[Potential pathways for traditional Chinese medicine intervention in diabetic kidney disease: macrophage polarization].

Diabetic kidney disease(DKD) is a prevalent and severe microvascular complication of type 2 diabetes mellitus(T2DM). Chronic microinflammation is an important factor exacerbating renal tissue damage in DKD individuals. Macrophages play a crucial role in immune-inflammatory responses, and they can transiently and reversibly polarize into the pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype based on microenvironmental differences. The imbalance in M1/M2 macrophage polarization can exacerbate DKD progression by fostering inflammatory cytokine aggregation in the glomeruli and renal interstitium. Therefore, restoring the balance of macrophage is a pivotal avenue to ameliorate the chronic microinflammation state in DKD. Macrophage polarization is a complex and dynamic process. Various information molecules and cytokines involved in the polarization process play important roles in regulating phenotypes during the progression of DKD. They are closely related to various mechanisms such as metabolism, inflammation, fibrosis, and mitochondrial autophagy in DKD. By coordinating the inflammatory responses through polarization, they play a key role in regulating inflammation in metabolic-related diseases. The complex network of pathways involved in macrophage polarization corresponds well with the multi-pathway, multi-target treatment model of traditional Chinese medicine(TCM). Active ingredients and formulas of TCM can intervene in DKD by regulating macrophage polarization. Studies on relieving renal inflammation, repairing renal tissues, and promoting renal function recovery through macrophage polarization modulation are not uncommon. Therefore, based on exis-ting evidence, this study reviews TCM in targeting M1/M2 macrophage polarization balance to improve DKD, aiming to explore the potential of macrophage polarization in regulating DKD, which is expected to provide evidence support for the clinical diagnosis and treatment of DKD with TCM as well as the exploration of its biological mechanisms.

Corrigendum: Pretreatment level of serum sialic acid predicts both qualitative and quantitative bone metastases of prostate cancer.

[This corrects the article DOI: 10.3389/fendo.2024.1338420.].

Clinical application of eight-zone laparoscopic dissection strategy for rectal cancer: Experience and discussion.

BACKGROUND: The incidence of rectal cancer is increasing worldwide, and surgery remains the primary treatment modality. With the advent of total mesorectal excision (TME) technique, the probability of tumor recurrence post-surgery has significantly decreased. Surgeons' focus has gradually shifted towards minimizing the impact of surgery on urinary and sexual functions. Among these concerns, the optimal dissection of the rectal lateral ligaments and preservation of the pelvic floor neurovascular bundle have become critical. To explore the optimal surgical technique for TME and establish a standardized surgical protocol to minimize the impact on urinary and sexual functions, we propose the eight-zone dissection strategy for pelvic floor anatomy. AIM: To compare the differences in surgical specimen integrity and postoperative quality of life satisfaction between the traditional pelvic floor dissection strategy and the innovative eight-zone dissection strategy. METHODS: We analyzed the perioperative data of patients who underwent laparoscopic radical resection of rectal cancer at Qilu Hospital of Shandong University between January 1, 2021 and December 1, 2023. This study included a total of 218 patients undergoing laparoscopic radical surgery for rectal cancer, among whom 109 patients underwent traditional pelvic floor dissection strategy, and 109 patients received the eight-zone dissection strategy. RESULTS: There were no significant differences in general characteristics between the two groups. Patients in the eight-zone dissection group had higher postoperative specimen integrity (88.1% vs 78.0%, P = 0.047). At the 3-month follow-up, patients in the eight-zone surgery group had better scores in urinary issues (6.8 ± 3.3 vs 5.3 ± 2.5, P = 0.045) and male sexual desire (2.2 ± 0.6 vs 2.5 ± 0.5, P = 0.047) compared to the traditional surgery strategy group. CONCLUSION: This study demonstrates that the eight-zone dissection strategy for laparoscopic lateral ligament dissection of rectal cancer is safe and effective. Compared with the traditional pelvic floor dissection strategy, this approach can reduce the risk of nerve injury and minimize the impact on urinary and sexual functions. Therefore, we recommend the clinical application of this strategy to better serve patients with rectal cancer.

Cancer-associated fibroblast-derived circFARP1 modulates non-small cell lung cancer invasion and metastasis through the circFARP1/miR-338-3p/SOX4 axis.

