[Study on the expression of microRNA-1825 in serum of pre-operative and post-operative patients with breast cancer].

By measuring the relative expression level of miR-1825 in serum of pre-operative and post-operative patients with breast cancer and healthy subjects, the clincal value of miR-1825 for pre-operative and post-operative breast cancer patients was evaluated.The serum of pre-operative breast cancer patients(n=92), post-operative breast cancer patients(n=64) and healthy subjects(n=60) were collected from General Hospital of Southern Theatre Command of PLA from October 2018 to March 2021. Real-time quantitative PCR was used to detect the relative expression of miR-1825 in the serum of breast cancer patients and healthy controls. The clinicopathological data were used to analyze the correlation between the expression level of miR-1825 and serum tumor markers level. The receiver operating characteristic curve (ROC) was used to evaluate the diagnosis value of breast cancer with miR-1825, CA15-3. Mann-Whitney U test was used for comparisons between two groups,and Kruskal-Wallis H test was used for multiple group comparisons. The correlation between miR-1825 and CEA, CA15-3, CA-125 expression were analyzed using Spearman correlation test.The relative expression level of miR-1825 in serum of pre-operative patients with breast cancer 1.290(0.705, 1.793) was significantly higher than that of healthy controls 0.18(-0.876, 0.725), but decreased after surgery and chemotherapy -0.080(-0474, 0.405). The analysis of clinicopathological characteristics found that the expression level of miR-1825 was higher in patients with stage Ⅲ-Ⅳ, low degree of tissue differentiation, and tumor larger than 2 cm[stageⅠ-Ⅱ:0.975(0.458, 1.380), stageⅢ-Ⅳ: 1.955(1.663, 2.535), U=98.000, P<0.001;low degree of tissue differentiation:1.685(1.448, 2.143), high/medium degree of tissue differentiation:0.700(0.395, 0.898), U=15.500, P<0.001; tumor smaller than 2 cm:0.935(0.438, 1.370), tumor larger than 2 cm:1.915(1.580, 2.288), U=215.500, P<0.001].Spearman analysis result showed that the expression of serum miR-1825 in breast cancer patients was linearly correlated with the expression of CEA (r=0.274, P=0.008) and CA15-3 (r=0.587, P<0.001); ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. When using one biomarker to discriminate pre-operation and post-operation patients,miR-1825 had the best diagnostic efficiency,with an area under the ROC curve(AUC) of 0.914(95%CI: 0.872-0.956). miR-1825 may become a potential serum marker for the diagnosis of breast cancer and monitoring of therapeutic efficacy.

Sequence variability in internal transcribed spacers of nuclear ribosomal DNA among isolates of the oxyurid nematodes Syphacia obvelata and Aspiculuris tetraptera from mice reared in laboratories in China.

This study examined sequence variability in internal transcribed spacers (ITS) of nuclear ribosomal DNA among Syphacia obvelata and Aspiculuris tetraptera isolates from laboratory mice from different geographical locations in China. ITS1, 5.8S and ITS2 rDNA were amplified separately from adult S. obvelata and A. tetraptera individuals by polymerase chain reaction (PCR), and the amplicons were subjected to sequencing from both directions. The lengths of the sequences of ITS1, 5.8S and ITS2 rDNA from both nematodes were 314 bp and 456 bp, 157 bp, and 273 bp and 419 bp, respectively. The intraspecific sequence variations in S. obvelata ITS1 were 0-0.3%. For A. tetraptera they were 0-0.7% in ITS1 and 0-1.0% in ITS2. However, the interspecific sequence differences among members of the infraorder Oxyuridomorpha were significantly higher, being 54.0-65.5% for ITS1 and 55.3-64.1% for ITS2. Phylogenetic analysis based on the combined partial sequences of ITS1 and ITS2 using three inference methods - Bayesian inference, maximum likelihood and maximum parsimony - revealed that all the S. obvelata and A. tetraptera samples formed independent monophyletic groups. Syphacia obvelata was closer to Syphacia muris than to A. tetraptera, consistent with morphological classification. These results demonstrate that ITS1 and ITS2 rDNA sequences are useful markers for population genetic studies of oxyurid nematodes.

