The aim of this study was to evaluate the early and sustained effects of tinnitus educational counseling on chronic primary tinnitus and related problems. A descriptive longitudinal cohort study was conducted with 159 adult patients suffering from chronic primary tinnitus and sleep problems. All patients received tinnitus educational counseling, sleep adjustment, and vegan dietary advice. At short-term assessment within 3 months and long-term follow-up at 6–26 months, perceived changes in tinnitus were assessed with the Tinnitus Handicap Inventory (THI) and the Tinnitus Evaluation Questionnaire (TEQ), respectively. In TEQ, the volume of subjective tinnitus was scored according to realistic environments in which tinnitus could be heard. Sleep quality was assessed with questionnaires developed in our laboratory. Most of the subjects showed significant early improvement in their THI scores (96/159, 60.38%; from 46.11 ± 22.74 to 31.94 ± 20.41, t = 11.16, p < 0.001, Cohen's d = 0.66). Tinnitus volume (39/159, 24.53%, from 2,2 to 2,1, z = -3.56, p < 0.001) and sleep quality (68/159, 42.77%; from 7.13 ± 3.11 to 6.31 ± 2.75, t = 3.73, p < 0.001, Cohen's d = 0.28) were also improved. Long-term follow-up TEQ results indicated that tinnitus loudness, the impact of tinnitus on sleep, concentration, and emotional state were all improved since the prior consultation (p = 0.001, 0.026, 0.012, and <0.001). Short-term improvement of tinnitus severity correlated directly with improvement of sleep quality (odds ratio (OR) = 0.30, 95% confidence interval (CI): 0.14–0.64, p = 0.002), initial THI score (OR = 1.02, 95% CI: 1.01 to 1.04, p = 0.006), compliance with sleep advice (OR = 2.27, 95% CI: 1.02–5.05, p = 0.044), and nervous disposition (OR = 2.80, 95% CI: 1.25–6.30, p = 0.013). A future randomized controlled trial would be carried out to examine the effect of sole tinnitus educational counseling.

Sorafenib is one a first-line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance.We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib-resistant SMMC-7721 cells compared to parental cells. NFIB knockdown not only sensitized drug-resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib-induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.

ObjectiveLocal invasion is the first step of metastasis, the main cause of colorectal cancer (CRC)-related death. Recent studies have revealed extensive intertumoral and intratumoral heterogeneity. Here, we focused on revealing local invasion-related genes in CRC. MethodsWe used spatial transcriptomic techniques to study the process of local invasion in four CRC tissues. First, we compared the pre-cancerous, cancer center, and invasive margin in one section (S115) and used pseudo-time analysis to reveal the differentiation trajectories from cancer center to invasive margin. Next, we performed immunohistochemical staining for RPL5, STC1, AKR1B1, CD47, and HLA-A on CRC samples. Moreover, we knocked down AKR1B1 in CRC cell lines and performed CCK-8, wound healing, and transwell assays to assess cell proliferation, migration, and invasion.ResultsWe demonstrated that 13 genes were overexpressed in invasive clusters, among which the expression of CSTB and TM4SF1 was correlated with poor PFS in CRC patients. The ribosome pathway was increased, while the antigen processing and presentation pathway was decreased along CRC progression. RPL5 was upregulated, while HLA-A was downregulated along cancer invasion in CRC samples. Pseudo-time analysis revealed that STC1, AKR1B1, SIRPA, C4orf3, EDNRA, CES1, PRRX1, EMP1, PPIB, PLTP, SULF2, and EGFL6 were unpregulated along the trajectories. Immunohistochemic3al staining showed the expression of STC1, AKR1B1, and CD47 was increased along cancer invasion in CRC samples. Knockdown of AKR1B1 inhibited CRC cells’ proliferation, migration, and invasion.ConclusionsWe revealed the spatial heterogeneity within CRC tissues and uncovered some novel genes that were associated with CRC invasion.