[Research on the variation in distortion product otoacoustic emissions in patients with auditory neuropathy during the natural course of the disease].

Objective: The purpose of this study was to investigate the characteristics of distortion product otoacoustic emissions (DPOAE) in patients with auditory neuropathy (AN). The factors affecting DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate of first and last diagnosis in the natural course were analyzed. Methods: The sample was obtained from the Multicenter Study on Clinical Diagnosis and Intervention of AN (registration number: ChiCTR2100050125), and the diagnostic criteria for AN were based on the Chinese Clinical Practice Guidelines of Auditory Neuropathy (version 2022). Patients with bilateral AN who underwent 2 or more DPOAE tests were screened and divided into infant groups (≤3 years old) and non-infant groups (>3 years old) according to the age of detection, and the trend of DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate in the natural course of disease were analyzed, in order to explore the relevant influencing factors. Results: A total of 165 patients (330 ears) with AN were included in the study. The overall DPOAE elicitation rate per ear was 77.0%±29.4% at the initial diagnosis and 65.1%±35.2% at the final diagnosis, with a reduction observed in the elicitation rate of 171 ears (51.82%). In the infant group, there were 49 cases (98 ears), including 28 males and 21 females, whose found age ranged from 0 to 3 years old, with a median age of 0.7 years. DPOAE elicitation rate per ear was 57.9%±35.5% in the initial diagnosis, and 32.4%±32.1% in the final diagnosis, with a reduction observed in the elicitation rate of 69 ears (70.41%). In the non-infant group, there were 116 cases (232 ears), including 59 males and 57 females, ranging in found age from 3.9 to 40 years old, with a median age of 14 years old. DPOAE elicitation rate per ear was 84.6%±23.4% in the initial diagnosis, and 78.3%±27.1% in the final diagnosis, with a reduction observed in the elicitation rate of 102 ears (43.97%). Age was found to be correlated with DPOAE changes by multicategorical unordered logistic regression analysis (B=-0.224, OR=0.799, P<0.001). Conclusions: The elicitation rate of DPOAE in AN patients decreases or even disappears with increasing disease duration; The rate of DPOAE extraction is found to be lower in infant patients with auditory neuropathy (AN) compared to non-infant AN patients. Additionally, it is observed that the decrease in DPOAE extraction rate is more pronounced in infant AN patients as the disease progressed, as compared to non-infant AN patients. DPOAE and cochlear microphonic potentials should be fully combined for accurate diagnosis, and regular follow-up should be conducted to understand the natural course of the disease and give personalized guidance and assistance.

[Study on the clinical characteristics of auditory neuropathy patients with normal pure tone average or mild hearing loss].

Objective: The purpose of this study was to analyze the clinical characteristics of auditory neuropathy (AN) patients with normal hearing or mild hearing loss. Methods: Data from Multicenter Study on Clinical Diagnosis and Intervention of Acoustic Neuropathy (registration number: ChiCTR2100050125). According to the Chinese clinical practice guideline of auditory neuropathy (version 2022), these patients divided into two groups: the normal hearing group (PTA Normal, PTAN group, the average hearing threshold<20 dB HL) and the mild hearing loss group (PTA Mild hearing loss, PTAM group, the average hearing threshold between 20-35 dBHL). The audiology characteristics, clinical features, and follow-up were analyzed. Data analysis was conducted using GraphPad Prism 8 and SPSS 20.0 software. Results: A total of 75 AN with normal hearing or mild hearing loss were included in this study. The PTAN group consisted of 19 patients (38 ears), including 12 males and 7 females. The average onset age was (16.9±4.5) years old, while the test age was (22.1±5.8) years old for PTAN group. The PTAM group consisted of 56 patients (112 ears), including 29 males and 27 females. The average onset age was (16.2±7.9) years old, while the test age was (23.9±9.0) yeas old for PTAM group. The average hearing threshold of low frequency (0.125-0.5 kHz) was significantly decreased. ABR disappeared in 86.00% (126/150) of the patients. The speech recognition rate was 71.80±22.44% in the PTAN group and 58.08±29.28% in the PTAM group.-SP/AP was 0.98±0.47 in the PTAN and 1.07±0.63 in PTAM group; 40 (53.33%) patients had tinnitus. 29 patients (58 ears) were followed up, including 10 patients (20 ears) in the PTAN group and 19 patients (38 ears) in the PTAM group. There was no significant change in hearing threshold in short-term follow-up (<3 years). With the extension of the disease duration (>3 years), the PTAN group tended to decrease at low frequency, and the PTAM group decreased at high frequency first. The hearing threshold at 0.25 kHz in the PTAN group and 4 kHz in the PTAM group decreased significantly. Conclusions: AN patients with normal hearing or mild hearing loss exhibit abnormal results in audiological examination results, including ABR, electrocochleography and speech discrimination score. A combination of audiological tests should be used to make the diagnosis of AN. With the progression of the disease, AN with normal hearing or mild hearing loss tends to decrease.

