Integrated multi-omics profiling landscape of organising pneumonia.

BACKGROUND: Organising pneumonia (OP) is one of the most common and lethal diseases in the category of interstitial pneumonia, along with lung cancer. Reprogramming of lipid metabolism is a newly recognized hallmark of many diseases including cancer, cardiovascular disorders, as well as liver fibrosis and sclerosis. Increased levels of ceramides composed of sphingosine and fatty acid, are implicated in the development of both acute and chronic lung diseases. However, their pathophysiological significance in OP is unclear. The aim of this study was to investigate the role of lipid metabolism reprogramming in OP, focusing on inflammation and fibrosis. METHODS: Comprehensive multi-omics profiling approaches, including single-cell RNA sequencing, Visium CytAssist spatial transcriptomics, proteomics, metabolomics and mass spectrometry, were employed to analyze the tissues. OP mice model was utilized and molecular mechanisms were investigated in macrophages. RESULTS: The results revealed a significant association between OP and lipid metabolism reprogramming, characterized by an abnormal expression of several genes related to lipid metabolism, including CD36, SCD1, and CES1 mainly in macrophages. CD36 deficiency in alveolar macrophages, led to an increased expression of C16/24 ceramides that accumulated in mitochondria, resulting in mitophagy or mitochondrial dysfunction. The number of alveolar macrophages in OP was significantly reduced, which was probably due to the ferroptosis signaling pathway involving GSH/SLC3A2/GPX4 through CD36 downregulation in OP. Furthermore, macrophage secretion of DPP7 and FABP4 influenced epithelial cell fibrosis. CONCLUSIONS: CD36 inhibited the ferroptosis pathway involving SLC3A2/GPX4 in alveolar macrophages of OP tissue by regulating lipid metabolism, thus representing a new anti-ferroptosis and anti-fibrosis effect of CD36 mediated, at least in part, by ceramides. HIGHLIGHTS: Our findings reveal a significant association between organising pneumonia and lipid metabolism reprogramming and will make a substantial contribution to the understanding of the mechanism of organising pneumonia in patients.

Innovative insights: ITLN1 modulates renal injury in response to radiation.

Radiation-induced kidney injury is a common side effect of radiotherapy, as the pelvic region is in close proximity to the kidneys, posing a risk of inducing radiation-induced kidney injury when treating any pelvic malignancies with radiotherapy. This type of injury typically manifests as chronic kidney disease a few months after radiotherapy, with the potential to progress to end-stage renal disease. Radiation-induced damage involves various components of the kidney, including glomeruli, tubules, interstitium, and extracellular matrix. Therefore, investigating its molecular mechanisms is crucial. In this study, we extensively searched literature databases, selecting recent transcriptomic studies related to acute kidney injury (AKI) published in the past decade. We downloaded the raw RNA sequencing datasets GSE30718 and GSE66494 related to AKI from the GEO database and identified that intestinal-type lectin ITLN1 plays a significant role in regulating radiation-induced kidney injury in rats. Differential gene analysis was performed using chip data from the GEO database, and further bioinformatics analysis identified 13 genes that may be involved in regulating kidney injury, with ITLN1 being the most relevant to kidney damage, thus selected as the target gene for this study. Subsequently, a rat model of radiation-induced kidney injury was established for experimental validation, assessing kidney tissue morphology and injury extent through staining observation and immunohistochemical staining. The protective effect of ITLN1 on kidney function was evaluated by measuring changes in rat body weight and blood pressure, serum kidney injury markers, and kidney structure. The experimental results indicate that overexpression of ITLN1 can improve kidney function in rats with radiation-induced kidney injury by activating the Akt/GSK-3ß/Nrf2 signaling pathway, suppressing oxidative stress, cell apoptosis, inflammation, cellular senescence, and fibrosis. This study highlights the significant role of ITLN1 in regulating kidney injury, providing a novel target for future treatments of radiation-induced kidney injury.