[Predictive value of D-dimer for deep venous thrombosis of lower extremity in adult burn patients].

Objective: To investigate the predictive value of D-dimer for deep venous thrombosis (DVT) of lower extremity in adult burn patients. Methods: A retrospective case series study was conducted. The clinical data of 3 861 adult burn patients who met the inclusion criteria and were admitted to the Department of Burns of Zhengzhou First People's Hospital from January 1, 2015 to December 31, 2019 were collected. The patients were divided into DVT group (n=77) and non-DVT group (n=3 784) according to whether DVT of lower extremity occurred during hospitalization or not. Data of patients in the two groups were collected and compared, including the gender, age, total burn area, D-dimer level, with lower limb burn and inhalation injury or not on admission, with sepsis/septic shock, femoral vein indwelling central venous catheter (CVC), history of surgery, and infusion of concentrated red blood cells or not during hospitalization. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. The indicators with statistically significant differences between the two groups were analyzed with multivariate logistic regression analysis to screen the independent risk factors for DVT of lower extremity in 3 861 adult burn patients. The receiver operating characteristic (ROC) curve of the independent risk factors predicting DVT of lower extremity in 3 861 adult burn patients were drawn, and the area under the curve (AUC), the optimal threshold value, and the sensitivity and specificity under the optimal threshold value were calculated. The quality of the AUC was compared by Delong test, and the sensitivity and specificity under the optimal threshold value were compared using chi-square test. Results: There were no statistically significant differences in gender, occurrence of sepsis/septic shock or history of surgery during hospitalization between patients in the two groups (P>0.05), while there were statistically significant differences in age, total burn area, D-dimer level, lower limb burn and inhalation injury on admission, and femoral vein indwelling CVC and infusion of concentrated red blood cells during hospitalization between patients in the two groups (t=-8.17, with Z values of -5.04 and -10.83, respectively, χ2 values of 21.83, 5.37, 7.75, and 4.52, respectively, P<0.05 or P<0.01). Multivariate logistic regression analysis showed that age, total burn area, and D-dimer level were the independent risk factors for DVT of lower extremity in 3 861 adult burn patients (with odds ratios of 1.05, 1.02, and 1.14, respectively, 95% confidence intervals of 1.04-1.06, 1.00-1.03, and 1.10-1.20, respectively, P<0.05 or P<0.01). The AUCs of ROC of age, total burn area, and D-dimer level for predicting DVT of lower extremity in 3 861 adult burn patients were 0.74, 0.67, and 0.86, respectively (with 95% confidence intervals of 0.68-0.80, 0.60-0.74, and 0.83-0.89, respectively, P values<0.01), the optimal threshold values were 50.5 years old, 10.5% total body surface area, and 1.845 mg/L, respectively, the sensitivity under the optimal threshold values were 71.4%, 70.1%, and 87.0%, respectively, and the specificity under the optimal threshold values were 66.8%, 67.2%, and 72.9%, respectively. The AUC quality and sensitivity and specificity under the optimal threshold value of D-dimer level were significantly better than those of age (z=3.29, with χ2 values of 284.91 and 34.25, respectively, P<0.01) and total burn area (z=4.98, with χ2 values of 326.79 and 29.88, respectively, P<0.01), while the AUC quality and sensitivity and specificity under the optimal threshold values were similar between age and total burn area (P>0.05). Conclusions: D-dimer level is an independent risk factor for DVT of lower extremity in adult burn patients, its AUC quality and sensitivity and specificity under the optimal threshold value are better than those of age and total burn area, and it has good predictive value for DVT of lower extremity in adult burn patients.

[Comparison of the treatment effect for stage â epitympanic cholesteatoma with atticotomy and Bondy modified radical mastoidectomy].

