Optimal timing of GnRH antagonist initiation in IVF-ET: a retrospective cohort study on advanced maternal age women.

Background: Several studies have compared the effects of fixed and flexible gonadotropin releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization and embryo transfer (IVF-ET). However, which GnRH-ant initiation strategy is better remains controversial. Moreover, no studies have assessed the optimal timing of GnRH-ant initiation in women of advanced maternal age (AMA). Methods: In this retrospective cohort study, a total of 472 infertile women aged ≥ 35 years old undergoing their first IVF cycle from August 2015 to September 2021 at a tertiary academic medical center were recruited, of whom 136 followed fixed GnRH-ant protocol and 336 followed flexible GnRH-ant protocol. The primary outcomes measured were the cumulative live birth rate (CLBR) per IVF cycle and the time to live birth (TTLB) from the date of oocyte retrieval. Cox proportional models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of CLBR regarding GnRH-ant timing. Results: No significant difference in CLBR was found between the fixed and flexible GnRH-ant groups (27.9% vs 20.5%, p=0.105). The TTLB was also comparable between groups (10.56 vs 10.30 months, p=0.782). The Kaplan-Meier analysis for CLBR also showed comparable results between groups (P=0.351, HR=0.83; 95%CI: 0.56-1.23). After establishing a multiple Cox proportional hazard model, the fixed GnRH-ant group still had comparable CLBR with the flexible GnRH-ant group (HR=0.85; 95%CI: 0.53-1.38; P=0.518). Subgroup and sensitivity analyses also demonstrated similar results. Conclusion: GnRH-ant protocols can be tailored to the needs of AMA women, and timing of GnRH-ant initiation can be adjusted flexibly.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

Stroke-like onset of calcified brain metastases with Wallerian degeneration: a case report and review of the literature.

INTRODUCTION: Metastatic brain tumors are a common complication of systemic cancer. They tend to have a chronic onset and are located at the gray-white junction of the cerebral hemispheres, those larger than 9.4 mm in diameter are often accompanied by substantial vasogenic edema. Herein, we report a rare case of calcified metastatic adenocarcinoma with Wallerian degeneration. In addition, we discuss the atypical manifestations of brain metastases. CASE REPORT: A 71-year-old man who went through stroke-like onset twice during 8 months with a history of resection of the left pulmonary adenocarcinoma 5 years prior was examined. Diffusion weighted magnetic resonance imaging of the brain showed an enlarged open-ring-shaped hyperintensity on the left periventricular white matter and basal ganglia, with Wallerian degeneration on the left cerebral peduncle. Brain computed tomography revealed nodular calcification of the lesion. The pathology of stereotactic biopsy indicated metastatic adenocarcinoma. CONCLUSION: When patients present with acute nervous system symptoms and a previous history of cancer, the possibility of metastases should be considered, even if neuroimaging is atypical.

Effectiveness of oestrogen pretreatment in patients with expected poor ovarian response (POSEIDON groups 3 and 4) undergoing GnRH antagonist protocol: study protocol for a randomised controlled trial.

INTRODUCTION: Women characterised by diminished ovarian reserve are considered to have poor ovarian response (POR) according to Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria. Patients in this population often have a poor prognosis for treatment with assisted reproductive technology. In previous studies, oestrogen pretreatment before ovarian stimulation has been shown to have a beneficial effect. However, recent studies presented conflicting conclusions. This study aims to evaluate the effectiveness of oestrogen pretreatment in patients with expected POR (POSEIDON groups 3 and 4) undergoing gonadotrophin releasing hormone antagonist (GnRH-ant) protocol. METHODS AND ANALYSIS: A prospective superiority randomised parallel controlled trial will be conducted at a tertiary university-affiliated hospital. A total of 316 patients will be randomly divided into two groups at a ratio of 1:1. In the intervention group, oral oestrogen pretreatment will be administered from day 7 after ovulation until day 2 of the next menstrual cycle. Afterwards, a flexible GnRH-ant protocol will be initiated. The control group will receive no additional intervention beyond routine ovarian stimulation. The primary outcome is the number of oocytes retrieved. Secondary outcomes include the total number of retrieved metaphase II oocytes, average daily dose of gonadotropin, total gonadotropin dose and duration of ovarian stimulation, cycle cancellation rate, top quality embryos rate, blastocyst formation rate, embryo implantation rate, clinical pregnancy rate, early miscarriage rate and endometrial thickness on trigger day. All data will be analysed according to the intention-to-treat and per-protocol principles. ETHICS AND DISSEMINATION: The ethical approval has been confirmed by the reproductive ethics committee of the affiliated hospital of Shandong University of Traditional Chinese Medicine (SDUTCM/2022.9.20). In addition, written informed consent will be obtained from all the participants before the study. The results will be disseminated via publications. TRIAL REGISTRATION NUMBER: ChiCTR2200064812.

