Optimizing the outcome of non-pre-stented flexible ureteroscopic lithotripsy regarding the quality of life, when to remove the stent?

OBJECTIVES: To investigate the safety of short-term stenting following flexible ureteroscopic lithotripsy (fURL) for patients without preoperative stents. Retaining double-J stent for 1-2 weeks after fURL is a common practice. At present, data on short-term stenting after non-pre-stented fURL is still lacking. METHODS: 182 patients who met inclusion criteria were retrospectively divided into the 2-days group (2-day removal, 76 cases) and the 1-week group (1-week removal, 106 cases). The study endpoint was stent-associated adverse symptoms assessed by follow-up and completed validated questionnaires on postoperative days (POD) 7 and 12. A postoperative imaging review was performed 1 month after the surgery. RESULTS: No statistical differences were found in the patients' demographic and stone-related characteristics. The 2-days group showed fewer urinary tract symptoms and lower scores on the ureteral stent symptom questionnaire on POD 7: less backache during urination (p = 0.004), less hematuria (p = 0.031), less frequent urination (p = 0.004), lower urinary symptoms index (p < 0.001), lower general health index (p < 0.001), and lower performance index (p < 0.001). There were no significant differences in fever (p = 0.372), visual analogue scale score (p = 0.760), and painkiller requirements (p = 0.160) on POD 7. The average general health score and work performance score remained significantly higher in the 1-week group patients at 5 days after removal compared to the 2-days group patients at 5 days after removal. (p < 0.001, p = 0.005). Five patients in the 2-days group and 15 patients in the 1-week group returned to the emergency department for additional treatments. No patient required rehospitalization. Stone-free rates were 85.5% in the 2-days group and 80.2% in the 1-week group (p = 0.499), respectively, and none of the patients got aggravating hydronephrosis. CONCLUSIONS: Compared to the common 1-week stent removal option, short-term stenting after non-pre-stented fURL is safe, which can enhance the patient's quality of life.

Network-based analysis on the genes and their interactions reveals link between schizophrenia and Alzheimer's disease.

Schizophrenia (SCZ) is a heterogeneous psychiatric disorder marked by impaired thinking, emotions, and behaviors. Studies have suggested a strong connection between SCZ and Alzheimer's disease (AD), however, controversies exist and the underlying mechanisms linking these two disorders remain largely unknown. Therefore, systematic studies of SCZ- and AD-related genes will provide valuable insights into the molecular features of these two diseases and their comorbidities. In this study, we obtained 331 SCZ-related genes, 650 AD-related genes, 65 shared genes between SCZ and AD. Enrichment analysis shown that these 65 shared genes were mainly involved in cognition, neural development, synaptic transmission, drug reactions, metabolic processes and immune related processes, suggesting a complex mechanism for the co-existence of SCZ and AD. In addition, we performed pathway enrichment analysis and found a total of 57 common pathways between SCZ and AD, which could be largely grouped into three modules: immune module, neurodevelopment module and cancer module. We eventually identified the potential disease-related genes whose interactions provide clues to the overlapping symptoms between SCZ and AD.

Vacuum-assisted dedusting lithotripsy in the treatment of kidney and proximal ureteral stones less than 3 cm in size.

PURPOSE: This study aimed to compare the outcomes of vacuum-assisted dedusting lithotripsy (VADL) using flexible vacuum-assisted ureteral access sheath (FV-UAS) versus traditional flexible ureteroscopic lithotripsy (fURL) in patients with kidney or proximal ureteral calculi less than 3 cm in size. METHODS: A total of 371 patients who successfully underwent fURL treatment were enrolled. These patients were divided into traditional fURL group and VADL group. Outcomes of both groups were compared using 1:1 propensity score-matched analysis. Stratified analyses based on stone size and location were also conducted. RESULTS: Finally, 103 well-matched patients in each group were identified. No septic shock or death occurred. The immediate stone-free rate (SFR) and follow-up SFR of VADL group were significantly higher (78.6% vs. 50.5%, p < 0.001; 94.2%% vs. 75.7%, p < 0.001). No difference was observed in postoperative fever rate (2.9% vs. 3.9%, p = 1.000) and duration of lithotripsy (37.7 ± 20.1 min vs. 40.3 ± 18.9 min, p = 0.235). For patients with stones ≤ 2 cm in size, the immediate SFR and follow-up SFR in VADL group were higher (86.7% vs. 60.6%, p < 0.001; 96.0% vs. 83.1%, p = 0.010). The same trend was observed in the 2-3 cm subgroup (57.1% vs. 28.1%, p = 0.023; 89.3% vs. 59.4%, p = 0.009). Although the in situ fragmentation strategy was employed more frequently in VADL group for lower pole stones, the SFR was still higher. Subgroup analyses did not reveal any significant differences in either infectious complications or duration of lithotripsy. CONCLUSION: VADL technique can significantly improve the postoperative SFR for the patients with kidney or proximal ureteral stones less than 3 cm in size treated by flexible ureteroscope.