Objective:To compare the efficacy and safety between Bondy modified radical mastoidectomy (BMRM) and atticotomy for stage Ⅰ epitympanic cholesteatoma. Method:A retrospective analysis of 36 cases with stage Ⅰ epitympanic cholesteatoma was performed. According to different surgery methods, the cases were divided into the atticotomy group (21 cases) and the BMRM group (15 cases). Hearing function, the dry ear ratio after two months of the surgery, and the epithelial time were observed. The complications for the retraction of tympanic membrane, residual or recurrence of cholesteatoma, and otorrhea were analyzed. Result:There was no significant difference between the two groups in average air-bone gaps (ABG) and ABG gain before and after surgery (P>0.05). The preoperative hearing was preserved both in the atticotomy group and the BMRM group. However, more surgery time, lower ratio of the dry ear after two months of the surgery, and longer epithelial time were observed in the BMRM group than those in the atticotomy group(P<0.05). No cholesteatoma residual or recurrence was observed in both groups. Conclusion:For stage Ⅰ epitympanic cholesteatoma lateral to an intact ossicular chain, atticotomy has the advantage of complete removal of the cholesteatoma matrix, avoiding big mastoidal cavity, keeping normal anatomical structure of external auditory canal, better hearing preservation, and faster healing. Therefore, atticotomy has better clinical and practical value.

[Crouzon syndrome with secretory otitis media: a case report and literature review].

Summary Clinical data from a case of Crouzon syndrome with secretory otitis media in our department was collected and the related literatures were reviewed. Whole exome sequecing and Sanger sequencing were performed to analyze genetic cause. The 6-year old patient with Crouzon syndrome had snoring and mouth breathing during sleep for 2 years, and was found hearing loss for 2 weeks. The results of endoscopy showed adenoid hypertrophy and secretory otitis media of both ears. And CT scan proved chronic rhinosinusitis. Myringotomy and adenoidectomy were done under general anesthesia. The follow-up at 6 months showed normal sleep and hearing level. A heterozygous fibroblast growth factor receptor 2 missense mutation（c.1061C>G, p.S354C） in exon 8 was identified in this patient.

[Analysis of predictors for Frey syndrome after parotidectomy].

Objective:To analysis the data of the patients with parotid tumors, clarify the contributing factors of Frey syndrome, and to evaluate the role of soft tissues membrane SIS in prevention of Frey syndrome after parotidectomy. Method:The data of 95 patients who suffered from parotid tumors and underwent parotidectomy were included in this study. The relationship between the patients' age, sex, tumor location ,tumor size, disease pathology, type of resection, SIS application and the incidence of Frey syndrome were statistically analyzed . Result:The incidence of Frey syndrome after parotidectomy for 95 patients was 25.3%. Age, sex, tumor location and size, disease pathology, type of resection did not appear to be associated with development of Frey syndrome（P>0.05）. SIS application was the only statistically significant factor（P<0.01）, and SIS could prevent Frey syndrome after parotidectomy. Conclusion:Frey syndrome is one of the common complicationsafter parotidectomy. Implantation of SIS is an effective method for prevention of Frey syndrome after parotidectomy.

[Effect of sublingual dust mite drops on single or multiple allergens allergic rhinitis in children].