T-Cell Non-Hodgkin Lymphoma of the Ileum Presenting as Perforation and Peritonitis: A Case Report.

Background: Non-Hodgkin lymphoma (NHL) of the ileum, presenting as perforation and peritonitis, is a rare disease, derived from intestinal intraepithelial T lymphocytes. The degree of malignancy is extremely high. The pathogenesis of ileal perforation caused by NHL remains unclear, as well as the chromosome and immune system abnormalities, which may be related to NHL, and are indistinguishable from other benign and malignant conditions and are clinically nonspecific. Case Report: We describe an 84-year-old man with abdominal pain for 4 days, which was aggravated for 3 h. The pain was in the upper abdominal region and was initially considered to be due to gastrointestinal perforation. He had persistent insidious pain, accompanied by nausea, vomiting, and fever. Physical examination indicated that the patient had pain all over the abdomen; also, rebound pain and muscle tension, and bowel sounds were reduced on auscultation. An abdominal CT scan showed free gas in the abdominal cavity. The patient was diagnosed with peritonitis due to hollow viscus perforation. A prompt exploratory laparotomy was performed. Intraoperative findings showed perforations in the ileum that are approximately 40 cm from the ileocecal region, which were 3-8 mm in size. A segmental distribution was observed, and the intestinal contents overflowed with purulent discharge around the perforation surface. Resection and ileostomy were performed, and the clinical histopathological examination confirmed T-cell lymphoma. The patient was advised to visit the Oncology Department for further chemotherapy. Conclusion: Timely emergency surgery is the key to the treatment of ileal perforation caused by T-cell lymphoma. Resection and ileostomy were performed as intervention measures, and subsequent histopathological examination manifested T-cell lymphoma.

Research Progress on the Relationship Between Inflammation and Colorectal Cancer.

Colorectal cancer is one of the common malignant tumors. Relevant epidemiology and a large number of experimental studies have proved that chronic inflammation is highly correlated with the occurrence and development of colorectal cancer. And inflammatory bowel disease has been proven to be an independent risk factor for colorectal cancer. Various inflammatory cells participate in the establishment of the chronic inflammatory intestinal microenvironment required for the onset of colorectal cancer. The abnormal signal pathways mediated by various inflammatory factors and inflammatory mediators promote the occurrence of tumors, which are related to colorectal cancer and pathogenesis-related inflammation mechanisms. At the gene level, miRNAs can also affect the pathogenesis of colorectal cancer by regulating mesenchymal epithelial transformation. This article reviews the relationship between inflammation and colorectal cancer as well as the related inflammatory mechanisms.

Evaluation of the Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes in China.

