[Clinical characteristics of 114 patients with iridocorneal endothelial syndrome].

Objective: To investigate the clinical features in patients with iridocorneal endothelial (ICE) syndrome. Methods: A retrospective case series study. Data of clinical manifestations of patients with ICE syndrome including clinical subtypes, presenting visual acuity, clinical features and secondary glaucoma were collected from January 2014 to May 2020 in the Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University. The Wald's Chi-square test of generalized estimating equations was performed to analyze the differences in three clinical subtypes. Results: A total of 127 eyes of 114 subjects (64 females and 50 males) were included. Mean±SD age at presentation was (49±13) years. There were 53 patients (46.5%) with Chandler's syndrome (CS), 36 patients (31.6%) with progressive iris atrophy (PIA), 24 patients (21.0%) with Cogan-Reese syndrome (CRS) and one patient (0.9%) with an undetermined subtype. And 101 patients (88.6%) had uniocular ICE syndrome. Approximately 81.7% (49/60), 56.1% (23/41) and 41.7% (10/24) of eyes presented visual acuity <0.3 in patients with CS, PIA and CRS, respectively. Corneal edema was most common in CS (52.5%, 32/61), followed by PIA (29.3%, 12/41) and CRS (20.8%, 5/24). Corectopia was found in 95.8% (23/24) of eyes with CRS, 95.1% (39/41) of eyes with PIA and 78.7% (48/61) of eyes with CS. Polycoria was observed in 29.3% (12/41) of eyes with PIA, 3.3% (2/61) of eyes with CS and 8.3% (2/24) of eyes with CRS. Ectropion uvea was most common in CRS (54.2%, 13/24), followed by 16.4% (10/61) in CS and 12.2% (5/41) in PIA. Glaucoma was found in 94 eyes (74.0%, 94/127). Among them, 60.7% (37/61) of CS, 80.5% (33/41) of PIA and 95.8% (23/24) of CRS had secondary glaucoma. The difference of presenting visual acuity, corneal edema, corectopia, polycoria, ectropion uveae and secondary glaucoma in three clinical subtypes all had statistical significance (Wald χ2=13.87, 10.77, 965.78, 11.45, 15.00, 222.04; all P<0.05). And 86.2% of eyes (81/94) had glaucoma surgeries and 41 eyes (43.6%, 41/94) had the intraocular pressure well controlled with various interventions. Conclusions: ICE syndrome is mostly uniocular and more common in middle-aged patients. CS is the most common clinical subtype with poor presenting visual acuity. About 3/4 of eyes have secondary glaucoma, and the majority of them require surgical interventions, but prognoses are discouraging.

[Programmed cell death protein 1 and its ligands regulate immune balance in allergic rhinitis].