Objective:Evaluation of the efficacy of standardized dust mite drops in sublingual immunotherapy(SLIT) for allergic rhinitis in children.Method:A retrospective analysis of 174 children who received SLIT with standardized dermatophagoides farinae drops for 2 years.These patients had been divided into two groups:monoasensitized group(n=61) and polysensitized group(n=113).The total medication score(TMS),total nasal symptoms score(TNSS) and inflammatory factors were evaluated before and after SLIT treatment.Result:①After SLIT treatment for 2.0 year,the TNSS in the monosensitized group is(11.27±1.46) and(3.48±1.50),polyasensitized group is (11.54±1.50) and (3.59±1.56),there are significant difference of TNSS between two groups(P<0.01).But the improvements of the TNSS between the two groups have no significant difference(P>0.05),the monosensitized group is(7.68±3.23); polysensitized group is (8.14±2.56). ②Two groups of children with TMS before and after treatment were obviously improved, monosensitized group is (1.67±0.43) and (0.52±0.40),polysensitized group is(1.64±0.44) and (0.55±0.41). There are significant difference of TMS between two groups(P<0.01).But the improvements of the TMS between the two groups have no obvious difference(P>0.05),the monsensitized group is(1.16±0.61); polysensitized group is(1.28±0.55).③Specific IgG4 serum is increased after treatment(P<0.01).④After immunotherapy,the expression of IL4 and IL-17α is downregulated, IL-2 and TGF-ß1 is up-regulated.Conclusion:①Dust mites under the SLIT,can significantly improve the monosensitized and polyasensitized allergic children nasal symptoms,reduce the drug use, and two groups have the equivalent effect.②Dust mite drops SLIT,can be used to the monosensitized and polyasensitized allergic children.③The rise of dust mites specific IgG4 can be used as immunotherapy effective predictors.④After immunotherapy, Thl/Th2 /Thl7 and Treg can be rebalanced.

LncRNA HOTAIR participates in the development and progression of adrenocortical carcinoma via regulating cell cycle.

OBJECTIVE: To explore the role of HOTAIR in the pathogenesis of adrenocortical carcinoma (ACC) and its underlying mechanism. PATIENTS AND METHODS: Differentially expressed lncRNA (HOTAIR) in ACC was screened out from the GEO database. The survival analysis and ROC curve were performed according to HOTAIR expressions in ACC patients. The correlation between HOTAIR expression and clinical information of ACC patients was analyzed by chi-square test. The univariate and multivariate COX regression analysis was carried out to analyze the relationship between HOTAIR expression, disease-free survival (DFS) and overall survival (OS) of ACC patients. We then detected HOTAIR expression in 77 ACC tissues and 30 normal tissues by qRT-PCR (quantitative Real-time polymerase chain reaction). ACC cell lines were further screened out for the following in vitro experiments. After altering HOTAIR expression in ACC cells by plasmid transfection, proliferation and cell cycle were detected by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Finally, Western blot was utilized to detect expressions of cell cycle-related genes in ACC cells. RESULTS: HOTAIR was overexpressed in ACC tissues than that of normal tissues. HOTAIR expression was remarkably increased in ACC with T3 and T4 stage than that of T1 and T2 stage. Moreover, HOTAIR expression was remarkably increased in ACC with stage III and IV than that of stage I and II. HOTAIR was an independent prognostic factor for DFS and OS of ACC patients. For in vitro experiments, inhibited proliferation and arrested cell cycle were observed in H295R cells transfected with si-HOTAIR. Opposite results were obtained after SW-13 cells were transfected with HOTAIR overexpression plasmid. Furthermore, expressions of cell cycle-related genes, including Cyclin D1, p-Rb and p-GSK3ß were remarkably decreased after HOTAIR knockdown. CONCLUSIONS: We demonstrated for the first time that HOTAIR is overexpressed in ACC and is a prognostic risk factor in ACC patients. HOTAIR participates in the development and progression of ACC via shortening cell cycle and promoting proliferation of ACC cells.

[The study for the characteristics of secondary acquired cholesteatoma].