Background: Recently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to evaluate the diagnostic performance and clinical utility in China. Methods: An eligible cohort of 113 Chinese patients diagnosed with PNSs from the Second Affiliated Hospital School of Medicine Zhejiang University and published data were enrolled retrospectively. Data including clinical phenotype, antibody type, the presence of cancer, and duration of follow-up were reviewed and re-evaluated to classify the diagnostic levels for the 2004 and 2021 PNS criteria. The performances of these 2 criteria were compared. The critical parameters of antibody and cancer for the updated criteria were further explored. Results: The cohort consisted of 69 males and 44 females with a median age of 60 years. Limbic encephalitis (23, 20.4%), anti-Hu antibody (32, 28.3%), and small-cell lung cancer (32, 28.3%) were the most common clinical phenotype, detected antibody, and concomitant cancer, respectively. A total of 97 (85.8%) patients were diagnosed with definite PNS according to the 2004 criteria: only 42.3% (41/97) fulfilled the 2021 criteria, while the remaining 40, 14, and 2 re-diagnosed with probable PNS, possible PNS, and non-PNS. The requirement of cancers consistent with antibody and phenotype increased the specificity and thus greatly enhanced the accuracy of the 2021 criteria. Conclusion: The updated criteria for PNS emphasized the consistency between cancer phenotype and antibody and showed a better diagnostic value. A better diagnostic yield could benefit disease management.

Identification and verification of HCAR3 and INSL5 as new potential therapeutic targets of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and ranks third in cancer-related deaths worldwide. This study was conducted to identify novel biomarkers related to the pathogenesis of CRC based upon a bioinformatics analysis, and further verify the biomarkers in clinical tumor samples and CRC cell lines. METHODS: A series of bioinformatics analyses were performed using datasets from NCBI-GEO and constructed a protein-protein interaction (PPI) network. This analysis enabled the identification of Hub genes, for which the mRNA expression and overall survival of CRC patients data distribution was explored in The Cancer Genome Atlas (TCGA) colon cancer and rectal cancer (COADREAD) database. Furthermore, the differential expression of HCAR3 and INLS5 was validated in clinical tumor samples by Real-time quantitative PCR analysis, western blotting analysis, and immunohistochemistry analysis. Finally, CRC cells over-expressing INSL5 were constructed and used for CCK8, cell cycle, and cell apoptosis validation assays in vitro. RESULTS: A total of 286 differentially expressed genes (DEGs) were screened, including 64 genes with increased expression and 143 genes with decreased expression in 2 CRC database, from which 10 key genes were identified: CXCL1, HCAR3, CXCL6, CXCL8, CXCL2, CXCL5, PPY, SST, INSL5, and NPY1R. Among these genes, HCAR3 and INSL5 had not previously been explored and were further verified in vitro. CONCLUSIONS: HCAR3 expression was higher in CRC tissues and associated with better overall survival of CRC patients. INSL5 expression in normal tissue was higher than that in tumor tissue and its high expression was associated with a better prognosis for CRC. The overexpression of INSL5 significantly inhibited the proliferation and promoted the shearing of PARP of CRC cells. This integrated bioinformatics study presented 10 key hub genes associated with CRC. HCAR3 and INSL5 were expressed in tumor tissue and these were associated with poor survival and warrant further studies as potential therapeutic targets.

Seasonal variation in autoimmune encephalitis: A multi-center retrospective study.

OBJECTIVE: The aim of this study was to examine the seasonal distribution in clinical onset of autoimmune encephalitis (AE) in a multi-center cohort in China. METHODS: This retrospective study consecutively recruited patients with new-onset definite neuronal surface antibody-associated AE between January 2015 and December 2020 from 3 tertiary hospitals. Demographic and clinical characteristics of the participants were comprehensively collected. Statistical analyses were performed using R. RESULTS: Of the 184 patients of AE in our database, 149 (81.0%) were included in the final analysis. The median age of onset was 40.0 years, and 66 (44.3%) patients were female. AE predominantly started in autumn (47, 31.5%) and summer (43, 28.9%) months. Summer-autumn predominance of the clinical onsets was also present in the anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis group (54, 60.0%) and anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis group (20, 76.9%). No obvious seasonal variations were observed among gender, onset age, disease duration, prodromal symptoms, clinical type of initial symptoms, and disease severity by the time of admission. CONCLUSION: This study suggested summer-autumn predominance of the clinical onsets in patients with AE, especially anti-NMDAR and anti-LGI1 encephalitis. Therefore, clinicians should have a high index of suspicion for AE in encephalopathy patients in summer and autumn period.

