobacter pylori (H. pylori). METHODS: A genomic barcode imaging method (converting frequency matrices to grey-scale levels) was designed to visually distinguish origin-specific genomic regions in H. pylori. The complete genome sequences of the six H. pylori strains published in the National Center for Biotechnological Information prokaryotic genome database were scanned, and compared to the genome barcodes of Escherichia coli (E. coli) O157:H7 strain EDL933 and a random nucleotide sequence. The following criteria were applied to identify potential pathogenicity islands (PAIs): (1) barcode distance distinct from that of the general background; (2) length greater than 10000 continuous base pairs; and (3) containing genes with known virulence-related functions (as determined by PfamScan and Blast2GO). RESULTS: Comparison of the barcode images generated for the 26695, HPAG1, J99, Shi470, G27 and P12 H. pylori genomes with those for the E. coli and random sequence controls revealed that H. pylori genomes contained fewer anomalous regions. Among the H. pylori-specific continuous anomalous regions (longer than 20 kbp in each strain's genome), two fit the criteria for identifying candidate PAIs. The bioinformatic-based functional analyses revealed that one of the two anomalous regions was the known pathogenicity island cag-PAI, this finding also served as proof-of-principle for the utility of the genomic barcoding approach for identifying PAIs, and characterized the other as a novel PAI, which was designated as tfs3-PAI. Furthermore, the cag-PAI and tfs3-PAI harbored genes encoding type IV secretion system proteins and were predicted to have potential for functional synergy. CONCLUSION: Genomic barcode imaging represents an effective bioinformatic-based approach for scanning bacterial genomes, such as H. pylori, to identify candidate PAIs.

Syntheses of quinolone hydrochloride enantiomers from synthons (R)- and (S)-2-methylpiperazine.

A series of R and S enantiomers of 7-(3-methylpiperazin-1-yl) quinolone derivatives were synthesized from (R)- and (S)-tert-butyl 2-methylpiperazine-1-carboxylate and tested for their antibacterial activities on 14 kinds of bacteria. Although no distinct difference in in vitro antibacterial activities was observed, 2-64-fold difference between R and S enantiomers was observed in approximately 52% of cases.