Association of cumulative monocyte to high-density lipoprotein ratio with the risk of type 2 diabetes: a prospective cohort study.

BACKGROUND: Recent studies have established that monocyte-derived inflammation plays a central role in the pathogenesis of type 2 diabetes mellitus (T2DM). It is unclear whether chronic metabolic inflammation, reflected by the cumulative monocyte to high-density lipoprotein ratio (CumMHR), predisposes the general population to T2DM. METHODS: This study included 40,813 participants without diabetes from a real-life, community-based cohort (the Kailuan Study) attending a 2-year cycle of health survey since 2006. Cumulative exposure was obtained from 2006/2007 to 2010/2011. Follow-up started at 2010/2011 and through 2020. Multivariable-adjusted Cox regression models were used to calculate the CumMHR-associated risk of incident T2DM. RESULTS: Over a median follow-up period of 7.98 (IQR: 5.74-8.87) years, 4,848 T2DM cases occurred. The CumMHR was positively associated with the risk of incident T2DM after adjusting for age, sex, smoking, drinking habits, physical activities, BMI, triglyceride-glycemia index, log(leukocyte count), log(hsCRP), blood pressure, renal function, and medication uses with adjusted HRs of 1.0 (ref.), 1.18 (1.05‒1.25), 1.17 (1.07‒1.27), 1.38 (1.26‒1.50), respectively, in CumMHR Quartiles 1, 2, 3 and 4. When follow-up ended at 2014/2015, the short-term (4‒year) adjusted T2DM risks in CumMHR Quartiles 2, 3, and 4 were 1.14 (1.01‒1.29), 1.17 (1.04‒1.32), 1.40 (1.25‒1.58), respectively, relative to Quartile 1. A significant interaction between CumMHR and cumulative high-sensitivity C-reactive protein (CumCRP) was observed (P-interaction: 0.0109). The diabetic risk in the highest quartile of CumMHR was higher (1.53 [1.28‒1.84]) when CumCRP < 1 mg/L, attenuated with increasing CumCRP levels (1 ~ 10 mg/L) and disappeared in CumCRP ≥ 10 mg/L. Hypertension, overweight, or smoking habits further modified the CumMHR-associated diabetic risk. CONCLUSIONS: Cumulative MHR may be a promising supplement to hsCRP for more comprehensively assessing the influence of metabolic inflammation on T2DM susceptibility. For primary prevention, targeting high CumMHR, especially in cases at low risk of diabetes defined by traditional risk factors, may further help reduce the diabetic risk.

A Patient with Fragmentation of a Calcified Ureteric Stent Requiring Ureteroscopy and Laser Lithotripsy.

BACKGROUND Encrustation of the ureteral stent is a common complication that occurs after a prolonged indwelling duration. Other identified risk factors in the literature include urinary sepsis, chemotherapy, chronic renal failure, metabolic or congenital abnormalities, and nephrolithiasis. This report presents the case of a 39-year-old man with nephrolithiasis and fragmentation of a calcified right ureteric stent that required ureteroscopy and laser lithotripsy. CASE REPORT A 39-year-old man was initially admitted for ureteroscopy and laser lithotripsy after the diagnosis of bilateral urolithiasis. Ureteral stents were placed. One postoperative month later, the patient returned for follow-up and stent withdrawal. Follow-up computed tomography revealed a normal left kidney, intact bilateral ureteral stents, and residual right renal stones. However, an attempt to completely withdraw the stent failed and the patient had to undergo a secondary right ureteroscopy with laser lithotripsy. The fragmented proximal section of a calcified right ureteral stent with occluded lumen was found intraoperatively and sent for product analyses. After successful reintervention, the patient had a new right ureteral stent placed, which was successfully withdrawn during his next follow-up. CONCLUSIONS Ureteral stent encrustation may occur earlier than anticipated, possibly due to underlying patient risk factors. Complications, such as fragmentation of the ureteral stent, may occur during withdrawal. Physicians should be aware of any predictors for early ureteral stent encrustation to prevent unnecessary reintervention.

