Cytomegalovirus Diseases of the Gastrointestinal Tract in Immunocompetent Patients: A Narrative Review.

Cytomegalovirus (CMV) is a potential pathogen that causes gastrointestinal (GI) tract diseases regardless of host immunity. In contrast to immunocompromised individuals, immunocompetent patients lack a comprehensive overview of the gastrointestinal manifestations. This study aims to provide a comprehensive summary of the current evidence regarding presentations, diagnostics, management, risk assessment, and outcomes in immunocompetent patients with CMV GI disease. A thorough literature search of English publications up to April 2022 was conducted across electronic databases to identify relevant articles, with eligible case series selected for detailed analysis. The majority of immunocompetent patients affected by CMV GI disease are typically elderly, critically ill, or burdened with comorbidities that compromise immunity. Clinical presentations range from subtle symptoms to severe surgical conditions, including instances of mortality. Specific clinical presentations, blood test results, or endoscopic features are lacking, necessitating reliance on histopathological tests such as immunohistochemistry staining for diagnosis. While antiviral therapy may offer benefits in improving outcomes, careful individual assessment is warranted due to diverse comorbidities and potential side effects. Mortality rates vary considerably based on underlying medical conditions and therapeutic approaches. It is imperative for clinicians to maintain vigilance for CMV GI disease among high-risk groups, despite their baseline immunocompetence, in order to enhance clinical outcomes.

Resorbable nanofibrous membranes for local and sustained co-delivery of acyclovir and ketorolac in herpes therapy.

Herpes simplex and herpes zoster are both viral infections caused by members of the herpesvirus family. The former is characterized by painful, fluid-filled blisters or sores on the skin and mucous membranes, while the latter presents as a painful rash with blisters, typically occurring in a single band or patch along one side of the body. The treatment remains a challenge since current antiviral therapy via oral administration may lead to unfavorable side effects such as headaches, nausea, and diarrhea. This study used electrospinning to develop biodegradable nanofibrous poly(lactic-co-glycolic acid) (PLGA) membranes for delivery of both acyclovir and ketorolac. The structure of the spun nanofibers was assessed via scanning electron microscopy (SEM), and the appearance of loaded acyclovir and ketorolac in the nanofibers was confirmed with Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Release profiles of these drugs from the nanofibrous membranes were assessed using in vitro elution studies, high-performance liquid chromatography (HPLC) assays, and in vivo drug release patterns. The electrospun nanofibers had a size range of 283-725 nm in diameter, resembling the extracellular matrix of natural tissue and demonstrated excellent flexibility and extensibility. Notably, the drug-eluting nanofibers exhibited an extended release of high levels of acyclovir and ketorolac over a 21-day period. Thus, biodegradable drug-eluting membranes with a prolonged drug release could be a potential therapeutic approach for treating herpes infections.

Comparative Analysis of Cytomegalovirus Gastrointestinal Disease in Immunocompetent and Immunocompromised Patients.

BACKGROUND: Cytomegalovirus (CMV) gastrointestinal (GI) diseases impact both immunocompromised and immunocompetent individuals, yet comprehensive studies highlighting the differences between these groups are lacking. METHODS: In this retrospective study (January 2000 to July 2022) of 401 patients with confirmed CMV GI diseases, we categorized them based on immunological status and compared manifestations, treatments, outcomes, and prognostic factors. RESULTS: The immunocompromised patients (n = 193) showed older age, severe illnesses, and higher comorbidity rates. GI bleeding, the predominant manifestation, occurred more in the immunocompetent group (92.6% vs. 63.6%, p = 0.009). Despite longer antiviral therapy, the immunocompromised patients had higher in-hospital (32.2% vs. 18.9%, p = 0.034) and overall mortality rates (91.1% vs. 43.4%, p < 0.001). The independent factors influencing in-hospital mortality in the immunocompromised patients included GI bleeding (OR 5.782, 95% CI 1.257-26.599, p = 0.024) and antiviral therapy ≥ 14 days (OR 0.232, 95% CI 0.059-0.911, p = 0.036). In the immunocompetent patients, age (OR 1.08, 95% CI 1.006-1.159, p = 0.032), GI bleeding (OR 10.036, 95% CI 1.183-85.133, p = 0.035), and time to diagnosis (OR 1.029, 95% CI 1.004-1.055, p = 0.021) were significant prognostic factors, with the age and diagnosis time cut-offs for survival being 70 years and 31.5 days, respectively. CONCLUSIONS: GI bleeding is the most common manifestation and prognostic factor in both groups. Early diagnosis and effective antiviral therapy can significantly reduce in-hospital mortality.

