Research progress on morphology and mechanism of programmed cell death.

Programmed cell death (PCD) is a basic process of life that is closely related to the growth, development, aging and disease of organisms and is one of the hotspots of life science research today. PCD is a kind of genetic control, autonomous and orderly important cell death that involves the activation, expression, and regulation of a series of genes. In recent years, with the deepening of research in this field, new mechanisms of multiple PCD pathways have been revealed. This article reviews and summarizes the multiple PCD pathways that have been discovered, analyses and compares the morphological characteristics and biomarkers of different types of PCD, and briefly discusses the role of various types of PCD in the diagnosis and treatment of different diseases, especially malignant tumors.

Nomogram for predicting the risk of postoperative delirium in elderly patients undergoing orthopedic surgery.

OBJECTIVE: To retrospectively analyze the risk factors for postoperative delirium (POD) after orthopedic surgery in elderly patients and establish an individualized nomogram to predict the risk of POD. METHODS: The data of 1011 patients who underwent orthopedic surgery from January 2019 to January 2022 were retrospectively analyzed. Univariate and multivariate logistic analyses were used to screen for independent risk factors. Stepwise regression was conducted to screen risk factors to construct a nomogram to predict the risk of POD after orthopedic surgery in elderly individuals, and nomogram validation analyses were performed. RESULTS: The logistic regression results showed that age (≥ 75 years old vs. < 75 years old; odds ratio (OR) = 2.889; 95% confidence interval (CI), 1.149, 7.264), sex (male vs. female, OR = 2.368; 95% CI, 1.066, 5.261), and preoperative cognitive impairment (yes vs. no, OR = 13.587; 95% CI, 4.360, 42.338) were independent risk factors for POD in elderly patients who underwent orthopedic surgery (P < 0.05). A nomogram was constructed using 7 risk factors, i.e., age, American Society of Anesthesiologists (ASA) classification, sex, preoperative hemoglobin (Hb), preoperative pulmonary disease, cognitive impairment, and intraoperative infusion volume. The area under the curve (AUC) showed good discrimination (0.867), the slope of the calibration curve was 1.0, and the optimal net benefit of the nomogram from the decision curve analysis (DCA) was 0.01-0.58. CONCLUSION: This study used 7 risk factors to construct a nomogram to predict the risk of POD after major orthopedic surgery in elderly individuals, and the nomogram had good discrimination ability, accuracy, and clinical practicability.

Ghrelin Induces the Production of Hypothalamic NPY Through the AMPK-mTOR Pathway to Alleviate Cancer-induced Bone Pain.

BACKGROUND/AIM: Cancer-induced bone pain (CIBP) is one of the most common symptoms of bone metastasis of tumor cells. The hypothalamus may play a pivotal role in the regulation of CIBP. However, little is known about the exact mechanisms. MATERIALS AND METHODS: First, we established a CIBP model to explore the relationship among hypothalamic ghrelin, NPY and CIBP. Then, we exogenously administered NPY and NPY receptor antagonists to investigate whether hypothalamic NPY exerted an antinociceptive effect through binding to NPY receptors. Finally, we exogenously administered ghrelin to investigate whether ghrelin alleviated CIBP by inducing the production of hypothalamic NPY through the AMPK-mTOR pathway. Body weight, food intake and behavioral indicators of CIBP were measured every 3 days. Hypothalamic ghrelin, NPY and the AMPK-mTOR pathway were also measured. RESULTS: The expression of hypothalamic ghrelin and NPY was simultaneously decreased in cancer-bearing rats, which was accompanied by CIBP. Intracerebroventricular (i.c.v.) administration of NPY significantly alleviated CIBP in the short term. The antinociceptive effect of NPY was reversed with the i.c.v. administration of the Y1R and Y2R antagonists. The administration of ghrelin activated the AMPK-mTOR pathway and induced hypothalamic NPY production to alleviate CIBP. This effect of ghrelin on NPY and antinociception was reversed with the administration of a GHS-R1α antagonist. CONCLUSION: Ghrelin could induce the production of hypothalamic NPY through the AMPK-mTOR pathway to alleviate CIBP, which can provide a novel therapeutic mechanism for CIBP.

Amphiphilic Rhodamine Fluorescent Probes Combined with Basal Imaging for Fine Structures of the Cell Membrane.