Anti-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review.

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis, was first reported by Lai et al. The AMPAR antibodies target against extracellular epitopes of the GluA1 or GluA2 subunits of the receptor. AMPARs are expressed throughout the central nervous system, especially in the hippocampus and other limbic regions. Anti-AMPAR encephalitis was more common in middle-aged women and most patients had an acute or subacute onset. Limbic encephalitis, a classic syndrome of anti-AMPAR encephalitis, was clinically characterized by a subacute disturbance of short-term memory loss, confusion, abnormal behavior and seizure. Magnetic resonance imaging often showed T2/fluid-attenuated inversion-recovery hyperintensities in the bilateral medial temporal lobe. For suspected patients, paired serum and cerebrospinal fluid (CSF) testing with cell-based assay were recommended. CSF specimen was preferred given its higher sensitivity. Most patients with anti-AMPAR encephalitis were complicated with tumors, such as thymoma, small cell lung cancer, breast cancer, and ovarian cancer. First-line treatments included high-dose steroids, intravenous immunoglobulin and plasma exchange. Second-line treatments, including rituximab and cyclophosphamide, can be initiated in patients who were non-reactive to first-line treatment. Most patients with anti-AMPAR encephalitis showed a partial neurologic response to immunotherapy.

LINC00202 attenuates the progression of gastric cancer via suppressing expression level of KLF2.

PURPOSE: We aimed to investigate the function of LINC00202 in influencing the malignant progression of gastric cancer (GC). METHODS: The relative level of LINC00202 in GC and adjacent normal tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The difference in LINC00202 level among GC patients with different TNM stages was compared. Subsequently, regulatory effects of LINC00202 on proliferative capacity of AGS and SGC-7901 cells were evaluated. Subcellular distribution of LINC00202 was analyzed. The interaction and correlation between LINC00202 and Krüppel-like factor 2 (KLF2) were analyzed by RNA immunoprecipitation (RIP), Chromatin immunoprecipitation (ChIP) and linear regression test. Finally, the involvement of KLF2 in LINC00202-mediated proliferative ability of GC cells was clarified. LINC00202 was upregulated in GC tissues compared with that in adjacent normal ones. Its level remained higher in GC patients with stage III-IV than those with stage I-II. Silencing LINC00202 markedly attenuated the proliferation of GC cells. RESULTS: LINC00202 was mainly enriched in nucleus. KLF2 level was negatively correlated to and interacted with LINC00202. Transfection of LINC00202 decreased the recruitment ability of EZH2 on KLF2. Importantly, KLF2 partially reversed the regulatory effect of LINC00202 on the proliferative ability of GC cells. CONCLUSIONS: LINC00202 enhances the proliferative ability of GC cells via negatively regulating KLF2, thus aggravating the progression of GC.

The immunologic changes during different phases of intestinal anastomotic healing.

Intestinal anatomosis is a complex and multicellular process that involving three overlapped phases: exudative phase, proliferative phase, and reparative phase. Undisturbed anastomotic healings are crucial for the recovery of patients after operations but unsuccessful healings are linked with a considerable mortality. This time, we concentrate on the immunologic changes during different phases of intestinal anastomotic healing and select several major immune cells and cytokines of each phase to get a better understanding of these immunologic changes in different phases, which will be significant for more precise therapy strategies in anastomoses.

Integrated analysis of differentially expressed lncRNAs in Medial Temporal Lobe Epilepsy.