The pleiotropic effect of cancer-associated fibroblasts (CAFs) on tumour progression depends on the environment. circFARP1 is critical for CAFs-induced gemcitabine (GEM) resistance in pancreatic cancer. Its specific role and mechanism in non-small cell lung cancer (NSCLC) have not been reported yet. We prepared a cancer-associated fibroblasts-conditioned medium (CAF-CM) to incubate the A549 cells. Quantitative real-time polymerase chain reaction was used to detect RNA levels. We detected protein expression by immunohistochemistry, immunocytochemistry, western blot and immunofluorescence. We also detected the targeting impact between circFARP1, miR-338-3p and SRY-box transcription factor 4 (SOX4) by using dual-luciferase reporter and RNA pull-down assays. We determined cell proliferation, migration and invasion capabilities through Cell Counting Kit-8 and transwell assays. In addition, we measured tumour volume and weight in vivo by establishing a xenograft tumour model. CircFARP1 levels were remarkably high in the CAFs. The transfection experiments found that circFARP1 downregulation in CAFs caused migration, proliferation and invasion inhibition of CAFs and A549 cells, whereas inhibiting miR-38-3p or overexpressing SOX4 in CAFs could significantly reverse the inhibition. In vivo study in nude mice confirmed that CAFs could promote NSCLC tumour growth and knockdown of circFARP1 could inhibit tumour growth of NSCLC, whereas miR-38-3p downregulation or SOX4 overexpression could significantly reverse the inhibition. circFARP1 promotes NSCLC development by stimulating miR-338-3p/SOX4 signalling axis to regulate CAFs.

High-Precision Implant Cavity Fabrication Using Femtosecond Lasers.

Objective: This study aims to enhance the precision of implant cavity preparation, addressing a notable challenge in the current state of the field by utilizing femtosecond lasers. Background: The application of femtosecond lasers in implant cavity preparation heralds a noninvasive and efficient technique, characterized by diminished thermal damage and high biocompatibility. Despite these promising attributes, the realization of precise cavity preparation remains a significant challenge in the contemporary domain. Materials and Methods: Our research group devised a specialized femtosecond laser microsurgery robotic system tailored for sophisticated implant cavity preparation. This system facilitated the meticulous analysis of sheep shank bone samples, enabling precise three-dimensional cutting. The analysis included an extensive examination of ablation effects, using a laser scanning microscope and VK Analyzer software. This investigation spanned the phases of laser flux calibration and experimental validation, offering a critical evaluation of the automated preparation process. Results: The study delineated that at the focus position of our custom-made oral clinical femtosecond laser microsurgery robotic system, the laser spot diameter is 75.69 µm, and ascertained the ablation threshold for sheep shank cortical bone to be 1.47 J/cm2. Utilizing low laser flux with minimal ablation craters overlap compromised the sidewall precision of the implant cavity, whereas employing high laser flux with extensive ablation craters overlap resulted in an enlarged ablation angle. At a laser energy setting of 2.2362 J/cm2 and a 50% ablation crater overlap, an implant cavity was successfully crafted featuring a top diameter of 4.41 mm, a bottom diameter of 3.98 mm, and a depth of 3 mm, devoid of any adverse thermal effects such as cracking or carbonization. Conclusions: The oral clinical femtosecond laser microsurgery robotic system can achieve automated and precise implant cavity preparation. This advancement promotes the broader application of femtosecond lasers in the field of orthopedics.

Three-dimensional visualization technology for guiding one-step percutaneous transhepatic cholangioscopic lithotripsy for the treatment of complex hepatolithiasis.

