Multiple inflammatory pseudotumor formation after craniopharyngioma resection via an extended nasal endoscopic approach: A case report.

BACKGROUND: This report describes a case of intracranial multiple inflammatory pseudotumors (IP) after endoscopic resection of a craniopharyngioma, which is relatively rarely reported in the literature, and neurosurgeons should be aware of its existence. CASE SUMMARY: Herein, we report the case of a 56-year-old man who developed decreased visual acuity and blurred vision without obvious cause or inducement on April 27, 2020. To seek further treatment, he went to the Department of Neurosurgery, Clinical Medical College, Yangzhou University. After falling ill, there was no nausea, vomiting, limb convulsions, obvious disturbance of consciousness, speech disorders, cough, or persistent fever. The neurological examination findings were normal, and pituitary magnetic resonance imaging (MRI) revealed multiple nodules with abnormal signals in the sellar region. The diagnosis was craniopharyngioma. We performed total resection of the tumor via transnasal endoscopy, and the postoperative pathology suggested that the type of tumor was craniopharyngioma. Six months after the operation, the patient experienced sudden hearing loss in the right ear, tinnitus in both ears, and numbness on the right side of the face and head. Meanwhile, cranial MRI showed multiple IP. After steroid hormone and anti-inflammatory therapy, the above symptoms did not significantly improve. Finally, the patient's symptoms were well improved by surgery, and the postoperative pathological diagnosis was multiple IP. CONCLUSION: Intracranial inflammatory pseudotumor is a benign disease with slow progression, but the clinical symptoms and imaging findings are not typical, there are no pathological findings, and the diagnosis is relatively difficult. Most of the cases are treated by surgical resection, and the prognosis is good after surgery.

Three undescribed compounds from Diaporthe biguttusis T-24, an endophytic fungus isolated from Ligularia fischeri.

Diaporthpyran A (1), diaporthester E (2) and diaporthester F (3), three new compounds along with four known compounds (4-7) were isolated from the crude extract of Diaporthe biguttusis T-24, an endophytic fungus isolated from Ligularia fischeri. The planar structures of compounds 1-3 including the relative and absolute configurations were elucidated on the basis of HRMS, NMR, J-based coupling constant analysis, CD, and calculated ECD analysis. In addition, compounds 1 and 3 were evaluated for their cytotoxic activities against four human cancer cell lines.

Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1.

Aim: AMPK is the key regulatory kinase mediating the effect of berberine (BBR) and metformin on metabolic improvement. The present study investigated the mechanism of BBR on AMPK activation at low doses, which was different from that of metformin. Methods: Lysosomes were isolated, and AMPK activity assay was performed. PEN2, AXIN1 and UHRF1 were investigated through gain/loss of function approaches, including overexpression, RNA interfering and CRISPR/Cas9-mediated gene knockout. Immunoprecipitation was utilized for detecting the interaction of UHRF1 and AMPKα1 after BBR treatment. Results: BBR activated lysosomal AMPK, but weaker than metformin. AXIN1 mediated BBR's effect on lysosomal AMPK activation, while PEN2 did not. BBR, but not metformin, decreased UHRF1 expression by promoting its degradation. BBR reduced the interaction between UHRF1 and AMPKα1. And overexpression of UHRF1 abolished the effect of BBR on AMPK activation. Conclusion: BBR activated lysosomal AMPK as dependent on AXIN1, but not PEN2. BBR maintained cellular AMPK activity by reducing UHRF1 expression and its interaction with AMPKα1. The mode of action of BBR was different from that of metformin on AMPK activation.

Targeting BRCA-mutant biliary tract cancer: Current evidence and future perspectives.