Comparison of immediate germline sequencing and multi-step screening for Lynch syndrome detection in high-risk endometrial and colorectal cancer patients.

OBJECTIVE: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome with a significantly increased risk of colorectal and endometrial cancers. Current standard practice involves universal screening for LS in patients with newly diagnosed colorectal or endometrial cancer using a multi-step screening protocol (MSP). However, MSP may not always accurately identify LS cases. To address this limitation, we compared the diagnostic performance of immediate germline sequencing (IGS) with MSP in a high-risk group. METHODS: A total of 31 Taiwanese women with synchronous or metachronous endometrial and colorectal malignancies underwent MSP which included immunohistochemical staining of DNA mismatch repair (MMR) proteins, MLH1 promoter hypermethylation analysis, and germline sequencing to identify pathogenic variants. All patients who were excluded during MSP received germline sequencing for MMR genes to simulate IGS for the detection of LS. RESULTS: Our findings indicate that IGS surpassed MSP in terms of diagnostic yield (29.0% vs. 19.4%, respectively) and sensitivity (90% vs. 60%, respectively). Specifically, IGS successfully identified nine LS cases, which is 50% more than the number detected through MSP. Additionally, germline methylation analysis revealed one more LS case with constitutional MLH1 promoter hypermethylation, bringing the total LS cases to ten (32.3%). Intriguingly, we observed no significant differences in clinical characteristics or overall survival between patients with and without LS in our cohort. CONCLUSION: Our study suggests that IGS may potentially offer a more effective approach compared to MSP in identifying LS among high-risk patients. This advantage is evident when patients have been pre-selected utilizing specific clinical criteria.

Machine Learning Radiomics Signature for Differentiating Lymphoma versus Benign Splenomegaly on CT.

BACKGROUND: We aimed to develop and validate a preoperative CT-based radiomics signature for differentiating lymphoma versus benign splenomegaly. METHODS: We retrospectively analyzed CT studies from 139 patients (age range 26-93 years, 43% female) between 2011 and 2019 with histopathological diagnosis of the spleen (19 lymphoma, 120 benign) and divided them into developing (n = 79) and testing (n = 60) datasets. The volumetric radiomic features were extracted from manual segmentation of the whole spleen on venous-phase CT imaging using PyRadiomics package. LASSO regression was applied for feature selection and development of the radiomic signature, which was interrogated with the complete blood cell count and differential count. All p values < 0.05 were considered to be significant. RESULTS: Seven features were selected for constructing the radiomic signature after feature selection, including first-order statistics (10th percentile and Robust Mean Absolute Deviation), shape-based (Surface Area), and texture features (Correlation, MCC, Small Area Low Gray-level Emphasis and Low Gray-level Zone Emphasis). The radiomic signature achieved an excellent diagnostic accuracy of 97%, sensitivity of 89%, and specificity of 98%, distinguishing lymphoma versus benign splenomegaly in the testing dataset. The radiomic signature significantly correlated with the platelet and segmented neutrophil percentage. CONCLUSIONS: CT-based radiomics signature can be useful in distinguishing lymphoma versus benign splenomegaly and can reflect the changes in underlying blood profiles.

