[Early vocabulary development in Mandarin children with cochlear implantation].

Objective: To investigate the development of receptive and expressive vocabulary in Mandarin-speaking children with cochlear implants (CI) during the first year after CI activation. Methods: A total of 827 children (411 boys and 416 girls) who were implanted CI before 2.5 years of age from October 2019 to December 2022 in the Department of Auditory Implantation, Shandong Provincial ENT Hospital were included in this study. The Infant Checklist of the Mandarin Early Vocabulary Inventory (EVI) was used to assess the quantity and content of receptive and expressive vocabulary at the time of CI activation and at the 1st, 3rd, 6th, 9th, 12th months post-activation. SPSS 22.0 was used to describe the receptive and expressive vocabulary of CI children at the first year after activation. Results: During the first year after CI activation, CI children's receptive and expressive vocabulary consistently increased with the CI usage. The average number of receptive vocabulary and expressive vocabulary respectively increased from 0 to 178, and from 0 to 97. At the first year of post-activation, the number of receptive and expressive vocabulary of CI children were superior to that of hearing-age matched typical-hearing children, but fell behind of that of chronological age matched typical-hearing children. In terms of lexical categories, receptive and expressive vocabulary was acquired in the following order: nouns, verbs, adjectives, and pronouns. Among the top 50 words that CI children could express, nouns were the most common, then followed by verbs, adjectives, and pronouns. Father's education level can significantly and positively predictethe receptive vocabulary of CI children at the first year post-activation. At the first year after CI activation, the 10th, 25th, 50th, 75th, and 90th percentiles were 113, 149, 178, 202, 223 for the receptive vocabulary, and 9, 37, 97, 148, 188 for expressive vocabulary. Conclusion: For Mandarin speaking children with CI, the receptive and expression vocabulary continuely increased within the first year after CI activation. The ability to grasp receptive vocabulary precedes the ability to express expressive vocabulary. Compared to hearing-age matched typical-hearing children, CI children showed faster rate of the vocabulary growth, and earlier and more frequently verb expression. However, it still larged behind that of chronological age matched hearing normal children. CI children respectively understood and expressed nouns and verbs the first. In children with CI, the first concepts understood and expressed were nouns and verbs. Among the first 50 words expressed, nouns were the most numerous, and the age at which verbs were acquired was earlier than that for hearing-age matched typical-hearing children.

Causal association between complement system FHR-5, CTRP9, and breast carcinoma in situ: a Mendelian randomization study.

OBJECTIVE: Breast carcinoma in situ accounts for a significant number of newly diagnosed breast cancer cases. However, the cause of this type of cancer is unclear, which has led to debates regarding treatment strategies. A Mendelian randomization (MR) study was conducted to explore whether complement system or complement C1q/tumor necrosis factor-related proteins (CTRPs) are causally associated with breast carcinoma in situ. MATERIALS AND METHODS: This two-sample multivariable MR study used genome-wide association study (GWAS) data for all complement system factors and CTRPs. Summary-level statistics were obtained from the breast carcinoma in situ GWAS database. The study employed the MR-Egger method, inverse variance weighted (IVW) method, and weighted median method. Additionally, sensitivity analyses, including the MR-Egger intercept, funnel plot, and leave-one-out analysis, were conducted to address uncertainties and enhance the reliability of the findings. RESULTS: The study indicated that certain immunomodulatory molecules might increase the risk of breast carcinoma in situ, with consistent results. Specifically, CTRP9 showed a 57.0% increased risk [IVW: odds ratio (OR) 0.570 (0.350, 0.928), p < 0.05], and complement factor H (FH)-related protein 5 (FHR-5) was linked to a 67.2% higher risk [IVW: OR 0.672 (0.477, 0.947), p < 0.05]. However, no associations were found with other molecules, suggesting the relationship between immunomodulatory molecules and cancer may be context-specific. CONCLUSIONS: This MR study marks the initial identification of a direct link between FHR-5 and CTRP9 and the susceptibility to breast carcinoma in situ. Delving into the roles of immunomodulatory molecules and immune responses within the tumor microenvironment holds considerable importance for the management of breast carcinoma in situ.

[Establishment of acute graft-versus-host disease model after non-myeloablative haploidentical peripheral blood stem cell transplantation in aged mice].