S100A family is a group of immune markers associated with poor prognosis and immune cell infiltration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human cancers with poor prognosis in the world. HCC has become the second leading cause of cancer-related death in China. It is urgent to identify novel biomarker and valid target to effectively diagnose, treat or predict the prognosis of HCC. It has been reported that S100A family is closely related to cell proliferation and migration of different cancers. However, the values of S100As in HCC remain to be further analyzed. METHODS: We investigated the transcriptional and translational expression of S100As, as well as the value of this family in HCC patients from the various databases. RESULTS: S100A10 was most relevant to HCC. CONCLUSIONS: The results from HCC patients' tissues and different cells also confirmed the role of S100A10 in HCC. Furthermore, we proved that S100A10 could influenced the cell proliferation of HCC cells via ANXA2/Akt/mTOR pathway. However, it would appear that the relationship between S100A10 and HCC is complex and requires more research.

Vascular endothelial growth factor A is a potential prognostic biomarker and correlates with immune cell infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths among cancer patients. Vascular endothelial growth factor A (VEGFA) is involved in regulating biological processes, such as angiogenesis and vascular permeability, and is very closely related to the pathogenesis of various tumours, especially vascular-rich, solid tumours. Clinical data of patients with HCC and other tumours were analysed through public databases, such as the TCGA database, Gene Expression Omnibus database, Human Protein Atlas database, STRING, Tumour Immune Estimation Resource and Kaplan-Meier Plotter. The tumour tissues and adjacent normal tissues of patients with HCC from Hunan Provincial People's Hospital were collected to verify the expression of VEGFA by immunohistochemistry, immunofluorescence, Western blotting and qPCR. VEGFA expression is elevated in multiple tumour types and correlates with the prognosis of tumour patients. VEGFA is involved in regulating the tumour microenvironment and immune cell function in tumour development. Inhibition of VEGFA reduces proliferation, invasion, and migration and promotes apoptosis in HCC cells. VEGFA is a potential predictive biomarker for the diagnosis and prognosis of HCC.

Quercetin Inhibits Intrahepatic Cholangiocarcinoma by Inducing Ferroptosis and Inhibiting Invasion via the NF-[Formula: see text]B Pathway.

Intrahepatic cholangiocarcinoma (ICC) is a rare, highly fatal hepatobiliary malignancy, with very limited treatment options and, consequently, a poor prognosis. Recently, emerging evidence has suggested the potential of quercetin (QE) for use in cancer therapy. The purpose of this study is to investigate whether QE could inhibit ICC. The effects of QE on the proliferation, apoptosis, and invasion of ICC were analyzed in vitro. The inhibitory effect of QE on ICC was also verified in vivo. The RNA sequence was applied to explore the mechanism of QE. Functional verification was also performed after RNA sequencing using activators and inhibitors of nuclear factor-kappa-B (NF-[Formula: see text]B) and ferroptosis. The results showed that QE could inhibit the proliferation and survival of ICC cells, induce the arrest of ICC cells in the G1 phase, promote the apoptosis of ICC cells, and inhibit the invasion of ICC cells. Furthermore, QE could promote ferroptosis in ICC cells by inhibiting the NF-[Formula: see text]B pathway. In conclusion, QE is a new ferroptosis inducer and NF-[Formula: see text]B inhibitor that can not only induce ferroptosis, but also inhibit the invasion of ICC cells, providing a prospective strategy for the treatment of ICC.

Hypoalbuminemia within One Hour After Surgery as a Predictor of Post-Operative Urosepsis in Patients Undergoing Flexible Ureteroscopy Lithotripsy: A Retrospective Study.