Prognostic role of the systemic immune-inflammation index and pan-immune inflammation value for outcomes of breast cancer: a systematic review and meta-analysis.

OBJECTIVE: This review examined the literature for evidence on the prognostic ability of systemic immune-inflammation index (SII) and pan-immune inflammation value (PIV) for predicting overall survival (OS) and disease-free survival (DFS) in breast cancer patients. MATERIALS AND METHODS: PubMed, Embase, Scopus, and Web of Science were searched with Google Scholar for gray literature. All types of studies reporting the association between SII or PIV and OS or DFS of breast cancer were eligible. RESULTS: 13 studies on SII and 4 studies on PIV were included. Meta-analysis showed that a high SII was a significant predictor of OS (HR: 1.97 95% CI: 1.54, 2.52 I2=76%) and DFS (HR: 2.07 95% CI: 1.50, 2.86 I2=79%) in breast cancer patients. These results did not change on sensitivity analysis and were more or less stable on multiple subgroup analyses. Pooled analysis showed that high PIV was also a significant predictor of poor OS (HR: 2.63 95% CI: 1.46, 4.74 I2=71%) and DFS (HR: 1.64 95% CI: 1.23, 2.17 I2=0%) in breast cancer patients. CONCLUSIONS: High SII and PIV can predict poor OS and DFS in breast cancer patients. High heterogeneity and the observational nature of data are important limitations of the review. Further studies are needed specifically on PIV to increase the strength of the evidence.

Itaconic acid and dimethyl itaconate exert antibacterial activity in carbon-enriched environments through the TCA cycle.

Itaconic acid (IA), a metabolite generated by the tricarboxylic acid (TCA) cycle in eukaryotic immune cells, and its derivative dimethyl itaconate (DI) exert antibacterial functions in intracellular environments. Previous studies suggested that IA and DI only inhibit bacterial growth in carbon-limited environments; however, whether IA and DI maintain antibacterial activity in carbon-enriched environments remains unknown. Here, IA and DI inhibited the bacteria with minimum inhibitory concentrations of 24.02 mM and 39.52 mM, respectively, in a carbon-enriched environment. The reduced bacterial pathogenicity was reflected in cell membrane integrity, motility, biofilm formation, AI-2/luxS, and virulence. Mechanistically, succinate dehydrogenase (SDH) activity and fumaric acid levels decreased in the IA and DI treatments, while isocitrate lyase (ICL) activity was upregulated. Inhibited TCA circulation was also observed through untargeted metabolomics. In addition, energy-related aspartate metabolism and lysine degradation were suppressed. In summary, these results indicated that IA and DI reduced bacterial pathogenicity while exerting antibacterial functions by inhibiting TCA circulation. This study enriches knowledge on the inhibition of bacteria by IA and DI in a carbon-mixed environment, suggesting an alternative method for treating bacterial infections by immune metabolites.

Probiotic characterization and comparison of broiler-derived lactobacillus strains based on technique for order preference by similarity to ideal solution analysis.

A total of 10 lactobacillus strains were isolated from broiler chickens and their probiotic properties including tolerance to gastrointestinal fluids and heat treatment, antimicrobial activity, adhesion capacity to intestinal cells, surface hydrophobicity, autoaggregation, antioxidative activity, and immunomodulatory effects on chicken macrophages were evaluated. The Limosilactobacillus reuteri (LR) was the most frequently isolated species, followed by Lactobacillus johnsonii (LJ) and Ligilactobacillus salivarius (LS). All isolates showed good resistance to simulated gastrointestinal conditions and antimicrobial activity against 4 indicator strains including Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Proteus mirabilis LR 21 exhibited excellent performances on autoaggregation, hydrophobicity and adhesion capacity to Caco-2 intestinal cells. In the meantime, this strain also possessed considerable tolerance to heat treatment, which indicated great potential to be used in the feed industry. However, LJ 20 strain had the highest free radical scavenging activity compared with the other strains. Furthermore, qRT-PCR results revealed that all isolated strains significantly increased the transcriptional levels of proinflammatory genes and tended to induce the M1-type polarization on HD11 macrophages. Particularly, the technique for order preference by similarity to ideal solution (TOPSIS) was adopted in our study to compare and select the most promising probiotic candidate based on in vitro evaluation tests.