BACKGROUND: Biliary stone disease is a highly prevalent condition and a leading cause of hospitalization worldwide. Hepatolithiasis with associated strictures has high residual and recurrence rates after traditional multisession percutaneous transhepatic cholangioscopic lithotripsy (PTCSL). AIM: To study one-step PTCSL using the percutaneous transhepatic one-step biliary fistulation (PTOBF) technique guided by three-dimensional (3D) visualization. METHODS: This was a retrospective, single-center study analyzing, 140 patients who, between October 2016 and October 2023, underwent one-step PTCSL for hepatolithiasis. The patients were divided into two groups: The 3D-PTOBF group and the PTOBF group. Stone clearance on choledochoscopy, complications, and long-term clearance and recurrence rates were assessed. RESULTS: Age, total bilirubin, direct bilirubin, Child-Pugh class, and stone location were similar between the 2 groups, but there was a significant difference in bile duct strictures, with biliary strictures more common in the 3D-PTOBF group (P = 0.001). The median follow-up time was 55.0 (55.0, 512.0) days. The immediate stone clearance ratio (88.6% vs 27.1%, P = 0.000) and stricture resolution ratio (97.1% vs 78.6%, P = 0.001) in the 3D-PTOBF group were significantly greater than those in the PTOBF group. Postoperative complication (8.6% vs 41.4%, P = 0.000) and stone recurrence rates (7.1% vs 38.6%, P = 0.000) were significantly lower in the 3D-PTOBF group. CONCLUSION: Three-dimensional visualization helps make one-step PTCSL a safe, effective, and promising treatment for patients with complicated primary hepatolithiasis. The perioperative and long-term outcomes are satisfactory for patients with complicated primary hepatolithiasis. This minimally invasive method has the potential to be used as a substitute for hepatobiliary surgery.

Precisely Manipulating Steric Hindrance Effect on DNA Walker for Tunable Detection of MicroRNA Using Enzymatic Strand Displacement Amplification.

The spatial constraints imposed by the DNA structure have significant implications for the walking efficiency of three-dimensional DNA walkers. However, accurately quantifying and manipulating steric hindrance remains a challenging task. This study presents a steric hindrance-controlled DNA walker utilizing an enzymatic strand displacement amplification (ESDA) strategy for detecting microRNA-21 (miR-21) with tunable dynamic range and sensitivity. The steric hindrance of the DNA walker was precisely manipulated by varying the length of empty bases from 6.5 Što 27.4 Šat the end of the track strand and adjusting the volumetric dimensions of the hairpin structure from 9.13 nm3 to 26.2 nm3 at the terminus of the single-foot DNA walking strand. This method demonstrated a tunable limit of detection for miR-21 ranging from 3.6 aM to 35.6 nM, along with a dynamic range from ∼100-fold to ∼166 000-fold. Impressively, it exhibited successful identification of cancer cells and clinical serum samples with high miR-21 expression. The proposed novel strategy not only enables tunable detection of miRNA through the regulation of steric hindrance but also achieves accurate and quantitative analysis of the steric hindrance effect, promising broader applications in personalized medicine, early disease detection, and drug development.

Characterization of the gut microbiota and fecal metabolome in the osteosarcoma mouse model.

Previous studies have reported the correlation between gut microbiota (GM), GM-derived metabolites, and various intestinal and extra-intestinal cancers. However, limited studies have investigated the correlation between GM, GM-derived metabolites, and osteosarcoma (OS). This study successfully established a female BALB/c nude mouse model of OS. Mice (n = 14) were divided into the following two groups (n = 7/group): OS group named OG, injected with Saos-2 OS cells; normal control group named NCG, injected with Matrigel. The GM composition and metabolites were characterized using 16S rDNA sequencing and untargeted metabolomics, respectively. Bioinformatics analysis revealed that amino acid metabolism was dysregulated in OS. The abundances of bone metabolism-related genera Alloprevotella, Rikenellaceae_RC9_gut_group, and Muribaculum were correlated with amino acid metabolism, especially histidine metabolism. These findings suggest the correlation between GM, GM-derived metabolites, and OS pathogenesis. Clinical significance: The currently used standard therapeutic strategies for OS, including surgery, chemotherapy, and radiation, are not efficacious. The findings of this study provided novel insights for developing therapeutic, diagnostic, and prognostic strategies for OS.

The clinicopathologic significance of psammoma bodies in cytology specimens: A series of 78 cases.