Update of Diagnosis and Targeted Therapy for ALK+ Inflammation Myofibroblastic Tumor.

OPINION STATEMENT: Inflammatory myofibroblastic tumor (IMT), characterized by intermediate malignancy and a propensity for recurrence, has presented a formidable clinical challenge in diagnosis and treatment. Its pathological characteristics may resemble other neoplasms or reactive lesions, and the treatment was limited, taking chemotherapies as the only option for those inoperable. However, discovering anaplastic lymphoma kinase (ALK) protein expression in approximately 50% of IMT cases has shed light on a new diagnostic approach and application of targeted therapies. With the previous success of combating ALK+ non-small-cell lung cancers with ALK tyrosine kinase inhibitors (TKIs), crizotinib, a first-generation ALK-TKI, was officially approved by the U.S. Food and Drug Administration in 2020, to treat unresectable ALK+ IMT. After the approval of crizotinib, other ALK-TKIs, such as ceritinib, alectinib, brigatinib, and lorlatinib, have proven their efficacy on ALK+ IMT with sporadic case reports. The sequential treatments of targeted therapies in may provide the insight into the choice of ALK-TKIs in different lines of treatment for unresectable ALK+ IMT.

Hypoxia-associated genetic signature in ovarian steroid cell tumor NOS.

Steroid cell tumors, not otherwise specified (SCT-NOS), are uncommon ovarian neoplasms accompanied by virilization symptoms due to hyperandrogenism, which are malignant in approximately one-third of the cases. Given the rarity of SCT-NOS, their molecular underpinnings have not yet been studied in depth. In this case series, we performed the first comprehensive analysis of the genetic landscape of this rare ovarian tumor. A detailed clinicopathological description of an index case is also provided. Over a 20-year period, a total of eight patients were seen at our institution. Total nucleic acids (RNA and DNA) were extracted from evaluable formalin-fixed, paraffin-embedded tumor specimens (n = 7) and subjected to TruSight Oncology 500 testing and/or exome sequencing. The results identified pathogenic variants in several hypoxia-related genes - including HIF1A, VHL, SDHB, SRC, IDH2, and FOXO4. As the first comprehensive genetic analysis of SCT-NOS, this study shows that dysregulation in the hypoxia signaling pathway is a key molecular feature of this rare tumor. Clinically, long-term follow-up with periodic measurements of androgen levels should be pursued in all cases since recurrences may occur several years after the initial diagnosis.

Hybrid Resorbable 3D-Printed Mesh/Electrospun Nanofibrous Drug/Biomolecule-Eluting Mats for Alveolar Ridge Preservation.

In this research study, we developed hybrid resorbable three-dimensional (3D)-printed mesh/electrospun nanofibrous biomolecule-eluting mats for alveolar ridge preservation. The fabrication process involved the use of 3D printing and coaxial electrospinning technologies. Specifically, we utilized a lab-developed solution-extrusion 3D printer to fabricate polycaprolactone (PCL) meshes. Then, bi-layered poly(lactic-co-glycolic acid) (PLGA) nanofibrous membranes, which embedded ibuprofen and epidermal growth factor (EGF), were prepared utilizing electrospinning and coaxial electrospinning techniques, respectively. To ensure the quality of the produced mesh and spun nanofibers, we carried out a characterization process. Furthermore, we estimated the in vitro and in vivo release characteristics of ibuprofen and EGF, respectively, using high-performance liquid chromatography and enzyme-linked immunosorbent assays. In addition, we assessed the effectiveness of hybrid nanofibrous mats for preserving the alveolar ridge by adopting an animal model and conducting a histology examination. The study findings demonstrate that the nanofibrous mats provided a continuous discharge of ibuprofen and EGF for more than four weeks. Moreover, the animal test carried out in vivo showed that animals implanted with this combination of mesh and drug-eluting mats displayed considerably greater mobility than those without mats. The histological analysis revealed no unfavorable impacts from the drug-eluting mats. Our study demonstrated the successful fabrication of resorbable drug-eluting nanofibrous mats for alveolar ridge preservation by utilizing both 3D printing and coaxial electrospinning technologies.

