The Regulation of Microglial Cell Polarization in the Tumor Microenvironment: A New Potential Strategy for Auxiliary Treatment of Glioma-A Review.

Glioma is the most common primary tumor of the central nervous system and normally should be treated by synthetic therapy, mainly with surgical operation assisted by radiotherapy and chemotherapy; however, the therapeutic effect has not been satisfactory, and the 5-year survival rates of anaplastic glioma and glioblastoma are 29.7% and 5.5%, respectively. To identify a more efficient strategy to treat glioma, in recent years, the influence of the inflammatory microenvironment on the progression of glioma has been studied. Various immunophenotypes exist in microglial cells, each of which has a different functional property. In this review, references about the phenotypic conversion of microglial cell polarity in the microenvironment were briefly summarized, and the differences in polarized state and function, their influences on glioma progression under different physiological and pathological conditions, and the interactive effects between the two were mainly discussed. Certain signaling molecules and regulatory pathways involved in the microglial cell polarization process were investigated, and the feasibility of targeted regulation of microglial cell conversion to an antitumor phenotype was analyzed to provide new clues for the efficient auxiliary treatment of neural glioma.

Adenoid cystic carcinoma in children and young adults: A clinicopathological study of 12 cases.

OBJECTIVE: To investigate the clinicopathological characteristics, immunoprofile, and molecular alterations of adenoid cystic carcinoma (ACC) in children and young adults. MATERIALS AND METHODS: Twelve cases of ACC were included. MYB, MYBL1, Ki-67, type IV Collagen, Laminin, and LAMB1 expression were detected by immunohistochemistry. MYB and MYBL1 rearrangements were detected by fluorescence in situ hybridization. RESULTS: Among 12 patients, four were female and eight were male. Seven cases (58.3%) located in major salivary glands and eight cases (66.7%) were classified as Grade I. Ten tumors (83.3%) had collagenous and hyalinized stroma. MYB was positive in 83.3% cases, and the average Ki-67 labeling index (LI) was 8.3%. LAMB1, type IV Collagen, and Laminin were positive in 91.7%, 66.7%, and 58.3% cases, respectively. Besides, three out of eight tumors had MYB rearrangement. Cases without MYB rearrangement were negative for MYBL1 expression and MYBL1 rearrangement. The average follow-up time was 91.8 months. Four patients had recurrent diseases. CONCLUSIONS: ACC in children and young adults was seen more frequently in males and major salivary glands. Most cases had ECM and hyaline stroma. Grade III tumors, higher Ki-67 LI, negative expression of type IV Collagen, and Laminin showed a tendency of higher recurrence rate.

Epithelioid sarcoma: A clinicopathological study of 12 head and neck cases.

OBJECTIVES: To determine the clinicopathological features of epithelioid sarcoma presenting in head and neck region (HNES) and elucidate diagnostic key points and treatment options for HNES. MATERIALS AND METHODS: A total of 12 HNES cases were collected in our department from 2010 to 2020. Their clinical information and pathological features were documented, and relevant follow-up was performed. Immunohistochemistry was carried to analyze the protein markers of HNES. RESULTS: Of the 12 HNES cases, 10 were primary tumors and 2 were metastasized from foot and shoulder, respectively. The patients with primary tumors were significantly younger than those with metastasized ones (22.7 vs 41.5, p = .0157), and male patients outnumbered female patients (3:1). Of all HNES cases, 9 were classic subtype, and 3 were proximal subtype. HNES patients had a poor prognosis, with 5-year overall survival of 41.5% and 5-year relapse-free survival of 22.5%. A loss of INI1 was identified as the hallmark of HNES with 83.3% (10/12) of HNES cases presenting as EZH2 positive. CONCLUSIONS: HNES is more prevalent at younger ages and in males, has a poor prognosis, and exhibits a greater proportion of classic subtype than proximal subtype. EZH2 inhibitor has therapeutic potential in HNES.

