The role of upfront lenalidomide maintenance for primary central nervous system lymphoma following first-line methotrexate treatment: A retrospective study.

BACKGROUND: Consolidation therapy improves the duration of response among patients with primary central nervous system lymphoma (PCNSL). Lenalidomide maintenance has shown encouraging results in older patients with PCNSL. Herein, we performed a retrospective, single-center analysis to evaluate the effect of lenalidomide maintenance on the duration of response in patients with newly-diagnosed PCNSL. METHODS: Sixty-nine adult patients with PCNSL who achieved complete remission or partial remission (PR) after induction therapy were enrolled. The median age of patients was 58.0 years. The maintenance group (n = 35) received oral lenalidomide (25 mg/day) for 21 days, every 28 days for 24 months; the observation group did not undergo any further treatment. RESULTS: After a median follow-up of 32.6 months, the maintenance group experienced fewer relapse events. However, the median progression-free survival (PFS) was similar between groups (36.1 vs. 30.6 months; hazard ratio, 0.78; 95% confidence interval, 0.446). Lenalidomide maintenance significantly improved PFS and overall survival (OS) only among patients who experienced PR after induction. The median duration of lenalidomide maintenance was 18 months; lenalidomide was well tolerated and minimally impacted the quality of life. CONCLUSIONS: The present study was the first to evaluate lenalidomide maintenance as a frontline treatment among patients with PCNSL, PFS and OS did not improve, although the safety profile was satisfactory.

Keratin 17 modulates the immune topography of pancreatic cancer.

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival. METHODS: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs. RESULTS: K17 expression had profound effects on the exclusion of intratumoral CD8+ T cells and was also associated with decreased numbers of peritumoral CD8+ T cells, CD16+ macrophages, and CD163+ macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8+ T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations. CONCLUSIONS: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer.

Expression of RIPK1 and FADD are associated with chemosensitivity and survival in head and heck squamous cell carcinoma via tanshinone IIA-mediated modulation of the RIPK1-FADD-Caspase 8 complex.

Tanshinone IIA (Tan IIA), a main active ingredient of salvia miltiorrhiza, has a wide range of antitumor effects, while its specific role and mechanism in head and neck squamous cell carcinomas (HNSCC) is not fully understood. Totally 59 primary HNSCC patients underwent two courses of induction chemotherapy before surgery. The association between expression of Fas-Associated Death Domain (FADD) and receptor interacting protein kinase 1 (RIPK1) and chemotherapy resistance and survival were evaluated. The cell counting kit-8 was used to detect the effect of Tan IIA on the activity of cisplatin in chemoresistant HNSCC cells through a series of in vitro experiments. The quantitative real-time reverse-transcription polymerase chain reaction, Western blot analysis and flow cytometry were used. FADD and RIPK1 expressions were differentially expressed in Chemosensitive and drug-resistant patients. Furthermore, patients with tumors exhibiting high expression of FADD and RIPK1 had significantly greater risk for chemoresistance and mortality than patients with tumors that had low levels of these proteins. Moreover, Tan IIA reduced the expression of RIPK1 and FADD in HNSCC chemoresistant cell lines, which could increase the chemosensitivity of cisplatin and promote apoptosis. Overexpression of RIPK1 led to attenuation of therapeutic effects of Tan IIA, which were mainly realized through regulation of the RIPK1-FADD-Caspase 8 complex. This study is the first to demonstrate the clinical value and role of FADD and RIPK1 in the treatment of HNSCC. This work establishes the proapoptotic effects of Tan IIA and its potential to enhance chemosensitivity in HNSCC by modulating the RIPK1-FADD-Caspase 8 complex.

Biphasic scaffold loaded with autologous cartilage yields better clinical outcome and MRI filling compared with Marrow Stimulation for Focal Osteochondral Lesions in the Knee.

