[Phenotype-genotype analysis of the autosomal recessive hereditary hearing loss caused by OTOA variations].

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.

Application of B-flow imaging and its enhanced mode in perforator mapping.

AIM: To explore the value of B-flow (B-mode blood flow) imaging and its enhanced mode in perforator mapping. MATERIALS AND METHODS: Before surgery, B-flow imaging, enhanced B-flow imaging, colour Doppler flow imaging (CDFI), and contrast-enhanced ultrasound (CEUS) were used to detect the skin-perforating vessels and small vessels in the fat layer of the donor site. Taking the intra-operative results as the reference standard, the diagnostic consistency and efficiency of the four modes were compared. Statistical analysis was performed using the Friedman M-test, Cochran's Q-test, and the Z-test. RESULTS: Thirty flaps were excised, with 34 skin-perforating vessels and 25 non-skin-perforating vessels, as confirmed during surgery. In order of the number of skin-perforating vessels detected, the results showed that enhanced B-flow imaging detected more vessels than B-flow imaging and CDFI (all p<0.05), CEUS detected more vessels than B-flow imaging and CDFI (all p<0.05), B-flow imaging detected more vessels than CDFI (p<0.05). All four modes had remarkable and satisfactory diagnostic consistency and effectiveness, but B-flow imaging was the best (sensitivity 100%, specificity 92%, Youden index 0.92). In order of the number of small vessels in the fat layer detected, the results showed that enhanced B-flow imaging detected more vessels than CEUS, B-flow imaging, and CDFI (all p<0.05). CEUS detected more vessels than B-flow imaging and CDFI (all p<0.05). CONCLUSION: B-flow imaging is an alternative method for perforator mapping. Enhanced B-flow imaging can reveal the microcirculation of flaps.

[Epidemiological characteristics of pulmonary tuberculosis in Guangdong province from 2016 to 2020].

Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis (TB) in Guangdong province from 2016 to 2020 and provide evidence for the prevention and control of pulmonary TB. Methods: Descriptive epidemiological methods were used to analyze the incidence data of pulmonary TB reported in Guangdong from 2016 to 2020. Dynamic geometric series averaging and circular distribution methods were used to reveal the epidemic pattern. Results: A total of 356 748 pulmonary TB cases were reported in Guangdong from 2016 to 2020. The reported incidence of pulmonary TB decreased from 71.82/100 000 to 50.40/100 000 (trend χ2=6 905.57,P<0.001) , with an annual decline rate of 8.47%. Results from the circular distribution methods showed that the incidence peak would occur on May 4th-5th (Z=1 176.96,P<0.05), and the incidence was relatively higher in May compared with other months. The area distribution of the pulmonary TB epidemic was uneven, and the reported average annual incidence was in the order of the eastern area (72.15/100 000), the northern area (68.14/100 000), the western area (65.31/100 000) and the Pearl River Delta area (60.05/100 000). Results of dynamic geometric series averaging analysis showed a declining trend in the reported incidence of pulmonary TB in all areas, except Dongguan, with the average growth rate less than 0.00. The decline rate in the eastern area (-10.90%) and northern area (-10.63%) was higher than the provincial average (-8.47%). The male to female ratio of the cases was 2.63∶1 (258 562∶98 186). The reported average annual pulmonary TB incidence in men (88.37/100 000) was higher than that in women (36.86/100 000), the difference was significant (χ2=75.19, P<0.001). The reported incidence of pulmonary TB generally increased with age (trendχ2=123 849.44, P<0.001), and reached peak in age group ≥65 years (164.54/100 000). Dynamic geometric series averaging analysis showed an increasing trend of the reported pulmonary TB incidence in age groups 5-14 years and 15-24 years, with the average growth rate of 0.05% and 3.60%. Conclusions: The reported annual incidence of pulmonary TB showed a declining trend year by year in Guangdong from 2016 to 2020. However, an increasing incidence was reported in children and adolescents. Active case finding should be strengthened in the elderly and other key populations. With comprehensive TB prevention and control measures, it is still necessary to pay attention to the prevention and control of pulmonary TB in men, low-income groups and less developed areas in Guangdong and strengthen the comprehensive prevention and control in winter and spring.