Small cell neuroendocrine carcinoma of the cervix: From molecular basis to therapeutic advances.

Small cell neuroendocrine carcinoma of the cervix (SCNECC) is an uncommon but aggressive uterine malignancy, the cause of which is generally associated with human papillomavirus (HPV) infection. A lack of clinical trials and evidence-based treatment guidelines poses therapeutic challenges to this rare tumor. At present, published data remain limited to case series and case reports. While clinical management has traditionally followed those of small cell neuroendocrine (SCNE) lung cancer relying on surgery, chemoradiation, and systemic chemotherapy, the prognosis remains dismal. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies that target programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1), atezolizumab and durvalumab have proven effective in extensive-stage SCNE lung cancer. Moreover, pembrolizumab has also proven beneficial effects when added onto chemotherapy in metastatic and recurrent HPV-associated non-SCNE cervical cancer. It holds promise to use ICIs in combination with chemoradiation to improve the clinical outcomes of patients with SCNECC. Future advances in our understanding of SCNECC biology - associated with the study of its genomic and molecular aberrations as well as knowledge from SCNE of lung and other extrapulmonary sites- would be helpful in discovering new molecular targets for drug development. Collaborative efforts and establishment of a SCNECC-specific biobank will be essential to achieve this goal.

Intraductal papillary neoplasm of the bile duct presenting with hepatogastric fistula: a case report and literature review.

Intraductal papillary neoplasm of the bile duct (IPNB) is an uncommon entity characterized by papillary growth within the bile duct lumen. IPNB is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas, which sometimes complicates with fistula formation to adjacent organs, mainly due to high-pressure related erosion from mucin-filled ducts. However, fistula formation from IPNB is quite rare. Here we report a case of IPNB complicated with hepatogastric fistula. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed disproportional dilatation of left intrahepatic duct with intraluminal soft tissue nodules and fistulous connections to gastric high body. Endoscopy revealed ulcers with two fistulous orifices at upper gastric body. The patient underwent left hepatectomy with gastric wedge resection. Histopathology examination revealed IPNB with invasive cholangiocarcinoma, directly invading to gastric wall leading to hepatogastric fistula. In summary, we have presented the clinical, imaging and pathological findings, along with a comprehensive review of relevant literature, in order to enhance the understanding of this rare condition.

Targeted next-generation sequencing for the detection of cancer-associated somatic mutations in adenomyosis.

Adenomyosis is a condition characterised by the invasion of endometrial tissues into the uterine myometrium, the molecular pathogenesis of which remains incompletely elucidated. Lesion profiling with next-generation sequencing (NGS) can lead to the identification of previously unanticipated causative genes and the detection of therapeutically actionable genetic changes. Using an NGS panel that included 275 cancer susceptibility genes, this study examined the occurrence and frequency of somatic mutations in adenomyotic tissue specimens collected from 17 women. Extracted DNA was enriched using targeted formalin-fixed paraffin-embedded tissue cores prior to the identification of lesion-specific variants. The results revealed that KRAS and AT-rich interactive domain 1A (ARID1A) were the two most frequently mutated genes (mutation frequencies: 24% and 12%, respectively). Notably, endometrial atypical hyperplasia did not involve adenomyotic areas. We also identified, for the first time, two potentially pathogenic mutations in the F-box/WD repeat-containing protein 7 (FBXW7) and cohesin subunit SA-2 (STAG2) genes. These findings indicate that mutations in the KRAS, ARID1A, FBXW7 and STAG2 genes may play a critical role in the pathogenesis of adenomyosis. Additional studies are needed to assess whether the utilisation of oncogenic driver mutations can inform the surveillance of patients with adenomyosis who had not undergone hysterectomy.Impact statementWhat is already known on this subject? Although somatic point mutations in the KRAS oncogene have been recently detected in adenomyosis, the molecular underpinnings of this condition remains incompletely elucidated. Lesion profiling with next-generation sequencing (NGS) can lead to the identification of previously unanticipated causative genes and the detection of therapeutically actionable genetic changes.What do the results of this study add? The results of NGS revealed that KRAS and AT-rich interactive domain 1A (ARID1A) were the two most frequently mutated genes (mutation frequencies: 24% and 12%, respectively). We also identified, for the first time, two potentially pathogenic mutations in the F-box/WD repeat-containing protein 7 (FBXW7) and cohesin subunit SA-2 (STAG2) genes.What are the implications of these findings for clinical practice and/or further research? The utilisation of oncogenic driver mutations has the potential to inform the surveillance of patients with adenomyosis who had not undergone hysterectomy.