BACKGROUND: Currently the clinicopathologic significance of psammoma bodies in cytology specimens are not completely understood, including types of cytology specimens and pathologic conditions frequently associated with this unique cytologic feature. In this study, we undertook a retrospective approach to review the specimen types, cytology preparations, patient characteristics, organs or tissues involved and differential diagnoses in cytology specimens with the finding of psammoma bodies. METHODS: Cytology cases with the finding of psammoma bodies from January 2004 to December 2022 were retrieved from our institution's pathology databases, and their clinicopathological features were reviewed. RESULTS: A total of 78 cytology specimens with the finding of psammoma bodies were recorded in our CoPath system. The mean age at diagnosis was 59 years. The patient group showed female gender predominancy (90%). FNA specimens comprised about 38.5% of total cases. Other common specimen types were body cavity fluids (38.5%), including pleural effusion and peritoneal fluid, and about 20.5% of the cases were pelvic washing performed during gynecologic surgeries. Most cytology cases with psammoma bodies had a malignant diagnosis (69%). About 18% of the cases were in the indeterminate diagnostic categories, with 12% suspicious for malignancy and 6% of the cases with atypical cells. About 5% of cases were placed in the neoplastic category, while 8% of cases were negative for malignancy. About 79% of peritoneal cytology with psammoma bodies were neoplastic and mostly gynecologic tumors. Pleural fluids with psammoma bodies were very likely to be malignant and involved by serous carcinoma (15 of 16 cases, 94%). Papillary thyroid carcinoma was the second most common malignancy in our series, present in about 53% of thyroid cytologies with the finding of psammoma bodies. CONCLUSION: Our study showed that psammoma bodies in cytology preparations were more often associated with malignancies in our study of 78 cytology specimens (69%). The most sampled location in our study was peritoneal cavity, followed by pleural cavity, thyroid, lymph nodes, neck masses, and omentum. The clinicopathologic value of psammoma bodies in predicting malignancy varies depending on locations and specimen types.

Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies.

Cytology-histology correlation of atypical glandular cells on cervical Papanicolaou tests: A study of 628 cases.

INTRODUCTION: The finding of atypical glandular cells (AGC) on Papanicolaou test is becoming more important as the incidence of squamous intraepithelial lesions decreases in recent decades. Therefore, the interpretation and follow-up of patients with AGC are particularly important. The aim of our study was to assess the histologic findings and clinical correlations in patients with AGC identified on Papanicolaou test. MATERIALS AND METHODS: A total of 714 patients with AGC identified on cervical Papanicolaou tests were studied for their clinicopathologic features, such as follow-up histology and patient age. We investigated the histologic follow-up results for each individual subcategories of AGC and their correlation with patients' age. RESULTS: Most of the glandular cell abnormalities (80.0%) in the study group were classified as "atypical glandular cells, not otherwise specified (NOS)". About 28.9% of patients' follow-up histology showed malignant or precancerous lesions. The mean age of patients with malignant or precancerous lesions was significantly higher than that of patients with benign or non-precancerous lesions. The malignant histologies included 52 cases of endometrial cancers and 31 cases of cervical carcinomas. The second most common subcategory was "atypical glandular cells, favor neoplastic" (5.0%), while "atypical endocervical cells, favor neoplastic" constituted about 2.7% of cases in our study. The average age of patients with "atypical glandular cells, favor neoplastic" was significantly higher than that of patients with "atypical endocervical cells, favor neoplastic". The follow-up histology of about 82.1% of "atypical glandular cells, favor neoplastic" showed endometrial (73.9%) or cervical malignancies (26.1%). The follow-up histology of about 70.6% of "atypical endocervical cells, favor neoplastic" showed endometrial (50.0%) or cervical cancers (50.0%). Other glandular abnormalities included 25 of 714 cases of "atypical endometrial cells" (3.5%) and 6 of 714 cases of "atypical endocervical cells" (0.8%). CONCLUSION: Based on our data, we have observed significantly more endometrial malignancies in both "atypical glandular cells, NOS" and "atypical glandular cells, favor neoplastic" subcategories and even some in "atypical endocervical cells, favor neoplastic" category. This predominance of endometrial malignancies is also associated with patients' age and tumor types.

KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma.

BACKGROUND: Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. METHODS: Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. RESULTS: There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. CONCLUSIONS: We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. HIGHLIGHTS: Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.

Prognostic value of systemic immune-inflammation index/albumin ratio for immunotherapy-treated patients receiving opioids.