Effects of early post-hatch feeding on the growth performance, hormone secretion, intestinal morphology, and intestinal microbiota structure in broilers.

This study aimed to investigate the effects of time access to post-hatch feeding on the growth performance, hormone secretion, intestinal morphology, and intestinal microbiota structure of broilers. A total of 900 broilers were randomly allocated to 3 treatment groups, with 6 replicates of 50 broilers each. The 3 treatments were: immediate feeding (Group 2 h), delayed access to feed for 24 h (Group 24 h), and delayed access to feed for 48 h (Group 48 h). The experiment lasted for 50 d. Results revealed that Group 2 h had a higher average daily gain (ADG) and average daily feed intake (ADFI) as well as a lower feed-to-gain ratio (F/G) than Group 48 h during the starter period (P < 0.05). Compared with Group 48 h, broilers in Group 2 h exhibited significantly elevated villus height (VH) and villus height to crypt depth ratio (VH: CD) in the duodenum, increased Occludin, and Claudin-1 mRNA expression in the jejunum but decreased crypt depth (CD) in the duodenum at 50 d (P < 0.05). Meanwhile, broilers in Groups 2 h and 24 h had increased glycogen (Gn) and protein (Pro) levels in breast muscle and TG levels in the liver, as well as a higher concentration of serum T3, T4, and IGF-1 compared with Group 48 h at 21 d (P < 0.05). Besides, intestinal microbiota consisted primarily of Firmicutes, Bacteroidetes, and Proteobacteria at the phylum level at 21 d and 50 d; at the genus level, broilers in Group 2 h displayed significantly reduced abundance of Escherichia at 21 d and Bacteroides at 50 d compared with Group 48 h (P < 0.05). Collectively, these findings signal that early post-hatch feeding measures, especially at 21 d, improve hormone secretion, intestinal morphology, and the growth performance of broilers by enhancing intestinal health and modulating the intestinal microbiota.

[Identification of a novel mutation of SOX10 gene and analysis of the phenotype].

Objective: To explore the clinical features and pathogenic mechanisms of a special syndrome with congenital sensorineural hearing loss, albinism, heterochromia iridis, nystagmus and myelin dysplasia. Methods: Detailed medical history, systematic audiology tests, ophthalmic and neurological examinations were carried out to analyze the clinical features of the child, and further molecular genetic tests including chromosome karyotype analysis, and deafness gene screening were conducted. Results: A new de novo heterozygous mutation (c.336G>T/p.Met112Ile) was detected in the child, while both his parents were demonstrated to be wild-type and symptom free. The analysis of clinical features indicated the diagnosis of PCW syndrome. Conclusion: This study identified a new mutation of SOX10 gene, which enriched the mutation spectrum of this gene. And the analysis of clinical characteristics of this patient also expanded the phenotype of this gene. This study provided a reference for clinical diagnosis and genetic diagnosis of PCW syndrome.

MiR-185-3p downregulates advanced glycosylation end product receptor expression and improves renal function in diabetic nephropathy mice.