Lymphocyte disturbance and functional assessment of the [Asp521Asn] ZAP70 mutation.

Activated zeta-chain-associated protein kinase 70 (ZAP70) phosphorylates the TCRαß:CD3:zeta complex to diversify and amplify TCR signaling. Patients with ZAP70 mutations can present with phenotypes of immune dysregulation as well as infection. We identified the first Taiwanese boy with the [Asp521Asn] ZAP70 mutation who presented with recurrent pneumonia, inflammatory bowel disease-like diarrhea, transient hematuria and autoimmune hepatitis. He had isolated CD8 lymphopenia, eosinophilia, hypogammaglobulinemia, and impaired lymphocyte proliferation. Downstream CD3/CD28 signaling, phosphorylation of AKT, ZAP70 and Ca2+ influx were decreased in [Asp521Asn] ZAP70 lymphocytes. Immunophenotyping analysis revealed expansion of transitional B and CD21-low B cells, Th2-skewing T follicular helper cells, but lower Treg cells. The Asp521Asn-ZAP70 hindered TCR-CD3 downstream phosphorylation and disturbed lymphocyte subgroup "profiles" leading to autoimmunity/autoinflammation. Further large-scale studies are warranted to clarify this lymphocyte disturbance. The prognosis significantly depends on hematopoietic stem cell transplantation, but not the genotype, the presence of opportunistic infections or immune dysregulation.

Mutations in circulating tumor DNA detected in the postoperative period predict poor survival in patients with ovarian cancer.

BACKGROUND: We investigated whether mutations in plasma circulating tumor DNA (ctDNA) can provide prognostic insight in patients with different histological types of ovarian carcinoma. We also examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding formalin-fixed paraffin-embedded (FFPE) tumor specimens. METHODS: Between July 2016 and December 2017, 29 patients with ovarian carcinoma were prospectively enrolled. FFPE tumor specimens were obtained from all participants. A total of 187 blood samples for ctDNA analysis were collected before surgery (C0), immediate after surgery before adjuvant chemotherapy (C1), and at six-month intervals. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: The study cohort consisted of 13 (44.8%) patients with high-grade serous carcinomas (HGSC), 9 (31.0%) with clear cell carcinoma, 2 (6.9%) with mucinous carcinomas, 4 (13.8%) with low-grade serous carcinomas, and 1 (3.4%) with endometrioid carcinoma. Twenty-four (82.8%) patients had at least one detectable ctDNA variant. The concordance rate between mutations identified in pretreatment ctDNA and corresponding FFPE tumor specimens was 92.3% for patients with HGSC and 58.6% for the entire cohort. The median follow-up time was 33.15 months (range: 0.79-46.13 months). Patients with an advanced stage disease more likely had detectable ctDNA mutations before surgery (C0) and after surgery at C1, while those with HGSC more likely had ctDNA mutations detected before surgery. The presence of ctDNA mutations at C1 was an independent predictor of worse OS with a hazard ratio of 6.56 (95% confidence interval, (1.07-40.17) for detectable versus undetectable C1 ctDNA variants, p = 0.042). CONCLUSIONS: ctDNA mutations are common in patients with ovarian carcinoma. The presence of ctDNA mutations after surgery was an independent predictor of less favorable PFS and OS.