Confocal fluorescence imaging of fine structures of the cell membrane is important for understanding their biofunctions but is often neglected due to the lack of an effective method. Herein, we develop new amphiphilic rhodamine fluorescent probe RMGs in combination with basal imaging for this purpose. The probes show high signal-to-noise ratio and brightness and low internalization rate, making them suitable for imaging the fine substructures of the cell membrane. Using the representative probe RMG3, we not only observed the cell pseudopodia and intercellular nanotubes but also monitored the formation of migrasomes in real time. More importantly, in-depth imaging studies on more cell lines revealed for the first time that hepatocellular carcinoma cells secreted much more adherent extracellular vesicles than other cell lines, which might serve as a potential indicator of liver cells. We believe that RMGs may be useful for investigating the fine structures of the cell membrane.

Clinicopathological and molecular genetic alterations in monomorphic-epitheliotropic intestinal T-cell lymphoma of the small intestine.

BACKGROUND: Small intestinal monomorphic-epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL. METHODS: The clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein-Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed. RESULTS: Of the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up. CONCLUSIONS: Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

Role of body mass index and weight change in the risk of cancer: A systematic review and meta-analysis of 66 cohort studies.

Background: This study was designed to evaluate the effects of body mass index (BMI) and weight change on the risk of developing cancer overall and cancer at different sites. Methods: We searched PubMed and other databases up to July 2023 using the keywords related to 'risk', 'cancer', 'weight', 'overweight', and 'obesity'. We identified eligible studies, and the inclusion criteria encompassed cohort studies in English that focused on cancer diagnosis and included BMI or weight change as an exposure factor. Multiple authors performed data extraction and quality assessment, and statistical analyses were carried out using RevMan and R software. We used random- or fixed-effects models to calculate the pooled relative risk (RR) or hazard ratio along with 95% confidence intervals (CIs). We used the Newcastle-Ottawa Scale to assess study quality. Results: Analysis included 66 cohort studies. Compared to underweight or normal weight, overweight or obesity was associated with an increased risk of endometrial cancer, kidney cancer, and liver cancer but a decreased risk of prostate cancer and lung cancer. Being underweight was associated with an increased risk of gastric cancer and lung cancer but not that of postmenopausal breast cancer or female reproductive cancer. In addition, weight loss of more than five kg was protective against overall cancer risk. Conclusions: Overweight and obesity increase the risk of most cancers, and weight loss of >5 kg reduces overall cancer risk. These findings provide insights for cancer prevention and help to elucidate the mechanisms underlying cancer development. Registration: Reviewregistry1786.

HMGA1 regulates the mitochondrial apoptosis pathway in sepsis-induced cardiomyopathy.

High mobility group protein AT-hook 1 (HMGA1), an architectural transcription factor, has previously been reportedto play an essential role in architectural remodeling processes. However, its effects on cardiovascular diseases, particularly sepsis-induced cardiomyopathy, have remained unclear. The study aimed to investigate the role of HMGA1 in lipopolysaccharide-induced cardiomyopathy. Mice subjected to lipopolysaccharide for 12 h resulted in cardiac dysfunction. We used an adeno-associated virus 9 delivery system to achieve cardiac-specific expression of the HMGA1 gene in the mice. H9c2 cardiomyocytes were infected with Ad-HMGA1 to overexpress HMGA1 or transfected with si-HMGA1 to knock down HMGA1. Echocardiography was applied to measure cardiac function. RT-PCR was used to detect the transcriptional level of inflammatory cytokines. CD45 and CD68 immunohistochemical staining were used to detect inflammatory cell infiltration and TUNEL staining to evaluate the cardiomyocyte apoptosis, MitoSox was used to detect mitochondrial reactive oxygen species, JC-1 was used todetect Mitochondrial membrane potential. Our findings revealed that the overexpression of HMGA1 exacerbated myocardial inflammation and apoptosis in response to lipopolysaccharide treatment. Additionally, we also observed that H9c2 cardiomyocytes with HMGA1 overexpression exhibited enhanced inflammation and apoptosis upon stimulation with lipopolysaccharide for 12 h. Conversely, HMGA1 knockdown in H9c2 cardiomyocytes attenuated lipopolysaccharide-induced cardiomyocyte inflammation and apoptosis. Further investigations into the molecular mechanisms underlying these effects showed that HMGA1 promoted lipopolysaccharide-induced mitochondrial-dependent cardiomyocyte apoptosis. The study reveals that HMGA1 worsens myocardial inflammation and apoptosis in response to lipopolysaccharide treatment. Mechanically, HMGA1 exerts its effects by regulating the mitochondria-dependent apoptotic pathway.

