Effect of bladder emptying status on the ureteral access sheath insertion resistance and following ureteral injury in RIRS: a prospective randomized controlled trial in academic hospital.

PURPOSE: To evaluate the effect of bladder emptying status on the ureteral access sheath (UAS) insertion resistance and following ureteral injury. METHODS: Eighty patients were enrolled and randomly divided into bladder emptying group and control group before UAS placement. A digital force gauge (Imada Z2-50N) was used to measure the resistance during the UAS insertion. The ureteral injury was evaluated and graded with Post-Ureteroscopic Lesion Scale (PULS) system at the end of procedure. The mean resistance, maximum resistance in different ureteral segments, and ureteral injury were compared between the two groups. RESULTS: The mean resistance (3.12 ± 0.49 vs. 4.28 ± 0.52 N, P < 0.001), maximum resistance in the whole procedure (5.17 ± 0.72 vs. 6.39 ± 0.96 N, P < 0.001) and distal ureter (3.07 ± 0.75 vs. 6.18 ± 1.17 N, P < 0.001) in the bladder emptying group were significantly lower when compared to the control group. In subgroup analysis, the similar result was also noted in patients with BMI ≥ 25 when compared to patients with BMI < 25, while there was no significant difference between men and women, age ≥ 50 years versus age < 50 years. The incidence of PULS 1-2 ureteral injury in the bladder emptying group was lower than the control group (35% vs. 55%, P = 0.045). The ureteral injury in distal ureteral was less frequently noted in bladder emptying group than the control group (22.5% vs. 55%, P = 0.006); however, there was no significant difference in middle and upper ureter (P > 0.05). CONCLUSION: Emptying the bladder before UAS insertion can effectively reduce the UAS insertion resistance and the risk of distal ureteral injury in RIRS.

The Flavonoid Naringenin Alleviates Collagen-Induced Arthritis through Curbing the Migration and Polarization of CD4+ T Lymphocyte Driven by Regulating Mitochondrial Fission.

Rheumatoid arthritis (RA) is a progressive autoimmune disease. Due to local infiltration and damage to the joints, activated CD4+ T cells play a crucial role in the progression of RA. However, the exact regulatory mechanisms are perplexing, which makes the effective management of RA frustrating. This study aimed to investigate the effect of mitochondria fission on the polarization and migration of CD4+ T cells as well as the regulatory mechanism of NAR, so as to provide enlightenment on therapeutic targets and novel strategies for the treatment of RA. In this study, a collagen-induced arthritis (CIA) model was established, and rats were randomly given saline or naringenin (NAR, 10 mg/kg, 20 mg/kg, 50 mg/kg, i.p.) once a day, before being euthanized on the 42nd day of primary immunization. The pain-like behavior, articular index scores, account of synovial-infiltrated CD4+ T cells, and inflammatory factors were investigated in each group. In vitro, spleen CD4+ T lymphocytes were derived from each group. In addition, mitochondrial division inhibitor 1 (Mdivi-1) or NAR was added to the cell medium containing C-X-C motif chemokine ligand 12 (CXCL12) in order to induce CD4+ T lymphocytes, respectively. The polarization capacity of CD4+ T cells was evaluated through the immunofluorescence intensity of the F-actin and myosin light chain phosphorylated at Ser19 (pMLC S19), and the mitochondrial distribution was determined by co-localization analysis of the translocase of outer mitochondrial membrane 20 (TOM20, the mitochondrial marker) and intercellular adhesion molecule 1 (ICAM1, the uropod marker). The mitochondrial fission was investigated by detecting dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1) using Western blot and immunofluorescence. This study revealed that high-dose NAR (50 mg/kg, i.p.) alleviated pain-like behavior and articular index scores, reduced the serum level of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), and accounted for CD4+ T lymphocytes that infiltrated into the synovial membrane of the CIA group. Meanwhile, NAR (50 mg/kg, i.p.) suppressed the polarization of spleen CD4+ T lymphocytes, reduced the redistribution of mitochondria in the uropod, and inhibited the expression of Drp1 and Fis1 in the CIA model. Furthermore, the in vitro experiments confirmed that NAR reduced mitochondrial fission, which in turn inhibited the CXCL12-induced polarization and migration of CD4+ T lymphocytes. Our results demonstrated that the flavonoid NAR was a promising drug for the treatment of RA, which could effectively interfere with mitochondrial fission, thus inhibiting the polarization and migration of CD4+ T cells in the synovial membrane.