OBJECTIVE: To investigate the effects of the downregulation of AGER by miRNA-185-3p on renal function in diabetic nephropathy (DN) mice. MATERIALS AND METHODS: Mice were divided into normal, model, NC, miR-185-3p mimic, si-AGER, and miR-185-3p mimic + si-AGER groups. Eight weeks following the establishment of the model, various indicators were assessed. RESULTS: Compared to control groups, miR-185-3p expression, body weight, superoxide dismutase (SOD) content, catalase (CAT) content, proliferation, S-phase ratios, and proliferating cell nuclear antigen (PCNA) expression were significantly lower in all experimental groups, whilst AGER expression, water intake, food intake, urine volume, urine protein content, serum creatinine (Scr), Blood Urea Nitrogen (BUN), MDA content, G0/G1 status, and rates of apoptosis were significantly higher (all p<0.05). Compared to the model group, miR-185-3p mimics, si-AGER, and miR-185-3p mimic + si-AGER groups had a significantly higher SOD content, CAT content, proliferation, S phase ratios, PCNA expression and lower AGER expression, water intake, food intake, urine output, urine protein, Scr, BUN, MDA content, G0/G1 ratios, and apoptosis rates (all p<0.05). In addition, the effects of the miR-185-3p mimics + si-AGER were superior to miR-185-3p mimics and si-AGER monotherapy groups (both p<0.05). CONCLUSIONS: MiR-185-3p inhibits AGER, downregulates AGER expression, and improves renal function in DN mice.

[A comparative study of retinal nerve fiber layer thickness in AIDS patients with different fundus diseases].

Objective: To investigate the characteristics of retinal nerve fiber layer (RNFL) thickness in AIDS patients with normal fundus, HIV-related microvascular retinopathy (MVR), and cytomegalovirus retinitis (CMVR). Methods: In this cross-sectional study, 111 patients were diagnosed with AIDS from 2012 to 2017 by infectious disease physicians in Beijing You'an Hospital. There were 105 males and 6 females, aged 20-65 years. According to the results of ophthalmic examination, the patients were divided into three groups: 31 patients in the active-stage CMVR group, 47 patients in the MVR group, and 33 patients with normal fundus in the control group. RNFL thickness was measured by optical coherence tomography in all patients. At the same time, visual acuity, intraocular pressure, and fundus were examined, and AIDS-related systemic examination (CD4(+) T lymphocyte count, HAART treatment status, and blood cytomegalovirus DNA level) was performed. The measurement data were compared by t-test, variance analysis or rank sum test. The counting data were compared by chi square test or Fisher exact probability method. Results: In the control group, the thickness of RNFL in the superior quadrant in the left and right eyes was 145 (79, 231) µm and 142 (46, 179) µm, respectively; the difference was statistically significant (Z=-2.481, P=0.013). The RNFL thickness of the diseased and healthy eyes in the MVR group was 116 (91, 138) µm and 122 (82, 192) µm, respectively, with no significant difference (Z=-0.861, P=0.389); the best corrected visual acuity was 0.0 (0.0, 0.2) and 0.0 (0.0, 0.2), respectively, with no significant difference (Z=-0.378, P=0.705). In the CMVR group, the best corrected visual acuity of the diseased and healthy eyes was (0.23±0.48) and (0.02±0.82), respectively, and the difference was statistically significant (t=-2.944, P=0.003); the RNFL thickness was 133 (61, 219) µm and 121 (69, 146), respectively, in the whole optic disc, with statistically significant difference (Z=-2.385, P=0.017), 104 (41, 374) µm and 82 (55, 121) µm, respectively, in the nasal quadrant, and 99 (14, 173) µm and 72 (36, 111) µm, respectively, in the temporal quadrant, with statistically significant difference (Z=-2.045, -2.543; P=0.041, 0.011). The RNFL thickness in the CMVR group, the MVR group, and the control group was 149 (61, 350) µm, 126 (71, 304) µm, and 113 (87, 149) µm, respectively, with statistically significant difference (H=20.908, P=0.000). Conclusions: The fundus of AIDS patients had different characteristics on optical coherence tomography. In active CMVR patients, the thickness of RNFL was generally thickened. In MVR patients, the average thickness of RNFL was thicker than that in the normal control group.(Chin J Ophthalmol, 2020, 56:258-265).

[The consistency of ultra-wide-field retinal imaging and the Superfield lens for fundus screening in HIV/AIDS patients].