TGF-ß2-induced alterations of m6A methylation in hTERT RPE-1 cells.

N6-methyladenosine (m6A) is a major type of RNA modification implicated in various pathophysiological processes. Transforming growth factor ß2 (TGF-ß2) induces epithelial-mesenchymal transition (EMT) in retinal pigmental epithelial (RPE) cells and promotes the progression of proliferative vitreoretinopathy (PVR). However, the role of m6A methylation in the EMT of human telomerase reverse transcriptase (hTERT) retinal pigmental epithelium (RPE)-1 cells has not been clarified. Here, we extracted RNA from RPE cells subjected to 0 or 20 ng/mL TGF-ß2 for 72 h and identified differentially methylated genes (DMGs) by m6A-Seq and differentially expressed genes (DEGs) by RNA-Seq. We selected the genes related to EMT by conjoint m6A-Seq/RNA-Seq analysis and verified them by qRT-PCR. We then confirmed the function of m6A methylation in the EMT of RPE cells by knocking down the methyltransferase METTL3 and the m6A reading protein YTHDF1. Sequencing yielded 5814 DMGs and 1607 DEGs. Conjoint analysis selected 467 genes altered at the m6A and RNA levels that are closely associated with the EMT-related TGF-ß, AGE-RAGE, PI3K-Akt, P53, and Wnt signaling pathways. We also identified ten core EMT genes ACTG2, BMP6, CDH2, LOXL2, SNAIL1, SPARC, BMP4, EMP3, FOXM1, and MYC. Their RNA levels were evaluated by qRT-PCR and were consistent with the sequencing results. We observed that METTL3 knockdown enhanced RPE cell migration and significantly upregulated the EMT markers N-cadherin (encoded by CDH2), fibronectin (FN), Snail family transcription repressor (SLUG), and vimentin. However, YTHDF1 knockdown had the opposite effects and decreased both cell migration and the N-cadherin, FN, and SLUG expression levels. The present study clarified TGF-ß2-induced m6A- and RNA-level differences in RPE cells, indicated that m6A methylation might regulate EMT marker expression, and showed that m6A could regulate TGF-ß2-induced EMT.

m6A-methylated KCTD21-AS1 regulates macrophage phagocytosis through CD47 and cell autophagy through TIPR.

Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.

Allicin Overcomes Doxorubicin Resistance of Breast Cancer Cells by Targeting the Nrf2 Pathway.

Breast cancer (BC) is a lethal disorder that threatens the life safety of the majority of females globally, with rising morbidity and mortality year by year. Doxorubicin is a cytotoxic anthracycline antibiotic that is widely used as one of the first-line chemotherapy agents for patients with BC. However, the efficacy of doxorubicin in the clinic is largely limited by its serious side effects and acquired drug resistance. Allicin (diallyl thiosulfinate), as the major component and key active compound present in freshly crushed garlic, has shown potential effects in suppressing chemotherapy resistance in various cancers. Our research aimed to explore the relationship between allicin and doxorubicin resistance in BC. To generate doxorubicin-resistant BC cell lines (MCF-7/DOX and MDA-MB-231/DOX), doxorubicin-sensitive parental cell lines MCF-7 and MDA-MB-231 were continuously exposed to stepwise increased concentrations of doxorubicin over a period of 6 months. CCK-8, colony formation, flow cytometry, RT-qPCR, and western blotting assays were performed to investigate the effects of allicin and/or doxorubicin treatment on the viability, proliferation and apoptosis and the expression of Nrf2, HO-1, phosphate AKT and AKT in doxorubicin-resistant BC cells. Our results showed that combined treatment of allicin with doxorubicin exhibited better effects on inhibiting the proliferation and enhancing the apoptosis of doxorubicin-resistant BC cells than treatment with allicin or doxorubicin alone. Mechanistically, allicin suppressed the levels of Nrf2, HO-1, and phosphate AKT in doxorubicin-resistant BC cells. Collectively, allicin improves the doxorubicin sensitivity of BC cells by inactivating the Nrf2/HO-1 signaling pathway.