Biliary tract cancers (BTCs) are aggressive tumors of the biliary system, which are often diagnosed at the advanced stage with a dismal prognosis. Among BTC patients, germline or somatic breast cancer-related gene 1/2 (BRCA1/2) mutation has been reported and the use of poly(ADP-ribose) polymerase inhibitor (PARPi) has achieved a certain effect, with no obvious severe side effects. The frequencies and mutated types of BRCA1/2 in advanced BTCs vary among studies. BRCA1 and BRCA2 play distinct roles in the development of BTC regardless of age or gender difference. Surprisingly, some BTC patients with germline BRCA mutation can achieve better therapeutic effects than those with a somatic mutation, and patients who carry BRCA mutation are more likely to benefit from immunotherapy alone or in combination. Herein, we provide an overview of the targeted therapies in BRCA-mutant BTCs, with a particular focus on the differences between germline and somatic BRCA1/2 mutations, as well as review the current status and perspectives.

Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model.

Chemoprevention of hepatocellular carcinoma (HCC) is highly desirable in clinic. Berberine (BBR) is reported to play potential roles in cancer treatment and prevention. We studied the chemopreventive effect of BBR on hepatocellular carcinogenesis in an inflammation-driven mouse model, as it was enriched in liver after oral administration. Oral BBR significantly decreased the number and volume of visible nodular tumors, and prolonged the median overall survival by 9 and 8 weeks in the diethylnitrosamine (DEN)-injected male and female mice respectively. The nodular tumors were induced through activation of the lysophosphatidic acid (LPA) pathway in liver. LPA stimulated the abnormal leptin transcription through interacting with LPA receptor-2 (LPAR2) followed by p38 activation, and BBR inhibited carcinogenesis by suppressing the bioactivity of LPA. Specifically, BBR significantly reduced the expression of the LPA synthetase autotaxin (ATX) and LPAR2 in the nodular tumors of DEN-injected mice. Subsequently, BBR repressed the abnormal transcription of leptin stimulated by LPA-induced phosphorylation of p38 in hepatoma cells. In fact, BBR reduced the abnormal expression of leptin in livers of DEN-injected male mice throughout the course of an 8-month experiment. BBR might be a preventive agent for HCC, working at least partially through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in liver.

Four new fatty acid derivatives from Diaporthe sp. T24, an endophytic fungus isolated from Ligularia fischer.

The endophytic fungus Diaporthe sp. is known to contain many secondary metabolites, but fatty acid derivatives have rarely been found. In this study, four new fatty acid derivatives (1-4), together with four known compounds (5-8), were isolated from Diaporthe sp., which was obtained from the stem of Ligularia fischeri. The absolute configurations of the new compounds 1-4 were deduced based on spectroscopic technique and J-based coupling constant analysis. Moreover, compound 1 exhibited cytotoxic activities against HCT-8 and MCF-7 cancer cells, and compounds 3 and 4 showed modest selectivity for HCT-8 cells by MTT assay.

Effect of Pharmacological and Neurostimulation Interventions for Cognitive Domains in Patients with Bipolar Disorder: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The priority of interventions to alleviate cognitive deficits in patients with bipolar disorder (BD) is inconclusive. We systematically evaluate the efficacy of pharmacological or neurostimulation interventions for cognitive function in BD through a network meta-analysis. METHODS: The PubMed, PsycINFO, Embase, and Cochrane Library databases were searched from database inception to September 30, 2021. Following PRISMA guidelines, all eligible studies were randomized controlled trials of adult bipolar patients that provided detailed cognitive outcomes. Studies were excluded if participants limited to comorbid substance use disorder or the intervention was a psychotherapy. Network meta-analysis comparing different interventions was conducted for 8 cognitive domains. Partially ordered set with Hasse diagram was used to resolve conflicting rankings between outcomes. The study was preregistered on PROSPERO database (CRD42020152044). RESULTS: Total 21 RCTs including 42 tests for assessing intervention effects on cognition were retrieved. Adjunctive erythropoietin (SMD = 0.61, 95% CI = 0.00-1.23), Withania somnifera (SMD = 0.58, 95% CI = 0.03-1.13), and galantamine (SMD = 1.22, 95% CI = 0.10-2.35) was more beneficial for attention, working memory, and verbal learning in euthymic BD patients than treatment as usual, respectively. Hasse diagram suggested ranking of choice when multiple domains were combined. CONCLUSION: Considerable variability in measurements of cognitive domains in BD was observed, and no intervention resulted in superior benefits across all domains. We suggested interventions priority can be tailored according to individual patients' cognitive deficits. As current findings from relatively small and heterogeneous dataset, future trials with consensus should be applied for building further evidence.