Retrograde intrarenal surgery for a staghorn renal calculus in a patient with solitary kidney and urinary tract deformity: a case report.

Staghorn renal calculi are large, branched stones in the kidney that partially or completely fill the renal pelvis and renal calyces. Percutaneous nephrolithotomy (PCNL) is the gold standard treatment for staghorn calculi. However, we report a retrograde intrarenal surgery (RIRS) performed to treat a staghorn calculus in a patient with a solitary kidney and a deformed urinary tract. The 37-year-old male patient presented with right-sided lumbar pain. The computed tomography (CT) scan found a solitary kidney on the right side with an opaque 4.5 cm × 2.4 cm renal stone and grade I hydronephrosis. Additionally, a urinary tract deformity was observed, and it was secondary to the deformity of the pelvis caused by a previous pubis fracture, which significantly increased the risk and the difficulty of intrarenal surgery. A total number of 3 sessions of RIRS were conducted, and the patient was discharged 3 days after each session on average. The postoperative X-ray exam of the third session revealed that the renal stone was completely removed. The patient recovered well without any complications. This case demonstrates that RIRS is a safe and effective treatment of staghorn calculi with the presence of urinary tract deformation. This suggests RIRS may be of particular interest in minimizing the procedure-related damage of a solitary kidney.

Human Umbilical Cord Mesenchymal Stem Cell Therapy Mitigates Interstitial Cystitis by Inhibiting Mast Cells.

BACKGROUND Interstitial cystitis (IC) is a recurrent and chronic inflammatory disease that compromises patients' quality of life. Effective treatments for IC are limited. This study aimed to evaluate the therapeutic potency of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in an IC-induced rat model and investigate the potential molecular mechanism in a mast cell model (rat basophilic leukemia cells, RBL-2H3) in treating IC in a coculture system. MATERIAL AND METHODS The rat model of IC was induced by cyclophosphamide (CYP). Rats were randomly divided into 3 groups: sham, IC+PBS, and IC+MSC. In the coculture system, RBL-2H3 cells were sensitized overnight to Compound 48/80 (C48/80), cocultured with UC-MSCs for 3 days, and collected for subsequent experiments. RBL-2H3 cells were randomly divided into 3 groups: sham, C48, and UC-MSCs (C48+MSC). RESULTS The UC-MSCs marked by thymidine analog 5-ethynyl-2-deoxyuridine (EdU) were transplanted in the treatment group, and were densely distributed in the bladder. Accordingly, the conscious cystometry was measured and the bladder tissues were harvested. Compared with the sham group, the treated IC rats exhibited shorter bladder voiding intervals (307±35 vs 217±37 s; P<0.01), more integral epithelia, and less collagen fiber aggregation, infiltration and degranulation of mast cells, and inflammatory cytokines in the bladder tissue. In the coculture system, compared with the C48 group, the UC-MSC-treated RBL-2H3 cells had suppressed degranulation. CONCLUSIONS UC-MSCs treatment showed a promising therapeutic effect on treating IC in vivo and in vitro. UC-MSCs inhibit mast cell degranulation in IC and could be a potential therapeutic target to ameliorate inflammation in IC.

Neuregulin-1-ErbB signaling promotes microglia activation contributing to mechanical allodynia of cyclophosphamide-induced cystitis.

