Impact of Detrusor Muscle Activity on Short-term Prognosis Following 1470 nm Semiconductor Laser Surgery in Elderly Patients with Benign Prostatic Hyperplasia.

Objective: To investigate the influence of preoperative detrusor muscle activity on the short-term prognosis of elderly patients diagnosed with benign prostatic hyperplasia (BPH) undergoing 1470 nm semiconductor laser surgery. Methods: A retrospective study was conducted on clinical data from 165 elderly BPH patients who underwent 1470 nm semiconductor laser surgery between May 2019 and April 2023. Patients were stratified based on preoperative urodynamic study findings, specifically their bladder contractility index (BCI). Patients with a BCI ≤100 constituted the detrusor underactivity (DU) group (n=64), while those with a BCI >100 formed the non-DU group (n=101). Surgical parameters, including duration, intraoperative blood loss, postoperative hospital stay, bladder irrigation, and catheterization duration, were compared. Additionally, changes in International Prostate Symptom Score (IPSS), Quality of Life (QOL) score, residual urine volume, and peak urinary flow rate (Qmax) were assessed before and three months after surgery in both groups. Results: There were no statistically significant differences observed between the DU and non-DU groups concerning surgical duration, intraoperative blood loss, postoperative hospitalization duration, bladder irrigation duration, and postoperative catheterization duration (P > .05). Similarly, no significant disparities were noted in the IPSS and QOL scores preoperatively and at the three-month follow-up in both groups (P > .05). Both cohorts exhibited no significant differences in residual urine volume before surgery and at the three-month mark postoperatively (P > .05). However, the postoperative Qmax was significantly reduced in the DU group compared to the non-DU group (P < .05). Conclusions: Detrusor muscle activity does not exert a significant impact on clinical symptom improvement and quality of life in elderly BPH patients treated with 1470 nm semiconductor laser surgery. However, patients with DU exhibited inferior postoperative recovery in Qmax, underscoring the importance of preoperative urodynamic studies for early intervention and enhanced surgical outcomes in this patient population.

[PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position improves urinary continence and protects erectile function in BPH patients].

OBJECTIVE: To evaluate the effect of transurethral plasmakinetic enucleation of the prostate (PKEP) with complete preservation of the urethral mucosa in the 11－1 o'clock position on urinary continence and erectile function in BPH patients. METHODS: We retrospectively analyzed the clinical data on 84 cases of BPH treated by traditional PKEP (group A, n = 48) or modified PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position (group B, n = 36) from January 2017 to December 2021. All the patients had sexual activities within three months preoperatively. We followed up the patients for 12 months after surgery and compared the baseline, surgery-related and follow-up data between the two groups of patients. RESULTS: There were no statistically significant differences between the two groups of patients in age, disease duration, prostate volume, preoperative postvoid residual urine (PVR), preoperative maximum urinary flow rate (Qmax), IPSS, PSA level, QOL scores or IIEF-5 scores, nor in the operation time, intraoperative hemoglobin decrease, volume of resected tissue, bladder flushing time, postoperative hospital stay, or postoperative improvement of Qmax and IPSS. The rate of urinary continence was significantly higher in group B than in A at 1 month postoperatively (66.67% ï¼»24/36ï¼½ vs 43.25% ï¼»20/48ï¼½, P = 0.025) and so were IIEF-5 scores at 6 months (16.69 ± 3.21 vs 15.27 ± 2.74, P = 0.032) and 12 months (18.04 ± 2.04 vs 16.96 ± 2.54, P = 0.039), while the incidence rate of retrograde ejaculation markedly lower in the former than in the latter group at 6 months (33.33% ï¼»12/36ï¼½ vs 56.25% ï¼»28/48ï¼½, P = 0.018) and 12 months (25% ï¼»9/36ï¼½ vs 47.92% ï¼»23/48ï¼½, P = 0.027). At 1, 3, 6 and 12 months after surgery, the patients in group B also showed remarkably higher QOL scores than those in group B (2.61 ± 0.81 vs 2.12 ± 0.69, P = 0.005; 2.24 ± 0.66 vs 1.94 ± 0.51,P = 0.026; 2.12 ± 0.83 vs 1.80 ± 0.53,P = 0.047; and 1.94 ± 0.65 vs 1.72 ± 0.58, P = 0.038). CONCLUSION: Modified PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position can improve urinary continence, protect erectile function and ameliorate QOL in patients with BPH.