Ameloblastoma with mucous cells: A clinicopathological, BRAF mutation, and MAML2 rearrangement study.

OBJECTIVES: To investigate the clinicopathological features, BRAF V600E mutation, and MAML2 rearrangement of ameloblastoma with mucous cell differentiation. MATERIALS AND METHODS: Five cases of ameloblastoma with mucous cell differentiation were retrospectively studied. Clinicopathological features, BRAF V600E mutation, and MAML2 rearrangement were analyzed. Follow-up information was available for all cases. RESULTS: Of five cases, two cases were male and three were female, aged 18-55 years. Four cases were located in the mandible and one case in the maxilla. Histologically, four of the five cases (80%) presented with cystic features and three of the five cases (60%) with varying degrees of squamous metaplasia. The mucous cells were located in the epithelial islands or the luminal aspect of the cystic cavities. The BRAF V600E mutation was found in three of five cases (60%). All the cases showed no MAML2 rearrangement. Two cases were recurrent lesions, and one case had a local recurrence during the follow-up. CONCLUSIONS: Ameloblastoma with mucous cell differentiation is closely related to the cystic features, squamous metaplasia, and shows a high prevalence of BRAF V600E mutation. The absence of MAML2 rearrangement reveals that ameloblastoma with mucous cell differentiation and central mucoepidermoid carcinoma (MEC) are two distinct tumor entities.

[An investigation of severe neonatal hyperbilirubinemia in 13 hospitals of Jiangsu Province, China].

OBJECTIVE: To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China. METHODS: The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data. RESULTS: In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates. CONCLUSIONS: Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.

Reference values for serum cystatin C in very low-birthweight infants: From two centres of China.

AIM: To determine the level of cystatin C (Cys-C) values in preterm babies for the purpose of becoming a good endogenous marker of renal function. METHODS: A total of 366 very low-birthweight infants (including 70 extremely low-birthweight babies) with gestational age <37 weeks born in two centres were studied. RESULTS: In very low-birthweight infants, the mean level of Cys-C was 1.96 ± 0.44 mg/L in blood samples taken on day 1, 1.78 ± 0.49 mg/L on day 7 and 1.71 ± 0.47 mg/L on day 28. In extremely low-birthweight infants, the mean level of Cys-C was 2.00 ± 0.49 mg/L on day 1, 1.63 ± 0.38 mg/L on day 7 and 1.62 ± 0.55 mg/L on day 28, respectively. Compared to serum creatinine and blood urea nitrogen, Cys-C level was independent of birthweight and gestational age. CONCLUSION: Cys-C is regarded as an alternative for assessing renal function in very low-birthweight infants, but its advantages over serum creatinine and blood urea nitrogen has not been fully proved yet. Hence, larger sample study is still necessary.

Is neutrophil gelatinase-associated lipocalin a good diagnostic marker for renal injury in asphyxiated preterm infants?

BACKGROUND: The objective of this study is to evaluate the value of neutrophil gelatinase-associated lipocalin (NGAL) for becoming a good endogenous marker of renal function in asphyxial preterm babies. MATERIALS AND METHODS: This is a two-center retrospective study. Between October 2016 and October 2017, 71 asphyxial preterm infants were included in asphyxia group. Seventy babies were randomly included in control group. Samples were tested at 24, 48, and 96 h after birth. Quantitative data were compared by independent sample t-test or repeated measures ANOVA. For qualitative data, Pearson's Chi-squared test was performed. Draw ROC and compare the area under the curve (AUC), 95% confidence interval for AUC, specificity (Spe), sensitivity (Sen), and Youden index (Sen+Spe-1) at 24-h, 48-h, and 96-h time points. RESULTS: (1) There are no significant differences concerning on baseline data. However, blood gas, Apgar score, and resuscitation showed a significant difference (P < 0.05). (2) In 24-h samples, only uNGAL and estimated glomerular filtration rate (eGFR) showed differences between the two groups (P < 0.05). In 48-h samples, significant differences could be found in uKIM-1, uNGAL, blood urea nitrogen, and eGFR (P < 0.05). In 96-h samples, almost all indicators have significant differences except urine output and eGFR (P < 0.05). (3) All biomarkers showed statistical difference in the three time points (P < 0.05), but only uNGAL showed a downward trend after the increase of expression. (4) uNGAL has better Sen and Spe than other indicators (24-h AUC 0.870, Youden index 0.606; 48-h AUC 0.879, Youden index 0.692; and 96-h AUC 0.806, Youden index 0.606). CONCLUSION: uNGAL has a better distinguishability in asphyxial neonates compared with other indicators. Certainly, a larger sample, prospective study is still needed.

