Application of a supporting catheter in surgery for forearm arteriovenous fistula construction.

INTRODUCTION: This study explored the feasibility of a supporting catheter combined with modified end-to-side anastomosis in the operation of radio-cephalic arteriovenous fistula (RC-AVF) and evaluated the clinical application value of this technique. METHODS: Sixty patients underwent RC-AVF operations in our hospital from January 2022 to June 2022. All the patients were treated with modified end-to-side AVF anastomosis and divided into the control group or the test group depending on whether a supporting catheter was applied. The clinical data of 60 cases were analysed retrospectively. Intraoperative related indices, the first time the fistula was used, the success rate of first puncture, the blood flow of first dialysis, the maturity condition of fistula, the size of anastomosis, the diameter of radial artery and drainage vein, the blood flow of brachial artery 8 weeks after operation and the incidence of complications within 6 months after operation were compared between the two groups. RESULTS: Compared with that in the control group, the time spent on the vascular anastomosis in the test group was significantly shortened (p<0.05). The blood flow of the first dialysis, the size of the anastomosis, the diameter of the drainage vein, the blood flow of the brachial artery 8 weeks after the operation and the incidence of complications within 6 months after operation were significantly different between the two groups (p<0.05). CONCLUSION: In the RC-AVF operation, using a supporting catheter can not only increase operation efficiency by reducing surgical injury and difficulty of vascular anastomosis, but also improve postoperative prognosis. RC-AVF is worth promoting in clinical practice.

Gint4.T-siHDGF chimera-capped mesoporous silica nanoparticles encapsulating temozolomide for synergistic glioblastoma therapy.

Due to glioblastoma (GBM) being the most intractable brain tumor, the continuous improvement of effective treatment methods is indispensable. The combination of siRNA-based gene therapy and chemotherapy for GBM treatment has now manifested great promise. Herein, Gint4.T-siHDGF chimera-capped mesoporous silica nanoparticles (MSN) encapsulating chemotherapy drug temozolomide (TMZ), termed as TMSN@siHDGF-Gint4.T, is developed to co-deliver gene-drug siHDGF and TMZ for synergistic GBM therapy. TMSN@siHDGF-Gint4.T possesses spherical nucleic acid-like architecture that can improve the enzyme resistance of siHDGF and increase the blood-brain barrier (BBB) permeability of the nanovehicle. The aptamer Gint4.T of chimera endows the nanovehicle with GBM cell-specific binding ability. When administered systemically, TMSN@siHDGF-Gint4.T can traverse BBB and enter GBM cells. In the acidic lysosome environment, the cleavage of benzoic-imine bond on MSN surface leads to an initial rapid release of chimera, followed by a slow release of TMZ encapsulated in MSN. The sequential release of siHDGF and TMZ first allows siHDGF to exert its gene-silencing effect, and the downregulation of HDGF expression further enhances the cytotoxicity of TMZ. In vivo experimental results have demonstrated that TMSN@siHDGF-Gint4.T significantly inhibits tumor growth and extends the survival time of GBM-bearing mice. Thus, the as-developed TMSN@siHDGF-Gint4.T affords a potential approach for the combination treatment of GBM.

Gene signature and prediction model of the mitophagy-associated immune microenvironment in renal ischemia-reperfusion injury.

Background: Renal ischemia-reperfusion injury (IRI) is an inevitable occurrence during kidney transplantation. Mitophagy, ferroptosis, and the associated immune microenvironment (IME) have been shown to play important roles in renal IRI. However, the role of mitophagy-associated IME genes in IRI remains unclear. In this study, we aimed to construct a prediction model of IRI prognosis based on mitophagy-associated IME genes. Method: The specific biological characteristics of the mitophagy-associated IME gene signature were comprehensively analyzed using public databases such as GEO, Pathway Unification, and FerrDb. Correlations between the expression of prognostic genes and immune-related genes and IRI prognosis were determined by Cox regression, LASSO analysis, and Pearson's correlation. Molecular validation was performed using human kidney 2 (HK2) cells and culture supernatant as well as the serum and kidney tissues of mice after renal IRI. Gene expression was measured by PCR, and inflammatory cell infiltration was examined by ELISA and mass cytometry. Renal tissue damage was characterized using renal tissue homogenate and tissue sections. Results: The expression of the mitophagy-associated IME gene signature was significantly correlated with IRI prognosis. Excessive mitophagy and extensive immune infiltration were the primary factors affecting IRI. In particular, FUNDC1, SQSTM1, UBB, UBC, KLF2, CDKN1A, and GDF15 were the key influencing factors. In addition, B cells, neutrophils, T cells, and M1 macrophages were the key immune cells present in the IME after IRI. A prediction model for IRI prognosis was constructed based on the key factors associated with the mitophagy IME. Validation experiments in cells and mice indicated that the prediction model was reliable and applicable. Conclusion: We clarified the relationship between the mitophagy-related IME and IRI. The IRI prognostic prediction model based on the mitophagy-associated IME gene signature provides novel insights on the prognosis and treatment of renal IRI.