[Nasopharyngeal carcinoma with non-squamous immunophenotype: a clinicopathological analysis of 23 cases].

Objective: To investigate the pathological subtypes and clinicopathological characteristics of the non-squamous immunophenotype nasopharyngeal carcinoma (NSNPC). Methods: The clinicopathological features of the non-squamous immunophenotype nasopharyngeal carcinoma diagnosed between 2011 and 2019 at the First Affiliated Hospital of Zhengzhou University were analyzed using hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, transmission electron microscopy and PCR gene rearrangement. Follow-up data were also collected. Results: There were 14 males and 9 females with a median age of 46 years (ranging from 16 to 76 years) with an average age of 45 years. Microscopically, patterns were similar to the classic nasopharyngeal carcinoma. Immunohistochemistry showed that most NSNPC cases expressed low molecular weight keratin (CK8/18, CK8 and CKL) and expressed pathway proteins in a low level (EGFR, PI3K, p-AKT and p-mTOR), which had significant difference from classic nasopharyngeal carcinoma group (P<0.05). Other proteins including CK5/6, CKpan, CK7, Syn, CD56, CgA, SOX-10, AKT, mTOR, Notch, STAT3 and p-STAT3 showed no statistical difference between the two groups. Pathogen detection showed that EBER was positive (18/23, 78.3%) and HPV positive(2/23, 8.7%)which were HPV35 and HPV38. The cancer suppressor gene BLU was highly expressed in NSNPC; RASSF1 and Rbms3 were less expressed in NSNPC, in line with classic NPC. As a whole, NSNPC was characterized by ultrastructures of low-differentiated squamous cell carcinoma. Compared with classic nasopharyngeal carcinoma, NSNPC had a lower recurrence rate and earlier clinical stage(P<0.05),but there was no significant correlation with age, sex, distant metastasis and death (P>0.05). Conclusions: The histological morphology, etiology and gene changes of NSNPC are similar to those of classical nasopharyngeal carcinoma and ultrastructural findings show that NSNPC still belongs to undifferentiated type in non-keratinized squamous cell carcinoma. The malignant degree of NSNPC is low and the prognosis is good.

[Interleukin 33 inhibits lipopolysaccharide-induced high permeability of cardiac microvascular endothelial cells].

Objective: To investigate the effect of interleukin-33 (IL-33) on lipopolysaccharide (LPS)-induced permeability of rat cardiac microvascular endothelial cells (RCMECs). Methods: RCMECs were cultured in vitro to be divided into control group, LPS group, IL-33 group and LPS+IL-33 group. The effect of IL-33 on the proliferation of RCMECs was detected by cell counting reagent (CCK8). Fluorescein isothiocyanate (FITC)-dextran assay was used to evaluate the permeability of RCMECs. The expression of vascular endothelial calmodulin, ras homologous gene family (Rho) member A (RhoA) and phosphorylated Rho-associated coiled-coil-containing protein kinase (p-ROCK2) proteins were tested by western blot. High-throughput sequencing and gene ontology (GO) were performed for gene expression in LPS and LPS+IL-33 groups. Results: No significant effect of IL-33 at 10-50 ng/ml on the proliferation of RCMECs was observed (P>0.05). Compared with the control group, the permeability of RCMECs (permeability coefficient ratio 1.404±0.029 vs. 1.000±0.200, P<0.05) was significantly increased in LPS group and the expression of vascular endothelial calmodulin (relative gray value 0.429 5±0.012 9 vs. 0.594 9±0.014 2, P<0.05) was down-regulated, while the permeability of monolayers (permeability coefficient ratio, 0.948±0.013, P<0.01) was decreased in LPS+IL-33 group and the expression of vascular endothelial calmodulin (relative grayscale value 0.549 1±0.012 0, P<0.005) was up-regulated compared with the LPS group. High-throughput sequencing data revealed that the differential genes downregulated in the LPS and LPS+IL-33 groups were associated with cytoskeleton and Rho signaling pathway. Compared with the control group, RhoA (relative gray value 0.211 4±0.009 9 vs. 0.135 0±0.007 6, P<0.000 1) and p-ROCK (relative gray value 0.656 3±0.013 2 vs. 0.503 6±0.036 2, P<0.000 1) protein expression was upregulated in the LPS group. When compared with LPS group, RhoA (relative gray value 0.157 7±0.010 7, P=0.000 2), p-ROCK (relative gray value 0.427 7±0.003 8, P<0.000 1) protein expression was decreased in LPS+IL-33 group. Conclusion: IL-33 may improve LPS-induced hyperpermeability of RCMECs by inhibiting RhoA and p-ROCK protein expression in Rho/Rho-associated coiled-coil-containing protein kinase signaling pathway.