Objective:Retrospctive analysed the Characteristics and outcomes of surgical treatment of 18 patients who were diagnosed as secondary acquired cholesteatoma (SAC).Method:Patients with SAC accepted operations were enrolled in this study. Then the factors such as sex, age, cource of history, otorrhea before operation, the size of perforation of tympanic membrane, entry site of epithelium, extension direction, ossicular destruction, tympanosclerosis, tympanum tympani tendon involvement, stage of cholesteatoma（JOS, 2015, Japan），degree of gasification of mastoid（JOS，2015，Japan），air conductive threshold, bone conductive threshold, air-bone gap, the healing of tympanic membrane and the auditory improvement were analyzed.Result:Eighteen patients were enrolled in this study, with course of history range from 2 months to 50 years (average: 20.20±16.31) years. There were 14 cases with wet ear before operation. All patients were conformed with perforation of membranal tensa by otoendoscopic photography before operation, with nearly total in 5 ears,large size in 10 ears,medium size in 2 ears and small size in 1 ear. Ossicular erosion were found in 13 patients (malleus involved in 6, incus involved in 12 and stapes involved in 4). Thirteen patients with tendon of tensor tympani involved and 9 patients with tympanosclerosis were conformed during operation. The epithelium entered through the malleus manubrium to the promontory in 13 cases, through the edge of the perforation in 3 cases and through the incus long process to around stapes in 1 case. Cholesteatoma invasion extend to anterosuperior area in 3 cases, posterosuperior area in 3 cases,both in anterosuperior and posterosuperior area in 12 cases. The cholesteatomas classified: stage Ⅰ in 11 cases, stage Ⅱ in 7 cases. Mastoid gasification classified MC0 in 6 cases, MC1 in 10 cases and MC2 in 2 cases. The average air conductive threshold was (56.32±10.15) dB, bone conductive threshold was (20.76±6.22) dB and air-bone gap (35.56±9.84) dB.Tympanic membrane healed in all patients during following up, without recurrent of cholesteatoma, and the post-operative air conductive threshold (43.02±14.96) dB and air-bone gap (21.04±12.90)dB were improved significantly(P<0.05).Conclusion:Most of SAC were secondary to nearly total or large perforation of membranal tensa (83.33%), with relative long history of chronic otitis media (average 20.20 ± 16.31) years and otorrhea before operation. The epithelium entered mainly through the malleus manubrium to the promontory，then through edge of the perforation，by extending anterosuperior and posterosuperior area and usually accompanied with tendon of tensor tympani involved, ossicular destruction, and poor mastoid gasification and tympanosclerosis. The characteristics of SAC were different from other type of cholesteatoma which need further researches.

[Etiology analysis and vestibular assessment of bilateral vestibular vestibulopathy].

Objective:To define clinical and laboratory characteristics of bilateral vestibulopathy(BVP) and to propose diagnostic criteria of this disorder based on clinical and laboratory vestibular function test findings.Method:Forty-two case series with a clinical suspicion of BVP were retrospectively analyzed, in an attempt to determine etiology. Presenting auditory-vestibular symptoms, bedside dynamic visual acuity tests and laboratory test were reviewed, including bithermal caloric test, rotatory chair tests, video head impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP).Result:Among these 42 patients, dizziness was seen in 42 cases(100%), oscillopsia was seen in 21 cases(50%), hearing loss was seen in 30(71.4%). Eight cases(19%) had tinnitus. Twenty-five cases showed vestibular loss in dynamic visual acuity test (69.4%). Definite diagnosis of complete BVP was made in 36 patients when the patients showed abnormal findings on caloric test, rotatory chair test and vHIT in addition to the symptoms. Whereas probable diagnosis of partial BVP was obtained in 6 patients with abnormal caloric test and rotatory chair test but no pathological vHIT. VEMP (ocular or cervical) could be recorded in 20 patients. Fourteen cases were caused by ototoxic drugs while no causes could be determined in 6 cases among these 42 cases.Conclusion:The diagnosis of BVP is a challenge. Vestibular laboratory test battery which reflect full frequency function of VOR has great value to confirming the diagnosis and differentiate complete BVP to partial BVP. Diagnosis standard shall be made combining clinical history, characteristic symptoms and the results of auditory-vestibular function testing. Ototoxic drugs contribute most considering etiology.

[Applied anatomy of the cerebelloponotine angle through retrosigmoid approach].