Duodenal malignant melanoma: Primary and metastatic case series and literature review.

RATIONALE: Duodenal malignant melanoma is rare, and its early clinical symptoms are insidious, making it difficult to diagnose in its early stages. Combined with previous literature, We explored the clinicopathological characteristics and v-raf murine sarcoma viral oncogene homolog B1 mutations in primary and metastatic duodenal malignant melanoma, in order to provide some experience on its differential diagnosis and treatment. PATIENT CONCERNS: The 2 patients (a 63-year-old female [Patient 1] and a 54-year-old male [Patient 2]) experienced pain and discomfort in their upper abdomen. Additionally, one of them had a history of skin malignant melanoma. DIAGNOSES: Patient 1 was diagnosed with primary duodenal malignant melanoma; and Patient 2 was diagnosed with metastatic duodenal malignant melanoma. INTERVENTIONS: Patient 1 underwent pancreaticoduodenectomy; and patient 2 underwent complete surgical resection and lymph node dissection. OUTCOMES: After surgery, Patient 1 survived after 26 months follow-up, and Patient 2 died of systemic multi-organ circulatory failure after 1 month follow-up. LESSONS: Primary and metastatic cases should be diagnosed through previous medical history analysis and detailed physical and auxiliary examinations. This would enable a diagnosis based on characteristic histomorphology and immunohistochemical markers. An early diagnosis and surgical treatment can prolong patient survival and the molecular inspection of v-raf murine sarcoma viral oncogene homolog B1 mutations can guide follow-up treatment.

A case of neoadjuvant chemotherapy in pregnancy with cervical cancer (IB3).

Compared with the early symptoms of non-pregnancy, the early pregnancy with cervical cancer is often confused with threatened abortion, so it is difficult to diagnose and delay the time of treatment. At present, compared with cervical cancer, there is no clear and standard treatment for cervical cancer in pregnancy. At present, the diagnosis and treatment plan is mainly made according to the pathological examination, staging, fetal development (whether there is abnormality on ultrasound and whether the chromosome karyotype is normal or not) and the pregnant women and their family members' pregnancy wishes. A case of pregnancy complicated with cervical cancer who was terminated by planned cesarean section after neoadjuvant chemotherapy (NACT) with irregular vaginal bleeding as the first symptom was analyzed retrospectively.

Octanoic acid-rich enteral nutrition attenuated hypercatabolism through the acylated ghrelin-POMC pathway in endotoxemic rats.

OBJECTIVES: Metabolic disorders and no response to intravenous nutrition because of sepsis have been urgent problems for clinical nutrition support. Enteral nutrition (EN) has been an important clinical therapeutic measure in septic patients; however, simple EN has not demonstrated good performance. This study aimed to investigate the effects of different concentrations of octanoic acid (OA)-rich EN on hypercatabolism in endotoxemic rats and test whether OA-rich EN could attenuate hypercatabolism through the acylated ghrelin-proopiomelanocortin (POMC) pathway. METHODS: Rats were randomly divided into six groups: sham, lipopolysaccharide (LPS), LPS + EN and LPS + EN + OA (0.25, 0.5, and 1 g/kg, respectively) groups to investigate the effects of different concentrations of OA-rich EN on hypercatabolism in endotoxemic rats. The rats were then randomly divided into four groups: sham, LPS, LPS + OA, and LPS + OA + Go-CoA-Tat, to test whether OA-rich EN attenuated hypercatabolism through the acylated ghrelin-POMC pathway. Rats received nutrition support via a gastric tube for 3 d (100 kcal/kg daily). Insulin resistance, muscle protein synthesis and atrophy, inflammatory cytokines, ghrelin in circulation and hypothalamus, ghrelin O-acyltransferase (GOAT), and the adenosine 5'-monophosphate-activated protein kinase (AMPK)-autophagy-POMC pathway were measured. RESULTS: Compared with simple EN, OA-rich EN promoted the acylation of ghrelin in a dose-dependent manner and attenuated POMC-mediated hypercatabolism in endotoxemic rats. Inhibition of GOAT activity decreased the level of acylated ghrelin and aggravated POMC-mediated hypercatabolism conferred by OA-rich EN. CONCLUSIONS: OA-rich EN could increase the level of acylated ghrelin and attenuate hypercatabolism through the acylated ghrelin-POMC pathway compared with simple EN in endotoxemic rats.