Objective: To explore the expression and significance in regulating immune balance of programmed cell death protein 1 (PD-1) and its ligands PD-L1, PD-L2 in allergic rhinitis (AR). Methods: Eighty-two patients who received outpatient treatment due to high nasal reaction symptoms or were hospitalized due to nasal septum deviation and underwent nasal septum correction surgery in Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from May 2018 to May 2019 were enrolled, including 42 males and 40 females, with the age ranging from 14 to 38 years old. Blood, inferior turbinate nasal mucosal tissue and relevant clinical data were collected. Patients were divided into AR group and control group due to clinical manifestation, skin prick test and detection of specific IgE (sIgE) in serum. Immunohistochemistry was used to detect the expression of PD-1 and its ligands in nasal mucosa of the two groups. Flow cytometry was used to detect the proportions of PD-1(+)CD4(+)T cells, PD-L1(+) myeloid dendritic cells (mDCs), PD-L2(+)mDCs and Th2 cells in peripheral blood of the two groups. The expression levels of total IgE, sPD-1, sPD-L1 and sPD-L2 in serum of the two groups were detected by ELISA. The measurement data of normal distribution or normal distribution after the logarithm conversion to Ln were compared by t test. Pearson correlation or Spearman correlation was used to analyze the correlation among the indicators. P<0.05 was considered statistically significant. Results: The expression of PD-1 and its ligands on the surface of immune cells in the nasal mucosa of the AR group was significantly higher than that of the control group. The ratio of PD-1(+)CD4(+)T cells, PD-L1(+)mDCs and Th2 cells in peripheral blood of AR group was significantly higher than that of the control group ((15.24±6.45)% vs (8.71±5.33)%, (8.79±2.01)% vs (5.74±2.90)%, (7.89±1.95)% vs (2.52±1.34)%, all P<0.05). There was no significant difference in the ratio of PD-L2(+)mDCs between the two groups. Correlation analysis found that the proportion of PD-1(+)CD4(+) T cells was positively correlated with the Visual Analogue Scale (VAS) score of AR, total IgE concentration and the serum sIgE concentration (r value was 0.501, 0.541, 0.608, respectively, all P<0.05). The proportion of PD-L1(+)mDCs was positively correlated with the VAS score of AR and the serum sIgE concentration (r value was 0.604, 0.563, respectively, all P<0.05). The proportion of Th2 cells in peripheral blood was positively correlated with the proportion of PD-L1(+)mDCs and PD-1(+)CD4(+)T cells (r value was 0.538, 0.623, respectively, all P<0.05). Serum total IgE, sPD-1 and sPD-L1 in the AR group were significantly higher than those in the control group ((6.34±1.38) ng/ml vs (4.89±1.10) ng/ml, (4.40±1.01) pg/ml vs (3.79±1.21) pg/ml, (3.88±0.25) pg/ml vs (3.57±0.23) pg/ml, all P<0.05), and there was no significant difference in sPD-L2 levels between the two groups. Correlation analysis showed that sPD-L1 was positively correlated with total IgE and sIgE concentration (r values was 0.32, 0.45, respectively, all P<0.05). Conclusions: PD-1 and PD-L1 are highly expressed on the surface of immune cells in peripheral blood and nasal mucosa of AR patients, and sPD-1 and sPD-L1 expression levels in peripheral blood of AR patients are increased. The PD-1/PD-L1 signaling pathway promote AR inflammatory response by inducing Th2 type immune response.

[Advances of studies on the occurrence of the upper respiratory disease correlative with immunity and tobacco].

SummaryTobacco smoke exposure has obvious and complex effects on the immune system of the human upper respiratory tract, including pro-inflammatory and anti-immune effects. Exposure to tobacco smoke is closely related to the occurrence and development of allergic rhinitis, the common rhinitis and sinusitis. The innate immune system is influenced by tobacco smoking through its effects on the respiratory mucosa and its adjuncts, natural killer cells, dendritic cells, neutrophils and innate immune receptors. Cigarette smoke can also affect the humoral immunity and cellular immunity, altering the acquired immune condition of the upper respiratory tract. Tobacco smoke exposure promotes the occurrence and development of the upper respiratory tract infectious diseases and allergic diseases by changing the composition of microflora in the upper respiratory tract.

LncRNA SNHG1 promotes cell proliferation in laryngeal cancer via Notch1 signaling pathway.