[Clinical efficacy of compound glycyrrhizin tablets in the treatment of children with nonalcoholic fatty liver disease].

Department of Pediatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. zhuchuanlong@jsph.org.cn.

Mild encephalitis/encephalopathy with a reversible splenial lesion: five cases and a literature review.

The aim of this study was to explore the clinical characteristics and etiology of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in China by retrospectively analyzing five MERS cases from the Jiangsu Provincial Hospital within a total of 27 reported MERS cases from available Chinese literature. Most of the 27 cases originated near the eastern and southern parts of China. Ages for 23 MERS cases were under 30 years and the female-to-male ratio was 1:1.25. The major causes of MERS included infection, antiepileptic drug withdrawal, high-altitude cerebral edema, and cesarean section (C-section). Hyponatremia was also observed in 10 MERS cases. All patients had a complete recovery within a month. Steroids and IVIG were the most commonly used therapy for MERS, but their efficiency remained questionable.

Heteroplasmy levels of mtDNA1555A>G mutation is positively associated with diverse phenotypes and mutation transmission in a Chinese family.

The mtDNA 1555A>G mutation was considered to be one of the most common causes of aminoglycoside-induced and non-syndromic hearing loss. However, this mutation was always found in homoplasmy with high phenotypic heterogeneity. Recently this mutation in heteroplasmy has been reported in several studies. In the present study, we have collected a large Chinese family harboring heteroplasmic mtDNA 1555A>G mutation with diverse clinical phenotypes. To investigate the relationship between the mutation load and the severity of hearing loss under Eastern Asian background, we performed clinical, molecular, genetic and phylogenic analysis. This pedigree was characterized by coexistence of eight subjects with homoplasmic mutation and ten subjects with various degrees of heteroplasmy, and the results suggested that there was a strong correlation between the mutation load and the severity/age-onset of hearing loss (r=0.758, p<0.001). We noticed that the mutation level of offspring was associated with their mothers' in this pedigree, which indicated that maybe exist a regular pattern during the process of the heteroplasmic transmission. In addition, analysis of the complete mtDNA genome of this family revealed that it belonged to Eastern Asian haplogroup B4C1. In addition, a rare homoplasmic mtDNA 9128T>C variant was identified, it located at a strictly conserved site of mtDNA ATP6 gene.

Mechanism of RIP2 enhancing stemness of glioma cells induces temozolomide resistance.