Abstract Background: To investigate retrospectively whether changes in serum albumin levels within one hour of flexible ureteroscopy (fURS) lithotripsy can be used as a predictor of post-operative urosepsis. Patients and Methods: Eligible patients with unilateral upper urinary calculi who underwent fRUS lithotripsy performed by a single surgeon at our center were included in the analysis. The patients were divided into sepsis and non-sepsis groups. The change ratio of albumin and white blood cell (WBC) count was calculated by post-operative/pre-operative index*100%. Univariable and multivariable logistic regression analyses were used to assess whether there was a correlation between risk factors and post-operative urosepsis. The receiver operating characteristic (ROC) curve was used to analyze factors that showed significant differences in multivariable logistic regression analysis. Results: A total of 314 patients were included in the analysis, 20 of whom had post-operative urosepsis and five developed septic shock; no deaths occurred. Multivariable logistic regression analysis showed that urine culture results, WBC counts within one hour after surgery, post-operative albumin levels, and the degree of albumin changes after surgery were independent predictors of post-operative urosepsis. Receiver operating characteristic curve analysis showed that noteworthy hypoalbuminemia after surgery and positive pre-operative urine culture could help screen high-risk patients for post-operative urosepsis effectively. Conclusions: Hypoalbuminemia shortly after operation can be utilized as a predictor for early diagnosis of post-operative urosepsis in patients undergoing fURS lithotripsy.

Iodine-125 seed implantation combined chemotherapy for metastatic pancreatic adenocarcinoma with primary colon cancer: A case report.

RATIONALE: Colon cancer has a distinct migration aptitude. However, pancreatic metastasis is rare and treatment of inoperable pancreatic cancers is seldom seen. PATIENT CONCERNS: A 47-year-old woman presented 2-month history of abdominal pain and abdominal distention, with anal cessation of exhaust and defecation for 4 days. A colon cancer radical resection was performed when she diagnosed with colon cancer. After 26 months, the patient complained shoulder and back pain. Multiple intraperitoneal metastases and nonisolated pancreatic metastasis of colon cancer were diagnosed. DIAGNOSIS: Metastatic pancreatic adenocarcinoma (MPA) with primary colon cancer. INTERVENTION: Iodine-125 seed implantation combined chemotherapy. OUTCOMES: She remains free of cancer metastasis and recurrence, and has a good quality of life during the period. LESSONS SUBSECTIONS: Iodine-125 seed implantation is an effective and safe strategy for unresectable metastatic pancreatic cancer. Iodine-125 seed implantation combined with chemotherapy improve survival for advanced pancreatic metastasis of colon cancer.

MED1 Downregulation Contributes to TGFß-Induced Metastasis by Inhibiting SMAD2 Ubiquitination Degradation in Cutaneous Melanoma.

Metastasis is the main reason for the high mortality of patients and indeed a difficult task in the treatment of cutaneous melanoma. Therefore, it is of great clinical value to explore the molecular mechanism of cutaneous metastatic melanoma and develop novel therapies. MED1, acting as a factor required for activator-dependent transcription, is reported to be involved in carcinogenesis and progression. In this study, we found that MED1 was highly expressed in patients with cutaneous melanoma. MED1 downregulation could induce cellular epithelial-to-mesenchymal transition and promote migration, invasion, and metastasis of cutaneous melanoma in vivo and in vitro. Further analysis showed that in Med1 knockdown cells, the TGFß/SMAD2 signaling pathway mediated an increase in epithelial-to-mesenchymal transition phenotype and migration. The opposite results were observed after treatment with TGFß inhibitors. To further explore the mechanism, we found that MED1 interacted with SMAD2, and MED1 downregulation could protect SMAD2 from degradation by inhibiting SMAD2 ubiquitination. Together, these results suggest that MED1 inhibited TGFß signaling pathway to reduce cell epithelial-to-mesenchymal transition phenotype and migration through SMAD2 ubiquitination in the metastasis of cutaneous melanoma. Our findings elucidated the role of MED1 in the metastasis of cutaneous melanoma and provided a target for the therapeutic strategies of cutaneous melanoma.

Phospholipase C epsilon mediates cytokine cascade induced by acute disruption of epidermal permeability barrier in mice.