Objective: To establish an acute graft-versus-host disease (aGVHD) model in aged mice after non-myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PSCT). Methods: C57BL/6 (H-2b) male mice aged 6-8 weeks were used as donor mice, and CB6F1 (H-2b×d) female mice aged 14-16 months were used as recipient mice. The donor mice were injected subcutaneously with rehuman granulocyte-colony stimulating factor (rhG-CSF) 5 days before transplantation for hematopoietic stem cell mobilization.The recipient mice were divided into control group (CG), spleen cell low-dose group (SL), spleen cell medium-dose group (SM) and spleen cell high-dose group (SH) according to random number table method, with 16 rats in each group, all of which received total linear accelerator X-ray irradiation (TBI) with a total dose of 6 Gy. Peripheral blood mononuclear cells (PBMC) and spleen cells of different doses (0.5×107/each, 1.0×107/each and 2.0×107/each in SL group, SM group and SH group, respectively) were transfused through the tail vein within 4 hours after TBI, and only the same amount of normal saline was transfused in CG group. After transplantation, the survival and weight changes of mice in each group were observed for 30 days, and the changes of blood routine were monitored regularly. Mice peripheral blood was collected 21 days after transplantation to detect the chimerism rate of the donor. Hematoxylin-eosin staining was performed on the skin, liver and colon of mice 21 days after transplantation to analyze the histopathological changes of aGVHD target organs. Results: All the mice in each group were successfully transplanted. After TBI, the weight and activity of mice in all groups decreased, and the phenomenon of bone marrow suppression appeared. During the observation period, all mice in CG group and SL group survived, 3 mice in SM group died with survival time of (26.0±5.8) days, and 6 mice in SH group died with survival time of (20.9±7.3) days. The body weight of mice in SH group was lower than that in CG group, SL group and SM group 21days after transplantation [(25.0±0.7), (25.5±0.4), (25.0±1.4) vs (20.8±0.8) g, all P<0.05]. Compared with CG group, SL group and SM group, the levels of leukocyte, erythrocyte, hemoglobin and platelet in SH group decreased 21 days after transplantation (all P<0.05). There was no significant difference in donor chimerism rate among SL group, SM group and SH group [(95.8%±0.8%), (95.5%±1.4%) and (95.1%±1.3%), respectively, all P>0.05]. Compared with CG group, SL group and SM group, the tissue structure of aGVHD target organs in SH group was severely damaged, with a large number of inflammatory cells infiltratedand higher histopathological scores than SL group and SM group (all P<0.05). Conclusion: For aging CB6F1 mice, after 6 Gy TBI pretreatment with linear accelerator X-ray, PBMC (1×107/each) and spleen cells (2.0×107/each) were injected to successfully induce aGVHD model after non-myelablative haplo-PSCT.

[17-year study on the curative effect of treatment to prevent the recurrence of hepatitis B in different risk groups after liver transplantation].

Objective: To observe the recurrence condition of hepatitis B in different risk groups after liver transplantation in an attempt to provide useful information on whether to discontinue hepatitis B immunoglobulin (HBIG) in the future at an early stage. Methods: The patient population was divided into high, low-risk, and special groups [especially primary hepatocellular carcinoma (HCC)] according to the guidelines for the prevention and treatment of hepatitis B recurrence after liver transplantation. The recurrence condition and risk factors in this population were observed for hepatitis B. Measurement data were analyzed using a t-test and a rank-sum test. Count data were compared using a χ(2) test between groups. Results: This study finally included 532 hepatitis B-related liver transplant cases. A total of 35 cases had HBV recurrence after liver transplantation, including 34 cases that were HBsAg positive, one case that was HBsAg negative, and 10 cases that were hepatitis B virus (HBV) DNA positive. The overall HBV recurrence rate was 6.6%. The recurrence rate of HBV was 9.2% and 4.8% in the high- and low-risk HBV DNA positive and negative groups before surgery (P = 0.057). Among the 293 cases diagnosed with HCC before liver transplantation, 30 had hepatitis B recurrence after surgery, with a recurrence rate of 10.2%. The independent related factors for the recurrence of hepatitis B in patients with HCC after liver transplantation were HCC recurrence (HR =181.92, 95%CI 15.99~2 069.96, P < 0.001), a high postoperative dose of mycophenolate mofetil dispersible tablets (MMF) ( HR =5.190, 95%CI 1.289~20.889, P = 0.020), and a high dosage of HBIG (HR = 1.012, 95%CI 1.001~1.023, P = 0.035). Among the 239 cases who were non-HCC before liver transplantation, five cases (recurrence rate of 2.1%) arouse postoperative hepatitis B recurrence. Lamivudine was used in all cases, combined with on-demand HBIG prophylaxis after surgery. There was no hepatitis B recurrence in non-HCC patients who treated with entecavir combined with HBIG after surgery. Conclusion: High-barrier-to-resistance nucleotide analogues combined with long-term HBIG have a good effect on preventing the recurrence of hepatitis B after liver transplantation. The discontinuation of HBIG may be considered at an early stage after administration of a high-barrier-to-resistance nucleotide analogue in low-risk patients. Domestically, the HBV infection rate is high, so further research is still required to explore the timing of HBIG discontinuation for high-risk patients, especially those with HCC.