Objective: To screen the retinopathy in HIV/AIDS patients with both non-mydriatic ultra-wide-field (UWF) retinal imaging and mydriatic fundus examinations with the Superfield lens and a slit lamp biomicroscope, and to evaluate the consistency of two methods and provide reference for future clinical screening work and even technological innovation (such as telemedicine screening and artificial intelligence). Methods: Cross sectional study. One hundred and fifty-eight eyes of 80 HIV-positive patients from the Ophthalmology Department of Beijing Youan Hospital were enrolled in this prospective observational study. All patients underwent comprehensive ophthalmological examination. A single image was obtained from each eye using the UWF fundus imaging system (Daytona, Optos, Dunfermline, UK), and then a dilated fundal examination with the Superfield lens was conducted by another expert. The possible type and location of the lesion with these two methods was recorded respectively. The consistency was compared using the detection rate and Kappa value. Results: Fifty-two patients (65%) had fundus changes, and 28 patients (35%) were normal. Seventy-nine eyes (50%) were normal and 79 eyes (50%) had fundus lesions. Sixty-one eyes (77.2%) had HIV-related fundus lesions, while 18 eyes (22.8%) had non-HIV-related fundus lesions. Fifty-two eyes (65.8%) suffered posterior or posterior involving lesions, and 27 eyes (34.2%) suffered isolated peripheral lesions. The detection rate of UWF retinal imaging and slit lamp biomicroscopy with the Superfield lens was 17.7% (28/158) and 18.4% (29/158) (P=1.000>0.05) for HIV-related microvascular retinopathy, 8.2% and 8.2% (13/158) (χ(2)=158.00, P=1.000) for cytomegalovirus retinitis (CMVR), 36.1% and 36.1% (57/158) (χ(2)=71.066, P=1.000) for HIV-related fundus lesions, 41.8% (66/158) and 47.5% (75/158) (χ(2)=63.514, P=0.136) for fundus lesions, 33.5% (53/158) and 31.0% (49/158) (χ(2)=108.268, P=0.388) for posterior/posterior involving lesions, and 6.4% (10/158) and 16.5% (26/158) (χ(2)=42.001, P=0.000) for isolated peripheral lesions, respectively. In general, the consistency of these two methods was moderate in detecting fundus lesions (Kappa=0.630), HIV-related fundus lesions (Kappa=0.671), HIV-related microvascular retinopathy (Kappa=0.551), and isolated peripheral lesions (Kappa=0.450). According to the fundus location, the two methods showed high consistency in the detection of posterior/posterior involving lesions (Kappa=0.826>0.75) and perfect consistency for CMVR (Kappa=1.0). Conclusions: The UWF retinal imaging system and the Superfield lens showed reasonable consistency in fundus screening in HIV/AIDS patients, especially for CMVR, or lesions in the posterior pole. (Chin J Ophthalmol, 2019, 55:763-768).

[The ability of gap detection in patients with acoustic neuroma].

Objective:We aimed to provide a basis for the clinical study of acoustic neuroma through investigating the ability of temporal gap detection in acoustic neuroma patients and comparing the abilities with those in people with normal and impaired hearing. Method:Twenty-two patients with confirmed acoustic neuroma, 30 normal hearing patients and 16 patients with sensorineural hearing loss were enrolled in this study, and the interval threshold for awareness of each group was tested. Result:The mean temporal gap detection test（TGDT） threshold of the normal hearing group was （3.56±0.82） ms; the sensorineural hearing loss group's was （3.91±1.46） ms; TGDT threshold of healthy side of acoustic neuroma patients was （4.01±1.86） ms; TGDT threshold of the impaired side of acoustic neuroma patients was （9.48±9.46）ms. After statistical analysis, we found that excepting for the test of phonetically balanced maximum （PBmax） and TGDT, other results in the sensorineural hearing loss group and normal hearing group is of no statistical difference. The difference between the affected side of the acoustic neuroma group and the other groups was statistically significant （P<0.05）. There was no linear correlation between the value of TGDT threshold and PBmax （P> 0.05）. TGDT value of normal people has no significant difference among people of different genders and ears of different individuals. Conclusion:The TGDT of the healthy ear of the patients with acoustic neuroma is not affected, and there is no significant change compared with normal people. The TGDT test has a good consistency with the PBmax results. The time interval response ability of the affected ear of the acoustic neuroma is significantly weaker than that of the normal person. The combined test of PBmax and TGDT will contribute to the diagnosis of retrocochlear disease.

[Classification of sudden deafness prognosis based on deep learning method].