PURPOSE: The purpose of this study was to evaluate the effectiveness of Marrow stimulation (MS) versus biphasic scaffold loaded with autologous cartilage (Scaffold) in treating focal osteochondral lesions of the knee. METHODS: 54 patients with symptomatic focal chondral or osteochondral lesion in the knee were randomized to either the Scaffold group or the MS group. International Knee Documentation Committee (IKDC) subjective score, the Knee Injury Osteoarthritis Outcome Score (KOOS), and Magnetic Resonance Imaging (MRI) were assessed preoperatively, and at one and two years postoperatively to compare treatment outcomes. Biopsy and second-look arthroscopy were performed one year postoperatively for consenting patients. RESULTS: There were 27 patients (Mean age 31.33 ± 10.95) in the Scaffold group, and 27 patients (31.74 ± 11.44) in the MS group. The scaffold group and the MS group both included 23 patients with lesions ≤12.5 × 12.5 mm2 mm in size. Additionally, each group had 4 patients with lesions between than 12.5 × 12.5 mm2 and ≤ 12.5 × 25 mm2. Both interventions achieved significant improvement in clinical outcome scores at two years. The Scaffold group had higher IKDC score than the MS group at two years (93.85 ± 9.55 vs 92.11 ± 9.84) and in the Symptoms/stiffness and Sport/recreation subscales of KOOS at two years (96.57 ± 5.97 vs 93.57 ± 6.52, P < 0.05) and (90.2 ± 17.76 vs 82.8 ± 16.08, P < 0.05). CONCLUSION: The use of biphasic scaffold loaded with autologous cartilage in treating focal osteochondral lesions demonstrates superior clinical outcomes and better cartilage refill on MRI at the two-year follow-up compared to marrow stimulation.

Outcomes of surgical repair of Type III and IV laryngotracheoesophageal clefts with posterior cartilage grafting.

PURPOSE: To describe the clinical outcomes of patients who underwent surgical repair through an anterior approach that involved interposition a posterior cartilage for Type III or Type IV laryngotracheoesophageal cleft (LTEC). METHODS: A chart view was performed on patients with Type III or Type IV LTEC between May 2017 and May 2022. Demographic features and surgical outcomes were collected and analyzed. RESULTS: Seven patients were finally included. Five patients were diagnosed with Type III LTEC and two patients were diagnosed with Type IV LTEC. All but one patients survived and thrived. Four patients were able to successfully extubate with acceptable voice, and two patients were tracheostomized. Five patients were deemed safe for all consistencies food and one was safe for thickened food. After a mean follow-up of 49 months (18-83 months), neither complications nor recurrences were observed. CONCLUSION: An anterior laryngofissure approach to the cleft repair with a posterior cartilage grafting is an effective and safe treatment for Type III or IV LTEC, which enables closure of LTEC and reconstruction of cricoid plate in order to avoid tracheoesophageal fistula formation or subglottic stenosis postoperatively. Severe tracheomalacia and GERD are two main causes for surgical failure.

Longitudinal Imaging of Tumor Perfusion after Preoperative Endovascular Embolization in Meningiomas: Surgical Time Window Selecting, Clinical Consideration and Outcomes.

OBJECTIVE: To quantitatively investigate the longitudinal computed tomography perfusion (CTP) imaging in meningiomas preoperatively embolized using microcatheters. METHODS: This retrospective monocentric study included 27 patients with symptomatic supratentorial meningiomas. Quantitative CTP images before and post-embolization were evaluated and correlated with angiographic, immunohistochemical, and clinical data. RESULTS: The mean age of the patients was 45±18 years, with a female-to-male ratio of 1.45:1. After embolization, both the embolized (Eb) and unembolized (UEb) regions showed hypoperfusion. A steady state was achieved on days 4-6 post-embolization, during which differences in regional cerebral blood volume (rCBV) (Eb 0.5±0.3 ml/100mg, UEb 3.3±1.4 ml/100mg; P<0.05), and mean transit time (MTT) (Eb 3.5 ±1.8 s, UEb 3.1±0.4 s) were observed. The cerebral blood flow (rCBF) and time to the peak (TTP) exhibited opposite patterns between Eb and UEb. A steady state was reached in rCBF (Eb 1.7± 1.2 ml/100 g/min, UEb 30± 5.4 ml/100 g/min; P<0.01), and TTP (Eb 5± 4.8 s, UEb 1.8± 1.5 s; P<0.01) within 4-6 days. Estimated blood loss (EBL) showed significant association with the surgical time interval among the three groups (p<0.05). Tissue necrosis predominated over 7 days post-embolization, indicating a correlation with the devascularization process. The overall incidence of post-embolized headache, seizures, extremity weakness/paralysis, and post-operational headache was 11.1%, 7.4%, 3.7%; and 7.4%, respectively. All symptoms resolved by the last follow-up (3 months). CONCLUSION: Preoperative embolization of meningiomas using N-butyl cyanoacrylate effectively induced significant and sustained tissue transformation and decreased EBL over 7 days. Hemodynamic fluctuations tended to stabilize within 4-6 days.