Mucinous Adenocarcinoma of the Lung Diagnosed by Radial Endobronchial Ultrasound-guided Bronchoscopic Cryobiopsy and Presenting as Interstitial Lung Disease in a Patient with Systemic Sclerosis.

We report a patient with systemic sclerosis who was diagnosed with advanced-stage mucinous adenocarcinoma of the lungs. The clinical presentation, imaging findings, pathological results, and molecular diagnoses are presented. A 64-year-old woman with systemic sclerosis was administered prednisolone and hydroxychloroquine sulfate to control her disease. High-resolution computed tomography (HRCT) revealed an interstitial pattern in both lungs during annual imaging. Connective tissue disease-associated interstitial lung disease (CTD-ILD) was diagnosed using blood tests, pulmonary function tests, and imaging findings. One year later, the patient underwent follow-up chest HRCT, which showed progressive lung disease. The patient underwent endobronchial ultrasound (EBUS)-guided transbronchial lung cryobiopsy and computed tomography-guided biopsy for a pathological diagnosis. The pathology reports of bilateral lungs disclosed mucinous adenocarcinoma. After tumor staging and mutation testing, the patient received chemotherapy with pemetrexed and cisplatin. The bilateral lung lesions subsided after four cycles of first-line chemotherapy. Patients with CTD and lung involvement may be diagnosed with CTD-ILD. Although histopathological results are not mandatory for ILD diagnosis, EBUS-guided transbronchial lung biopsy or lung cryobiopsy should be considered when ILD has atypical or unexplained features.

Analysis of endometrial lavage microbiota reveals an increased relative abundance of the plastic-degrading bacteria Bacillus pseudofirmus and Stenotrophomonas rhizophila in women with endometrial cancer/endometrial hyperplasia.

The pathogenic influences of uterine bacteria on endometrial carcinogenesis remain unclear. The aim of this pilot study was to compare the microbiota composition of endometrial lavage samples obtained from women with either endometrial hyperplasia (EH) or endometrial cancer (EC) versus those with benign uterine conditions. We hypothesized that specific microbiota signatures would distinguish between the two groups, possibly leading to the identification of bacterial species associated with endometrial tumorigenesis. A total of 35 endometrial lavage specimens (EH, n = 18; EC, n = 7; metastatic EC, n = 2; benign endometrial lesions, n = 8) were collected from 32 women who had undergone office hysteroscopy. Microbiota composition was determined by sequencing the V3-V4 region of 16S rRNA genes and results were validated by real-time qPCR in 46 patients with EC/EH and 13 control women. Surprisingly, we found that Bacillus pseudofirmus and Stenotrophomonas rhizophila - two plastic-degrading bacterial species - were over-represented in endometrial lavage specimens collected from patients with EC/EH. Using computational analysis, we found that the functional profile of endometrial microbiota in EC/EH was associated with fatty acid and amino acid metabolism. In summary, our hypothesis-generating data indicate that the plastic-degrading bacteria Bacillus pseudofirmus and Stenotrophomonas rhizophila are over-represented within the endometrial lavage microbiota of women with EC/EH living in Taiwan. Whether this may be related to plastic pollution deserves further investigation.

Management and Prognosis of Patients with Recurrent or Persistent/Progressive Uterine Carcinosarcoma.