Objective:This study aimed to develop predictive models for sudden sensorineural hearing loss through deep belief network (DBN) and explore whether the model performances differ when adopting different outcome criteria. Method: 228 potential predictors involving the clinical characteristics, audio logical data, and serological parameters out of 1 220 hospitalized SSHL patients who were admitted from June 2008 to December 2015 were analyzed retrospectively. The hearing data of sudden deafness were classified into two or four categories based on Chinese criteria and Siegel criteria, which were used to develop the DBN models. The area under the receiver operating characteristic curve (ROC-AUC) and accuracy were used to compare the predictive performance of different models. Result: The DBN model developed for predicting the dichotomized outcomes had better performance than that of the fourcategory outcomes. When the iteration number reached 500 times, DBN model constructed for prediction of dichotomized outcomes based on Siegel's criteria had demonstrated the best performance with an accuracy of 76.25% and an AUC of 0.81. According to indices from first layer weights, DBN gave a rank of top 10 sensitive features for hearing outcome prediction focusing on indicators regarding coagulation, demographics and pre-treatment hearing levels independent of the outcome assessment criteria. Conclusion: DBN provides a robust outcome prediction ability in SSHL datasets with rich and complex variables, especially when utilized to predict dichotomized outcomes based on the Siegel criteria. In addition, this advanced deep learning technique can automatically extract valuable predictors, which is consistent with those that had been verified in previous studies by traditional statistical methods. This study provides further evidence for extending the use of DBN algorithm to the field of developing prediction or classification models for other otological diseases in the future..

Fulvestrant inhibits the glycolysis of prolactinoma GH3 cells by downregulating IRE1/XBP1 signaling pathway.

OBJECTIVE: We aimed to evaluate the effects of fulvestrant on the glycolysis of prolactinoma GH3 cells, and reveal the potential regulatory mechanisms. MATERIALS AND METHODS: Prolactinoma cell line GH3 was treated with different concentrations of fulvestrant (0, 0.12, 0.25, 0.5 and 1 ng/ml) for 4 h. siRNAs XBP1s and XBP1u were constructed to treat GH3 cells. The expression levels of XBP1s, XBP1u, IRE1, PKM2 and GRP78 of GH3 cells were detected by Western blot. Meanwhile, the glycolytic activity of GH3 cells, including the glucose uptake, ATP/ADP, and lactate production were detected. RESULTS: The expression levels of XBP1s and XBP1u were significantly inhibited by fulvestrant in a dose-dependent manner. The glucose uptake, ATP/ADP and lactate production of GH3 cells were significantly inhibited by fulvestrant as well as siRNA XBP1s and XBP1u (p < 0.05). Western blot analysis suggested that the expression levels of IRE1, PKM2 and GRP78 were significantly decreased in GH3 cells treated by fulvestrant as well as siRNA XBP1s and XBP1u, compared with those in normal control (p < 0.05). CONCLUSIONS: Fulvestrant could inhibit the glycolysis of GH3 cells by downregulating IRE1/XBP1 signaling pathway, and this process was closely related with the downregulation of PKM2.

Construction of a recombinant baculovirus expressing swine hepatitis E Virus ORF2 and preliminary research on its immune effect.

In the swine hepatitis E virus (HEV), open reading frame 2 (ORF2) is rich in antigenic determinants and neutralizing epitopes that could induce immune protection. We chose the Bac-to-Bac® Baculovirus Expression System to express fragments containing the critical neutralizing antigenic sites within the HEV ORF2 protein of pigs to obtain a recombinant baculovirus. The fragment of swine HEV ORF2 region (1198-1881bp) was cloned into vector pFastBacTM. A recombinant baculovirus, rBacmid-ORF2, was obtained after transposition and transfection. The molecular mass of the recombinant protein was 26 kDa. Mice were immunized by the intraperitoneal and oral routes with cell lysates of recombinant baculovirus rBacmid-ORF2. Serum and feces of the mice were collected separately at 0, 14, 28, and 42 d after immunization and the antibody levels of IgG and secretory IgA against swine HEV were determined using an enzyme-linked immunosorbent assay. The results suggested that rBacmid-ORF2 induced antibodies of the humoral and mucosal immune responses in mice and that the oral route was significantly superior to the intraperitoneal route. This is the first study to demonstrate that that recombinant baculovirus swine HEV ORF2 could induce humoral and mucosal immune responses in mice.

[Cytokine analysis of aqueous humor in AIDS patients].