High-expressed PTPN1 promotes tumor proliferation signature in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor that is associated with substantial morbidity and mortality rates. Despite the progress made in diagnostic technology, the survival rate of HCC patients remains unsatisfactory due to the complex nature and extensive metastasis of the disease. Consequently, the discovery of new molecular targets is of great practical significance for the diagnosis and treatment of HCC. Protein tyrosine phosphatases (PTPs) play a crucial role in cell signal transduction by catalyzing the dephosphorylation of tyrosine residues in proteins. The present study has revealed that the upregulation of protein tyrosine phosphatase non-receptor type 1 (PTPN1) is a characteristic feature of HCC and is associated with a poor prognosis. Additionally, our investigation into the functional roles of PTPN1-regulated genes in HCC has demonstrated that alterations in PTPN1 expression disrupt normal cell cycle progression metabolism. Additionally, the capacity for proliferation and migration of HCC cells was notably diminished subsequent to PTPN1 silencing, resulting in the prevention of cell entry into the S phase from the G1 phase. Our investigation indicates that PTPN1 may facilitate the onset and progression of HCC by disrupting the cell cycle, thereby presenting a promising molecular target for the diagnosis and treatment of liver cancer.

TRPs in Ovarian Serous Cystadenocarcinoma: The Expression Patterns, Prognostic Roles, and Potential Therapeutic Targets.

Ovarian cancer (usually ovarian serous cystadenocarcinoma, or OV) is the fifth leading cause of cancer-related deaths in women, with more than 184,000 deaths reported worldwide annually, and is a highly malignant carcinoma. However, the mechanism of etiology remains unclear. The lack of prognostic and diagnostic biomarkers is a main limitation for clinical diagnosis and treatment. The transient receptor potential (TRP) channels play essential roles in the occurrence and development of cancers which may have the potential as a therapeutic target for OV. In our study, we used bioinformatic methods to study the potential effect and function of the TRP family in patients with OV. Differential expression analysis showed that the expression of TRPC7, TRPV4, and other TRP family members was significantly different between tumor and normal tissues. Through survival analysis, we screened out that the high expression of TRPC7, TRPV4, and TRPM (2,4,8) was negatively correlated with the prognosis of patients. In contrast, the low expression of TRPM3 was negatively associated with the prognosis. Cox regression analysis further indicated that TRPV4 was OV's most likely therapeutic target. Finally, we conducted mRNA expression analysis, functional enrichment analysis, and immune infiltration analysis to confirm that TRPV4 was the most convincing therapeutic target of OV.

Massive renal urothelial carcinoma with renal vein tumor thrombus, pancreatic infiltration and adrenal metastasis: A case report.

A 49-year-old female patient presented with a massive left renal tumor, recurrent left flank pain and gross hematuria. The tumor was accompanied by a renal vein tumor thrombus, pancreatic infiltration and a solitary adrenal metastasis. Radical nephrectomy, distal pancreatectomy, ipsilateral adrenalectomy and splenectomy were performed. Histopathological examination suggested high-grade urothelial carcinoma (UC); however, tumor recurrence and multiple metastases were detected only 3 months after the surgery, and the patient succumbed during follow-up 1 month later. To the best of our knowledge, this is the first case of renal UC of such advanced stage with renal vein tumor thrombus, pancreatic infiltration and a solitary adrenal metastasis.

A systematic review and meta-analysis of comparative studies assessing the efficacy of luteinizing hormone-releasing hormone therapy for children with cryptorchidism.

PURPOSE: To assess the efficacy of intranasal luteinizing hormone-releasing hormone (LHRH) therapy for cryptorchidism. MATERIALS AND METHODS: Eligible studies were identified by two reviewers using PubMed, Embase, and Web of Science databases. Primary outcomes were complete testicular descent rate, complete testicular descent rate for nonpalpable testis, and pre-scrotal and inguinal testis. Secondary outcomes included testicular descent with different medicines strategy and a subgroup analysis. RESULTS: Pooled data including the 1255 undescended testes showed that complete testicular descent rate was 20.9 % in LHRH group versus 5.6 % in the placebo group, which was significantly different [relative risk (RR) 3.94, 95 % confidence interval (CI) 2.14-7.28, P < 0.0001]. There was also a significant difference in the incidence of pre-scrotal and inguinal position testis descent, with 22.8 % in the LHRH group versus 3.6 % in the placebo group (RR 5.79, 95 % CI 2.94-11.39, P < 0.00001). However, side effects were more frequent in the LHRH group (RR 2.61, 95 % CI 1.52-4.49, P = 0.0005). There were no significant differences for nonpalpable testes. CONCLUSIONS: LHRH had significant benefits on testicular descent, particularly for inguinal and pre-scrotal testes, which was also accompanied by temporary slight side effects.

Non-functioning paraganglioma occurring in the urinary bladder: A case report and review of the literature.

