Long-Term Indomethacin Treatment in a Chinese Child with Gitelman Syndrome: Case Report and Literature Review on its Efficacy and Tolerance.

BACKGROUND Gitelman syndrome (GS) is a rare inherited autosomal recessive salt-losing renal tubulopathy. Early-onset GS is difficult to differentiate from Bartter syndrome (BS). It has been reported in some cases that cyclooxygenase (COX) inhibitors, which pharmacologically reduce prostaglandin E2(PGE2) synthesis, are helpful for GS patients, especially in children, but the long-term therapeutic effect has not yet been revealed. CASE REPORT A 4-year-old boy was first brought to our hospital for the chief concern of short stature and growth retardation. Biochemical tests demonstrated severe hypokalemia, hyponatremia, and hypochloremic metabolic alkalosis. The patient's serum magnesium was normal. He was diagnosed with BS and treated with potassium supplementation and indomethacin and achieved stable serum potassium levels and slow catch-up growth. At 11.8 years of age, the patient showed hypomagnesemia and a genetic test confirmed that he had GS with compound heterozygous mutations in the SLC12A3 gene. At the age of 14.8 years, when indomethacin had been taken for nearly 10 years, the boy reported having chronic stomachache, while his renal function remained normal. After proton pump inhibitor and acid inhibitor therapy, the patient's symptoms were ameliorated, and he continued to take a low dose of indomethacin (37.5 mg/d divided tid) with good tolerance. CONCLUSIONS Early-onset GS in childhood can be initially misdiagnosed as BS, and gene detection can confirm the final diagnosis. COX inhibitors, such as indomethacin, might be tolerated by pediatric patients, and long-term therapy can improve the hypokalemia and growth retardation without significant adverse effects.

Electroacupuncture ameliorates AOM/DSS-induced mice colorectal cancer by inhibiting inflammation and promoting autophagy via the SIRT1/miR-215/Atg14 axis.

Colorectal cancer (CRC) is one of the most common tumors of the digestive tract, with the third-highest incidence and the second-highest mortality rate among all malignant tumors worldwide. However, treatment options for CRC remain limited. As a complementary therapy, acupuncture or electro-acupuncture (EA) has been widely applied in the treatment of various inflammation-related diseases, such as obesity, ulcerative colitis and tumors. Although numerous pre-clinical and clinical studies have investigated the beneficial effects of acupuncture on CRC, the mechanism underlying the therapeutic action of EA is largely unknown. Evidence from previous studies has revealed that SIRT1 participates in CRC progression by activating autophagy-related miRNAs. Using azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colorectal cancer model in mice, we explored whether EA treatment can inhibit inflammation and promote autophagy via the SIRT1/miR-215/Atg14 axis. Our results showed that EA notably alleviated the CRC in mice, by decreasing the tumor number and DAI scores, inflammation, and increasing body weight of mice. Besides, EA increased the expression of SIRT1 and autophagy. Further experiments showed that SIRT1 overexpression downregulated miR-215, and promoted the expression of Atg14, whereas SIRT1 knockdown induced opposite results. In conclusion, EA can ameliorate AOM/DSS-induced CRC through regulating the SIRT1-mediated miR-215/Atg14 axis by suppressing inflammation and promoting autophagy in mice. These findings reveal a potential molecular mechanism underlying the anti-CRC effect of EA indicating that EA is a promising therapeutic candidate for CRC.