Hepatic Krüppel-like factor 14 regulates lipid metabolism in nonalcoholic steatohepatitis mice.

Excessive lipid accumulation is a critical characteristic in the development of nonalcoholic steatohepatitis (NASH). The underlying molecular mechanism, however, is unclear. In this study, we explored whether and how Krüppel-like factor 14 (KLF14) affects hepatic lipid metabolism in NASH. KLF14 expression was detected in NASH patients and mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Adeno-associated viruses and adenoviruses were used to alter hepatic KLF14 expression in vivo or in vitro to investigate how KLF14 functions in lipid regulation. The molecular mechanisms were explored using RNA-seq, luciferase reporter, and ChIP assays. The fatty liver phenotype was analyzed histopathologically, and serum and hepatocyte biochemical parameters were measured. The NASH mouse model developed quickly in C57BL/6J mice fed a CDAHFD for 8 weeks. We found that KLF14 expression was decreased in NASH patients and CDAHFD mice. Oleic acid and palmitic acid treatment also reduced KLF14 levels in hepatocytes. KLF14 knockdown downregulated the genes involved in fatty acid oxidation, promoting the progression of hepatic steatosis. In contrast, hepatic KLF14 overexpression alleviated lipid accumulation and oxidative stress in CDAHFD mice. These effects resulted from direct activation of the PPARα signaling pathway. PPARα inhibition diminished the KLF14 overexpression-reduced protective effects against steatosis in OA&PA-treated MPHs and AAV-KLF14-infected CDAHFD mice. These data reveal that hepatic KLF14 regulates lipid accumulation and oxidative stress through the KLF14-PPARα pathway as NASH progresses. KLF14 may be a novel therapeutic target for hepatic steatosis.

Mammalian cleavage factor 25 targets KLF14 to inhibit hepatic stellate cell activation and liver fibrosis.

Liver fibrosis is primarily caused by the activation of hepatic stellate cells (HSCs), which results from chronic liver damage. Understanding the pathogenesis of HSC activation could identify new therapeutic targets to treat liver fibrosis. In this study, we examined the protective role of the mammalian cleavage factor I 25 kD subunit (CFIm25, NUDT21) in inhibiting hepatic stellate cell activation. CFIm25 expression was measured in liver cirrhosis patients and a CCl4-induced mouse model. Adeno-associated viruses and adenoviruses were used to alter hepatic CFIm25 expression in vivo and in vitro to investigate how CFIm25 functions in liver fibrosis. The underlying mechanisms were explored using RNA-seq and co-IP assays. Here, we found that CFIm25 expression was drastically decreased in activated murine HSCs and fibrotic liver tissues. CFIm25 overexpression downregulated the expression of genes involved in liver fibrosis, inhibiting the progression of HSC activation, migration and proliferation. These effects resulted from direct activation of the KLF14/PPARγ signaling axis. KLF14 inhibition abrogated the CFIm25 overexpression-mediated reduction in antifibrotic effects. These data reveal that hepatic CFIm25 regulates HSC activation through the KLF14/PPARγ pathway as liver fibrosis progresses. CFIm25 may be a novel therapeutic target for liver fibrosis.

Autotaxin promotes the degradation of the mucus layer by inhibiting autophagy in mouse colitis.

Autotaxin (ATX or ENPP2) is an autocrine enzyme associated with the metabolism of various phospholipids. ATX has recently been identified as a regulatory factor in immune-related and inflammation-associated diseases, such as inflammatory bowel disease, but the exact mechanism is unclear. Here, we treated mice with recombinant ATX protein or an ATX inhibitor to investigate the effect of ATX on colitis in mice and the underlying mechanism. In a mouse model of colitis, ATX expression was increased, autophagy was impaired, and the mucus barrier was disrupted. Recombinant ATX protein promoted intestinal inflammation, inhibited autophagy, and disrupted the mucus barrier, while an ATX inhibitor had the opposite effect. Next, we treated mice that received ATX with an autophagy activator and an adenosine 5'-monophosphate-activated protein kinase (AMPK) agonist. We observed that autophagy activator and AMPK agonist could repair the mucus barrier and alleviate intestinal inflammation in ATX-treated mice. In vitro, we obtained consistent results. Thus, we concluded that ATX could inhibit autophagy through the AMPK pathway, which consequently disordered the mucus barrier and aggravated intestinal inflammation.