Paraganglioma, also termed extra-adrenal pheochromocytoma, may be observed at the base of the skull and neck as well as within the mediastinum and periaortic region. The clinical symptoms of paraganglioma of the urinary bladder include intermittent hypertensive attacks, micturition, headaches and palpitations due to high catecholamine levels; these types of paragangliomas are extremely rare. However, certain bladder paragangliomas do not present with any of these symptoms; thus, surgeons are not pre-warned on how to prepare for their resection. Surgery to remove pheochromocytomas may therefore result in an intraoperative hypertensive crisis and increase the mortality rate. This infrequent type of paraganglioma is only recognized through histological examination following surgery. The current study reports the case of a 61-year-old male with urinary bladder paraganglioma. The patient presented with hypertension, which was controlled to within a normal range using diovan and norvasc treatment; in addition, the patient's blood pressure was not altered with urination or postural changes. The patient was not administered an α-blocking agent or a blood volume expander prior to the surgery, and during the partial cystectomy no hypertensive crisis occurred.

[Trans-lumbar-and-peritoneally joint approach for laparoscopic removal of large adrenal neoplasms].

OBJECTIVE: To explore the safety and efficacy of translumbar-and-peritoneally joint (TLPJ) approach for laparoscopic dissection of large neoplasms from adrenal glands. METHODS: Sixty patients with diameters > or = 6.0 cm adrenal neoplasms were recruited in this study. Of the participants, 30 were given transperitoneally laparoscopic adenectomy and 30 were given TLPJ approach. We compared the basic characteristics of the patients, as well as their conditions during and after operations. RESULTS: The two groups of patients had similar characteristics. No significant differences were found between the two approaches in terms of conversion to open surgery, estimated blood loss, transfusion, operating time, side injury, fluctuations of heart rate and blood pressure, and vascular accidents (P>0.05), although slight, but not significant, advantages were shown in the TLPJ patients on starting food intake and physical activities. Similar results were also found .in drainage volume, time to remove drainage, length of hospital stay, usage of analgesic, fever incidence, infection and intestinal obstruction etc (P>0.05). Above all, no significant differences were found between the two groups in recurrence, metastasis and overall survival rates (P>0.05). CONCLUSION: Laparoscopic surgery with TLPJ approach, translumbar combined with entirely side peritoneum opened, is safe and efficient compared with the traditional transperitoneal approach for patients with large adrenal neoplasms.

Diagnosis and treatment of adrenal medullary hyperplasia: experience from 12 cases.

Objective. To dissect the characteristics of adrenal medullary hyperplasia (AMH) and share our experience of diagnosis and treatment of AMH. Methods. From 1999 to 2013, 12 cases of AMH have been pathologically diagnosed after operation in our hospital. The clinical characteristics, process of diagnosis, treatment, and prognosis during follow-up of all patients are summarized retrospectively. Results. Four cases were trended to be AMH and 6 cases were trended to be pheochromocytoma before operation; moreover, the other two patients were diagnosed accidentally. All patients, except for the patient with mucinous tubular and spindle cell carcinoma of left kidney by open surgery, experienced a smooth laparoscopic adrenalectomy, including 2 with radical nephrectomy, 10 of which experienced unilateral adrenalectomy, 1 was bilaterally partial adrenalectomy, and the remaining one was unilaterally complete removal and then 2/3 partially contralateral excision. After a medium follow-up of 6.5 years, it demonstrated a satisfactory outcome of 8 cured patients and 4 symptomatic improved patients. Conclusions. AMH presents a mimicking morphology and clinical manifestation with pheochromocytoma. Surgery could be the only effective choice for the treatment of AMH and showed a preferable prognosis after a quite long follow-up.

A systematic review and meta-analysis of comparative studies on the efficacy of extended pelvic lymph node dissection in patients with clinically localized prostatic carcinoma.