OBJECTIVE: We aimed at elucidating the potential function of long noncoding ribonucleic acids (lncRNAs) small nucleolar RNA host gene 1 (SNHG1) in the progression of laryngeal cancer (LC) and its underlying mechanism. PATIENTS AND METHODS: Relative level of SNHG1 in LC tissues and controls was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Its expression in LC patients with different tumor stages and statues of lymph node metastasis was examined as well. Correlation between SNHG1 expression and prognosis of LC patients was evaluated by the Kaplan-Meier method. SNHG1 siRNA (si-SNHG1) was constructed for downregulation of SNHG1 expression. Potential effects of downregulated SNHG1 on viability and proliferation of LC cells were detected by cell counting kit-8 (CCK-8) and colony formation assay, respectively. After knockdown of SNHG1, relative levels of Notch1 and hairy, and enhancer of split homolog-1 (Hes1) were determined by qRT-PCR and Western blot. Regulatory effects of SNHG1/Notch1 axis on biological behaviors of LC were finally evaluated. RESULTS: SNHG1 was upregulated in LC tissues than that of controls. Besides, its level was higher in LC with T3-T4 relative to those of T1-T2. Higher abundance of SNHG1 was identified in LC patients with lymph node metastasis compared with those non-metastatic patients. Survival analysis indicated that LC patients with high-level SNHG1 had worse overall survival. Knockdown of SNHG1 in Tu212 and Hep2 cells downregulated relative levels of Notch1 and Hes1. Moreover, SNHG1 knockdown resulted in decreased viability and proliferative ability of LC cells. Notch1 overexpression could reverse the regulatory effects of SNHG1 on viability and proliferation of LC cells. CONCLUSIONS: LncRNA SNHG1 is highly expressed in LC tissues. It promotes the proliferation of LC cells by inhibiting Notch1 pathway, thereby promoting the progression of LC.

Effect of skeletal muscle fibers on porcine meat quality at different stages of growth.

In this study, we examined changes in meat quality and content of muscle types during porcine growth. The influence of the longissimus dorsi muscle fiber composition on meat quality and the correlation between 2 fiber-typing methods (histochemistry and real-time quantitative polymerase chain reaction) were examined. Type IIx and type IIb fibers accounted for most of the total number of fibers; the proportion of these fibers increased during porcine growth (75.42, 80.09, and 79.88%, respectively, at 3 different stages of growth). There was a strong positive correlation between the 2 fiber-typing methods; the correlation coefficients of type I, IIa, and IIx+IIb fiber contents were 0.65, 0.88, and 0.92, respectively. The a* value of meat color was significantly lower at 98 days and negatively correlated with white fiber content (r = -0.69, P < 0.01). Water-holding capacity decreased during porcine growth. The drip loss parameter was positively correlated with type IIx+IIb fiber content (r = 0.55, P < 0.05). Decreased pH was strongly positively correlated with type IIx+IIb fiber content (r = 0.61, P < 0.01) and negatively correlated with type IIa fiber content (r = -0.44, P < 0.05). Therefore, we found that the composition of muscle fibers influenced the establishment of meat quality and its alteration during the early postmortem period.

Effect of ß-hydroxy-ß-methylbutyrate calcium on growth, blood parameters, and carcass qualities of broiler chickens.

Beta-hydroxy-ß-methylbutyrate (HMB), the metabolite of leucine, plays an important role in muscle protein metabolism. To investigate the effect of dietary HMB calcium (HMB-Ca) on growth performance, breast muscle development, and serum parameters in broiler chickens, a total of two hundred seventy 1-d-old Arbor Acres male broiler chicks were randomly allotted into 3 dietary treatments supplemented with 0, 0.05%, or 0.1% HMB-Ca during the starter (1 to 21 d) and grower (22 to 42 d) period. The results showed that broilers fed 0.1% HMB-Ca diet had higher ADG during the starter or the whole period, and gain 148 g more BW than the chicks fed the control diet at 42 d of age (P < 0.05). At 21 d of age, birds receiving 0.1% HMB-Ca had more breast muscle yield, less abdominal fat than the control, and more dressing percentage than birds fed the control or 0.05% HMB-Ca diet (P < 0.05). At 42 d of age, 0.1% HMB-Ca increased breast muscle yield than the control and decreased abdominal fat compared with the control or 0.05% HMB-Ca group (P < 0.05). In comparison with the control, feeding 0.1% HMB-Ca increased the triiodothyronine, thyroxine, triiodothyronine/thyroxine ratio and decreased the serum uric acid level at d 21 (P < 0.05). At 42 d of age, serum thyroxine level was elevated in the 0.05% HMB-Ca treatment, and the uric acid concentration was significantly decreased by the 0.1% HMB-Ca-supplemented diet (P < 0.05). Dietary HMB-Ca did not affect the growth hormone or insulin content. This study suggested that dietary supplementation of HMB-Ca improved growth performance, stimulated the breast muscle development, and decreased the abdominal fat deposition in broiler chickens, and the favorable effects were more pronounced in the starter phase. The growth promotion effect of HMB-Ca may be partly related to the increased serum thyroid hormones in broiler chickens.