Enhanced super-mini-PCNL (eSMP): low renal pelvic pressure and high stone removal efficiency in a prospective randomized controlled trial.

OBJECTIVE: In the present prospective randomized controlled trial (RCT), enhanced-SMP (eSMP) and conventional Chinese mini-PCNL (mPCNL) were compared to test the low renal pelvic pressure (RPP) and high stone removal efficiency in eSMP. MATERIALS AND METHODS: Hundred patients with 2-5 cm renal calculus were enrolled. Renal pelvic pressure, operation time, lithotripsy time, removed stone volume, and complications were compared between eSMP and mPCNL statistically. RESULTS: There was no significant difference in removed stone volume between mPCNL and eSMP (8.09 ± 3.36 vs. 7.88 ± 3.07 mm3, t = 0.320, p = 0.750), lithotripsy time in mPCNL was longer than eSMP (49.6 ± 19.5 vs. 34.9 ± 14.2 min, t = 4.152, p < 0.001), thus stone removal efficiency was higher in eSMP (13.71 ± 1.18 vs. 9.82 ± 1.24 mm3/h, t = 15.499, p < 0.001). Intra-operative RPP in mPCNL was higher than eSMP (17.72 ± 3.33 vs. 12.03 ± 2.37 mmHg, t = 9.524, p < 0.001); accumulated time of backflow status (RPP > 30 mmHg) in mPCNL was longer than eSMP (23.3 ± 16.9 vs. 3.7 ± 4.2 s, t = 7.710, p < 0.001). There was no significant difference in postoperative fever rate between mPCNL and eSMP (12.77% vs. 4.34%, χ2 = 2.095, p = 0.148), nor final stone-free rate (87.2% vs. 91.3%, χ2 = 0.401, p = 0.526). Hospital stay in eSMP was shorter than mPCNL (2.54 ± 0.72 vs. 3.00 ± 0.88, t = 2.724, p = 0.008). CONCLUSION: Enhanced SMP (eSMP) was safe and effective in the management of 2-5 cm renal calculus. It can keep a lower renal pelvic pressure and a higher stone removal efficiency when compared to conventional Chinese mini-PCNL. CLINICAL TRIAL REGISTRATION: NC03206515.

A quick stone component analysis matters in postoperative fever: a propensity score matching study of 1493 retrograde intrarenal surgery.

OBJECTIVE: To evaluate the role of stone components in postoperative fever following RIRS, and to investigate the role of quick stone component analysis during RIRS procedure. PATIENTS AND METHODS: 1493 patients with RIRS were retrospectively reviewed. Propensity score matching (PSM) analysis was performed as infection stones (IS) vs. calcium-containing stones (CS) and IS vs. other compositions (OS). Independent risk factors of postoperative fever were identified by logistic analysis and nomogram was constructed. RESULTS: A total of 73 patients suffered postoperative fever (4.9%), 8 patients with sepsis (0.5%), 4 patients with septic shock (0.3%). In IS vs. CS, the incidence of positive urine test (28.4% vs. 14.7%, p = 0.001), residual stone (48.2% vs. 37.6%, p = 0.04), and postoperative fever (9.1% vs. 2.0%, p = 0.004) was significantly higher in IS. In IS vs. OS, IS had a higher incidence of positive urine test (30.9% vs. 9.3%, p < 0.001) and residual stone (47.4% vs. 18.6%, p < 0.001), while there was no significant difference in postoperative fever (10.3% vs. 4.1%, p = 0.17). Multivariate regression analysis revealed that gender (OR 1.82, CI 1.09-3.07, p < 0.001), stone components (OR 0.6, CI 0.37-0.97, p = 0.038), urine test (OR 3.72, CI 2.23-6.20, p < 0.001), and neutrophil ratio > 75% (OR 5.17, CI 3.03-9.16, p < 0.001) were independent risk factors for postoperative fever. A nomogram with moderate discriminative ability (c-index: 0.813) was constructed to predict postoperative fever. CONCLUSION: Infection stones were closely associated with postoperative fever following RIRS, as well as female gender, preoperative positive urine test, and postoperative neutrophil ratio > 75%. A quick stone component analysis would help in prevention of infectious complications. Early and longer duration of antimicrobial therapy was recommended for patients with infection stones.