Disruption of epidermal barrier is an important trigger in abnormal cutaneous inflammation. Phospholipase C epsilon (PLCε), a Ras/Rap1 effector, is essential for regulating cytokines production in different types of skin inflammation. Our previous studies have demonstrated that elevated expression of PLCε participates in the psoriasis-like inflammation in PLCε overexpressing transgenic mice model, while the reduction in PLCε expression attenuates inflammatory responses in either TPA- or DNFB-induced cutaneous inflammation. Here, we determined the role of PLCε in cutaneous inflammation induced by acute abrogation of epidermal permeability barrier. In comparison to wild type controls, PLCε KO mice exhibited reduced ear swelling and infiltration of granulocytes after tape-stripping. Moreover, expression levels of pro-inflammatory cytokines (IL-1α, IL-1ß), chemokines (CXCL-1, CXCL-2, CCL20), and antimicrobial peptides (S100 proteins, MBD3) were lower in PLCε-deficient versus wild type mice. Likewise, expression levels of cytokines and chemokines were also lower in PLCε deficient keratinocytes and fibroblasts following IL-22 stimulation in vitro. Furthermore, knockdown of PLCε with its siRNA decreased expression of IL-1α, CCL20, and S100 proteins, and MBD3 in HEK cultures. Collectively, these results suggested that PLCε mediated cytokine cascade induced by acute barrier disruption. IL-22 is likely the upstream of PLCε-mediated cytokine cascade following acute barrier disruption.

Activation of ethylene signaling pathways enhances disease resistance by regulating ROS and phytoalexin production in rice.

Ethylene plays diverse roles in plant growth, development and stress responses. However, the roles of ethylene signaling in immune responses remain largely unknown. In this study, we showed that the blast fungus Magnaporthe oryzae infection activated ethylene biosynthesis in rice. Resistant rice cultivars accumulated higher levels of ethylene than susceptible ones. Ethylene signaling components OsEIN2 and the downstream transcription factor OsEIL1 positively regulated disease resistance. Mutation of OsEIN2 led to enhanced disease susceptibility. Whole-genome transcription analysis revealed that responsive genes of ethylene, jasmonates (JAs) and reactive oxygen species (ROS) signaling as well as phytoalexin biosynthesis genes were remarkably induced. Transcription of OsrbohA/B, which encode NADPH oxidases, and OsOPRs, the JA biosynthesis genes, were induced by M. oryzae infection. Furthermore, we demonstrated that OsEIL1 binds to the promoters of OsrbohA/OsrbohB and OsOPR4 to activate their expression. These data suggest that OsEIN2-mediated OsrbohA/OsrbohB and OsOPR transcription may play essential roles in ROS generation, JA biosynthesis and the subsequent phytoalexin accumulation. Therefore, the involvement of ethylene signaling in disease resistance is probably by activation of ROS and phytoalexin production in rice during M. oryzae infection.

Clinical observations and treatment of pediatric homozygous familial hypercholesterolemia due to a low-density lipoprotein receptor defect.

BACKGROUND: Clinical observation and treatment of children with homozygous familial hypercholesterolemia (HoFH) has rarely been reported. We report clinical observations and treatment of 10 ethnic Chinese children with HoFH due to low-density lipoprotein receptor (LDLR) defect. OBJECTIVES: In children with HoFH, we evaluated the response to conventional cholesterol-lowering drug therapy and performed LDLR gene analysis. METHODS: A retrospective review of lipid profile changes in pediatric patients diagnosed with HoFH seen in our pediatric endocrinology outpatient clinic was performed. HoFH was diagnosed by molecular study of these patients and their parents. RESULTS: One novel (c.64del G) and 12 known mutations were found in the LDLR gene. Mutation of p.C308Y was the most common and was found in 26% of the studied alleles.Seven patients had fair responses to conventional drug therapy (high-dose statin with ezetimibe) with a reduction of 50% or more of the total cholesterol levels. The low-density lipoprotein-cholesterol levels of three patients decreased to lower than 160 mg/dL. One who had a good response to conventional drug therapy developed significant atheromatous plaques (largest plaque: 7.4 × 2.7 cm) in the extracranial carotid arteries and myocardial ischemia changes at 11 years old. CONCLUSION: The results suggest that despite aggressive therapy, many patients are not well controlled; atherosclerosis may progress, and novel therapies are required.