Effectiveness of low level laser therapy versus cryotherapy in cancer patients with oral mucositis: Systematic review and network meta-analysis.

OBJECTIVE: The purpose of this network meta-analysis was to analyze the relative effects of low level laser therapy (LLLT) and/or cryotherapy in cancer patients with oral mucositis (OM). METHODS: This literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Physiotherapy Evidence Database (PEDro) up to 2020. Only randomized control trials which involved comparisons of groups receiving the interventions of combined cryotherapy and LLLT, LLLT, cryotherapy and usual care (the control group) in patients with cancer were eligible for inclusion. The effect sizes are presented as odds ratios for the occurrence of severe, moderate and none/mild OM. The mixed treatment comparison was conducted using generalized linear mixed models to analyze the direct and indirect comparisons of interventions. The critical appraisal was assessed using Cochrane Collaboration's tool. Heterogeneity between studies was assessed using I2 statistics, and publication bias was evaluated by constructing a funnel plot. RESULTS: Twenty-six randomized controlled trials with a total enrollment of 1830 cancer patients with OM were included. The outcome of none/mild OM is desirable, and odds ratios of more than 1 favor the intervention group. Moderate and severe OM are defined as adverse outcomes, and ORs less than 1 favor the intervention group. The treatment effects of the combined cryotherapy and LLLT were better than those of usual care for none/mild and severe OM (ORs = 106.23 [95% CI = 12.15 to 929.17] and 0.01 [95% CI = 0 to 0.57], respectively). Treatment effects with cryotherapy alone and LLLT alone were better than those with usual care for none/mild and severe OM (ORs = 3.13 [95%CI = 1.56 to 6.27]; ORs = 7.56 [95%CI = 3.84 to 14.88] and 0.25 [95%CI = 0.11 to 0.54]; ORs = 0.13 [95%CI = 0.07 to 0.24], respectively). Nevertheless, for patients with none/mild OM, treatment effects with combined use of cryotherapy and LLLT were better than those with only LLT or cryotherapy (ORs = 14.06 [95%CI = 1.79 to 110.30] and 33.95 [95%CI = 3.50 to 329.65], respectively). For patients with moderate OM, treatment effect did not reach statistical significance among comparisons. The limitations include the wide variability in treatment protocols and the non-uniform outcome measurements across the studies examined. CONCLUSION: Compared with no intervention, the treatment effects of combined cryotherapy and LLLT, laser alone, and cryotherapy alone are beneficial for the reduction of severe OM. There is no difference in treatment effects among cryotherapy and/or LLLT intervention in cancer patients with moderate OM. Results of this study provide an implicative basis for LLLT and cryotherapy as viable interventions that can significantly improve severe OM.

Systematic review and sequential network meta-analysis on the efficacy of periodontal regenerative therapies.

AIMS: We aimed to update a previous network meta-analysis comparing the efficacy of periodontal regenerative therapies on the treatment of infrabony lesions. MATERIALS AND METHODS: Seven clinical trials were added after literature research for studies published between January 2011 and September 2019. We conducted network meta-analysis (NMA) to compare the effects of guided tissue regeneration (GTR), enamel matrix derivatives (EMD) and their combination therapies on probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain. Sequential network meta-analysis (SNMA) was also used to control the type-I error rate due to multiple testing. RESULTS: A total of 60 studies were included. For both PPD reduction and CAL gain, the flap operation (FO) was the least effective treatment. Although the differences between periodontal regenerative therapies were small, GTR attained the greatest reduction in PPD, and EMD with bone graft the greatest CAL gain compared to other therapies. SNMA used stricter efficacy criteria, yielding slightly different results from NMA. CONCLUSIONS: EMD, GTR, and their combined therapies were more effective than flap operation, although the differences between regenerative therapies remain small in this updated study. SNMA reduces the risk of false-positive findings, thereby providing more robust evidence on the superiority of treatments.