Uterine carcinosarcoma (UCS) is a highly aggressive gynecologic malignancy. Recurrent or persistent/progressive disease is usually fatal. We aimed to investigate the management and prognosis of these patients. Clinical records of UCS patients from June 1987 to April 2020 were retrospectively reviewed. The stage was re-assigned with the FIGO 2009 staging system. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). Of the 168 patients, 98 experienced treatment failure. The median time to treatment failure (TTF) was 8.1 months (range: 0.0-89.1). The median follow-up time of censored patients was 32.0 months (range: 16.8-170.7). The 5-year SAR rates of those with recurrent or persistent/progressive disease were 7.6%. On multivariate analysis, salvage therapy mainly using radiotherapy (HR 0.27, 95% CI: 0.10-0.71) or chemotherapy (HR 0.41, 95% CI: 0.24-0.72) or chemoradiotherapy (CRT) (HR 0.33, 95% CI: 0.15-0.75) were associated with improved SAR, whereas disseminated recurrence was associated with significantly worse SAR (HR 3.94, 95% CI: 1.67-9.31, p = 0.002). Salvage therapy using radiotherapy or chemotherapy or CRT significantly improved SAR. Surgery significantly improved CSS but not SAR, adjusting for confounding factors.

Alterations in Gut Microbiota and Upregulations of VPAC2 and Intestinal Tight Junctions Correlate with Anti-Inflammatory Effects of Electroacupuncture in Colitis Mice with Sleep Fragmentation.

The relationship between inflammatory bowel disease and sleep disturbances is complicated and of increasing interest. We investigated the inflammatory and immunological consequences of EA in sleep-deprived colitis and found that dextran sulfate sodium (DSS)-induced colitis in sleep-fragmented (SF) mice was more severe than that in mice with normal sleep. This increase in the severity of colitis was accompanied by reduced body weight, shortened colon length, and deteriorated disease activity index. DSS with SF mice presented obvious diminished intestinal tight junction proteins (claudin-1 and occludin), elevated proinflammatory cytokines (CRP, IFN-γ, IL-6), lowered melatonin and adiponectin levels, downregulated vasoactive intestinal peptide (VIP) type 1 and 2 receptor (VPAC1, VPAC2) expression, and decreased diversity of gut bacteria. EA ameliorated colitis severity and preserved the performance of the epithelial tight junction proteins and VIP receptors, especially VPAC2. Meanwhile, the innate lymphoid cells-derived cytokines in both group 2 (IL-4, IL5, IL-9, IL-13) and group 3 (IL-22, GM-CSF) were elevated in mice colon tissue. Furthermore, dysbiosis was confirmed in the DSS group with and without SF, and EA could maintain the species diversity. Firmicutes could be restored, such as Lachnospiraceae, and Proteobacteria become rebalanced, mainly Enterobacteriaceae, after EA intervention. On the other hand, SF plays different roles in physiological and pathological conditions. In normal mice, interrupted sleep did not affect the expression of claudin-1 and occludin. But VPAC1, VPAC2, and gut microbiota diversity, including Burkholderiaceae and Rhodococcus, were opposite to mice in an inflamed state.

A case of adult granulosa cell tumor of the ovary with long-term survival after multiple recurrences.

OBJECTIVE: To illustrate the clinical course of a rare case of recurrent adult granulosa cell tumor (AGCT) and discuss the features and management for recurrences. CASE REPORT: A 56-year-old female was first diagnosed with AGCT in 2008 and had uneventful, regular follow-ups until 2013. Recurrence was suspected and proven by computed tomography-guided biopsy. After undergoing complete cytoreductive surgery (CRS) followed by adjuvant megestrol acetate then leuprolide acetate, another recurrence sprouted at the presacral area in 2017. On both occasions, CRS with no visible residual tumor were attained. The patient has remained in complete remission to date with progestin therapy. CONCLUSION: There are currently no standardized tumor markers, imaging exams, or therapies for managing AGCT recurrences. Whole exome sequencing analysis of our patient suggested possible association with triosephosphate isomerase 1 mutation. Regular follow-ups with at least two types of imaging exams and indefinite hormone therapy are crucial for this patient's remission.