Objective:To privde anatomical basis for the surgical operation of endoscope-assisted retrosigmoid approach. Method:In 20 adult head cadavers fixed with formalin (40 sides), the surgery via retrosigmoid approach was simulated. The anatomic features of the cerebellopontine angle were examined and measured. Result:The distance from the midpoint of posterior border of sigmoid sinus to acoustic nerve near internal acoustic pore, trigeminal nerve near Meckel's cave, glossopharyngeal nerve near jugular foramen and the posterior margin of internal acoustic meatus were (32.8±1.7)mm, (46.3±1.8)mm, (29.4±3.0)mm, (31.2±2.0)mm. The tracks of degree of angle of median sagittal plane were (32.6±7.7)°, (31.4±4.1)°, (40.2±6.9)°, (32.7±4.9)°. Conclusion:The measurement provides some useful references for defining the position in operating.

[A retrospective study of 54 cases with chronic otitis media prepared for staging tympanoplasty].

Objective:To analyze the clinical effect of 54 cases with chronic otitis media prepared for staging tympanoplasty and 19 cases finished staging ossicular reconstruction surgery, evaluate the advantages of different surgery technique.Method:Fifty-four cases with chronic otitis media were planned for staging tympanoplasty surgery and had been received the first stage surgery. Silicagel plates were placed in the tympanic cavity in order to prevent adhesions. Among them, 19 cases had received the second stage ossicular reconstruction, including 10 cases with TORPs and 9 cases with PORPs. The average air bone gaps (ABG) were measured at four frequencies: 500, 1 000, 2 000 and 4 000 Hz.Result:Among the 54 cases, 45 cases had swollen mucosa in the tympanic cavity and eustachian tube, 18 cases had tympanic fibrous adhesions, and 12 cases had fixed or sclerotic stapes. The preoperative ABG of the 54 cases were (38.26±7.88)dB. As for the 19 cases finished the second stage surgery, their preoperative ABG in the first stage were (39.21±7.05)dB, the preoperative ABG in the second stage were (38.82±11.43)dB, and the postoperative ABG after the second stage were (21.77±11.92)dB. The hearing function after staging tympanoplasty was significantly improved compared with the preoperative hearing in the first and the second stage operation (P< 0.01). In addition, the second stage surgery of three cases was postponed because of a good postoperative hearing with (10.42±10.63)dB ABG after the first stage surgery. Up to now, none of the 54 cases suffered from facial palsy, infection and other complications after surgery.Conclusion:Staging tympanoplasty is an important technique to improving hearing and reducing the complications, especially for the cases with chronic otitis media unsuitable for one stage reconstruction of ossicular chain.

Survey of helminths in adult sheep in Heilongjiang Province, People's Republic of China.

The prevalence of helminths in adult sheep was investigated in Heilongjiang Province, People's Republic of China between January 1999 and September 2003. A total of 326 adult sheep representing local breeds (Xingjiang Fine Wool Sheep, Dongbei Fine Wool Sheep) as well as introduced breeds (Merino and Charollais) from representative geographical locations in Heilongjiang Province were slaughtered and examined for the presence of helminths. The worms were examined, counted and identified to species according to existing keys and descriptions. A total of 26 helminth species were found representing 2 phyla, 3 classes, 13 families and 20 genera. All sheep were infected by more than one helminth species. Oesophagostomum columbianum, Haemonchus contortus and Trichostrongylus colubriformis were the most common nematode species, and Paramphistomum cervi, Orientobilharzia turkestanica and Fasciola hepatica were the most common trematode species, whereas the infection of adult sheep with cestodes was uncommon. The results of the present investigation provide relevant "base-line" data for Heilongjiang Province, China, for assessing the effectiveness of future control strategies against helminth infections in sheep.

[Chronic subjective dizziness].