Stercoral perforation of the cecum: A case report.

BACKGROUND: With less than 90 reported cases to date, stercoral perforation of the colon is a rare occurrence. Stercoral ulceration is thought to occur due to ischemic pressure necrosis of the bowel wall, which is caused by the presence of a stercoraceous mass. To underscore this urgent surgical situation concerning clinical presentation, surgical treatment, and results, we present the case of a 66-year-old man with a stercoral perforation. CASE SUMMARY: A 66-year-old man with a history of hypertension, hyperlipidemia, and gout presented at the emergency department with lower abdominal pain and a low-grade fever lasting for a few hours. Abdominal computed tomography indicated a suspected bezoar (approximately 7.6 cm) in the dilated cecum, accompanied by pericolic fat stranding, mild proximal dilatation of the ileum, pneumoperitoneum, and minimal ascites. Intraoperatively, feculent peritonitis with isolated cecal perforation were observed. Consequently, a right hemicolectomy with peritoneal lavage was performed. A histopathological examination supported the intraoperative findings. CONCLUSION: In stercoral perforations, a diagnosis should be diligently pursued, especially in older adults, and prompt surgical intervention should be implemented.

A critical event frequent lead to reversible spinal cord injury during vertebral column resection surgery.

OBJECTIVE: To report a "critical phase" (between osteotomy completion and correction beginning) that will frequently lead to the reversible intraoperative neurophysiological monitoring (IOM) change during posterior vertebral column resection (PVCR) surgery. METHODS: The study sample consisted of 120 patients with severe spine deformity who underwent PVCR and deformity correction surgeries. Those patients were recruited consecutively from 2010 to 2018 January in our spine center. The detailed IOM data (the amplitude of MEP & SEP) and its corresponding surgical points were collected prospectively. Early and long-term postoperative neurologic outcomes were assessed for the following functions: motor, sensory, and pain at immediate postoperative and 1-year post-operation in this cases series. RESULTS: A total of 105 (105/120) patients presented varying degrees of IOM reduction in the critical phase; the mean IOM amplitude retention vs rescue rate was 27% ± 11.2 versus 58% ± 16.9, P < 0.01 (MEP) & 34% ± 8.3 versus 66% ± 12.4 P < 0.01 (SEP). Patients with postoperative spinal deficits often had a significantly longer IOM-alerting duration than the patients without (p < 0.01, Mann-Whitney U-test), and IOM-alerting duration greater than 39.5 min was identified as an independent predictor of the risk of postoperative spinal deficits. CONCLUSIONS: The reversible IOM events probably often appear in the critical phase during PVCR surgery. The new postoperative spinal deficits are possible for patients without satisfied IOM recovery or alerting duration greater than 39.5 min. Timely and suitable surgical interventions are useful for rescuing the IOM alerts.

FAT1 upregulation is correlated with an immunosuppressive tumor microenvironment and predicts unfavorable outcome of immune checkpoint therapy in non-small cell lung cancer.