The clinical research of 1,470 nm laser in percutaneous nephrolithotomy.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is the primary method for the treatment of renal calculi. The preservation of the nephrostomy tube after operation brings severe pain to the patients. We use a 1,470 nm semiconductor laser to stop bleeding after the operation, which cannot reserve the nephrostomy tube, fully reflect its safety and effectiveness, and provide a new method for clinical practice. METHODS: Forty-two patients with renal stones who came to our hospital from March 2016 to September 2019 were randomly divided into two groups: laser operation group (20 patients) and traditional operation group (22 patients). The stone removal rate, surgical effect, and postoperative complications were compared between the two groups. RESULTS: There was no significant difference in the stone clearance rate between the two groups at the 4th week after operation (P>0.05). However, the incidence of postoperative infection, incision pain, and massive bleeding in the laser surgery group were lower than those in the traditional surgery group (P<0.05). However, there was no significant difference in urine extravasation and postoperative hematuria between the two groups (P>0.05). The average postoperative hospital stay in the laser surgery group was shorter than that in the traditional surgery group, and the difference was statistically significant (P<0.05). Simultaneously, there was no significant difference in operation time, intraoperative blood loss, and medical expenses between the two groups (P>0.05). CONCLUSIONS: The 1,470 nm laser is safe, effective, and feasible in PCNL operation, especially in hemostasis of the renal puncture channel, and it is worth popularizing.

Overexpression of KLF14 protects against immune-mediated hepatic injury in mice.

The underlying immunopathogenic mechanisms of autoimmune hepatitis (AIH) have not yet been well elucidated. An impairment in regulatory T cells (Tregs) is key to the development of AIH. Krüppel-like factors (KLFs) regulate a broad of cellular processes including immunocyte maturation. KLF14 may regulate Treg differentiation, but the biological functions remain far from elucidated. In this study, we identified the hepatic expression of KLF14 in human and murine liver diseases. Immune-mediated hepatitis was induced by concanavalin A (Con A). A KLF14 recombinant adenoviruses plasmid (Ad-KLF14) was constructed and injected into mice. Tregs were assessed by flow cytometry analysis; inflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), were tested by enzyme-linked immunosorbent assay (ELISA). The expression of KLF14 was suppressed in a time-and dose-dependent manner. Changes in cytokine levels were consistent with the degree of hepatic injury. Overexpression of KLF14 protected the liver from immune-mediated damage in vivo. Ad-KLF14 transfection before Con A challenge increased the frequency of Tregs in liver mononuclear cells (MNCs), and suppressed the expression of cytokines. All of these improvements were completely abrogated after Treg deletion in vivo by intraperitoneal injection of a CD25 antibody. In conclusion, these data suggest that KLF14 plays an as-yet unrecognized role in immune-mediated hepatitis mainly via induced Treg differentiation. Our findings extend the knowledge of the biological function of KLF14 to the autoimmune disease field, and indicate the possibility of KLF14 as a therapeutic target in AIH patients.

Knockdown of KIAA1199 attenuates growth and metastasis of hepatocellular carcinoma.

Accumulating evidence indicates that KIAA1199 plays a vital role in tumor progression. However, the role of KIAA1199 in hepatocellular carcinoma (HCC) still remains unknown. In this study, we found that KIAA1199 was upregulated in human HCC tissues and in highly metastatic HCC cell lines. Furthermore, the expression of KIAA1199 was significantly correlated with tumor size and metastasis in HCC. Knockdown of KIAA1199 inhibited cell proliferation and migration in vitro, and suppressed tumorigenicity and lung metastasis in vivo. In addition, silencing of KIAA1199 induced G1 phase arrest by reducing cyclinD1 expression. Moreover, KIAA1199 knockdown induced apoptosis by activating endoplasmic reticulum (ER) stress, which was based on the upregulation of ER stress markers, activating transcription factor 4 (ATF4) and CAAT/enhancer-binding protein homologous protein (CHOP). In conclusion, our data demonstrated that KIAA1199 knockdown inhibited the growth and metastasis of HCC.