[Short-term observation of electrical acoustic stimulation in patients with low frequency residual hearing after cochlear implant].

Objective: To analyze the effects of electrical acoustic stimulation (EAS) on speech and tone recognition as well as music perception in children with low-frequency residual hearing (LFRH) after cochlear implant (CI). Methods: A total of twelve Mandarin patients with LFRH who underwent unilateral CI from January 2017 to October 2020 were recruited, including 8 males and 4 females. There were 5 cases of pre-lingual deafness and 7 cases of post-lingual deafness. The median age at implantation was 12 years old (3-62 years). All patients had residual hearing (RH) before surgery, wore hearing aid (HA) timely, had an effective rehabilitation and the duration of use of electrical stimulation was 37.0±16.2 months. On the implanted side, the thresholds of 125 Hz and 250 Hz were less than and equal to 80 dB HL after implantation. A two-month follow-up clinical study was conducted with the EAS devices. The EAS effects were evaluated before, immediately after and 2 months after upgrade, including speech recognition rate, tone recognition and music tests. SPSS 23.0 software was used for statistical analysis. Results: A total of ten patients completed a two-month clinical follow-up and efficiency evaluation. Compared to the electrical stimulation, the recognition rate of spondee word significantly decreased after the immediate use of EAS (71.7±4.3 vs 79.6±3.1, P=0.018). Compared to the electrical stimulation as well as immediate use of EAS, the results of sentence in noise, tone in noise, and SRT of sentence in noise were all significantly improved at 2 months after use of EAS (P<0.05). The pitch discrimination was significantly improved at 2 months after the use of EAS compared with that before the use of EAS (P=0.042). Compared with before (P=0.021) and immediately (P=0.017) use of EAS, the ability of rhythm resolution was significantly improved. There were no significant differences in other test results (P>0.05). Conclusions: The low-frequency acoustic information provided by EAS as well as the electrical-acoustic stimulation mode can provide rich auditory cues of speech perception in noise, tone recognition in noise, and musical discrimination for CI subjects. It can promote the improvement of complex listening ability of CI patients undergoing long-term electrical stimulation in a short time and comprehensively improve their hearing capacities.

Autophagy deficiency promotes lung metastasis of prostate cancer via stabilization of TWIST1

PurposeThe role of autophagy in prostate cancer metastasis remains controversial, and the effects of the autophagy-related gene ATG5 on prostate cancer metastasis are poorly understood. This study aims to explore the effects of ATG5 on prostate cancer metastasis and its molecular mechanism.MethodsThe metastatic characteristics of LNCaP and DU145 cells were assessed by NOD/SCID mouse experiments, western blot, transwell assay, and wound-healing assay. Double membrane autophagic vesicle observation and the adenovirus-expressing mCherry-GFP-LC3B fusion protein were used to assess the autophagic characteristics of LNCaP and DU145 cells. The role of p62 in the accumulation of TWIST1 was confirmed by western blot under different conditions. The lentivirus particles of shATG5, NOD/SCID mice experiments, western blot, transwell assay, and wound-healing assay were used to confirm the role of ATG5 in TWIST1 accumulation and prostate cancer cell metastasis.ResultsWe identified a stabilizing effect of p62 on TWIST1 in the autophagic regulation of EMT and prostate cancer metastasis. The loss of ATG5 in DU145 cells resulted in autophagy deficiency and p62 accumulation, which stabilized TWIST1 and increased the TWIST1 level in prostate cancer cells, and eventually promoted EMT and metastasis. In comparison, LNCaP cells with regular ATG5 expression and autophagy status retained remarkable epithelial cell characteristics and had limited metastatic characteristics. Similar results were also found in wild-type LNCaP cells and LNCaP cells with stable ATG5 interference.ConclusionsOur research revealed ATG5-mediated autophagy as a key mechanism that controls the metastasis of prostate cancer by regulating p62 abundance and TWIST1 stabilization.