Background: Previous studies found that FAT1 was recurrently mutated and aberrantly expressed in multiple cancers, and the loss function of FAT1 promoted the formation of cancer-initiating cells in several cancers. However, in some types of cancer, FAT1 upregulation could lead to epithelial-mesenchymal transition (EMT). The role of FAT1 in cancer progression, which appears to be cancer-type-specific, is largely unknown. Methods: QRT-PCR and immunochemistry were used to verify the expression of FAT1 in non-small cell lung cancer (NSCLC). QRT-PCR and Western blot were used to detect the influence of siFAT1 knockdown on the expression of potential targets of FAT1 in NSCLC cell lines. GEPIA, KM-plotter, CAMOIP, and ROC-Plotter were used to evaluate the association between FAT1 and clinical outcomes based on expression and clinical data from TCGA and immune checkpoint inhibitors (ICI) treated cohorts. Results: We found that FAT1 upregulation was associated with the activation of TGF-ß and EMT signaling pathways in NSCLC. Patients with a high FAT1 expression level tend to have a poor prognosis and hard to benefit from ICI therapy. Genes involved in TGF-ß/EMT signaling pathways (SERPINE1, TGFB1/2, and POSTN) were downregulated upon knockdown of FAT1. Genomic and immunologic analysis showed that high cancer-associated fibroblast (CAF) abundance, decreased CD8+ T cells infiltration, and low TMB/TNB were correlated with the upregulation of FAT1, thus promoting an immunosuppressive tumor microenvironment (TME) which influence the effect of ICI-therapy. Conclusion: Our findings revealed the pattern of FAT1 upregulation in the TME of patients with NSCLC, and demonstrated its utility as a biomarker for unfavorable clinical outcomes, thereby providing a potential therapeutic target for NSCLC treatment.

Mucinous neoplasm of the appendix: A case report and review of literature.

BACKGROUND: Appendiceal mucinous neoplasms (AMNs), although not classified as rare, are relatively uncommon tumors most often discovered incidentally during colorectal surgery. Accurate identification of AMNs is difficult due to non-specific symptoms, overlapping tumor markers with other conditions, and the potential for misdiagnosis. This underscores the urgent need for precision in diagnosis to prevent severe complications. CASE SUMMARY: This case report describes the unexpected discovery and treatment of a low-grade AMN (LAMN) in a 74-year-old man undergoing laparoscopic hemicolectomy for transverse colon adenocarcinoma (AC). Preoperatively, non-specific gastrointestinal symptoms and elevated tumor markers masked the presence of AMN. The tumor, presumed to be an AMN peritoneal cyst intraoperatively, was confirmed as LAMN through histopathological examination. The neoplasm exhibited mucin accumulation and a distinct immunohistochemical profile: Positive for Homeobox protein CDX-2, Cytokeratin 20, special AT-rich sequence-binding protein 2, and Mucin 2 but negative for cytokeratin 7 and Paired box gene 8. This profile aids in distinguishing appendiceal and ovarian mucinous tumors. Postoperative recovery was uncomplicated, and the patient initiated adjuvant chemotherapy for the colon AC. CONCLUSION: This case highlights the diagnostic complexity of AMNs, emphasizing the need for vigilant identification to avert potential complications, such as pseudomyxoma peritonei.

Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.

BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

Development of an Imidazopyridazine-Based MNK1/2 Inhibitor for the Treatment of Lymphoma.

The mitogen-activated protein kinase-interacting protein kinases (MNKs) are the only kinases known to phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at Ser209, which plays a significant role in cap-dependent translation. Dysregulation of the MNK/eIF4E axis has been found in various solid tumors and hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). Herein, structure-activity relationship studies and docking models determined that 20j exhibits excellent MNK1/2 inhibitory activity, stability, and hERG safety. 20j exhibits strong and broad antiproliferative activity against different cancer cell lines, especially GCB-DLBCL DOHH2. 20j suppresses the phosphorylation of eIF4E in Hela cells (IC50 = 90.5 nM) and downregulates the phosphorylation of eIF4E and 4E-BP1 in A549 cells. In vivo studies first revealed that ibrutinib enhances the antitumor effect of 20j without side effects in a DOHH2 xenograft model. This study provided a solid foundation for the future development of a MNK inhibitor for GCB-DLBCL treatment.