BACKGROUND: Medial temporal lobe epilepsy (MTLE) is the most frequent type of epilepsy. In recent years, the important roles of lncRNAs in regulating human diseases progression had been implicated, including in epilepsy. However, comprehensive analysis of differentially expressed lncRNAs in Medial Temporal Lobe Epilepsy was still lacking. OBJECTIVES: The aim of this study was to explore relevant lncRNAs in MTLE. METHODS: In present study, we analyzed a public dataset GSE25453 to identify differentially expressed lncRNAs and mRNAs in the MTLE. RESULTS: A total of 16 lncRNAs (C6orf176, NCRNA00259, PRO1768, TTTY11, LOC149620, GDEP, LOC400891, HLA-DRB6, TTTY21, TTTY3, NBR2, TTTY1, FAM183B, C15orf51, FAM74A3, and MALAT1) were identified. LncRNA co-expression network analysis showed these lncRNAs were mainly enriched in regulating transcription, inflammatory response, DNA binding, Jak Stat Signaling Pathway, and Mapk Signaling Pathway. Meanwhile, lncRNA-mRNA-biological processes networks were also performed to evaluate the potential roles of key lncRNAs in MTLE. CONCLUSIONS: This study will be useful to explore the potential candidate biomarkers for diagnosis, prognosis, and drug targets of MTLE.

Regulatory effects of the long non­coding RNA RP11­543N12.1 and microRNA­324­3p axis on the neuronal apoptosis induced by the inflammatory reactions of microglia.

The present study aimed to examine how the long non­coding RNA (lncRNA) RP11­543N12.1 interacted with microRNA (miR)­324­3p to modify microglials (MIs)­induced neuroblastoma cell apoptosis, which may pose benefits to the treatment of Alzhemier's disease (AD). The cell model of AD was established by treating SH­SY5Y cells with amyloid ß (Aß)25­35, and MI were acquired using primary cell culture technology. The lncRNAs that were differentially expressed between SH­SY5Y and control cells were screened through a microarray assay and confirmed via polymerase chain reaction. In addition, overexpression of RP11­543N12.1 and miR­324­3p was established by transfection of SH­SY5Y cells with pcDNA3.1(+)­RP11­543N12.1 and miR­324­3p mimics, respectively, while downregulation of RP11­543N12.1 and miR­324­3p was achieved by transfection with RP11­543N12.1­small interfering RNA (siRNA) and miR­324­3p inhibitor, respectively. The interaction between RP11­543N12.1 and miR­324­3p was confirmed with a dual­luciferase reporter gene assay. The results revealed that the expression levels of total and phosphorylated tau in SH­SY5Y cells were significantly elevated following Aß25­35 treatment (P<0.05), and RP11­543N12.1 was found to be differentially expressed between the control and Aß25­35­treated cells (P<0.05). Furthermore, the targeted association of RP11­543N12.1 and miR­324­3p was predicted based on miRDB4.0 and PITA databases, and then validated via the dual­luciferase reporter gene assay. SH­SY5Y cells transfected with siRNA or inhibitor, and treated with Aß25­35 displayed cellular survival and apoptosis that were similar to the normal levels (P<0.05). Finally, co­culture of MI and SH­SY5Y cells transfected with RP11­543N12.1­siRNA/miR­324­3p inhibitor significantly enhanced cell apoptosis (P<0.05). In conclusion, RP11­543N12.1 targeted miR­324­3p to suppress proliferation and promote apoptosis in the AD cell model, suggesting that RP11­543N12.1 and miR­324­3p may be potential biomarkers and therapeutic targets for AD.

Curcumin inhibiting Th17 cell differentiation by regulating the metabotropic glutamate receptor-4 expression on dendritic cells.