Chondroitin Sulfate Enhances Proliferation and Migration via Inducing ß-Catenin and Intracellular ROS as Well as Suppressing Metalloproteinases through Akt/NF-κB Pathway Inhibition in Human Chondrocytes.

BACKGROUND: Chondroitin sulfate (CS) is found in humans' cartilage, bone, cornea, skin, and arterial wall. It consists of the foundation substance in the extracellular matrix (ECM) of connective tissue. The oral supplement form of CS is clinically used in treating osteoarthritis (OA). METHODS: Cell migration was observed by the transwell assay. The EMT, Akt/IKK/IκB pathways, TIMPs, collagen and MMPs in cell lysate were determined by Western blotting. The expression of MMP activity was determined by gelatin zymography. The production of reactive oxygen species (ROS) was determined by using a fluorescence spectrophotometer. RESULTS: In the current report, we demonstrated that CS can increase the cell proliferation and migration of chon-001 chondrocytes. Treatment with CS induced the epithelial-mesenchymal transition and increased the expression of type II collagen and TIMP-1/TIMP2 and inhibited the expressions and activities of metalloproteinase-9 (MMP-9) and metalloproteinase-2 (MMP-2). The phosphorylation of Akt, IκB kinase (IKK), IκB and p65 was decreased by CS. CS treatment resulted in ß-catenin production and XAV939, a ß-catenin inhibitor, and inhibited the cell proliferation by CS treatment. In addition, also significantly induced intracellular ROS generation. Treatment with antioxidant propyl gallate blocked cell migration induced by CS. CONCLUSION: We demonstrated that CS induced cell proliferation and migration of chondrocytes by inducing ß-catenin and enhancing ROS production. Moreover, our studies demonstrated that CS can increase the activity of chondrocytes and help patients with osteoarthritis to restore cartilage function.

What Factors Influence Dental Faculty's Willingness to Treat Pregnant Women?

BACKGROUND: Despite evidence-based guidelines advocating for the provision of oral health care throughout pregnancy, dentists remain hesitant to provide dental treatment for pregnant women. However, little is known about attitudes toward treating pregnant women among dental school faculty, who may transmit their attitudes and treatment preferences to their students. METHODS: We collected cross-sectional survey data at the New York University College of Dentistry, which produces 10% of all US dentists and is the largest US dental school, to understand faculty attitudes and knowledge regarding providing dental treatment to pregnant women. This study was part of an educational effort to improve dental care access by pregnant women and to examine what factors influence willingness to treat pregnant patients among dental faculty members. RESULTS: We found that concerns about professional liability outweighed inadequate knowledge regarding treatment of pregnant patients in determining dental faculty's willingness to treat pregnant women. CONCLUSIONS: Educational interventions delivered to dental faculty regarding current dental treatment guidelines for pregnant women may not be sufficient to increase faculty's provision of dental care to women during pregnancy. Future work to design effective interventions to increase dental treatment of pregnant women among dental faculty should address liability concerns. KNOWLEDGE TRANSFER STATEMENT: Interventions addressing dental clinician and faculty knowledge about dental treatment for pregnant women may be insufficient to increase dental treatment among pregnant women. Instead, policy makers should consider designing, implementing, and evaluating interventions addressing malpractice and liability concerns.