Effects of constant and cyclic heat stress on muscle metabolism and meat quality of broiler breast fillet and thigh meat.

This study investigated the effects of constant and cyclic heat stress on muscle metabolism and meat quality of broiler breast fillet and thigh meat from 4 to 6 wk of age. Male Arbor Acres (AA) broilers (n = 270, 4 wk old) were raised under different temperature conditions: standard (temperature was 23°C); constant high temperature (temperature was 34°C); and cyclic high temperature (temperature was 36°C from 1000 h to 1600 h and 23°C from 1600 h to 1000 h). On d 42, broilers were stunned and sampled. The results showed that chronic high temperature significantly decreased the proportion of breast muscle and significantly increased the proportion of thigh muscle (P < 0.05). The moisture concentration was significantly higher in the breast muscle of the birds exposed to constant high temperature (P < 0.05), whereas the protein content was significantly lower (P < 0.05) and fat deposition was significantly higher (P < 0.05) in the breast muscle of the birds exposed to constant or diurnal cyclic high temperature than those grown under standard temperature. The breast and thigh muscle of the birds grown under constant high temperature had significantly higher lightness, cook loss, and shear force (P < 0.05) and significantly lower initial pH (pH(i)), ultimate pH (pH(u)), and redness compared with those grown under standard temperature (P < 0.05). The pH(i), pH(u), and redness were significantly lower (P < 0.05) while the lightness and shear force were significantly higher for the breast muscle of the chickens raised under diurnal cyclic high temperature (P < 0.05) than those grown under standard temperature. In contrast, lightness and yellowness of thigh muscle were significantly higher (P < 0.05) in the chickens grown under diurnal cyclic high temperature than under standard temperature. Breast and thigh muscle of broilers exposed to constant high temperature produced higher (P < 0.05) lactic acid and pyruvate kinase activities than those exposed to the standard temperature. These results indicated that chronic heat stress significantly increased lactate production, reduced meat pH value by accelerating meat glycolysis, and eventually reduced meat quality.

Loss of p53 function confers high-level multidrug resistance in neuroblastoma cell lines.

Neuroblastomas can acquire a sustained high-level drug resistance during chemotherapy and especially myeloablative chemoradiotherapy. p53 mutations are rare in primary neuroblastomas, but a loss of p53 function could play a role in multidrug resistance. We determined p53 function by measuring induction of p21 and/or MDM2 proteins in response to melphalan (L-PAM) in seven L-PAM-sensitive and 11 L-PAM-resistant neuroblastoma cell lines. p53 was functional in seven/seven drug-sensitive but in only 4/11 drug-resistant cell lines (P = 0.01). In four of the seven cell lines lacking p53 function, mutations of p53 were detected by the microarray GeneChip p53 Assay and automated sequencing, whereas six cell lines with functional p53 had no evidence of p53 mutations. All of the cell lines with wild-type (wt) p53 showed a strong transactivation of the p53-HBS/CAT reporter gene, whereas the four cell lines with mutant p53 failed to transactivate p53 HBS/CAT. Overexpression of MDM2 protein (relative to p53 functional lines) was seen in two p53-nonfunctional cell lines with wt p53; one showed genomic amplification of MDM2. Nonfunctional and mutated p53 was detected in a resistant cell line, whereas a sensitive cell line derived from the same patient before treatment had functional and wt p53. Loss of p53 function was selectively achieved by transduction of human papillomavirus 16 E6 (which degrades p53) into two drug-sensitive neuroblastoma cell lines with intact p53, causing high-level drug resistance to L-PAM, carboplatin, and etoposide. These data obtained with neuroblastoma cell lines suggest that the high-level drug resistance observed in some recurrent neuroblastomas is attributable to p53 mutations and/or a loss of p53 function acquired during chemotherapy. If confirmed in patient tumor samples, these data support development of p53-independent therapies for consolidation and/or salvage of recurrent neuroblastomas.