Th17 cells have been categorized as a new lineage of CD4+ T cells, and played a crucial role in the pathogenesis of numerous autoimmune disorders. Type 4 metabotropic glutamate receptor (mGluR4), a member of group III mGluRs, recently has been found to be expressed in many types of immune cells and mediate adaptive immunity. Curcumin has been shown to exhibit potent anti-inflammatory, antimutagenic and anticarcinogenic properties. For the past few years, it has gradually been regarded as an pluripotent immunomodulatory agent that can regulate the activation of immune cells. In the present study, we investigated the efficacy and mechanism of curcumin on Th17 cells. Treatment with curcumin significantly reduced IL-6 and IL-23 production by dendritic cells (DC). Additionally, it had a dramatic reduction in the proliferation of CD4+ T cells co-cultured with DC. Furthermore, expression of the Th17 cells related cytokine profiles (IL-17A and RORγt) was dramatically decreased in curcumin-treated groups. These findings indicated that curcumin inhibited the differentiation and development of Th17 cells. Besides, we found that mGluR4 was constitutively expressed in mouse bone marrow derived DC (BMDC) for the first time. In addition, mGluR4 siRNA-transfected BMDC tipped the balance of T cell differentiation in favor of the Th17 phenotype. We first reported that curcumin increased the mGluR4 expression in mouse BMDC activated with LPS, which likely contributed to the mechanism of inhibiting the Th17 cell differentiation. Our findings suggest that curcumin might be a potential candidate for Th17 related autoimmune disorders.

[Efficacy analysis on hip replacement for hip-joint diseases with Parkinson disease].

OBJECTIVE: To explore clinical efficacy of hip replacement for hip-joint diseases with Parkinson disease. METHODS: From December 2011 to December 2016, 18 patients with hip-joint diseases with Parkinson disease treated by hip replacement, including 8 males and 10 females aged from 59 to 87 years old with an average of 71 years old. Among them, 3 cases were developmental dysplasia of hip, 3 cases were femoral head necrosis and 12 cases were femoral neck fracture. All patients manifested with obvious pain and limitation of stepping ability. Postoperative complications were observed and Harris score were used to compare hip joint function after operation. RESULTS: The incision were healed well, and pain were alleviated or disappeared, and hip joint function were improved. Eighteen patients were followed up from 1 to 3 years with an average of 2.3 years. At the latest follow up, 14 cases recovered freedom-walk, 2 cases could walk with walking stick, 1 case could walk with walking aid and 1 case was died. Among 18 patients, 2 cases were occurred dislocation, and 1 case were died for cardiac disease at 3 months after operation. Four patients were occurred slight pain. There were significant differences in Harris scores among preoperative (41.7±1.4), 6 months after operation(80.1±5.4) and the final follow-up (83.4±2.1), and 10 cases got excellent result, 4 good, 1 fair and 2 poor. CONCLUSIONS: Application of hip replacement for hip-joint diseases with Parkinson disease is a safe and effective clinical therapy, and has advantages of less complications and rapid recovery of hip joint function.

Clinical, imaging, and follow-up observations of patients with anti-GABAB receptor encephalitis.

PURPOSE: Anti-gamma-aminobutyric acid B (anti-GABAB) receptor encephalitis is a newly described type of autoimmune encephalitis. We report a case series of patients diagnosed with anti-GABAB receptor encephalitis in China, focusing on their presentations, laboratory and imaging results, and outcomes, as well as the treatment strategies which were employed. METHODS: Data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital, School of Medicine, Zhejiang University, from January 2014 to June 2015 were retrospectively collected and analyzed. Based on specific diagnostic criteria, seven cases were included. RESULTS: Six of the seven patients were males, and a median age at presentation of 56 years (range: 4-71 years). Seizures were the most common initial symptom, and all patients developed symptoms of typical limbic encephalitis during their disease course. Additional types of autoantibodies were identified in four patients. After presentation, three patients were found to have small cell lung cancer and one patient was eventually diagnosed with thymoma. All patients accepted first-line immune therapy, but only one chose tumor treatment. The three tumor-free patients had a good outcome, whereas those with tumors had a poor one. Finally, there were no relapses during follow-up. CONCLUSION: Anti-GABAB receptor encephalitis is a rare, unique autoimmune disease, and is often associated with tumors. It should be considered in the differential diagnosis for middle and senior-aged patients who present with predominantly limbic encephalitis symptoms. Importantly, earlier recognition of this potentially treatable condition could improve its overall prognosis.

Effect of FK506 on apoptosis of facial motor neurons in rats and its possible mechanism.