Pharmacokinetic study of the interaction between luteolin and magnoflorine in rats.

Both luteolin and magnoflorine have been reported to regulate the development of breast cancer, which makes them easier to co-administrate. Luteolin was co-administrated with magnoflorine to evaluate their potential interaction. The pharmacokinetic study was performed on male Sprague-Dawley rats randomly grouped as the single administration of luteolin and the co-administration of luteolin and magnoflorine with six rats of each. CaCO-2 cell transwell assay was employed for transport evaluation, and the metabolic stability of luteolin and CYP3A activity were assessed in rat liver microsomes. The effect of luteolin on MDA-MB-231 cells was assessed with CCK8 assay. Magnoflorine significantly changed the pharmacokinetic profile of luteolin with increased area under the curve (AUC), prolonged t1/2 , and reduced clearance rate. Magnoflorine also suppressed the efflux ratio and improved the in vitro metabolic stability of luteolin. Magnoflorine also enhanced the inhibitory effect of luteolin on MDA-MB-231 cells. Magnoflorine significantly inhibited CYP3A activity with the IC50 of 18.99 µM. Magnoflorine prolonged the system exposure, enhanced the metabolic stability, and enhanced the anti-tumor effect of luteolin through inactivating CYP3A.

Multi-threshold Image Segmentation based on an improved Salp Swarm Algorithm: Case study of breast cancer pathology images.

Breast cancer poses a significant risk to women's health, and it is essential to provide proper diagnostic support. Medical image processing technology is a key component of all supporting diagnostic techniques, with Image Segmentation (IS) being one of its primary steps. Among various methods, Multilevel Image Segmentation (MIS) is considered one of the most effective and straightforward approaches. Many researchers have attempted to improve the quality of image segmentation by combining different metaheuristic algorithms with MIS. However, these methods often suffer from issues such as low convergence accuracy and a proclivity for converging towards Local Optima (LO). To overcome these challenges, this study introduces an integrated approach that combines the Salp Swarm Algorithm (SSA), Slime Mould Algorithm (SMA) and Differential Evolution (DE) algorithm. In this manuscript, we introduce an innovative hybrid MIS model termed SDSSA, which leverages elements from the SSA, SMA and DE algorithms. The SDSSA model fundamentally relies on non-local means 2D histogram and 2D Kapur's entropy. To evaluate the proposed method effectively, we compare it initially with similar algorithms using the IEEE CEC2014 benchmark functions. The SDSSA showcases enhanced convergence velocity and precision relative to similar algorithms. Furthermore, this paper proposes an excellent MIS method. Subsequently, IS experiments were conducted separately at both low and high threshold levels. The test results demonstrate that the segmentation outcomes of MIS, at both low and high threshold levels, outperform other methods. This validates SDSSA as a superior segmentation technique that provides practical assistance for future research in breast cancer pathology image processing.

Macrophages-derived exo-miR-4449 induced by Cryptococcus affects HUVEC permeability and promotes pyroptosis in BEAS-2B via the HIC1 pathway.

Macrophages have recently been discovered to assume a significant role in the progression of cryptococcosis. However, the potential involvement of macrophage-derived exosomes in the pathogenesis of cryptococcosis remains uncertain. In this study, we investigated the changes of microRNAs in macrophage exosomes (exo-miRNAs) in cryptococcal infections and the role of markedly altered exo-miRNAs in the modulation of Human Umbilical Vein Endothelial Cells (HUVEC) permeability and ROS accumulation and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B). Techniques such as microarray analysis and real-time quantitative PCR were used to detect different exo-miRNAs and to screen for the most highly expressed exo-miRNAs. Then its mimics were transfected into HUVEC to study its effect on the monolayer permeability of HUVEC. Finally, the relationship between this exo-miRNAs and the ROS accumulation and pyroptosis was verified by bioinformatics analysis. The results showed that five exo-miRNAs were overexpressed and two exo-miRNAs were reduced, among which, exo-miR-4449 was expressed at the highest level. Exo-miR-4449 could be internalized by HUVEC and enhanced its monolayer permeability. Moreover, exo-miR-4449 was found to promote ROS accumulation and pyroptosis in BEAS-2B through HIC1 pathway. Thus, exo-miR-4449 plays an important role in the pathogenesis of cryptococcosis and holds promise as a significant biomarker for treatment.