Fumarate hydratase mutation associated uterine leiomyomas: A case report and literature review.

The patient was found to have multiple uterine myomas at the age of 19, underwent laparoscopic myomectomy at the age of 20, and underwent laparotomic myomectomy again at the age of 23 due to the recurrence of uterine myoma. At the age of 25, the patient reappeared with symptoms and recurrence, and was diagnosed with uterine leiomyomas (ULMs) of FH mutation and high-grade squamous intraepithelial lesion (HSIL/CIN III) with gland involvement, after complete examination. Fumarate hydratase (FH) mutation screening is important when gynecologists encounter patients with early onset and multiple ULMs, it can give early diagnosis and treatment and fertility guidance. The patient had their uterus removed at the age of 26. FH mutation screening is important when gynecologists encounter patients with early onset and multiple ULMs, it can give early diagnosis and treatment and fertility guidance. It is also helpful for early diagnosis of renal cell carcinoma.

Enhanced PSO feature selection with Runge-Kutta and Gaussian sampling for precise gastric cancer recurrence prediction.

Gastric cancer (GC), characterized by its inconspicuous initial symptoms and rapid invasiveness, presents a formidable challenge. Overlooking postoperative intervention opportunities may result in the dissemination of tumors to adjacent areas and distant organs, thereby substantially diminishing prospects for patient survival. Consequently, the prompt recognition and management of GC postoperative recurrence emerge as a matter of paramount urgency to mitigate the deleterious implications of the ailment. This study proposes an enhanced feature selection model, bRSPSO-FKNN, integrating boosted particle swarm optimization (RSPSO) with fuzzy k-nearest neighbor (FKNN), for predicting GC. It incorporates the Runge-Kutta search, for improved model accuracy, and Gaussian sampling, enhancing the search performance and helping to avoid locally optimal solutions. It outperforms the sophisticated variants of particle swarm optimization when evaluated in the CEC 2014 test suite. Furthermore, the bRSPSO-FKNN feature selection model was introduced for GC recurrence prediction analysis, achieving up to 82.082 % and 86.185 % accuracy and specificity, respectively. In summation, this model attains a notable level of precision, poised to ameliorate the early warning system for GC recurrence and, in turn, advance therapeutic options for afflicted patients.

Adjuvant therapy for rare rectal gastrointestinal stromal tumors: A case report.

Key Clinical Message: Anorectal gastrointestinal stromal tumors are extremely rare, constituting less than 0.1% of rectal tumors. Surgical resection using a transanal wide excision followed by adjuvant therapy with tyrosine kinase inhibitors can be a successful treatment combination to remove the mass and prevent recurrence while preserving the integrity of the anal sphincter. Abstract: Gastrointestinal stromal tumors (GISTs) are a rare subset of neoplasms, accounting for about 1%-2% of primary gastrointestinal malignancies. The stomach is the most common site for GISTs, with anorectal GISTs being exceptionally rare, representing only 0.1% of all rectal tumors. The standard approach for managing localized GIST involves complete surgical excision to achieve negative microscopic margins (R0) while preserving the tumor capsule and maintaining anal sphincter function. Surgical resection with transanal wide excision followed by adjuvant therapy using tyrosine kinase inhibitors can successfully remove the mass, prevent recurrence, and preserve the anal sphincter's integrity. Adjuvant therapy with imatinib is the recommended treatment for all localized GISTs assessed to have an intermediate or high risk of relapse. Here, we report a case of a 63-year-old male with a rectal GIST who underwent transanal wide excision followed by adjuvant therapy with tyrosine kinase inhibitors.

Effects of quercetin on polycystic ovary syndrome in animal models: a systematic review and meta-analysis.