[Electroacupuncture postpones growth of tumors by activating SIRT1 expression to reduce inflammatory reaction and facilitate cellular autophagy in mice with transformed colorectal carcinomas].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on tumor number, body conditions, inflammatory factors and expression levels of silent information regulator 1 (sirtuin 1, SIRT1) and autophagy-related proteins Beclin-1, P62, and LC3 in colorectal tissues in inflammatory-transformed colorectal cancer mice, so as to explore its underlying mechanisms in resisting tumor growth. METHODS: A total of 100 C57BL/6 male mice were randomly divided into normal control, model, EA, EA + SIRT1 inhibitor (EA+inhibitor) and agonist resveratrol (agonist) groups, with 20 mice in each group. EA (2 Hz, 1 mA) was applied to "Zusanli"(ST36)and "Fenglong"(ST40) for 20 min every time, 3 times a week for 11 weeks. Mice of the EA +inhibitor group received intraperitoneal injection of SIRT1 inhibitor EX527 (5 mg/kg) at the same time of EA treatment, and those of the agonist group received gavage of resveratrol (200 mg/kg, an agonist of SIRT1), 3 times a week for 11 weeks. The body mass was measured weekly. The disease activity index (DAI), colorectal length and tumor number in each group were recorded. The histopathological changes of colorectal tissues were observed by H.E. staining; the contents of interleukin 6 (IL-6), IL-10, IL-17, in the colorectal tissues were detected by enzyme-linked immunosorbent assay, and the expression levels of SITR1, Beclin-1, P62, and LC3 in colorectal tissues were detected by Western blot and real-time fluorescence quantitative PCR, respectively. RESULTS: Compared with the normal control group, the body weight, length of colorectum, the contents of IL-10, and the expression levels of SIRT1,Beclin-1 and LC3 mRNAs and proteins were significantly decreased (P<0.001), whereas the DAI score, the number of tumors, the contents of IL-6 and IL-17, and the expression levels of P62 mRNA and protein were significantly increased (P<0.000 1, P<0.001) in the model group. In comparison with the model group, the body weight, the length of colorectum, the contents of IL-10, and the expression levels of SIRT1,Beclin-1 and LC3 mRNAs and proteins were significantly increased (P<0.01,P<0.05,P<0.001), while the DAI scores, the numbers of tumors, the contents of IL-6 and IL-17, and the expression levels of P62 mRNA and protein were obviously decreased in the EA and agonist groups (P<0.01,P<0.05, P<0.001). No significant changes were found in all the above-mentioned indexes in the EA+inhibitor group in comparison with the model group (P>0.05). CONCLUSION: EA can reduce the number of tumors and inflammation reaction in colorectal tissue and improve the body condition in mice with colorectal cancer, which may be related to its functions in activating the expression of intestinal SIRT1, and then facilitating cellular autophagy.

Corilagin ameliorates the extreme inflammatory status in sepsis through TLR4 signaling pathways.

BACKGROUND: Sepsis is one of the serious disorders in clinical practice. Recent studies found toll-like receptors 4 (TLR4) played an important role in sepsis. In this study, we tried to find the influence of Corilagin on TLR4 signal pathways in vitro and in vivo. METHODS: The cellular and animal models of sepsis were established by LPS and then interfered with Corilagin. Real-time PCR and western blot were employed to detect the mRNA and protein expressions of TLR4, MyD88, TRIF and TRAF6. ELISA was used to determine the IL-6 and IL-1ß levels in supernatant and serum. RESULTS: The survival rate was improved in the LPS + Corilagin group, and the mRNA and protein expressions of TLR4, MyD88, TRIF and TRAF6 were significantly decreased than that in the LPS group both in cellular and animal models (P < 0.01). The pro-inflammatory cytokines IL-6 and IL-1ß were greatly decreased in the LPS + Corilagin group both in supernatant and serum (P < 0.01). CONCLUSIONS: Corilagin exerts the anti-inflammatory effects by down-regulating the TLR4 signaling molecules to ameliorate the extreme inflammatory status in sepsis.

[A prospective, randomized, controlled clinical study of Huai Qi Huang granules in treatment of childhood primary nephrotic syndrome].

OBJECTIVE: To study the efficacy of Huai Qi Huang granules in the treatment of childhood primary nephrotic syndrome. METHODS: Between July 2009 and December 2011, patients who were admitted and diagnosed for the first time as childhood primary nephrotic syndrome were randomized into a treatment group (Huai Qi Huang granules plus glucocorticoid; n=23) and a control group (glucocorticoid alone; n=19) for a prospective study. The two groups were compared for regression time of edema, time to urinary protein clearance, relapse rate, incidence of infection, dosage of glucocorticoid, and humoral and cellular immunological indicators. RESULTS: There were no significant differences in regression time of edema, time to urinary protein clearance, and relapse rate between the treatment and control groups (P>0.05). The treatment group had significantly lower incidence of infection and daily dose of glucocorticoid (at month 6) than the control group (P<0.05). Humoral and cellular immunological indicators showed no significant differences between the two groups (P>0.05). No Huai Qi Huang-related adverse events were observed in this study. CONCLUSIONS: Huai Qi Huang granules treatment can reduce the dose of glucocorticoid and the incidence of infection in children with primary nephrotic syndrome and has a favourable safety.