Umbilical cord mesenchymal stem cells inhibited inflammation of bronchial epithelial cells by regulating Hedgehog pathway.

This study aimed to explore the role and mechanism of umbilical cord mesenchymal stem cells (UCMSCs) in regulating inflammation of bronchial epithelial cells. Transforming growth factor beta-1 (TGF-ß1) was used to induce inflammation in human bronchial epithelial cells. Cell proliferation was detected through CCK8 and cell apoptosis was detected by Annexin V and propidium iodide double staining. E-cadherin and α-smooth muscle actin (α-SMA) were detected by immunofluorescence, and tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in culture medium supernatant were detected by ELISA. The expression of E-cadherin, α-SMA, Sonic hedgehog (Shh), Gli1 and Snail was detected by Western blot analysis. Compared with the control group, bronchial epithelial cells treated with TGF-ß1 showed significantly decreased proliferation, increased apoptosis, increased secretion of TNF-α and IL-6, increased expression of α-SMA, Shh, Gli1 and Snail and decreased E-cadherin expression. However, co-culture with UCMSCs inhibited TGF-ß1-induced changes in human bronchial epithelial cell proliferation, apoptosis, secretion of TNF-α and IL-6 and activation of the Hedgehog pathway. In conclusion, UCMSCs have protective effects on TGF-ß1-induced inflammation in human bronchial epithelial cells by regulating the Hedgehog pathway.

Comparison of Regional Saturation Biopsy, Targeted Biopsy, and Systematic Biopsy in Patients with Prostate-specific Antigen Levels of 4-20 ng/ml: A Prospective, Single-center, Randomized Controlled Trial.

BACKGROUND: Despite the use of multiparametric magnetic resonance imaging (mpMRI)-guided targeted biopsy (TB) to identify suspicious prostate lesions, it may still miss clinically significant prostate cancer (csPCa) or result in false-negative findings. Recent evidence suggests that combining biopsies taken from within and around magnetic resonance imaging (MRI) lesions can improve the detection of csPCa. OBJECTIVE: This study aimed to compare the diagnostic performance of the regional saturation biopsy (RSB) method, involving template-based nine-core biopsies for suspected regions, with that of the MRI-directed TB and/or the systematic biopsy (SB) methods in biopsy-naïve patients with prostate-specific antigen (PSA) levels ranging from 4 to 20 ng/ml. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, randomized controlled trial included 434 biopsy-naïve patients with suspected lesions on mpMRI and PSA levels between 4 and 20 ng/ml (from January 2022 to July 2023). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The detection rates of csPCa for the RSB, TB, and SB methods were analyzed using the McNemar test for intrapatient comparisons. The Fisher's exact test was used for comparisons between RSB and TB. RESULTS AND LIMITATIONS: The RSB approach yielded a significantly higher detection rate of csPCa than both the TB approach (44.1% vs 31.8%, p = 0.01) and the SB approach (44.1% vs 34.1%, p = 0.03). The RSB approach exhibited a comparable detection rate of csPCa (44.1% vs. 40.7%, p = 0.3) to the combined approach (TB + SB), while requiring fewer biopsy cores and a higher positive core number to avoid sampling the entire prostate gland (32.7% vs 18.3%, p < 0.001). Upon conducting a whole-mount histopathological analysis, it was observed that the RSB approach successfully identified 97% (32 out of 33) of the prostate cancer foci as the index lesion, whereas only 59.18% (29 out of 49) were classified as index lesions using the SB approach. Furthermore, mpMRI underestimated the average diameter of histological tumor size by a median of 0.76 cm, highlighting the importance of an optimal biopsy area for the RSB procedure. CONCLUSIONS: For patients with suspected lesions on mpMRI and PSA levels between 4 and 20 ng/ml, the RSB approach has shown improved detection of clinically significant prostate cancer, accurately identifying index lesions, and minimizing biopsy cores compared with the MRI-directed TB and SB approaches. PATIENT SUMMARY: For patients with suspected lesions on multiparametric magnetic resonance imaging and prostate-specific antigen levels between 4 and 20 ng/ml, the regional saturation biopsy method provides enhanced detection of clinically significant prostate cancer, as well as precise identification of index lesions, surpassing both magnetic resonance imaging-directed targeted biopsy and the systematic biopsy method.