OBJECTIVE: This study evaluated the effect of the systemic immune-inflammation index/albumin ratio (SII/ALB) on the prognosis of immunotherapy-treated patients receiving opioids. METHODS: A retrospective analysis was conducted of 185 immunotherapy-treated patients who received opioids at Xuzhou Central Hospital from 01/09/2021 to 01/09/2023. The results of related clinical data were collected during the week before the cancer patients received immunotherapy. The SII/ALB cut-off value was determined, and the relationship between the SII/ALB and clinical pathological parameters was analyzed using the chi-square test. The effect of the SII/ALB on progression-free survival (PFS) was examined using Kaplan-Meier curves and the Cox proportional hazard model. RESULT: The SII/ALB cut-off value was 20.86, and patients were divided into low (SII/ALB ≤ 20.86) and high (SII/ALB > 20.86) SII/ALB groups. Adverse reactions (hazard ratio [HR] = 0.108; 95% confidence interval [CI]: 0.061-0.192, P < 0.001) and the SII/ALB (HR = 0.093; 95% CI: 0.057-0.151, P < 0.001) were independent prognostic factors for PFS. Compared with the high SII/ALB group, the low SII/ALB group had longer PFS after opioid treatment (12.2 vs. 5.2 months, P < 0.001). CONCLUSION: The SII/ALB is a potentially important prognostic parameter in immunotherapy-treated patients receiving opioids.

Development of a diagnostic algorithm to ascertain malignant pleural effusion utilizing clinical indicators and serum metal concentrations.

Background: Malignant pleural effusion (MPE) is prevalent among cancer patients, indicating pleural metastasis and predicting poor prognosis. However, accurately identifying MPE in clinical settings is challenging. The aim of this study was to establish an innovative nomogram-derived model based on clinical indicators and serum metal ion levels to identify MPE. Methods: From July 2020 to May 2022, 428 patients diagnosed with pleural effusion (PE) were consecutively recruited. Comprehensive demographic details, clinical symptoms, imaging data, pathological information, and laboratory results, including serum metal ion levels, were systematically collected. The nomogram was created by incorporating the most significant predictors identified through LASSO and multivariate logistic regression analysis. The predictors were assigned weighted points based on their respective regression coefficients, allowing for the calculation of a total score that corresponds to the probability of MPE. Internal validation using bootstrapping techniques assessed the nomogram's performance, including calibration, discrimination, and clinical applicability. Results: Seven key variables were identified using LASSO regression and multiple regression analysis, including dyspnea, fever, X-ray/CT compatible with malignancy, pleural carcinoembryonic antigen(pCEA), serum neuron-specific enolase(sNSE), serum carcinoembryonic antigen(sCEA), and pleural lactate dehydrogenase(pLDH). Internal validation underscored the superior performance of our model (AUC=0.940). Decision curve analysis (DCA) analysis demonstrated substantial net benefit across a probability threshold range > 1%. Additionally, serum calcium and copper levels were significantly higher, while serum zinc levels were significantly lower in MPE patients compared to benign pleural effusion (BPE) patients. Conclusion: This study effectively developed a user-friendly and reliable MPE identification model incorporating seven markers, aiding in the classification of PE subtypes in clinical settings. Furthermore, our study highlights the clinical value of serum metal ions in distinguishing malignant pleural effusion from BPE. This significant advancement provides essential tools for physicians to accurately diagnose and treat patients with MPE.

Genomic characterization reveals distinct mutational landscapes and therapeutic implications between different molecular subtypes of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has high heterogeneity, poor prognosis, and limited treatment success. Recently, an immunohistochemistry-based surrogate classification for the "Fudan University Shanghai Cancer Center (FUSCC) subtyping" has been developed and is considered more suitable for clinical application. Seventy-one paraffin-embedded sections of surgically resected TNBC were classified into four molecular subtypes using the IHC-based surrogate classification. Genomic analysis was performed by targeted next-generation sequencing and the specificity of the subtypes was explored by bioinformatics, including survival analysis, multivariate Cox regression, pathway enrichment, Pyclone analysis, mutational signature analysis and PHIAL analysis. AKT1 and BRCA1 mutations were identified as independent prognostic factors in TNBC. TNBC molecular subtypes encompass distinct genomic landscapes that show specific heterogeneities. The luminal androgen receptor (LAR) subtype was associated with mutations in PIK3CA and PI3K pathways, which are potentially sensitive to PI3K pathway inhibitors. The basal-like immune-suppressed (BLIS) subtype was characterized by high genomic instability and the specific possession of signature 19 while patients in the immunomodulatory (IM) subtype belonged to the PD-L1 ≥ 1% subgroup with enrichment in Notch signaling, suggesting a possible benefit of immune checkpoint inhibitors and Notch inhibitors. Moreover, mesenchymal-like (MES) tumors displayed enrichment in the receptor tyrosine kinase (RTK)-RAS pathway and potential sensitivity to RTK pathway inhibitors. The findings suggest potential treatment targets and prognostic factors, indicating the possibility of TNBC stratified therapy in the future.