BACKGROUND: Metformin is an insulin sensitizer that is widely used for the treatment of insulin resistance in polycystic ovary syndrome patients. However, metformin can cause gastrointestinal side effects. PURPOSE: This study showed that the effects of quercetin are comparable to those of metformin. Therefore, this study aimed to systematically evaluate the efficacy of quercetin in treating PCOS. METHODS: The present systematic search of the Chinese National Knowledge Infrastructure (CNKI), Wanfang Data Information Site, Chinese Scientific Journals Database (VIP), SinoMed, Web of Science, and PubMed databases was performed from inception until February 2024. The methodological quality was then assessed by SYRCLE's risk of bias tool, and the data were analyzed by RevMan 5.3 software. RESULTS: Ten studies were included in the meta-analysis. Compared with those in the model group, quercetin in the PCOS group had significant effects on reducing fasting insulin serum (FIS) levels (P = 0.0004), fasting blood glucose (FBG) levels (P = 0.01), HOMA-IR levels (P < 0.00001), cholesterol levels (P < 0.0001), triglyceride levels (P = 0.001), testosterone (T) levels (P < 0.00001), luteinizing hormone (LH) levels (P = 0.0003), the luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (P = 0.01), vascular endothelial growth factor (VEGF) levels (P < 0.00001), malondialdehyde (MDA) levels (P = 0.03), superoxide dismutase (SOD) levels (P = 0.01) and GLUT4 mRNA expression (P < 0.00001). CONCLUSION: This meta-analysis suggested that quercetin has positive effects on PCOS treatment. Quercetin can systematically reduce insulin, blood glucose, cholesterol, and triglyceride levels in metabolic pathways. In the endocrine pathway, quercetin can regulate the function of the pituitary-ovarian axis, reduce testosterone and luteinizing hormone (LH) levels, and lower the ratio of LH to follicle-stimulating hormone (FSH). Quercetin can regulate the expression of the GLUT4 gene and has antioxidative effects at the molecular level.

Protective effects of Jing-Si-herbal-tea in inflammatory cytokines-induced cell injury on normal human lung fibroblast via multiomic platform analysis.

Objectives: The protective effects and related mechanisms of Jing-Si herbal tea (JSHT) were investigated in cellular damage mediated by pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, on normal human lung fibroblast by multiomic platform analysis. Materials and Methods: The in silico high-throughput target was analyzed using pharmacophore models by BIOVIA Discovery Studio 2022 with ingenuity pathway analysis software. To assess cell viability, the study utilized the MTT assay technique. In addition, the IncuCyte S3 ZOOM System was implemented for the continuous monitoring of cell confluence of JSHT-treated cytokine-injured HEL 299 cells. Cytokine concentrations were determined using a Quantibody Human Inflammation Array. Gene expression and signaling pathways were determined using next-generation sequencing. Results: In silico high-throughput target analysis of JSHT revealed ingenuity in canonical pathways and their networks. Glucocorticoid receptor signaling is a potential signaling of JSHT. The results revealed protective effects against the inflammatory cytokines on JSHT-treated HEL 299 cells. Transcriptome and network analyses revealed that induction of helper T lymphocytes, TNFSF12, NFKB1-mediated relaxin signaling, and G-protein coupled receptor signaling play important roles in immune regulatory on JSHT-treated cytokine-injured HEL 299 cells. Conclusion: The findings from our research indicate that JSHT holds promise as a therapeutic agent, potentially offering advantageous outcomes in treating virus infections through various mechanisms. Furthermore, the primary bioactive components in JSHT justify extended research in antiviral drug development, especially in the context of addressing coronavirus.

Cellular angiofibroma arising from the rectocutaneous fistula in an adult: A case report.