AIMS: Central sensitization playsimportant roles in cyclophosphamide (CYP)-induced cystitis. In addition, as a visceral pain, CYP-induced chronic pain shares common pathophysiological mechanisms with neuropathic pain. Previous studies demonstrated that neuregulin-1 (Nrg1)-ErbB signaling contributes to neuropathic pain, but whether and how this signaling influences mechanical allodynia in CYP-induced cystitis is unclear. This study aimed to determine whether and how Nrg1-ErbB signaling modulates mechanical allodynia in a CYP-induced cystitis rat model. METHODS: Systemic injection with CYP was used to establish a rat model of bladder pain syndrome/interstitial cystitis (BPS/IC). An irreversible ErbB family receptor inhibitor, PD168393, and exogenous Nrg1 were intrathecally injected to modulate Nrg1-ErbB signaling. Mechanical allodynia in the lower abdomen was assessed with von-Frey filaments using the up-down method. Western blot analysis and immunofluorescence staining were used to measure the expression of Nrg1-ErbB signaling, Iba-1, p-p38, and IL-1ß in the L6-S1 spinal dorsal horn (SDH). RESULTS: We observed upregulation of Nrg1-ErbB signaling as well as overexpression of the microglia activation markers Iba-1 and p-p38 and the proinflammatory factor, interleukin-1ß (IL-1ß), in the SDH of the cystitis group. Further, treatment with PD168393 attenuated mechanical allodynia in CYP-induced cystitis and inhibited microglia activation, leading to decreased production of IL-1ß. The inhibitor PD168393 reversed the algesic effect of exogenous Nrg1 on the cystitis model. CONCLUSIONS: Nrg1-ErbB signaling may promote microglia activation, contributing to mechanical allodynia of CYP-induced cystitis. Our study showed that modulation of Nrg1-ErbB signaling may have therapeutic value for treating pain symptoms in BPS/IC.

Umbilical cord-derived mesenchymal stem cells alleviated inflammation and inhibited apoptosis in interstitial cystitis via AKT/mTOR signaling pathway.

Interstitial cystitis (IC) is a bladder syndrome characterized by pelvic pain and urinary frequency without infection or other identifiable pathology. There are no effective treatments to cure IC. This study investigated the effects of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) injection on IC rat model. Furthermore, we used a coculture system to find the possible molecular mechanism on the human uroepithelial cells (SV-HUC-1), which was the cell model of IC. A rat model of IC was established via systemic injection with cyclophosphamide (CYP) and a cell model of IC was induced by being exposed to tumor necrosis factor (TNF)-α (10 ng/ml). After one week, UC-MSCs injection significantly ameliorated the bladder voiding function in IC rat model. And the Histo- and immunohistochemical analyses showed that UC-MSCs can repair impaired bladder, reduce mast cell infiltration and inhibit apoptosis of urothelium. ELISA results showed that UC-MSCs can decrease IL-1ß, IL-6 and TNF-α in bladder. In the coculture system, UC-MSCs can promote proliferation of impaired SV-HUC-1 cells, and inhibit apoptosis. However, while knocked down EGF secreted by UC-MSCs with siRNA, the effects would be weaken. Western blot showed that UC-MSCs increase protein expression levels of p-AKT and p-mTOR in SV-HUC-1 cells, and decrease the levels of cleaved caspase-3. Taken together, we provide evidence that UC-MSCs therapy can successfully alleviate IC in a preclinical animal Model and cell model by alleviating inflammation, promoting proliferation and inhibiting apoptosis. In addition, we demonstrate that the AKT/mTOR signaling pathway was activated.

[FSH, LH, PRL, E2 and T in 8-17 year old males: investigation and analysis].

OBJECTIVE: To investigate the changes of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2) and testosterone (T) in male adolescents of different ages by determining their levels in 8-17 years old boys. METHODS: We included in this study 627 male adolescents aged 8-17 years and qualified through physical examinations. All the subjects underwent determination of FSH, LH, PRL, E2 and T with an automatic ACCESS microparticle chemiluminescence immunoassay analyzer and detection of liquid quality control by immunoassay. RESULTS: FSH remained at a low level in the 8-10 years old male adolescents and increased at 11 years; the levels of LH and T were low before the age of 12 years and began to increase at 13 years; and that of E2 was low before the age of 13 years and began to rise after that, all with statistically significant differences (P < 0.01). CONCLUSION: In the male adolescents, FSH, LH and T significantly increased at 11, 12 and 13 years old, respectively, which marked the beginning of sexual development.