[Analysis of COL1A1 gene variation and clinical prevention and treatment in patients with Van der Hoeve syndrome].

Objective: To investigate the clinical phenotype, treatment and prevention of Van der Hoeve syndrome, and analyze the variation characteristics of its related gene COL1A1. Methods: Hearing and sequencing data of syndromic deafness patients who had undergone genetic testing for deafness at the Chinese People's Liberation Army General Hospital since January 2008 to October 2020 were retrospectively reviewed. The variation of the COL1A1 gene and return visits to traceable patients and families were summarized, the disease progress and clinical treatment effects were analyzed, and the prevention strategies were discussed. Results: A total of 7 patients with COL1A1 gene mutation underwent clinical intervention. The mutation sites were c.1342A>T (p.Lys448*), c.124C>T (p.Gln42*), c.249insG(p.Ala84*), c.668insC(p.Gly224*), c.2829+1G>C, c.1081C>T (p.Arg361*), c.1792C>T (p.Arg598*), of which c.1081C>T and c.1792C>T had been previously reported, and the remaining 5 were novo mutations that have not been reported. All the 7 probands underwent stapes implantation and received genetic counseling and prevention guidance. Conclusions: Van der Hoeve syndrome belongs to osteogenesis imperfecta type Ⅰ. The disease has high penetrance. Timely surgical intervention for hearing loss can improve the life quality in patients. Accurate genetic counseling and preimplantation genetic diagnosis can achieve the primary prevention for the disease.

[Risk stratified management of cervical adenocarcinoma in situ based on cone margin state].

Objective: To investigate the hierarchical management scheme of cervical adenocarcinoma in situ (AIS) based on cervical conization margin state. Methods: All medical records of 249 patients diagnosed as AIS by loop electrosurgical excision procedure (LEEP) conization from Jan. 2010 to Dec. 2015 in Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed, to explore the relationship between the status of the resection margin and the residual lesion after LEEP, and the multivariate logistic regression method was used to analyze the related factors that affect the residual lesion after LEEP in cervical AIS patients. Results: (1) The age of 249 cervical AIS patients was (40±8) years old (range: 23-71 years old). Of the 249 patients, 19 (7.6%, 19/249) had residual lesions; 69 cases were pathologically diagnosed as AIS after LEEP, and the residual lesion rate was 13.0% (9/69), which was significantly higher than that of AIS + high-grade squamous intraepithelial lesion [5.6% (10/180); χ2=3.968,P=0.046]; 33 cases were multifocal lesions, the residual rate of lesions was 21.2% (7/33), which was significantly higher than that of single focal lesions patients [5.6% (12/216); χ2=7.858, P=0.005]; 181 patients underwent endocervical curettage (ECC) before surgery, the residual rate of lesions in ECC-positive patients was 14.0% (14/100) , significantly higher than that of ECC-negative patients [4.9% (4/81); χ2=4.103, P=0.043]. (2) Among 249 cases of AIS patients, the positive rate of resection margins after LEEP was 35.3% (88/249); the residual rate of lesions in patients with positive resection margins (14.8%, 13/88) was significantly higher than those with negative margins [3.8%(6/156); χ2=9.355, P=0.002]. The age of patients underwent total hysterectomy after LEEP was (43±7) years old, which was significantly higher than that of patients who did not undergo total hysterectomy [(37±8) years old; t=6.518, P<0.01].Among the patients underwent total hysterectomy after LEEP, 3 cases (2.0%, 3/152) had fertility requirements, while 38 cases (39.2%, 38/97) did not underwent total hysterectomy, the difference between the two groups was statistically significant (χ2=59.579, P<0.01). Among the 152 patients who underwent total hysterectomy after LEEP, the residual rate of lesions was 11.8% (18/152); the residual rate of lesions in patients with positive resection margins was significantly higher than that of patients with negative resection margins [18.8% (12/64) vs 7.0% (6/86); χ2=4.861, P=0.028]. The median follow-up time of 97 patients who did not undergo total hysterectomy after LEEP was 32 months (range: 4-70 months). During the follow-up period, 3 cases of cervical AIS recurrence (3.1%, 3/97) and were followed by hysterectomy,no invasive adenocarcinoma were seen. (3) Multivariate logistic regression analysis showed that the positive resection margin (OR=4.098, 95%CI: 1.235-13.595, P=0.021), multifocal lesions (OR=5.464, 95%CI: 1.494-19.981, P=0.010) were independent risk factors that affected the residual lesions in patients with cervical AIS after LEEP. Conclusions: The cervical AIS patients after LEEP conization suggested be stratified by cone margin state as the first-line stratified index, age and fertility needs as the second-line stratified management index. The individualized management plan should be developed based on comprehensive assessment of high-risk factors of residual lesions.