To investigate the effect of FK506 on apoptosis of facial motor neurons in rats and its possible mechanism. A total of 48 Wistar rats were randomly divided into experimental group and control group. Facial nerve injury model was established by transection of facial nerve at stylomastoid foramen. Rats in experimental group and control group were provided with FK506 and normal saline by intraperitoneal injection, respectively. The morphology of facial neurons was observed under light microscope at different time points after injury. Apoptotic facial motor neurons were detected by TdT-mediated dUTP-biotin nick and labeling (TUNEL) staining, and expression of bcl-2 and bax was evaluated by immunohistochemistry. After facial nerve transection, the apoptotic cells in experimental group significantly decreased compared to control group (P < 0.05), with higher expression of bcl-2 and lower expression of bax in experimental group. FK506 could inhibit apoptosis of facial motor neurons after facial nerve transection, possibly via up-regulation of bcl-2 expression and down-regulation of bax expression.

Curcumin induces autophagy, inhibits proliferation and invasion by downregulating AKT/mTOR signaling pathway in human melanoma cells.

Melanoma is the foremost malignant cutaneous cancer and it is extremely resistant to chemotherapy and radiotherapy. Curcumin is an active component of turmeric, the yellow spice derived from the rhizome of Curcuma longa, and is widely known for its anti-inflammatory and anti-cancerogenic properties. Several recent studies suggest that curcumin induces apoptosis by modulating multiple signaling pathways to exert its anticancer effect. In the present study, we investigated the effect of curcumin on the viability, invasion potential, cell cycle, autophagy and the AKT, mTOR, P70S6K proteins of AKT/mTOR signaling pathway in human melanoma A375 and C8161 cell lines in vitro and in an in vivo tumorigenesis model. Curcumin effectively inhibited the proliferation of melanoma cells in vitro and in vivo. It suppressed cell invasion, arrested the cancer cells at G2/M phase of the cell cycle, and induced autophagy. Furthermore, curcumin suppressed the activation of AKT, mTOR and P70S6K proteins. Curcumin, therefore, is a potent suppressor of cell viability and invasion, and simultaneously an inducer of autophagy in A375 and C8161 cells. Accordingly, curcumin could be a novel therapeutic candidate for the management of melanoma.

Biological intensity-modulated radiotherapy plus neoadjuvant chemotherapy for multiple peritoneal metastases of ovarian cancer: A case report.

The current study presents the case of a 68-year-old female patient who received biological intensity-modulated radiotherapy (BIMRT) and neoadjuvant chemotherapy for multiple peritoneal metastases of ovarian cancer. The International Federation of Gynecology and Obstetrics disease stage was IIIc. In addition, the patient presented with urination and defecation difficulties. The result of tumor marker detection showed a carcinoembryonic antigen level of 348.2ng/ml, a cancer antigen 125 level of 2,091 U/ml and a cancer antigen 19-9 level of 113 U/ml. Computed tomography (CT) indicated and ovarian cystic or solid package, enlargement of multiple abdominal and retroperitoneal lymph nodes and abdominal cavity effusion. Positron emission tomography/CT indicated multiple internal organ metastases. The center of the ovarian cystic or solid package was considered to be a malignant tumor. A large amount of ascites were detected, as well as abdominal and retroperitoneal lymph node metastasis. The patient was treated with BIMRT at a total dose of 48 Gy, administered as a single 4.0-Gy dose 12 times. In addition, 100 mg cisplatin was administered as a peritoneal perfusion, followed by two cycles of 180 mg Taxol and 100 mg cisplatin. Furthermore, the enlargement of the lymph nodes was reduced and the tumor in the region of the ovary had decreased in size by 90%. The ascites had disappeared and the abdominal pain was greatly improved. At the time of writing this manuscript, the patient was well and without relapse. Therefore, modern radiotherapy techniques, such as BIMRT, may be considered as a beneficial treatment option for ovarian cancer patients with multiple peritoneal metastases in whom surgery is not suitable.