AIMS: We aimed to investigate the role of receptor-interacting protein 2 (RIP2) in regulation of stemness of glioma cells and chemotherapy resistance. METHODS: Plasmid transfection was used to overexpress RIP2. Chemical inhibitors were used to inhibit RIP2 or NF-κB activity. Cancer stemness of glioma cells was investigated by sphere formation assays, clone formation assays, and xenograft tumor formation assays. The expression of RIP2, p-NF-κB, IκBα, CD133, or SOX-2 was detected by Western blotting and immunofluorescence. Apoptosis was detected by flow cytometry. Immunohistochemical staining was used to detect the expression of RIP2, CD133, and SOX-2 in xenograft tumor tissue. The effect of the RIP2/NF-κB pathway on temozolomide (TMZ) resistance was evaluated by xenograft tumor assay. RESULTS: Transfection with RIP2 plasmid enhanced the sphere formation capability of U251 cells, clone formation capability, and xenograft tumor formation capability. RIP2 could mediate TMZ resistance by upregulating the expression of CD133 and SOX-2 by activating the NF-κB pathway. Both RIP2 inhibitor GSK583 and the NF-κB inhibitor SC75741 could reverse the resistance of U251 cells to TMZ. CONCLUSION: RIP2 mediates TMZ resistance by regulating the maintenance of stemness in glioma cells through NF-κB. Interventions targeting the RIP2/NF-κB pathway may be a new strategy for TMZ-resistant gliomas.

Modification of STIM2 by m6A RNA methylation inhibits metastasis of cholangiocarcinoma.

Background: N6-methyladenosine (m6A) is the most frequent internal methylation of eukaryotic RNA (ribonucleic acid) transcripts and plays an important function in RNA processing. The current research aimed to investigate the role of m6A-STIM2 axis in cholangiocarcinoma (CCA) progression. Methods: The expression of STIM2 (Stromal Interaction Molecule 2) in CCA was measured using quantitative polymerase chain reaction (PCR) and immunohistochemistry (IHC). STIM2 was examined in vivo for its effects on the malignant phenotypes of CCA cells. The m6A modification of STIM2 was assessed through MeRIP (methylated RNA Immunoprecipitation)-PCR. Results: Based on the GEPIA (Gene Expression Profiling Interactive Analysis) 2 database findings, a low STIM2 mRNA (messenger RNA) level was related to a poor prognosis in individuals with CCA. Quantitative PCR and IHC assays indicated decreased protein satin in CCA tissues and were associated with extrahepatic metastasis. Vianude mice tail vein injection model indicated that increased STIM2 levels suppressed CCA cell metastasis in vivo, while KRT8 (keratin 8) was detected as the direct downstream target of STIM2-mediated CCA cell metastasis in vivo. Meanwhile, based on SRAMP database and MeRIP assays indicated that m6A alteration resulted in abnormal STIM2 expression in CCA via METTL14 and YTHDC2. Conclusions: Our findings revealed the epi-transcriptomic dysregulation in CCA and metastasis by proposing a complicated STIM2-KRT8 regulatory paradigm based on m6A alteration.

Malignant potential of oral and labial chronic discoid lupus erythematosus: a clinicopathological study of 87 cases.

AIMS: To investigate clinicopathological features and identify clinicopathological risk factors for the malignant transformation of oral and labial chronic discoid lupus erythematosus (DLE) in a relatively large number of patients from China. METHODS AND RESULTS: A total of 87 patients with clinical and histopathological diagnosis of DLE between 1993 and 2009 were reviewed retrospectively in our hospital. The average age at diagnosis was 51.7 years, with a male:female ratio of 1:1.8. The lower lip was the most common site (71.3%). We documented six DLE patients with malignant transformation. On univariate analysis, patients with high-risk dysplasia (P = 0.002) or aged >60 (P = 0.045) were associated with DLE malignant transformation, but gender, lesion site, smoking and alcohol intake were not risk factors. On multivariate analysis, high-risk dysplasia was a significant indicator for DLE malignant transformation. High-risk dysplasia was associated with a 14.24-fold [95% confidence interval (95% CI), 1.97-102.88; P = 0.008] increased risk of malignant transformation, compared with non/low-risk dysplasia. CONCLUSIONS: The utilization of high-risk dysplasia as a significant indicator for evaluating malignant transformation risk in patients with DLE is suggested, which may be helpful to guide treatment selection.

Regulation of temozolomide resistance in glioma cells via the RIP2/NF-κB/MGMT pathway.