CFIm25 inhibits hepatocellular carcinoma metastasis by suppressing the p38 and JNK/c-Jun signaling pathways.

Alternative polyadenylation (APA), a post-transcriptional modification, has been implicated in many diseases, but especially in tumor proliferation. CFIm25, the 25 kDa subunit of human cleavage factor Im (CFIm), is a key factor in APA. We show that CFIm25 expression is reduced in human hepatocellular carcinoma (HCC), and its expression correlates with metastasis. Kaplan-Meier analysis indicated that CFIm25 is related to overall survival in HCC. Moreover, CFIm25 expression is negatively related to the metastatic potential of HCC cell lines. CFIm25 knockdown promotes cell invasion and migration in vitro, while overexpression of CFIm25 inhibits cell invasion and migration in vitro and inhibits intrahepatic and lung metastasis in vivo. Additional studies showed that CFIm25 disrupts epithelial-mesenchymal transition by increasing E-cadherin, that it inhibits HCC cell migration and invasion by blocking the p38 and JNK/c-Jun signaling pathways, and that CFIm25 knockdown increases the transcriptional activity of activating protein-1 (AP-1). These findings indicate that therapy directed at increasing CFIm25 expression is a potential HCC treatment.

SLC26A3 (DRA) prevents TNF-alpha-induced barrier dysfunction and dextran sulfate sodium-induced acute colitis.

SLC26A3 encodes a Cl-/HCO3- ion transporter that is also known as downregulated in adenoma (DRA) and is involved in HCO3-/mucus formation. The role of DRA in the epithelial barrier has not been previously established. In this study, we investigated the in vivo and in vitro mechanisms of DRA in the colon epithelial barrier. Immunofluorescence (IF) and co-immunoprecipitation (co-IP) studies reveal that DRA binds directly to tight junction (TJ) proteins and affects the expression of TJ proteins in polarized Caco-2BBe cells. Similarly, DRA colocalizes with ZO-1 in the intestinal epithelium. Knockdown or overexpression of DRA leads to alterations in TJ proteins and epithelial permeability. In addition, TNF-α treatment downregulates DRA by activating NF-кB and subsequently affecting intestinal epithelial barrier integrity. Furthermore, overexpression of DRA partly reverses the TNF-α-induced damage by stabilizing TJ proteins. Neutralization of TNF-α in dextran sulfate sodium (DSS)-induced colitis mice demonstrates improved the outcomes, and the therapeutic effect of the TNF-α neutralizing mAb is mediated in part by the preservation of DRA expression. These data suggest that DRA may be one of the therapeutic targets of TNF-α. Moreover, DRA delivered by adenovirus vector significantly prevents the exacerbation of colitis and improves epithelial barrier function by promoting the recovery of TJ proteins in DSS-treated mice. In conclusion, DRA plays a role in protecting the epithelial barrier and may be a therapeutic target in gut homeostasis.

Paired related homeobox protein 1 regulates PDGF-induced chemotaxis of hepatic stellate cells in liver fibrosis.

Activation of the platelet-derived growth factor (PDGF)/PDGF beta receptor (PDGFßR) axis has a critical role in liver fibrosis. However, the mechanisms that regulate the PDGF signaling are yet to be elucidated. The present study demonstrates that paired related homeobox protein 1 (Prrx1) is involved in PDGF-dependent hepatic stellate cell (HSCs) migration via modulation of the expression of metalloproteinases MMP2 and MMP9. PDGF elevated the level of Prrx1 through the activation of ERK/Sp1 and PI3K/Akt/Ets1 pathways. In vivo, an adenoviral-mediated Prrx1 shRNA administration attenuated liver fibrosis in thioacetamide-induced fibrotic models. These studies reveal a role of Prrx1 as a modulator of PDGF-dependent signaling in HSCs, and inhibiting its expression may offer a therapeutic approach for hepatic fibrosis.

Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells.

The histidine-rich calcium-binding protein (HRC) is a regulator of Ca2+ homeostasis and it plays a significant role in hepatocellular carcinoma (HCC) progression. However, the relationship between HRC and liver fibrogenesis is still unknown. Our data demonstrates that HRC was upregulated in fibrotic liver and activated hepatic stellate cells (HSCs). TGF-ß treatment increased α-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced α-SMA, CTGF and collagen expression, and inhibited HSC proliferation and migration. In addition, we found that the anti-fibrosis effect of HRC knockdown was associated with endoplasmic reticulum (ER) stress. Silencing of HRC decreased the expression of ER stress and autophagy markers. Moreover, ER stress agonist thapsigargin (TG) enhanced, whereas ER stress antagonist 4-phenylbutyric acid (4-PBA) alleviated HSCs activation and autophagy. In conclusion, these data indicate that depletion of HRC inhibited HSC activation through the ER stress pathway, and HRC may be a potential regulator of liver fibrosis.

Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx.

Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, but its involvement in hepatic fibrogenesis remains unclear. Special AT-rich binding protein 1 (SATB1) has been implicated in reprogramming chromatin organization and transcription profiles in many cancers and non-cancer-related conditions. We found that hepatic SATB1 expression was significantly up-regulated in fibrotic tissues from chronic hepatitis B virus (HBV)-infected patients and HBV transgenic (HBV-Tg) mouse model. Knockdown of SATB1 in the liver significantly alleviated CCl4-induced fibrosis in HBV-Tg mouse model. Moreover, we suggested HBV encoded x protein (HBx) induced SATB1 expression through activation of JNK and ERK pathways. Enforced expression of SATB1 in hepatocytes promoted the activation and proliferation of hepatic stellate cells (HSCs) by secretion of connective tissue growth factor (CTGF), Interleukin-6 (IL-6) and platelet derived growth factor-A (PDGF-AA). Our findings demonstrated that HBx upregulated hepatic SATB1 which exerted pro-fibrotic effects by paracrine activation of stellate cells in HBV-related fibrosis.

Histidine-rich calcium binding protein promotes growth of hepatocellular carcinoma in vitro and in vivo.

We have recently shown that the histidine-rich calcium binding protein (HRC) promotes the invasion and metastasis of hepatocellular carcinoma (HCC). In the current study, we evaluated whether HRC may also affect the growth of HCC. We found that ectopic expression of HRC obviously enhanced proliferation and colony formation, while suppression of HRC exhibited inhibitory effects. Furthermore, we demonstrated that HRC promoted tumor growth in nude mice. These effects may result from the ability of HRC to upregulate cyclinD1 and cyclin-dependent kinase 2 (CDK2) expressions and promote G1/S transition. Further study showed that MEK/ERK signaling pathway was involved in HRC-induced cell proliferation. Interestingly, overexpression or depletion of HRC revealed its regulation on endoplasmic reticulum stress (ERS) and apoptosis, which was partially dependent on PERK/ATF4/CHOP signaling pathway. In addition, blocking ERS using 4-phenylbutyric acid (4-PBA) not only downregulated the expression of PERK, ATF4 and CHOP, but also significantly decreased apoptosis induced by HRC silence, whereas ERS inducer thapsigargin (TG) exerted the opposite effects. Our study thus demonstrates a role of HRC in promoting HCC growth, besides its role in inducing HCC metastasis, and highlights HRC as a promising intervention target for HCC.

Netrin-1 promotes cell migration and invasion by down-regulation of BVES expression in human hepatocellular carcinoma.