Objective: To explore the Cytokine of aqueous humor in AIDS patients with different eye diseases. Methods: A case-control study including 38 patients who was diagnosed as acquired immunodeficiency syndrome(AIDS) at Infectious Center and Department of Ophthalmology in Beijing You'an Hospital, Capital Medical University. And 16 cases of 38 patients were cytomegalovirus retinitis (CMVR), 14 cases were HIV-related retinal disease, and 8 cases presented as normal. A series of tests were performed including vision acuity check, intraocular pressure, fundus photography, blood cell count of CD4+ T lymphocyte and the content of cytokines in aqueous humor by Luminex 200(TM) liquid chip analyzer. Intraocular pressure was analyzed by one-way ANOVA, visual acuity, CD4(+) T lymphocyte count and cytokines were analyzed by Kruskal-Wallis test, the differences between the two groups were compared by Mann-Whitney U test corrected with Bonferroni. Results: Of the 38 AIDS patients [mean age (33.7±10.0) year], 37 were males and 1 was female. The mean visual acuity of 38 patients is logMAR 1.00(0.000, 1.000). The difference of visual acuity among three groups was statistically significant (χ(2)=9.963, P=0.007). The visual acuity in CMVR group was significantly higher than that in HIV-related retinal disease group and AIDS-normal eye group. There was no statistically significant difference of intraocular pressure among three groups (F=0.830, P<0.05). The mean CD4+ T lymphocyte count was 58(4, 550)/µl and the difference was statistically significant among three groups(χ(2)=6.106, P=0.047). The CD4+ T lymphocyte count in AIDS-normal eye group was significantly higher than that in CMVR group and HIV-related retinal disease group. There was no statistically significant difference in CD4+ T lymphocyte count between HIV-related retinal disease group and CMVR group. The following cytokines in CMVR group were significantly higher than the other two groups with statistically significant differences: MIP-1b, IL-6, TNF-α, VEGF, IL-8, MCP-1, IP-10. Conclusions: In patients who was diagnosed as AIDS, cytomegalovirus retinitis would damage vision acuity seriously. The elevated cytokines' level in aqueous humor such as MIP-1b, IL-6, TNF-α, VEGF, IL-8, MCP-1, IP-10, compared with HIV-related retinal disease and AIDS-normal eye cases, may be related to the activity of Th1 cell and monocyte-macrophages system including chemokines, inflammatory factors, and vascular endothelial factors. (Chin J Ophthalmol, 2017, 53: 746-752).

High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder.

Auditory neuropathy spectrum disorder (ANSD) is one of the most common diseases leading to hearing and speech communication barriers in infants and young children. The OTOF gene is the first gene identified for autosomal recessive non-syndromic ANSD, and patients with OTOF mutations have shown marked improvement of auditory functions from the cochlear implantation, but the true involvement of OTOF mutations in Chinese ANSD patients is still unknown which precludes the effective management of this disease. Here, we investigated the contribution of OTOF mutations to congenital ANSD patients in China. In all, 37 infants and young Children with ANSD were screened for all the exons of OTOF gene, of them 34 patients had no neonatal risk factors who were considered as congenital ANSD. The clinical manifestation and audiometric features were also investigated and compared in patients with and without OTOF mutations. In all, 14 of these subjects were shown to carry two or three mutant alleles of OTOF with the high frequency of 41.2% in congenital ANSD patients. In total, 15 novel pathogenic mutations and 10 reported mutations were identified. Our results confirmed that mutations in OTOF gene were a major cause of congenital ANSD in China. Identification of OTOF mutations can facilitate diagnosis, clinical intervention and counseling for congenital ANSD.

Nicotinamide Facilitates Mesenchymal Stem Cell Differentiation Into Insulin-Producing Cells and Homing to Pancreas in Diabetic Mice.

OBJECTIVE: This study aimed to investigate the effect of nicotinamide on differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) in vivo in mice and on homing of MSCs to the pancreas after being intravenously infused. METHODS: Streptozotocin (STZ)-induced diabetic Balb/c mice received syngeneic transplantation of carboxyfluorescein succinimidyl ester (CFSE)-labeled bone marrow MSCs into the liver or tail vein. Nicotinamide was intraperitoneally injected into mice at a dose of 500 mg/kg body weight per day after STZ administration. Mice who received saline solution injection instead of nicotinamide were involved as control. RESULTS: Mice that received nicotinamide injection showed lower blood glucose, higher serum insulin, and more improved glucose tolerance compared with the control group. Immunohistochemistry analysis showed that higher levels of insulin staining and higher percentages of CFSE+/insulin+ cells were observed in the liver and pancreas sections of mice who received nicotinamide injection compared with the control group. The percentage of CFSE+/insulin+ cells was positively correlated with serum insulin level. Real-time polymerase chain reaction results showed that the implanted MSCs in mice who received nicotinamide injection exhibited higher levels of ß-cell-related gene expression than the control group. More CFSE-labeled MSCs appeared in the pancreas of mice who received nicotinamide injection compared with the control group after being intravenously infused, whereas the amount of CFSE-labeled MSCs in the liver was not affected by nicotinamide injection. CONCLUSIONS: Nicotinamide facilitates MSCs differentiating into functional IPCs in vivo in diabetic mice and promotes intravenously infused MSCs to home to the pancreas.

