Objectives: Spontaneous rupture of the urinary bladder (SRUB) is extremely rare and might be misdiagnosed, leading to a high mortality rate. The current study aimed to identify the cause, clinical features, and diagnosis strategy of SRUB.Methodology: We presented a case report for two women (79 and 63 years old) misdiagnosed with acute abdomen and acute kidney injury, respectively, who were finally confirmed to have SRUB by a series of investigations and exploratory surgery. Meanwhile, literature from multiple databases was reviewed. PubMed, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Biological Medical Literature Database (CBM), WANFANG DATA, and the Chongqing VIP database for Chinese Technical Periodicals (VIP) were searched with the keywords “spontaneous bladder rupture” or “spontaneous rupture of bladder” or “spontaneous rupture of urinary bladder.” All statistical analyses were conducted using SPSS 20.0 software.Results: A total of 137 Chinese and 182 English literature papers were included in this article review. A total of 713 SRUB patients were analyzed, including the two patients reported by us. The most common cause of SRUB was alcohol intoxication, lower urinary tract obstruction, bladder tumor or inflammation, pregnancy-related causes, bladder dysfunction, pelvic radiotherapy, and history of bladder surgery or bladder diverticulum. Most cases were diagnosed by exploratory laparotomy and CT cystography. Patients with extraperitoneal rupture could present with abdominal pain, abdominal distention, dysuria, oliguria or anuria, and fever. While the main symptoms of intraperitoneal rupture patients could be various and non-specific. The common misdiagnoses include acute abdomen, inflammatory digestive disease, bladder tumor or inflammation, and renal failure. Most of the patients (84.57%) were treated by open surgical repair, and most of them were intraperitoneal rupture patients. Overall, 1.12% of patients were treated by laparoscopic surgery, and all of them were intraperitoneal rupture patients. Besides, 17 intraperitoneal rupture patients and 6 extraperitoneal rupture patients were treated by indwelling catheterization and antibiotic therapy. Nine patients died of delayed diagnosis and treatment.Conclusions: SRUB often presents with various and non-specific symptoms, which results in misdiagnosis or delayed treatment. Medical staff noticing abdominal pain suggestive of peritonitis with urinary symptoms should be suspicious of bladder rupture, especially in patients with a history of bladder disease. CT cystography can be the best preoperative non-invasive examination tool for both diagnosis and evaluation. Conservative management in the form of urine drainage and antibiotic therapy can be used in patients without severe infection, bleeding, or major injury. Otherwise, surgical treatment is recommended. Early diagnosis and management of SRUB are crucial for an uneventful recovery.

Patients with cystic fibrosis endure “chronic focal infections” with a variety of microorganisms. One microorganism, Pseudomonas aeruginosa, adapts to the host and develops resistance to a wide range of antimicrobials. Interestingly, as the infection progresses, multiple isogenic strains of P. aeruginosa emerge and coexist within the airways of these patients. Despite a common parental origin, the multiple strains of P. aeruginosa develop vastly different susceptibility patterns to actively used antimicrobial agents—a phenomenon we define as “heterogeneous MICs.” By sequencing pairs of P. aeruginosa isolates displaying heterogeneous MICs, we observed widespread isogenic gene lesions in drug transporters, DNA mismatch repair mechanisms, and many other structural or cellular functions. Coupled with the heterogeneous MICs, these genetic lesions demonstrated a symbiotic response to host selection and suggested evolution of a multicellular syntrophic bacterial lifestyle. Current laboratory standard interpretive criteria do not address the emergence of heterogeneous growth and susceptibilities in vitro with treatment implications.

Patatin-like phospholipase domain containing 3 (PNPLA3) is a non-secreted protein primarily expressed in liver and adipose tissue. Recently, numerous genetic studies have shown that PNPLA3 is a major susceptibility gene for nonalcoholic fatty liver disease (NAFLD). However, the mechanism involved in transcriptional regulation of the PNPLA3 gene remains unknown. We performed a detailed analysis of the human PNPLA3 gene promoter and identified two novel cis-acting elements (SRE and NFY binding motifs) located at -97/-88 and -26/-22 bp, respectively. Overexpression of SREBP-1c in HepG2 cells significantly increased PNPLA3 promoter activity. Mutation of either of the putative SRE or NFY binding motifs blocked the transactivation effects of SREBP-1c on the promoter. Overexpression of SREBP-1c and NFY together increased PNPLA3 promoter activity twice as much as that of SREBP-1c or NFY expression alone. This result suggests that SREBP-1c and NFY synergistically transactivate the human PNPLA3 gene. The ability of SREBP-1c and NFY to bind these cis-elements was confirmed using gel shift analysis. Putative SRE and NFY motifs also mediated synergistic insulin-induced transactivation of the PNPLA3 promoter in HepG2 cells. Additionally, the ability of SREBP-1c to bind to the PNPLA3 promoter was increased by insulin in a dose-dependent manner. Moreover, the treatment of HepG2 cells with the PI3K inhibitor LY294002 led to reduced insulin promoter-activating ability accompanied by a decrease in PNPLA3 and SREBP-1c protein expression. These results demonstrate that SREBP-1c is a direct activator of the human PNPLA3 gene and insulin transactivates the PNPLA3 gene via the PI3K-SREBP-1c/NFY pathway in HepG2 cells.

No abstract

Both PNPLA3 I148M and hepatic inflammation are associated with nonalcoholic fatty liver disease (NAFLD) progression. This study aimed to elucidate whether PNPLA3 I148M is involved in NF-kB-related inflammation regulation in NAFLD. HepG2 cells homozygous for the PNPLA3 I148M mutation were used. The human PNPLA3 promoter sequence was screened for NF-kB binding sites using the MATCH and PATCH tools. NF-kB-mediated transcriptional regulation of the PNPLA3 gene was assessed by luciferase reporter assay, EMSA and ChIP-qPCR. Wild-type (I148I) and mutant (M148M) PNPLA3 were overexpressed using stable lentivirus-mediated transfection. The pCMV vector and siRNA were transiently transfected into cells to direct NF-kB overexpression and PNPLA3 silencing, respectively. A putative NF-kB binding site in the human PNPLA3 promoter was shown to be necessary for basal and NF-kBdriven transcriptional activation of PNPLA3 and protein/DNA complex formation.Supershift analysis demonstrated a protein/DNA complex specifically containing the NF-kB p65 and p50 subunits. ChIP-qPCR confirmed the endogenous binding of NF-kB to the human PNPLA3 promoter in response to NF-kB overexpression and palmitic acid (PA) challenge. The silencing of PNPLA3 blocked the overexpression of NF-kB or PA-induced TNF-α up-regulation. Moreover, mutant PNPLA3 overexpression prevented NF-kB inhibitor-induced down-regulation of TNF-α expression in PA-treated HepG2 cells. Finally, the overexpression of mutant but not wild-type PNPLA3 increased TNF-α expression and activated the ER stress-mediated and NF-kB-independent inflammatory IRE-1α/JNK/c-Jun pathway. Human PNPLA3 was shown to be a target of NF-kB, and PNPLA3 I148M mediated the regulatory effect of NF-kB on inflammation in PA-treated HepG2 cells, most likely via the IRE-1α/JNK/c-Jun ER stress pathway. K E Y W O R D SER stress, inflammation, NAFLD, NF-kB, PNPLA3