BACKGROUND: Temozolomide (TMZ) is a first-line chemotherapy drug for the treatment of malignant glioma and resistance to it poses a major challenge. Receptor-interacting protein 2 (RIP2) is associated with the malignant character of cancer cells. However, it remains unclear whether RIP2 is involved in TMZ resistance in glioma. METHODS: RIP2 expression was inhibited in TMZ-resistant glioma cells and normal glioma cells by using small interfering RNA (siRNA) against RIP2. Plasmid transfection method was used to overexpress RIP2. Cell counting kit-8 assays were performed to evaluate cell viability. Western blotting or immunofluorescence was performed to determine RIP2, NF-κB, and MGMT expression in cells. Flow cytometry was used to investigate cell apoptosis. TMZ-resistant glioma xenograft models were established to evaluate the role of the RIP2/NF-κB/MGMT signaling pathway in drug resistance. RESULTS: We observed that RIP2 expression was upregulated in TMZ-resistant glioma cells, whereas silencing of RIP2 expression enhanced cellular sensitivity to TMZ. Similarly, upon the induction of RIP2 overexpression, glioma cells developed resistance to TMZ. The molecular mechanism underlying the process indicated that RIP2 can activate the NF-κB signaling pathway and upregulate the expression of O6-methylguanine-DNA methyltransferase (MGMT), following which the glioma cells develop drug resistance. In the TMZ-resistant glioma xenograft model, treatment with JSH-23 (an NF-κB inhibitor) and lomeguatrib (an MGMT inhibitor) could enhance the sensitivity of the transplanted tumor to TMZ. CONCLUSION: We report that the RIP2/NF-κB/MGMT signaling pathway is involved in the regulation of TMZ resistance. Interference with NF-κB or MGMT activity could constitute a novel strategy for the treatment of RIP2-positive TMZ-resistant glioma.

Melanotic Neuroectodermal Tumor of Infancy: A Clinicopathological and BRAF V600E Mutation Study of 11 Cases.

PURPOSE: To investigate the clinicopathological features and BRAF V600E mutation of melanotic neuroectodermal tumor of infancy (MNTI). MATERIALS AND METHODS: Eleven cases of MNTI diagnosed at the Department of Oral Pathology were collected. Clinicopathological characteristics were obtained from the medical records. Immunostaining was performed by immunohistochemistry (IHC). Amplification-Refractory Mutation System-qPCR (ARMS-qPCR) and Sanger Sequencing were used to detect BRAF V600E mutation. RESULTS: Of the 11 cases, 3 cases were female and 8 cases were male. The mean age of the first symptoms was 3.2 months (range: 1 to 6 months). Ten cases (90.9%) located in maxilla but only one (9.1%) in mandible. Most of the cases demonstrated well-defined mass with lytic bone destruction and tooth germ affecting radiologically. Histologically, MNTI was consisted of large polygonal melanin-producing epithelioid cells and small round neuroblast-like cells which arranged in irregular alveolar, tubuloglandular and fissured architecture. The epithelioid cells expressed Vim, Pan-CK, NSE and HMB45, while the smalls cells expressed Syn, NSE and scattered Vim. Most cases showed low Ki-67 index (range: <1% to 50%). None of the MNTI cases showed BRAF V600E mutation. Most cases were treated with enucleation (45.4%) or curettage (36.4%). Among the 11 cases, 6 cases had follow-up information, and 2 cases had recurrence lesions after surgery. CONCLUSION: MNTI, an extremely rare tumor, mainly affects male infants with strong preference for maxilla. Distinct histopathological features and immunohistochemical profile are helpful to distinguish from other melanin-containing tumors and small round cell tumors. No BRAF V600E mutation in MNTI is detected in the present study and needs further investigations. The factors that contribute to the local recurrence of MNTI are controversial, but the close follow-up for the patients is recommended.

Analysis of Immunological Characteristics and Genomic Alterations in HPV-Positive Oropharyngeal Squamous Cell Carcinoma Based on PD-L1 Expression.