Chronic subjective dizziness(CSD) was defined as persistent nonvertiginous dizziness or subjective unsteadiness. Patients are hypersensitivity to motion stimuli, such as head movement and motion of objects in the visual surrounding, and have difficulty with precise visual tasks. The concept of CSD was first proposed by Staab and Ruckenstein, which indicates relationships between chronic dizziness and acute vestibular or psychiatric disorders, including neuro-otologic type, psychiatric type or interactive type. Treatment includes vestibular rehabilitation therapy, pharmacologic interventions and psycho-behavioral interventions(cognitive behavioral therapy).

[Horizontal semicircular canalvideo head impulse test in normaladults:normal value and age distribution].

Objective:To study the parameters of video head impulse test (vHIT) for horizontal semicircular canal and explore its application when evaluating angular vestibular-ocular reflex (VOR) in adults.Method:vHIT were applied to 80 adults without prior vertigo or dizziness history.Parameters provided by the software included instantaneous gain(40 ms,60 ms,80 ms),regression gain,asymmetry value,corrective saccades(latency,peak velocity,occurrence rate).Result:The mean horizontal VOR velocity gain of normal subjects was 0.877±0.171,0.944±0.133,0.967±0.130 at 40 ms,60 ms,80 ms respectively.Regression gain of horizontal VOR is 0.944±0.090.The lower limit of normal horizontal VOR velocity gain was 0.73 at 60 ms and 0.80 as regression gain.All velocity gains declined by age,although there were no statistically significant difference(P>0.05).Asymmetry value was 5.60±3.46.Corrective saccades occurred in 28±15 of normal subjects,while latency and peak velocity was (200.87±0.34)ms and (97.7±40.1)°/s.Conclusion:The study found that horizontal VOR instantaneous gain value and regression gain value decreases slightly with age,which should be considered in clinical application.

Participation of B-cell-activating factor receptors in the pathogenesis of immune thrombocytopenia.

UNLABELLED: ESSENTIALS: Dysfunctional B-cell-activating factor (BAFF) system is related to many autoimmune diseases. The regulatory functions of BAFF/BAFF receptors were investigated in an in vitro coculture system. Different regulatory roles of BAFF were investigated via different receptors in immune thrombocytopenia. The upregulated BAFF receptors on autoreactive lymphocytes lead to their hypersensitivity to BAFF. BACKGROUND: The pathogenesis of immune thrombocytopenia (ITP) remains enigmatic. B-cell-activating factor (BAFF) and its receptors (BAFF receptor [BAFF-R], transmembrane activator and calcium modulator and cyclophilin ligand interactor [TACI], and B-cell maturation antigen) play central roles in the integrated homeostatic regulation of lymphocytes. OBJECTIVES: To investigate the pathologic roles of BAFF receptors in regulating the bioactivities of lymphocytes in ITP. METHODS: An in vitro culture system was established by stimulating CD14(-) peripheral lymphocytes with platelet-preloaded dendritic cells in the presence of recombinant human BAFF (rhBAFF; 20 ng mL(-1)). The functions of BAFF receptors were specifically blocked with blocking antibodies. RESULTS: BAFF-R, besides prolonging the survival of B cells in both patients and healthy controls, prominently promoted the survival of CD8(+) T cells and the proliferation of B cells in patients with ITP. TACI, as a positive regulator, not only promoted the proliferation of CD4(+) and CD8(+) T cells, but also significantly enhanced the secretion of interleukin-4 in patients with ITP, but not in controls. Besides revealing the pathologic roles of BAFF receptors, these results also indicate that lymphocytes of patients with ITP have enhanced antiapoptotic or proliferative capacity as compared with those from healthy controls when exposed under similar stimulation of rhBAFF. Further study demonstrated that activated autoreactive B cells and CD4(+) T cells from patients with ITP showed significantly higher expression of BAFF-R or TACI than those from healthy controls. CONCLUSIONS: Both BAFF-R and TACI are pathogenic participants in ITP. Their dysregulated expression in patients with ITP may lead to hyperreactivity of activated autoreactive lymphocytes in response to rhBAFF, and thus is highly significant in the pathogenesis of ITP.

[Prevalence of hearing disorders in China: a population-based survey in four provinces of China].