PURPOSE: Pelvic lymph node dissection (PLND) has been performed during radical prostatectomy in nearly all patients with clinically localized prostatic carcinoma (PCa), while the specific regions that needed to be removed demonstrated bifurcation among urologist. However, clinical studies comparing extended PLND (ePLND) with standard PLND (sPLND) and limited PLND (lPLND) reveal conflicting, or even opposing results. METHODS: All controlled trials comparing ePLND with sPLND or lPLND were identified through comprehensive searches of the PubMed, Cochrane Library and Embase databases. A systematic review and meta-analysis of these studies were then performed. RESULTS: Eighteen studies with a total of 8,914 patients were included. Regardless of being compared with sPLND or lPLND, ePLND significantly improved LN retrieval [ePLND vs. sPLND: weighted mean difference (WMD) 11.93, 95 % confidence interval (CI) 9.91-13.95, p < 0.00001; ePLND vs. lPLND: WMD 8.27, 95 % CI 3.53-13.01, p = 0.0006] and the detection of more LNs positive of metastasis [risk ratio (RR) 3.51, 95 % CI 2.14-5.75, p < 0.00001; RR 3.50, 95 % CI 2.20-5.55, p < 0.00001, respectively]. EPLND decreased the complication rate, but the differences were not statistically significant (RR 1.52, 95 % CI 0.87-2.65, p = 0.14; RR 1.52, 95 % CI 0.67-3.45, p = 0.32, respectively). Operating time, estimated blood loss, length of hospital stay and biochemical recurrence (BCR) were statistically insignificant between techniques. CONCLUSIONS: ePLND shows benefits associated with increased LNs yield, LNs positivity, and safety, significantly with no risk of side effects. However, ePLND did not decrease BCR. Additional high-quality, well-designed randomized controlled trials and comparative studies with long-term follow-up results are required to define the optimal procedure for patients with clinically localized PCa.

Perioperative Endocrine Therapy for Patients with Cushing's Syndrome Undergoing Retroperitoneal Laparoscopic Adrenalectomy.

Objectives. To investigate the efficacy and safety of perioperative endocrine therapy (PET) for patients with Cushing's syndrome (CS) undergoing retroperitoneal laparoscopic adrenalectomy (RLA). Methods. The novel, simplified PET modality of 82 patients who underwent RLA procedures for CS were studied. Clinical manifestations were observed for all patients on days 1 and 5 postoperatively, and clinical data, such as blood pressure (BP), levels of serum cortisol, adrenocorticotropin (ACTH), blood glucose, and electrolytes, were acquired and analyzed. Results. Supraphysiological doses of glucocorticoid were administered during the perioperative period, and the dosage was reduced gradually. In all 82 cases, the RLAs were performed successfully without any perioperative complication, such as steroid withdrawal symptoms. The patient's symptoms and signs were improved quickly and safely during the hospital days. The serum cortisol and potassium levels were rather stable on days 1 and 5 postoperatively, and most were within the normal range. The clinical manifestations, serum levels of cortisol, ACTH, and potassium in most patients restored to normal gradually after several months (mean, 6.7 ± 1.2 months), except for one patient undergoing bilateral adrenalectomy. Conclusions. This perioperative endocrine therapy for patients with Cushing's syndrome (mainly for adrenocortical adenoma) undergoing retro-laparoscopic adrenalectomy is both effective and safe.

Transient variations in the serum concentrations of cell adhesion molecules following retroperitoneal laparoscopic and open radical nephrectomy for localized renal-cell carcinoma.

PURPOSE: To evaluate differences in the serum concentrations of cell adhesion molecules (CAMs) after retroperitoneal laparoscopic and conventional open radical nephrectomies for localized renal-cell carcinoma (RCC). PATIENTS AND METHODS: A total of 62 patients with stage T(1)N(0)M(0) RCC were randomized to either a retroperitoneal laparoscopic radical nephrectomy group (n=31) or an open group (n=31). Serum levels of soluble cluster of differentiation 44 splice variant 6 (sCD44v6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble epithelial cadherin (sE-cadherin) were determined independently by enzyme linked immunosorbent assay (ELISA) preoperatively, and on postoperative days 1 and 5. In addition, follow-up results were compared. RESULTS: On postoperative day 1, sCD44v6, sICAM-1, and sVCAM-1 levels increased significantly compared with preoperative levels in both groups (P<0.05). sE-cadherin levels decreased compared with preoperative levels in both groups without statistically significant differences (P>0.05). sCD44v6 levels in the retro-laparoscopy group were significantly higher than in the open group (P<0.05), while sICAM-1, sVCAM-1, and sE-cadherin levels showed no statistically significant differences between both groups (P>0.05). On postoperative day 5, all parameters in both groups were similar to preoperative values (P>0.05). Follow-up ranged from 7 to 18 months postoperatively in all 62 patients, with a 100% cancer-specific survival rate in each group. CONCLUSION: Although postoperatively higher serum concentrations of CAMs in both groups and significantly elevated sCD44v6 in the retro-laparoscopy group may be facilitated, the differences in CAMs between both groups are small and transient. Together with the similar follow-up results, this further supports previous studies that failed to show a difference in the oncologic outcomes between open and laparoscopic radical nephrectomy and provides a probable molecular mechanism.