BACKGROUND: Rectocutaneous fistulae are common. The infection originates within the anal glands and subsequently extends into adjacent regions, ultimately resulting in fistula development. Cellular angiofibroma (CAF), also known as an angiomyofibroblastoma-like tumor, is a rare benign soft tissue neoplasm predominantly observed in the scrotum, perineum, and inguinal area in males and in the vulva in females. We describe the first documented case CAF that developed within a rectocutaneous fistula and manifested as a perineal mass. CASE SUMMARY: In the outpatient setting, a 52-year-old male patient presented with a 2-year history of a growing perineal mass, accompanied by throbbing pain and minor scrotal abrasion. Physical examination revealed a soft, well-defined, non-tender mass at the left buttock that extended towards the perineum, without a visible opening. The initial assessment identified a soft tissue tumor, and the laboratory data were within normal ranges. Abdominal and pelvic computed tomography (CT) revealed swelling of the abscess cavity that was linked to a rectal cutaneous fistula, with a track-like lesion measuring 6 cm × 0.7 cm in the left perineal region and attached to the left rectum. Rectoscope examination found no significant inner orifices. A left medial gluteal incision revealed a thick-walled mass, which was excised along with the extending tract, and curettage was performed. Histopathological examination confirmed CAF diagnosis. The patient achieved total resolution during follow-up assessments and did not require additional hospitalization. CONCLUSION: CT imaging supports perineal lesion diagnosis and management. Perineal angiofibromas, even with a cutaneous fistula, can be excised transperineally.

Significant improvements in the olfactory sensitivity of bipolar I disorder patients during euthymia versus manic episodes: a longitudinal study.

Introduction: Research has indicated that individuals diagnosed with bipolar disorder (BD) might experience alterations in their olfaction or levels of serum tumor necrosis factor-α (TNF-α), but no studies have investigated olfactory function and serum TNF-α in BD patients simultaneously. Moreover, there is a lack of existing research that compares the longitudinal olfactory function between individuals with manic and euthymic BD I. Methods: Patients with manic BD I (BDM, n=44) and healthy controls (HCs, n=32) were evaluated symptoms (measured via the Young Manic Rating Scale, YRMS), social function (measured via the Global Assessment Function, GAF), serum TNF-α, and olfactory function (via the Sniffin' Sticks test) including olfactory sensitivity (OS) and olfactory identification (OI). The BDM patients were followed up to the remission period and re-evaluated again. We compared OS, OI and serum TNF-α in manic and euthymic patients with BD I and HCs. We examined the correlation between olfactory function and symptoms, social function, and serum TNF-α in patients with BD I. Results: The BDM patients exhibited significantly lower OS and OI compared to the HCs (Z = -2.235, P = 0.025; t = -6.005, P < 0.001), while a positive correlation was observed between OS and GAF score (r = 0.313, P = 0.039). The OS in the BD I remission group (n=25) exhibited significantly superior performance compared to the BDM group (t = -4.056, P < 0.001), and the same as that in the HCs (P = 0.503). The change in OS showed a positive correlation with the decrease in YMRS score (r = 0.445, P = 0.026), and a negative correlation with the course of disease (r = -0.594, P = 0.002). The TNF-α in BD I patients was significantly lower compared to HCs (P < 0.001), and not significantly correlated with olfactory function (all P > 0.05). Conclusion: The findings suggest that OS and OI are impaired in BDM patients, and the impaired OS in those patients can be recovered in the remission stage. OI may serve as a potential characteristic marker of BD. OS might be useful as an index for BDM treatment efficacy and prognosis.

Genetic interactions reveal distinct biological and therapeutic implications in breast cancer.

Co-occurrence and mutual exclusivity of genomic alterations may reflect the existence of genetic interactions, potentially shaping distinct biological phenotypes and impacting therapeutic response in breast cancer. However, our understanding of them remains limited. Herein, we investigate a large-scale multi-omics cohort (n = 873) and a real-world clinical sequencing cohort (n = 4,405) including several clinical trials with detailed treatment outcomes and perform functional validation in patient-derived organoids, tumor fragments, and in vivo models. Through this comprehensive approach, we construct a network comprising co-alterations and mutually exclusive events and characterize their therapeutic potential and underlying biological basis. Notably, we identify associations between TP53mut-AURKAamp and endocrine therapy resistance, germline BRCA1mut-MYCamp and improved sensitivity to PARP inhibitors, and TP53mut-MYBamp and immunotherapy resistance. Furthermore, we reveal that precision treatment strategies informed by co-alterations hold promise to improve patient outcomes. Our study highlights the significance of genetic interactions in guiding genome-informed treatment decisions beyond single driver alterations.