Is physical therapy effective following extracorporeal shockwave lithotripsy and retrograde intrarenal surgery: a meta-analysis and systematic review.

BACKGROUND: Physical therapy, including percussion, inversion, vibration and combinations, was clinically performed to improve the stone free rate (SFR) following lithotripsy procedures. However, physical therapy is not widely accepted in clinical practice owing to lack of high level evidence support and a standard protocol. The present meta-analysis aimed to evaluate the efficacy and safety of physical therapy in improving SFR following extracorporeal shockwave lithotripsy (ESWL) and retrograde intrarenal surgery (RIRS). METHODS: Systematic review of literature from PubMed, Scopus, Cochrane library and Embase was performed in March 2019. The efficacy and safety of physical therapy after ESWL and RIRS were assessed by meta-analysis of SFR and complication rate. RESULTS: A total of 8 prospective studies with 1065 patients were enrolled. When compared to non-intervention, physical therapy provided a higher SFR (OR:3.38, 95% CI: 2.45-4.66, p < 0.0001) at all time points (week 1, week 2 and month 1), while there was no significant difference in complications such as hematuria, lumbago, dizziness and urinary tract infection (OR: 0.84; 95%CI: 0.62-1.13; p = 0.237). In subgroup analysis of different stone locations, lower calyx stone (OR: 3.51; 95%CI: 2.21-5.55; p < 0.0001), upper ureter and renal pelvic stones (OR:2.79; 95%CI:1.62-4.81; p = 0.0002) had a higher SFR after physical therapy, while there was no significant improvement in SFR in upper and middle calyx stones. In subgroup analysis of different techniques, EPVL (external physical vibration lithecbole, OR:3.47; 95%CI:2.24-5.37; p < 0.0001) and PDI (percussion, diuresis and inversion, OR:3.24; 95%CI:2.01-5.21; p < 0.0001) were both effective in improving SFR when compared to non-intervention. CONCLUSIONS: Physical therapy is effective in improving the SFR after ESWL and RIRS, especially for lower calyx stones, upper ureter and renal pelvic stones, while without significant side effects. External physical vibration lithecbole (EPVL) might provide a relative uniformed and repeatable protocol for clinical practice of physical therapy. TRIAL REGISTRATION: PROSPERO 2019 CRD42019130228 .