Congenital interruption between the ampulla and fimbria of the fallopian tube: case report.

We reported 5 patients with unilateral or bilateral tubal discontinuity between the ampulla and fimbria, occasionally detected through laparoscopy combined with hysteroscopy at the Reproductive Hospital Affiliated with Shandong University from 2017 to 2023. Three cases were observed to have this malformation on the left fallopian tube, 1 case on the right side, and 1 case bilaterally. None of these cases were combined with urological malformations. After surgery, there was 1 instance of postoperative delivery, 1 ongoing pregnancy, and 3 not yet conceived. The congenital ampulla and fimbria interruption of the fallopian tube may be independent of other significant deformities of reproductive or renal tracts. However, it can lead to hydrosalpinx and primary or secondary infertility. Surgical management options, such as salpingostomy, salpingectomy, and tubal ligation, have shown the potential to improve pregnancy outcomes.

Ketamine administration causes cognitive impairment by destroying the circulation function of the glymphatic system.

BACKGROUND: Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key role in metabolic waste removal and cognitive regulation in the central nervous system. METHODS: Focusing on the glymphatic system, this study evaluated the behavioral performance and circulatory function of the glymphatic system by building a short-term ketamine administration model in mice, and detected the expression levels of the 5-HT2c receptor, ΔFosb, Pten, Akt, and Aqp4 in the hippocampus. Primary astrocytes were cultured to verify the regulatory relationships among related indexes using a 5-HT2c receptor antagonist, a 5-HT2c receptor short interfering RNA (siRNA), and a ΔFosb siRNA. RESULTS: Ketamine administration induced ΔFosb accumulation by increasing 5-HT2c receptor expression in mouse hippocampal astrocytes and primary astrocytes. ΔFosb acted as a transcription factor to recognize the AATGATTAAT bases in the 5' regulatory region of the Aqp4 gene (-1096 bp to -1087 bp), which inhibited Aqp4 expression, thus causing the circulatory dysfunction of the glymphatic system, leading to cognitive impairment. CONCLUSIONS: Although this regulatory mechanism does not involve the Pten/Akt pathway, this study revealed a new mechanism of ketamine-induced cognitive impairment in non-neuronal systems, and provided a theoretical basis for the safety of clinical treatment and the effectiveness of withdrawal.

Highly expressed lncRNA H19 in endometriosis promotes aerobic glycolysis and histone lactylation.

In brief: Abnormal glucose metabolism may be involved in the pathogenesis of endometriosis. The present study identifies that highly expressed H19 leads to increased aerobic glycolysis and histone lactylation levels in endometriosis. Abstract: Previous studies from our group and others have shown increased IncRNA H19 expression in both the eutopic endometrium and the ectopic endometriosis tissue during endometriosis. In this study, we use immunofluorescence, immunohistochemistry, and protein quantification to determine that levels of aerobic glycolysis and histone lactylation are increased in endometriosis tissues. In human endometrial stromal cells, we found that high H19 expression resulted in abnormal glucose metabolism by examining the levels of glucose, lactate, and ATP and measuring protein levels of enzymes that participate in glycolysis. At the same time, immunofluorescence and western blotting demonstrated increased histone lactylation in H19 overexpressing cells. Altering aerobic glycolysis and histone lactylation levels through the addition of sodium lactate and 2-deoxy-d-glucose demonstrated that increased aerobic glycolysis and histone lactylation levels resulted in enhanced cell proliferation and cell migration, contributing to endometriosis. To validate these findings in vivo, we constructed an endometriosis mouse model, demonstrating similar changes in endometriosis tissues in vivo. Both aerobic glycolysis and histone lactylation levels were elevated in endometriotic lesions. Taken together, these data demonstrate elevated expression levels of H19 in endometriosis patients promote abnormal glucose metabolism and elevated histone lactylation levels in vivo, enhancing cell proliferation and migration and promoting the progression of endometriosis. Our study provides a functional link between H19 expression and histone lactylation and glucose metabolism in endometriosis, providing new insights into disease mechanisms that could result in novel therapeutic approaches.