Supplementary Material for: Comparison of Safety and Efficacy of Different Models of Target Vessel Regional Chemotherapy for Gastric Cancer with Liver Metastases

<b><i>Background/Aims:</i></b> We previously demonstrated the safety and efficacy of low-dose, short-interval target vessel regional chemotherapy (TVRC^LDSI) delivered through the hepatic artery with transarterial embolization (TAE) in patients with advanced gastric cancer (AGC). The present study aimed to compare the efficacy of TAE + TVRC^LDSI with that of standard TAE + TVRC in AGC patients with liver metastases who failed to respond to first- or second-line systemic chemotherapy. <b><i>Methods:</i></b> This study recruited a total of 58 GC patients with liver metastases after failure of first- or second-line systemic chemotherapy. Twenty-eight patients were assigned to the TAE + TVRC^LDSI group and 30 patients to the TAE + TVRC group. The primary end point was overall survival (OS^TVRC), which was defined as the time from the initiation of TVRC until the last follow-up or death. <b><i>Results:</i></b> OS^TVRC, time to progression (TTP) until appearance of intra- and extrahepatic metastases, and overall TTP and treatment periods in the TAE + TVRC^LDSI group were all significantly longer than in the TAE + TVRC group (all p < 0.001). <b><i>Conclusion:</i></b> TAE + TVRC^LDSI had a higher efficacy and safety, which was reflected by OS rates, progression-free survival rates, longer duration of treatment and milder side effects compared to standard TAE + TVRC

Supplementary Material for: Drug-Eluting Stent, but Not Bare Metal Stent, Accentuates the Systematic Inflammatory Response in Patients

<b><i>Objective:</i></b> The systematic pro-inflammatory responses after percutaneous coronary intervention with drug-eluting stents (DES) remain poorly defined. Therefore, we compared the systematic pro-inflammatory state of circulating mononuclear cells (MNCs) between DES and bare metal stent (BMS) implantation. <b><i>Methods:</i></b> Patients with indications for treatment with stents were randomized in a 1:1 ratio to placement of DES or BMS. The primary endpoint was a change of pro-inflammatory state at 12 weeks post-procedure. <b><i>Results:</i></b> Thirty-six consecutive patients received DES or BMS. At 12 weeks after stent implantation, the lipid profile and high-sensitivity C-reactive protein (hs-CRP) improved significantly in both groups. The mRNA levels and plasma concentrations of interleukin-6, tumor necrosis factor-a and matrix metalloproteinase-9 were significantly elevated in the DES group, which was not observed in the BMS group. An increase in NF-γB binding activity and a decrease in PPAR-γ expression in MNCs were observed in the DES group, along with increases in IγB phosphorylation and p50 expression. However, similar changes were not observed in the BMS group. <b><i>Conclusions:</i></b> Systematic inflammatory responses were accentuated after the patients were treated percutaneously with DES, despite their improved lipid profile and hs-CRP. These data may provide fundamental information for optimizing therapeutic strategy in the era of DES

Supplementary Material for: Effect of Type I Diabetes on the Proteome of Mouse Oocytes

<i>Background:</i> Type I diabetes is a global public health concern that affects young people of reproductive age and can damage oocytes, reducing their maturation rate and blocking embryonic development. Understanding the effects of type I diabetes on oocytes is important to facilitate the maintenance of reproductive capacity in female diabetic patients. <i>Methods:</i> To analyze the effects of type I diabetes on mammalian oocytes, protein profile changes in mice with streptozotocin-induced type I diabetes were investigated using proteomic tools; non-diabetic mouse oocytes were used as controls. Immunofluorescence analysis for the spindle and mitochondria of oocytes. Results: We found that type I diabetes severely disturbed the metabolic processes of mouse oocytes. We also observed significant changes in levels of histone H1, H2A/B, and H3 variants in diabetic oocytes (fold change: > 0.4 or < -0.4), with the potential to block activation of the zygotic genome and affect early embryo development. Furthermore, diabetic oocytes exhibited higher abnormal spindle formation and spatial remodeling of mitochondria than observed in the controls. <i>Conclusion:</i> Our results indicate that type I diabetes disrupts metabolic processes, spindle formation, mitochondria distribution and modulates epigenetic code in oocytes. Such effects could have a major impact on the reproductive dynamics of female patients with type I diabetes

Supplementary Material for: Whole-Genome Linkage Analysis with Whole-Exome Sequencing Identifies a Novel Frameshift Variant in <b><i>NEFH</i></b> in a Chinese Family with Charcot-Marie-Tooth 2: A Novel Variant in <b><i>NEFH</i></b> for Charcot-Marie-Tooth 2

<b><i>Background:</i></b> Charcot-Marie-Tooth disease (CMT) is the most common neurodegenerative disorder of the peripheral nervous system. More than 50 genes/loci were found associated with the disease. We found a family with autosomal-dominant CMT2. <b><i>Objective:</i></b> To reveal the pathogenic gene of the family and further investigate the function of the variant. <b><i>Methods:</i></b> DNA underwent whole-genome linkage analysis for all family members and whole-exome sequencing for 2 affected members. Neurofilament light polypeptide and wild-type or mutant neurofilament heavy polypeptide (NEFH) were co-transfected into SW13 (vim–) cells. The <i>nefh</i>-knockdown zebrafish model was produced by using morpholino antisense oligonucleotides. <b><i>Results:</i></b> We identified a novel insertion variant (c.3057insG) in <i>NEFH</i> in the family. The variant led to the loss of a stop codon and an extended 41 amino acids in the protein. Immunofluorescence results revealed that mutant <i>NEFH</i> disrupted the neurofilament network and induced aggregation of NEFH protein. Knockdown of<i> nefh</i> in zebrafish caused a slightly or severely curled tail. The motor ability of <i>nefh</i>-knockdown embryos was impaired or even absent, and the embryos showed developmental defects of axons in motor neurons. The abnormal phenotype and axonal developmental defects could be rescued by injection of human wild-type but not human mutant<i> NEFH</i> mRNA. <b><i>Conclusions:</i></b> We identified a novel stop loss variant in <i>NEFH</i> that is likely pathogenic for CMT2, and the results provide further evidence for the role of an aberrant assembly of neurofilament in CMT