Sinomenine ameliorates fibroblast-like synoviocytes dysfunction by promoting phosphorylation and nuclear translocation of CRMP2.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and arthritic pain. Sinomenine (SIN), derived from the rhizome of Chinese medical herb Qing Teng (scientific name: Sinomenium acutum (Thunb.) Rehd. Et Wils), has a longstanding use in Chinese traditional medicine for treating rheumatoid arthritis. It has been shown to possess anti-inflammatory, analgesic, and immunosuppressive effects with minimal side-effects clinically. However, the mechanisms governing its effects in treatment of joint pathology, especially on fibroblast-like synoviocytes (FLSs) dysfunction, and arthritic pain remains unclear. AIM: This study aimed to investigate the effect and underlying mechanism of SIN on arthritic joint inflammation and joint FLSs dysfunctions. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) was induced in rats and the therapeutic effects of SIN on joint pathology were evaluated histopathologically. Next, we conducted a series of experiments using LPS-induced FLSs, which were divided into five groups (Naïve, LPS, SIN 10, 20, 50 µg/ml). The expression of inflammatory factors was measured by qPCR and ELISA. The invasive ability of cells was detected by modified Transwell assay and qPCR. Transwell migration and cell scratch assays were used to assess the migration ability of cells. The distribution and content of relevant proteins were observed by immunofluorescence and laser confocal microscopy, as well as Western Blot and qPCR. FLSs were transfected with plasmids (CRMP2 T514A/D) to directly modulate the post-translational modification of CRMP2 protein and downstream effects on FLSs function was monitored. RESULTS: SIN alleviated joint inflammation in rats with CIA, as evidenced by improvement of synovial hyperplasia, inflammatory cell infiltration and cartilage damage, as well as inhibition of pro-inflammatory cytokines release from FLSs induced by LPS. In vitro studies revealed a concentration-dependent suppression of SIN on the invasion and migration of FLSs induced by LPS. In addition, SIN downregulated the expression of cellular CRMP2 that was induced by LPS in FLSs, but increased its phosphorylation at residue T514. Moreover, regulation of pCRMP2 T514 by plasmids transfection (CRMP2 T514A/D) significantly influenced the migration and invasion of FLSs. Finally, SIN promoted nuclear translocation of pCRMP2 T514 in FLSs. CONCLUSIONS: SIN may exert its anti-inflammatory and analgesic effects by modulating CRMP2 T514 phosphorylation and its nuclear translocation of FLSs, inhibiting pro-inflammatory cytokine release, and suppressing abnormal invasion and migration. Phosphorylation of CRMP2 at the T514 site in FLSs may present a new therapeutic target for treating inflammatory joint's destruction and arthritic pain in RA.

Mental health and its influencing factors of maintenance hemodialysis patients: a semi-structured interview study.

BACKGROUND: Maintenance hemodialysis (MHD) is a commonly used renal replacement therapy for end-stage renal disease patients. MHD patients have undergone multiple physiological stressors, which may cause physical problems and affect their mental health; however, few qualitative studies have been done on the mental health of MHD patients. Such qualitative research becomes the basis for further quantitative research and is critical to validating its results. Therefore, the current qualitative study used a semi-structured interview format, and aimed to explore the mental health and its influencing factors of MHD patients who are not receiving intervention treatment to determine how best to ameliorate their mental health. METHODS: Based on the application of Grounded Theory, semi-structured face-to-face interviews were conducted with 35 MHD patients, following consolidated criteria for reporting qualitative studies (COREQ) guidelines. Two indicators (emotional state and well-being) were used to assess MHD patients' mental health. All interviews were recorded, after which two researchers independently performed data analyses using NVivo. RESULTS: Acceptance of disease, complications, stress and coping styles, and social support were found to be the influencing factors of MHD patients' mental health. High acceptance of disease, healthy coping styles, and high social support were positively correlated with mental health. In contrast, low acceptance of disease, multiple complications, increased stress, and unhealthy coping styles were negatively correlated with mental health. CONCLUSION: One's acceptance of the disease played a more significant role than other factors in affecting MHD patients' mental health.

FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway.

Hepatocellular carcinoma (HCC) is the third-leading cause of cancer deaths globally. Although considerable progress has been made in the treatment, clinical outcomes of HCC patients are still poor. Therefore, it is necessary to find novel prognostic factors upon which prevention and treatment strategies can be formulated. Ficolin-3 (FCN3) protein is a member of the human ficolin family. It activates complement through pathways associated with mannose-binding lectin-associated serine proteases. Herein, we identified that FCN3 was downregulated in HCC tissues and decreased FCN3 expression was closely related to poor prognosis. Overexpression of FCN3 induced apoptosis and inhibited cell proliferation via the p53 signaling pathway. Mechanistically, FCN3 modulated the nuclear translocation of eukaryotic initiation factor 6 (EIF6) by binding ribosome maturation factor (SBDS), which induced ribosomal stress and activation of the p53 pathway. In addition, Y-Box Binding Protein 1 (YBX1) involved in the transcription and translation level regulation of FCN3 to SBDS. Besides, a negative feedback loop in the downstream of FCN3 involving p53, YBX1 and SBDS was identified.

