Gitelman syndrome caused by a rare homozygous mutation in the SLC12A3 gene:A case report

BACKGROUND Gitelman syndrome(GS)is an unusual,autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis,hypomagnesemia and hypocalciuria.It is caused by mutations in the solute carrier family 12 member 3(SLC12A3)gene resulting in disordered function of the thiazidesensitive NaCl co-transporter.To date,many types of mutations in the SLC12A3 gene have been discovered that trigger different clinical manifestations.Therefore,gene sequencing should be considered before determining the course of treatment for GS patients.CASE SUMMARY A 55-year-old man was admitted to our department due to hand numbness and fatigue.Laboratory tests after admission showed hypokalemia,metabolic alkalosis and renal failure,all of which suggested a diagnosis of GS.Genome sequencing of DNA extracted from the patient’s peripheral blood showed a rare homozygous mutation in the SLC12A3 gene(NM_000339.2:chr16:56903671,Exon4,c.536T>A,p.Val179Asp).This study reports a rare homozygous mutation in SLC12A3 gene of a Chinese patient with GS.CONCLUSION Genetic studies may improve the diagnostic accuracy of Gitelman syndrome and improve genetic counseling for individuals and their families with these types of genetic disorders.

Complications and management of penile augmentation with hyaluronic acid injection

Hyaluronic acid injection is becoming a popular way for penile augmentation.However,only few studies and follow-ups have investigated the various complications of hyaluronic acid injection and their corresponding management.In this study,a total of 230 patients who had penile augmentation with hyaluronic acid injection from January 2018 to December 2019 were examined on follow-up for penile girth,complications,and their corresponding management.At 1-month,3-month,and 6-month postoperative follow-ups,the penile circumference had increased by 2.66±1.24 cm,2.28±1.02 cm,and 1.80±0.83 cm,respectively.During the entire 6-month follow-up,4.3%had complications such as subcutaneous bleeding,subcutaneous nodules,and infection.There were no systemic or local allergic reactions among all the patients.All complications were treated accordingly,and no further deterioration or severe sequelae were observed.Although complications of hyaluronic acid injections are mild and rare,these may affect the patient's satisfaction postoperatively.Preoperative redundant prepuce may increase the incidence of penile edema or postoperative gel migration.Standardization of the surgery protocol and elucidation of the effects of other injection parameters are still lacking.Nevertheless,it still highlights the importance of preoperative preparation and surgical technique.

C-X3-C motif chemokine ligand 1/receptor 1 regulates the M1 polarization and chemotaxis of macrophages after hypoxia/reoxygenation injury

Background:Macrophages play an important role in renal ischemia reperfusion injury,but the functional changes of macrophages under hypoxia/reoxygenation and the related mechanism are unclear and need to be further clarified.Methods:The effects of hypoxia/reoxygenation on functional characteristics of RAW264.7 macrophages were analyzed through the protein expression detection of pro-inflammatory factors TNF-αand CD80,anti-inflammatory factors ARG-1 and CD206.The functional implications of C-X3-C motif chemokine receptor 1(CX3CR1)down-regulation in hypoxic macrophages were explored using small interfering RNA technology.Significance was assessed by the parametrict-test or nonparametric Mann-Whitney test for two group comparisons,and a one-way ANOVA or the Kruskal-Wallis test for multiple group comparisons.Results:Hypoxia/reoxygenation significantly increased the protein expression of M1-related pro-inflammatory factors TNF-α,CD80 and chemokine C-X3-C motif chemokine ligand 1(CX3CL1)/CX3CR1 and inhibited the protein expression of M2-related anti-inflammatory factors ARG-1 and CD206 in a time-dependent manner in RAW264.7 cells.However,the silencing of CX3CR1 in RAW264.7 cells using specific CX3CR1-siRNA,significantly attenuated the increase in protein expression of TNF-α(P<0.05)and CD80(P<0.01)and the inhibition of ARG-1(P<0.01)and CD206(P<0.01)induced by hypoxia/reoxygenation.In addition,we also found that hypoxia/reoxygenation could significantly enhance the migration(2.2-fold,P<0.01)and adhesion capacity(1.5-fold,P<0.01)of RAW264.7 macrophages compared with the control group,and CX3CR1-siRNA had an inhibitory role(40%and 20%reduction,respectively).For elucidating the mechanism,we showed that the phosphorylation levels of ERK(P<0.01)and the p65 subunit of NF-κB(P<0.01)of the RAW264.7 cells in the hypoxic/reoxygenation group were significantly increased,which could be attenuated by down-regulation of CX3CR1 expression(P<0.01,both).ERK inhibitors also significantly blocked the effects of hypoxic/reoxygenation on the protein expression of M1-related pro-inflammatory factors TNF-α,CD80 and M2-related anti-inflammatory factors ARG-1 and CD206.Moreover,we found that conditioned medium from polarized M1 macrophages induced by hypoxia/reoxygenation,notably increased the degree of apoptosis of hypoxia/reoxygenation-induced TCMK-1 cells,and promoted the protein expression of pro-apoptotic proteins bax(P<0.01)and cleaved-caspase 3(P<0.01)and inhibited the expression of anti-apoptotic protein bcl-2(P<0.01),but silencing CX3CR1 in macrophages had a protective role.Finally,we also found that the secretion of soluble CX3CL1 in RAW264.7 macrophages under hypoxia/reoxygenation was significantly increased.Conclusions:The findings suggest that hypoxia/reoxygenation could promote M1 polarization,cell migration,and adhesion of macrophages,and that polarized macrophages induce further apoptosis of hypoxic renal tubular epithelial cells by regulating of CX3CL1/CX3CR1 signaling pathway.