Programmed death-ligand 1 (PD-L1) expression has been approved as an immune checkpoint inhibitor (ICI) response predictive biomarker; however, the clinicopathological and molecular features of HPV-positive oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] based on PD-L1 expression are not well studied. We aimed to characterize clinicopathological, tumor immune microenvironmental, and molecular features of HPV(+)OPSCC with different PD-L1 expression scored by combined positive score (CPS). A total of 112 cases were collected from 2008-2021 and received PD-L1 and CD8 immunohistochemistry (IHC) staining. 71 samples received DNA sequencing out of which 32 samples received RNA sequencing for immune-related gene alterations or expression analysis. The 32 samples were also subjected to analysis of CD20, CD4, CD8, CD68, Foxp3 and P16 by multiplex immunofluorescence (mIF) staining, and the immune markers were evaluated in the tumor body (TB), tumor margin (TM) and normal stroma (NS) regions separately. Our results showed that of 112 HPV(+)OPSCC tumors, high(CPS≥20), intermediate(1≤CPS<20), and low(CPS<1) PD-L1 expression was seen in 29.5%, 43.8% and 26.8% cases respectively. Non-smoking patients and patients with tumors occurring at the tonsils or having rich lymphocytes infiltration had significantly higher PD-L1 expression. Patients with CPS≥20 had significantly higher tumor mutation burden (TMB, p=0.0058), and PD-L1 expression correlated significantly with CD8+ T cells infiltration, which were ample in tumor regions than in NS in mIF. CD20+, CD4+, CD68+, Foxp3+CD4+ cells were demonstrated to infiltrate higher in TM while CD20+ and CD68+ cells were also enriched in NS and TB regions respectively. However, none of them showed correlations with PD-L1 expression. ARID1A, STK11 alterations were enriched in the low PD-L1 group significantly, while anti-viral immune associated APOBEC mutation signature and immune-related genes expression such as XCL1 and IL11 were positively associated with PD-L1 expression (p<0.05). This is a comprehensive investigation revealing immune and molecular features of HPV(+)OPSCC based on PD-L1 expression. Our study suggested that 73.2% of HPV(+)OPSCC patients may benefit from immunotherapy, and high PD-L1 expression reflects immune-active status of HPV(+)OPSCC accompanied by higher immune effect factors such as TMB, CD8+ cytotoxic T cells and immune-related genomic alterations. Our study offers valuable information for understanding the immune features of HPV(+)OPSCC.

Primary pseudomyogenic hemangioendothelioma of right maxilla: a case with immunohistochemistry and FOSB rearrangement study.

OBJECTIVE: Primary pseudomyogenic hemangioendothelioma (PMH) of bone is an extremely rare vascular neoplasm. We present here a case of primary PMH occurring in the maxilla. STUDY DESIGN: A 34-year-old man was referred to our hospital for treatment because of possible recurrence after surgery and chemotherapy of a right maxillary malignant tumor. Morphologic features, immunophenotypes, and FOSB gene rearrangement status of the surgically sectioned sample were assessed by hematoxylin-eosin staining, immunohistochemistry, and fluorescence in situ hybridization, respectively. RESULTS: Morphologically, the tumor cells were arranged in a loose fascicular and sheet-like manner, with a large number of reactive woven bones forming. The most striking feature was the presence of epithelioid cells with abundant brightly eosinophilic cytoplasm, which resembled the rhabdomyoblast in appearance. The tumor was diffusely positive for AE1/AE3, CD31, erythroblast transformation-specific transcription factor, and Friend leukemia integration 1; negative for CD34, CAM5.2, epithelial membrane antigen, and desmin; and had retained expression of integrase interactor 1. The tumor harbored FOSB rearrangement. No distant metastasis was found during the follow-up period (18 months). CONCLUSIONS: To the best of our knowledge, this case represents the first report of PMH arising in the maxilla. The distinct morphologic features, immunophenotypes, and FOSB rearrangement could help achieve precise diagnosis and prevent misdiagnosis of mimics with overlapping features.