Sinomenine regulates immune cell subsets: Potential neuro-immune intervene for precise treatment of chronic pain.

Chronic pain is a disease of long-lasting pain with unpleasant feelings mediated by central and (or) peripheral sensitization, its duration usually lasts more than 3 months or longer than the expected recovery time. The patients with chronic pain are manifested with enhanced sensitivity to noxious and non-noxious stimuli. Due to an incomplete understanding of the mechanisms, patients are commonly insensitive to the treatment of first line analgesic medicine in clinic. Thus, the exploration of non-opioid-dependent analgesia are needed. Recent studies have shown that "sinomenine," the main active ingredient in the natural plant "sinomenium acutum (Thunb.) Rehd. Et Wils," has a powerful inhibitory effect on chronic pain, but its underlying mechanism still needs to be further elucidated. A growing number of studies have shown that various immune cells such as T cells, B cells, macrophages, astrocytes and microglia, accompanied with the relative inflammatory factors and neuropeptides, are involved in the pathogenesis of chronic pain. Notably, the interaction of the immune system and sensory neurons is essential for the development of central and (or) peripheral sensitization, as well as the progression and maintenance of chronic pain. Based on the effects of sinomenine on immune cells and their subsets, this review mainly focused on describing the potential analgesic effects of sinomenine, with rationality of regulating the neuroimmune interaction.

An Apriori Algorithm-Based Association Analysis of Analgesic Drugs in Chinese Medicine Prescriptions Recorded From Patients With Rheumatoid Arthritis Pain.

Chronic pain, a common symptom of people with rheumatoid arthritis, usually behaves as persistent polyarthralgia pain and causes serious damage to patients' physical and mental health. Opioid analgesics can lead to a series of side effects like drug tolerance and addiction. Thus, seeking an alternative therapy and screening out the corresponding analgesic drugs is the key to solving the current dilemma. Traditional Chinese Medicine (TCM) therapy has been recognized internationally for its unique guiding theory and definite curative effect. In this study, we used the Apriori Algorithm to screen out potential analgesics from 311 cases that were treated with compounded medication prescription and collected from "Second Affiliated Hospital of Zhejiang Chinese Medical University" in Hangzhou, China. Data on 18 kinds of clinical symptoms and 16 kinds of Chinese herbs were extracted based on this data mining. We also found 17 association rules and screened out four potential analgesic drugs-"Jinyinhua," "Wugong," "Yiyiren," and "Qingfengteng," which were promised to help in the clinical treatment. Besides, combined with System Cluster Analysis, we provided several different herbal combinations for clinical references.

Potential Neuroimmune Interaction in Chronic Pain: A Review on Immune Cells in Peripheral and Central Sensitization.

Chronic pain is a long-standing unpleasant sensory and emotional feeling that has a tremendous impact on the physiological functions of the body, manifesting itself as a dysfunction of the nervous system, which can occur with peripheral and central sensitization. Many recent studies have shown that a variety of common immune cells in the immune system are involved in chronic pain by acting on the peripheral or central nervous system, especially in the autoimmune diseases. This article reviews the mechanisms of regulation of the sensory nervous system by neutrophils, macrophages, mast cells, B cells, T cells, and central glial cells. In addition, we discuss in more detail the influence of each immune cell on the initiation, maintenance, and resolution of chronic pain. Neutrophils, macrophages, and mast cells as intrinsic immune cells can induce the transition from acute to chronic pain and its maintenance; B cells and T cells as adaptive immune cells are mainly involved in the initiation of chronic pain, and T cells also contribute to the resolution of it; the role of glial cells in the nervous system can be extended to the beginning and end of chronic pain. This article aims to promote the understanding of the neuroimmune mechanisms of chronic pain, and to provide new therapeutic ideas and strategies for the control of chronic pain at the immune cellular level.