First Report of Ageratum yellow vein virus Causing Tobacco Leaf Curl Disease in Fujian Province, China.

A leaf curling disease was observed on 7% of tobacco plants during December 2005 in research plots in the Cangshan District of Fuzhou, Fujian, China. Tobacco plants were infested with Bemisia tabaci, suggesting begomovirus etiology. To identify possible begomoviruses, total DNA was extracted from four symptomatic leaf samples (F1, F2, F3, and F4). The degenerate primers PA and PB were used to amplify part of the intergenic region and AV2 gene of DNA-A-like molecules (3). A 500-bp DNA fragment was amplified by PCR from all four samples. The PCR products were cloned and sequenced (GenBank Accession Nos. EF531601-EF531603 and EF527823). Alignment of the 500-bp sequences for the four isolates indicated that they shared 98.5 to 99.6% nt identity, suggesting that the plants were all infected by the same virus. Overlapping primers TV-Full-F (5'-GGATCCTCTTTTGAACGAGTTTCC-3') and TV-Full-R (5'-GGATCCCACATGTTTAAAATAATAC-3') were then designed to amplify the full-length DNA-A from sample F2. The sequence was 2,754 nucleotides long (GenBank Accession No. EF527823). A comparison with other begomoviruses indicated the F2 DNA-A had the highest nucleotide sequence identity (95.7%) with Ageratum yellow vein virus (AYVV; GenBank Accession No. X74516) from Singapore. To further test whether DNAß was associated with the four viral isolates, a universal DNAß primer pair (beta 01 and beta 02) was used (4). An amplicon of approximately 1.3 kb was obtained from all samples. The DNAß molecule from F2 was then cloned and sequenced. F2 DNAß was 1,345 nucleotides long (GenBank Accession No. EF527824), sharing the highest nucleotide sequence identity with the DNAß of Tomato leaf curl virus (97.2%) from Taiwan (GenBank Accession No. AJ542495) and AYVV (88.8%) from Singapore (GenBank Accession No. AJ252072). The disease agent was transmitted to Nicotiana tabacum, N. glutinosa, Ageratum conyzoides, Oxalis corymbosa, and Phyllanthus urinaria plants by whiteflies (B. tabaci) when field infected virus isolate F2 was used as inoculum. In N. tabacum and N. glutinosa plants, yellow vein symptoms were initially observed in young leaves. However, these symptoms disappeared later during infection and vein swelling and downward leaf curling symptoms in N. tabacum and vein swelling and upward leaf curling in N. glutinosa were observed. In A. conyzoides, O. corymbosa, and P. urinaria plants, typical yellow vein symptoms were observed. The presence of the virus and DNAß in symptomatic plants was verified by PCR with primer pairs TV-Full-F/TV-Full-R and beta 01/beta 02, respectively. The above sequence and whitefly transmission results confirmed that the tobacco samples were infected by AYVV. In China, Tobacco leaf curl Yunnan virus, Tobacco curly shoot virus, and Tomato yellow leaf curl China virus were reported to be associated with tobacco leaf curl disease (1,3). To our knowledge, this is the first report of AYVV infecting tobacco in China. A. conyzoides is a widely distributed weed in south China and AYVV was reported in A. conyzoides in Hainan Island, China (2). Therefore, this virus may pose a serious threat to tobacco production in south China. References: (1) Z. Li et al. Phytopathology 95:902, 2005. (2) Q. Xiong et al. Phytopathology 97:405, 2007. (3) X. Zhou et al. Arch. Virol. 146:1599, 2001. (4) X. Zhou et al. J. Gen. Virol. 84:237, 2003.