The axon guidance cues netrin-1 has been reported to be associated with cancer progression in various types of human cancers. However, the underlying molecular mechanism of netrin-1-mediated metastasis remains obscure. In this study, we found that overexpression of netrin-1 promoted HCC cell migration and invasion as determined by transwell assay and 3D cell culture assay. However, netrin-1 knockdown inhibited these processes. Further investigation indicated that netrin-1 decreased the expression of Blood Vessel Epicardial Substance (BVES), which was down-regulated in HCC. Interestingly, LY294002, a special inhibitor to PI3K/AKT signaling which was determined as a downstream pathway of netrin-1, restored the reduction in BVES caused by netrin-1. In addition, BVES exhibited an opposite effect on HCC cell metastasis to that of netrin-1. Importantly, up-regulating BVES expression significantly attenuated netrin-1-enhanced migration and invasion, whereas silencing BVES expression rescued the metastatic phenotype in netrin-1 knockdown cells. Moreover, netrin-1 expression was negatively correlated with BVES in HCC tissues and cell lines with different metastatic potential. Taken together, these results reveal that netrin-1 promotes HCC cell metastasis by regulating BVES expression via AKT activation.

Up-regulation of SPOCK1 induces epithelial-mesenchymal transition and promotes migration and invasion in esophageal squamous cell carcinoma.

Invasion and metastasis are the major causes of death in patients with esophageal squamous cell carcinoma (ESCC). Recent studies have confirmed that SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) plays multiple roles in cancer progression. This study aims to explore the clinical characteristics of SPOCK1 in ESCC and its roles in the migration and invasion of ESCC cell lines. In this study, the up-regulation of SPOCK1 expression was frequently detected in primary ESCC tumor tissues compared with those in non-tumor tissues, which was significantly associated with tumor invasion (p = 0.004) and distant metastasis (p = 0.010). SPOCK1 was expressed at higher level in TE13 cells as compared to the low malignant Eca109 and TE1 cells. Overexpression of SPOCK1 in Eca109 cells decreased the expressions of epithelial marker E-cadherin and ZO-1, while increased mesenchymal marker Vimentin and N-cadherin levels. After ectopic expression of SPOCK1, Eca109 cells exhibited a morphological change from an epithelial cobblestone phenotype to an elongated fibroblastic phenotype, concomitant with cytoskeletal rearrangements and increased migration and invasion, suggesting that EMT occurs. While silencing SPOCK1 in TE13 cells had the opposite effects. These results suggest that up-regulation of SPOCK1 in ESCC induces EMT, thus promotes migration and invasion in ESCC cells.

Chronic bronchitis with fungal infection presenting with marked elevation of serum carbohydrate antigen 19-9: a case report.

Carbohydrate antigen 19-9 (CA19-9) is the most frequently applied serum tumor marker for diagnosis of cancers in the digestive organs. However, some patients with benign diseases can have elevated serum levels of CA19-9 as well. The current study presents a 55-year-old female who was admitted to our hospital for further evaluation of a nodular cavity shadow in the right lower lobe and clarification of the cause of the marked elevation of serum CA19-9 levels. Abdominal MRI and gastrointestinal endoscopy did not find any malignancy. As lung cancer cannot be excluded in this patient, a video-assisted thoracoscopic surgery was carried, intraoperative and postoperative biopsy analysis both suggested chronic bronchitis with fungal infection (due to Histoplasma capsulatum or Penicillium marneffei) and organization. Immunohistochemistry showed marked positive staining for CA19-9 in the damaged lung tissue. The CA19-9 levels quickly returned to the normal range following lobe resection. Therefore, the marked elevation of serum CA19-9 levels, in this case, may have resulted from the chronic bronchitis with fungal infection.

[Comparison of incidence of BPH and related factors between urban and rural inhabitants in district of Wannan].

OBJECTIVES: To investigate the difference of BPH incidence in two groups. METHODS: 309 cadres and 314 farmers over 60 years old in district of Wannan have been investigated. The investigation included prostate volume (V), IPSS, L, Qmax, residual urine (R) and dietary constituents. RESULTS: The intake of animal protein in cadres is more than that in farmers (u = 24.10, P < 0.01), and the incidence rate of BPH is significantly higher (91.1% vs 11.8%, chi 2 = 24.64, P < 0.001). Logistic regression shows that the intake of animal protein has a parallel relationship with BPH. CONCLUSIONS: In the district of Wannan, the incidence of BPH in cadres is significantly higher than that of farmers, and it may be correlated with the amount of animal protein intake.