Alamandine, a derivative of angiotensin-(1-7), alleviates sepsis-associated renal inflammation and apoptosis by inhibiting the PI3K/Ak and MAPK pathways.

Sepsis is a frequent cause of kidney injury. The present study investigated whether Alamandine (Ala) could alleviate sepsis-associated renal injury by reducing inflammation and apoptosis. In addition, we investigated downstream signaling pathways modulated by Ala. Studies were performed in mice treated with lipopolysaccharide (LPS) and in the human proximal tubular epithelial cell line HK-2. The increase in serum creatinine, blood urea nitrogen, cystatin C and Fg, and neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in the kidneys of mice treated with LPS were reduced after administration of Ala. Exposure to LPS increased interleukin-1 beta (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) in mice and HK-2 cells, but were reduced after Ala treatment. Furthermore, increased levels of cleaved caspase 3, cleaved caspase 7, cleaved caspase 9, cleaved poly (ADP-ribose) polymerase (PARP) and Bax and reduced levels of Bcl2 in LPS-treated mice and HK-2 cells were reversed after Ala administration. In addition, LPS increased the levels of p-PI3K/PI3K, p-Akt/Akt, p-ERK/ERK, p-JNK/JNK, p-p38/p38 and p-FoxO1 in HK-2 cells, and all were reversed after Ala administration. These results indicate that Ala could improve renal function and inhibit inflammation and apoptosis in LPS induced sepsis mouse models. We demonstrated that Ala attenuated LPS induced sepsis by inhibiting the PI3K/Akt and MAPK signaling pathways.

Antisense oligonucleotide-based treatment of retinitis pigmentosa caused by USH2A exon 13 mutations.

Mutations in USH2A are among the most common causes of syndromic and non-syndromic retinitis pigmentosa (RP). The two most recurrent mutations in USH2A, c.2299delG and c.2276G > T, both reside in exon 13. Skipping exon 13 from the USH2A transcript presents a potential treatment modality in which the resulting transcript is predicted to encode a slightly shortened usherin protein. Morpholino-induced skipping of ush2a exon 13 in zebrafish ush2armc1 mutants resulted in the production of usherinΔexon 13 protein and a completely restored retinal function. Antisense oligonucleotides were investigated for their potential to selectively induce human USH2A exon 13 skipping. Lead candidate QR-421a induced a concentration-dependent exon 13 skipping in induced pluripotent stem cell (iPSC)-derived photoreceptor precursors from an Usher syndrome patient homozygous for the c.2299delG mutation. Mouse surrogate mQR-421a reached the retinal outer nuclear layer after a single intravitreal injection and induced a detectable level of exon skipping until at least 6 months post-injection. In conclusion, QR-421a-induced exon skipping proves to be a highly promising treatment option for RP caused by mutations in USH2A exon 13.

A case of suspected antibiotic-associated encephalopathy in a patient undergoing long-term peritoneal dialysis.

A man undergoing long-term peritoneal dialysis who had no history of mental illness suffered psychosis and auditory hallucination 2 days after clindamycin was initiated at a single dose of 0.6 g per day for pulmonary infection. His mental symptoms disappeared after clindamycin was discontinued and peritoneal dialysis was strengthened. The patient's body temperature was mildly elevated the day before he was admitted to the hospital, and no abnormalities were observed on head and chest computed tomography imaging at admission, except for a slow rhythm on electroencephalogram. Many factors were involved in this case; antibiotic-related encephalopathy caused by clindamycin may be one factor. Physicians should carefully consider the use of antibiotics, especially in patients with end-stage renal disease.