TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity

AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male SpragueDawley rats.Western blot analysis was employed to measure the expression of TLR4,NF-kB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia(DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation(NCI).Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques.Immunofluorescence was employed to determine the co-expression of TLR4,NF-kB and CBS in Dil-labeled DRG neurons.RESULTS:NCI significantly upregulated the expression of TLR4 in colon-related DRGs(0.34 ± 0.12 vs 0.72 ±0.02 for the control and NCI groups,respectively,P <0.05).Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats.CLI-095 treatment also markedly reversed the hyperexcitability of colonspecific DRG neurons and reduced the expression of CBS(1.7 ± 0.1 vs 1.1 ± 0.04,p < 0.05) and of the NF-kB subunit p65(0.8 ± 0.1 vs 0.5 ± 0.1,P< 0.05).Furthermore,the NF-KB-selective inhibitor pyrrolidine dithiocarbamate(PDTC) significantly reduced the upregulation of CBS(1.0 ± 0.1 vs 0.6 ± 0.1,P< 0.05)and attenuated visceral hypersensitivity in the NCI rats.In vitro,incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65(control vs 8 h:0.9 ± 0.1 vs1.3 ± 0.1;control vs 12 h:0.9 ± 0.1 vs 1.3 ± 0.1,P< 0.05;control vs 24 h:0.9 ± 0.1 vs 1.6 ± 0.1,P <0.01) and CBS(control vs 12 h:1.0 ± 0.1 vs 2.2 ±0.4;control vs 24 h:1.0 ± 0.1 vs 2.6 ± 0.1,P< 0.05),whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression(1.2 ± 0.1 vs 0.6 ± 0.0,P< 0.01).CONCLUSION:Our results suggest that the activation of TLR4 by NCI upregulates CBS expression,which is mediated by the NF-kB signaling pathway,thus contributing to visceral hypersensitivity.

Pseudothrombus deposition accompanied with minimal change nephrotic syndrome and chronic kidney disease in a patient with Waldenstrom’s macroglobulinemia: A case report

BACKGROUND Waldenstrom's macroglobulinemia (WM) is a rare lymphoid neoplasia, which can have renal complications. These rarely occur, and most common renal manifestations are mild proteinuria and microscopic hematuria. Herein we describe a case of WM that presented with pseudothrombi depositing in capillaries associated with minimal change nephrotic syndrome and chronic kidney disease (CKD). CASE SUMMARY A 52-year-old man presented with features suggesting nephrotic syndrome. Extensive workups were done, and there were elevated serum levels of interleukin-6 and vascular endothelial growth factor (VEGF), capillary pseudothrombus accumulation associated with minimal change nephrotic syndrome, CKD, and WM. Treatment was directed at the patient’s WM with bortezomib, thalidomide, and dexamethasone whereby serum immunoglobulin M (IgM) decreased. The damage of IgM on the kidney was corrected;thus, the patient’s proteinuria and serum creatinine had improved. The patient is still under clinical follow-up. CONCLUSION It is essential for clinicians to promptly pay more attention to patients presenting with features of nephrotic syndrome and do extensive workups to come up with a proper therapy strategy.

Therapeutic experience of an 89-year-old high-risk patient with incarcerated cholecystolithiasis:A case report and literature review

BACKGROUND The global pandemic of coronavirus disease 2019 pneumonia poses a particular challenge to the emergency surgical treatment of elderly patients with high-risk acute abdominal diseases.Elderly patients are a high-risk group for surgical treatment.If the incarceration of gallstones cannot be relieved,emergency surgery is unavoidable.CASE SUMMARY We report an 89-year-old male patient with acute gangrenous cholecystitis and septic shock induced by incarcerated cholecystolithiasis.He had several coexisting,high-risk underlying diseases,had a history of radical gastrectomy for gastric cancer,and was taking aspirin before the operation.Nevertheless,he underwent emergency laparoscopic cholecystectomy,with maintenance of postoperative heart and lung function,successfully recovered,and was discharged on day 8 after the operation.CONCLUSION Emergency surgery for elderly patients with acute abdominal disease is safe and feasible during the coronavirus disease 2019 pandemic,the key is to abide strictly by the hospital's epidemic prevention regulations,fully implement the epidemic prevention procedure for emergency surgery,fully prepare before the operation,accurately perform the operation,and carefully manage the patient postoperatively.

Eruptive Cutaneous Collagenoma: Report of Two Cases

Introduction:Eruptive cutaneous collagenoma is non familial connective tissue nevi of unknown etiology presented with an abrupt onset.To date,the literatures on eruptive cutaneous collagenoma are extremely rare in china.Case present:Two women presented with multiple asymptomatic,skin-colored papules and nodules on the trunk and extremities with no systemic involvement.Histopathology revealed dense,coarse collagen fibers by hematoxylin-esoin stain and decreased,fragmented elastic fibers by Elastic stain compared with the normal skin.Basing on these findings,the diagnosis of eruptive cutaneous collagenoma was made.No specific treatment was given.Discussion:Eruptive cutaneous collagenoma is a very rare dermatosis that is often misdiagnosed as other connective tissue nevi.The pathogenesis is unclear,and also no efficient treatment is available.It is usually diagnosed based on clinical and histopathological findings.Conclusion:The present cases are relatively rare type of eruptive cutaneous collagenoma that provide more experience for clinician,and may be helpful for them to make correct diagnosis for suspicious cases.

Tetracyclic triterpenoids isolated from semi-mangrove plant Hibiscus tiliaceus

A continuing phytochemical study on the semi-mangrove plant Hibiscus tiliaceus yielded two new tetracyclic triterpenoids （3β,24S）-19（10→9）-abeo-8α,9β,10α-eupha-5,25（26）-dien-3,24-diol （tiliacol A, 1 ）, and （3β,23Z）-19（10→9）-abeo-8α,9β,10α-tircalla-5,23-dien-3,25-diol （tiliacol B, 3）, together with one known analog （2）. Their structures were elucidated on the basis of extensive spectral analyses （MS, IR, 1D NMR and 2D NMR） and comparison with literature compounds. Compound 2 showed potent cytotoxicity against both P388 and HeLa cells with ICon values of 11.2 μmol/L and 11.5 μmol/L, resoectively.

Crystallization and Phase Behavior in Block Copolymer Solution:An in Situ Small Angle X-ray Scattering Study

Amphiphilic diblock copolymers self-assemble into a variety of micellar structures with diverse shapes in selective solvents. Here, we study the concentration and temperature dependence of the packing structure of spherical micelles of a polyisoprene-b-poly(2- vinylpyridine)(PI-b-P2VP) diblock copolymer in toluene using synchrotron radiation small angle X-ray scattering (SR-SAXS) and atomic force microscopy (AFM) techniques. Randomly packed spherical micelles are detected in dilute solutions, while in concentrated solutions, face-centered cubic (FCC), body-centered cubic (BCC) mixed crystal structures, and pure BCC crystal structures are observed with an increase in concentration. In situ SAXS experiments on the FCC/BCC mixed crystal structures reveal a novel FCC/BCC → BCC → Disorder → BCC phase behavior during the thermal annealing process. These results demonstrated that the BCC phase is apparently more stable than the FCC phase in the current sphere-packing system and FCC/BCC is a metastable state. The incompatibility of the PI and P2VP blocks decreases at a higher temperature and renders the variation of domain spacing.