[GJB2 gene mutation in deaf patients].

OBJECTIVE: To detect the GJB2 gene mutation in patients with autosomal-recessive deafness, and analyze the relationship between clinical phenotype and gene mutation. METHODS: Forty-two patients were examined clinically by pure tone audiometry, acoustic impedance and auditory brainstem response. The complete coding region of the GJB2 gene was amplified by polymerase chain reaction (PCR) and the PCR products were subjected to automatic DNA sequencing. RESULTS: Two cases had homozygous mutation of 235delC. One of them had sensorineural hearing loss while the other had mixed hearing loss. Heterozygous mutation of 176del16bp was detected in a pair of twins who had mixed hearing loss. The 109G to A, 79G to A and 341A to G mutations were observed in both the patients and the controls. CONCLUSION: Homozygous 235delC mutation is one of the pathogeni c mutations which could occur in patients with mixed hearing loss. The heterozygous 176del16bp mutation combined with environmental factor may cause hearing loss. The 109G to A, 79G to A and 341A to G variants were considered to be polymorphisms of the GJB2 gene.

[Construction of clinical practice system of oral pathology for long-term program students in stomatology].

PURPOSE: To construct clinical practice system, making up for the shortcomings in the instructional framework of oral histology and pathology, promoting the integration of theory and clinical practice, and enhancing teaching quality of long-term students of stomatology. METHODS: Laying down clinical practice plans and formulating technical operation criteria for pathological experiments, constructing a complete database and training high-level teachers, and evaluating through the following three aspects: practice assessment, teacher-student symposium and questionnaire survey. RESULTS: After completing the clinical practice, the students got the average score of 89.37. In questionnaire survey, the students generally expressed that they had a better understanding of the specialized characteristics and routine skills of the speciality, and improved their practical ability, thus stimulating their interest in self-directed learning. CONCLUSIONS: The construction and practice of clinical practice system of oral histology and pathology can effectively improve the educational objectives and teaching quality of this discipline, which will play a positive role in scientific research and future medical work of long-term students majoring in stomatology.

[The relationship between the effect of amlodipine on carotid intimal-medial thickness and angiotensin converting enzyme genotypes in elderly hypertensive patients].

OBJECTIVE: To investigate the association between the anti-atherosclerotic effects of amlodipine and angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in elderly essential hypertensive (EH) patients. METHODS: A total of 220 EH patients were treated with amlodipine (2.5 - 10 mg, once daily) for twelve months and complete data were obtained from 208 patients with genotypes of II (n = 90), ID (n = 91) and DD (n = 27). The indices of carotid arterial were compared before and post amlodipine treatment in patients with identical genotype and among different ACE genotypes and each genotype post therapy. RESULTS: The carotid mean intimal-medial thickness (MIMT) was slightly decreased in EH patients with ID and DD genotypes and significantly decreased in EH patients with II genotype (0.96 +/- 0.12 vs. 0.92 +/- 0.13, P < 0.01) compared to pre-treatment values. The decreased degree of MIMT (DeltaMIMT) in II genotype was significantly higher in II genotype than those in ID or DD genotype (0.05 +/- 0.03 vs. 0.01 +/- 0.02, 0.01 +/- 0.03 respectively, P < 0.01). The post treatment plaque score (PS) in patients with II genotype was significantly reduced (4.85 +/- 2.51 vs. 3.90 +/- 2.36, P < 0.05). Multivariate linear regression analysis showed the baseline SBP, the decreased degree of SBP (DeltaSBP) and the II genotype were the major factors affecting the DeltaMIMT. CONCLUSION: Hypertensive patients carrying II genotype ACE genotype are the best responders for the anti-atherosclerotic effects of amlodipine.