p53 mutations and loss of p53 function confer multidrug resistance in neuroblastoma.

BACKGROUND: Neuroblastomas often acquire sustained drug resistance during therapy. Sensitivities to carboplatin, etoposide, or melphalan were determined for 18 neuroblastoma cell lines; eight were sensitive and ten were resistant. As p53 mutations are rare in neuroblastomas studied at diagnosis, we determined if acquired p53 mutations and loss of function conferred multidrug resistance. RESULTS: Loss of p53 function (p53-LOF), defined as a failure to induce p21 and/or MDM2 in response to melphalan, was seen in 1/8 drug-sensitive and 6/10 drug-resistant cell lines. In four cell lines p53-LOF was associated with mutations in the DNA binding region of p53, while three cell lines with LOF and four cell lines with functional p53 had no evidence of p53 muta-tions. Nonfunctional and mutated p53 was detected in one resistant cell line, while a sensitive cell line derived from the same patient prior to treatment had functional and wild type (wt) p53. We transfected HPV 16 E6 (which mediates degradation of p53, causing LOF) into two drug-sensitive neuroblastoma cell lines with functional p53. LC(90) values of HPV 16 E6 transfected cell lines were 3-7-fold (melphalan), 8-109-fold (carboplatin), and 2-158-fold (etoposide) greater than that of LXSN-transfected controls. CONCLUSIONS: These data suggest that some neuroblastomas acquire p53 mutations during therapy, which is associated with a loss of p53 function, and can confer high-level multidrug resistance.

Telomerase activity by TRAP assay and telomerase RNA (hTR) expression are predictive of outcome in neuroblastoma.

BACKGROUND: Recent studies have associated telomerase with prognostic factors and survival in neuroblastoma. PROCEDURE: We examined telomerase activity by telomere repeat amplification protocol (TRAP) and expression of the RNA component of telomerase (hTR) by Northern blotting in 106 primary neuroblastoma tumors and 22 established cell lines. RESULTS: Overall survival at 5 years for all 106 tumors was significantly better for patients with undetectable TRAP (75% vs. 59%; P = 0.03) or low hTR expression (84% vs. 43%; P < 0.0001), and especially for patients whose tumors had both low hTR expression and undetectable TRAP (all patients, 91% vs. 54%, P = 0.0002; for 17 stage IV-S tumors, 100% vs. 72%, P = 0.04). Strong expression of hTR was seen in 22 cell lines from aggressive tumors, and all maintained telomere length, but 3/22 were TRAP negative. CONCLUSIONS: These data suggest that both hTR expression and telomerase activity via the TRAP assay should be performed concurrently to predict survival in neuroblastoma patients, particularly in stage 4-S.

Telomerase expression in primary neuroblastomas.

Maintenance of chromosomal telomeres is necessary for continued cell growth, and this is carried out in germline tissues by telomerase. In contrast to most somatic tissues, many tumours have telomerase activity. The RNA component of human telomerase (hTR) was measured by Northern analyses of 150 primary untreated neuroblastomas and compared with clinical stage at diagnosis. hTR expression > 33 (relative to cell line control = 100) was seen in 41% of all tumours and the frequency of hTR > 33 increased with stage of disease. Expression of hTR may be involved in progression of neuroblastoma.