Objective: To investigate the prevalence, severity of hearing disorders and demographics of people with hearing disorders based on the whole population in Jilin, Guangdong, Shannxi and Gansu provinces in China. Methods: According to " WHO Ear and Hearing Disorders Survey Protocol" , 144 clusters were chosen with probability proportional sampling(PPS) method from the four provinces covering 194, 688, 061 residents. Audiological test, otological examination and questionnaire surveying were conducted for all samples from August, 2014 to September, 2015. The hearing disorders were classified according to WHO criteria and classification. Results: Among 47 511 targeted residents, 45, 052 individuals (94.82% response rate) participated in the survey. The standardized prevalence rates of hearing disorders and disabling hearing disorders were 15.84 % and 5.17 % respectively. Almost 50% of people with hearing disorders had no awareness of it or its starting time. There was significant difference in the prevalence among people of different ages, genders, occupations, provinces, marital status and education levels. The prevalence of hearing disorders increased significantly as age grew. People above 60 years old occupied 55.31% of the total hearing disorders. The prevalence of hearing disorders among male, people of low education and those who lost husband or wife, as well as workers and farmers was relatively higher. Conclusions: The prevalence of hearing disorders is high, and hearing disorders are " invisible" . Demographics and socioeconomic factors significantly influence the prevalence of hearing disorders.

Proteasome inhibitors induce cytochrome c-caspase-3-like protease-mediated apoptosis in cultured cortical neurons.

The ubiquitin-proteasome protein degradation pathway is crucial in controlling intracellular levels of a variety of short-lived proteins and maintaining cellular growth and metabolism. In a previous study, we showed the accumulation of conjugated ubiquitin in CA1 neurons of the gerbil after 5 min of forebrain ischemia (; ). The accumulation of conjugated ubiquitin may reflect proteasome malfunction. In the present study, we investigated the effects of proteasome inhibitors on primary neuronal cultures to determine whether proteasomal malfunction induces neuronal death. When carbobenzoxy-Leu-Leu-Leu-aldehyde or lactacystin, two different types of proteasome inhibitors, were separately used to suppress proteasome activity, we observed induction of apoptotic neuronal cell death in both cases. During the apoptotic process, mitochondrial membrane potential was disrupted, cytochrome-c was released from mitochondria into the cytosol, and caspase-3-like proteases were activated. Apoptosis was inhibited by pretreatment with acetyl-aspartyl-glutamyl-valyl-aspart-1-aldehyde or overexpression of Bcl-x/(L). These results demonstrated that suppression of proteasome function induces neuronal apoptosis via the release of cytochrome c from mitochondria and activation of caspase-3-like proteases.

Ubiquitin stress response in postischemic hippocampal neurons under nontolerant and tolerant conditions.

Ubiquitin, an essential protein in nonlysosomal proteolytic system, is expressed after metabolic stress to the cell. The authors investigated stress response of ubiquitin in the hippocampus of the Mongolian gerbil after forebrain ischemia. The level of hippocampal ubiquitin was compared with that under ischemic tolerance induced by ischemic preconditioning. The authors also studied ubiquitin gene expression using in situ hybridization method. Transient ischemia resulted in consumption of free ubiquitin and an increase of multiubiquitin chains. These changes were transient in the hippocampus outside of the CA1 region where neurons survived, whereas it was persistent in the CA1 region where neurons were destined to die after ischemia. Under tolerant condition, subsequent ischemia provoked rapid recovery and further increase of free ubiquitin. The signal of ubiquitin messenger ribonucleic acid was continuously detected after ischemia, not only under tolerant conditions, but without tolerance induced by preconditioning. Thus, ubiquitin stress response takes place, at least at a transcriptional level, in dying CA1 neurons. Under tolerant conditions, however, subsequent ischemia in the CA1 region induces the stress response of ubiquitin up to the translational level, leading to the rapid restoration of protein synthesis and to eventual neuronal survival.