[Phenotype and genotype analysis of recessive hereditary moderate sensorineural hearing loss caused by new mutations in OTOGL gene].

Objective: To perform the phenotype and genetic analysis on two families with moderate sensorineural hearing impairment and determine the cause of deafness. Methods: The phenotype and genetic analysis was performed on the two hearing impairment pedigrees coming to Chinese PLA General Hospital from January 2014 to August 2020. DNA samples of the proband from family 1 and the parents from family 2 were collected and tested through next generation sequencing on all deafness genes, and Sanger sequencing was performed to verify the mutation sites. The reported pathogenic variants of the otogelin-like (OTOGL) gene, the autosomal recessive inherited deafness genes that cause moderate sensorineural hearing loss and the clinical manifestations of the deafness genes that have the similar expression location as the OTOGL gene were summarized and analyzed. Results: The pathogenic variants in the families were compound heterozygous variants in the OTOGL gene c.2773C>T/c.2826C>G (p.Arg925*/p.Tyr942*) and c.4455G>A/c.875C>G (Trp1485*/p.Ser292*), respectively. c.2773C>T was an already reported pathogenic variant causing hearing impairment in the literature, while c.2826C>G, c.4455G>A and c.875C>G were novel reported variant sites. The above four variants were classified as pathogenic variants according to the variant interpretation standards and guideline of the Amercian College of Medical Genetics and Genomics. Conclusions: Pathogenic variants in OTOGL gene is an important genetic factor leading to moderate sensorineural hearing loss. The newly discovered variant sites c.2826C>G, c.4455G>A and c.875C>G enrich the variant spectrum of OTOGL gene. The results of the current study provide a basis for genetic counseling of the related families and a new target for the treatment of hereditary hearing loss in the future.

Irradiation resistance mechanism of the CoCrFeMnNi equiatomic high-entropy alloy.

When face-centered cubic (FCC) metals and alloys with low stacking fault energy (SFE) are irradiated by high-energy particles or deformed at high speed, stacking fault tetrahedra (SFTs), which are a type of vacancy cluster defect, are often formed. Therefore, SFTs were expected to form in the CoCrFeMnNi equiatomic high-entropy alloy (HEA). However, no SFT was observed in the CoCrFeMnNi HEA with high-speed plastic deformation even after annealing at 873 K. To elucidate this mechanism, the binding energy of vacancy clusters in the CoCrFeMnNi HEA was calculated based on first principles. The binding energy of the di-vacancy cluster was positive (average of 0.25 eV), while that of the tri-vacancy cluster was negative (average of - 0.44 eV), suggesting that the possibility of formation of a tri-vacancy cluster was low. The inability to form a cluster containing three vacancies is attributed to the excellent irradiation resistance of the CoCrFeMnNi HEA. However, if an extra vacancy is added to a tri-vacancy cluster (with negative binding energy), the binding energy of the subsequent tetra-vacancy cluster may become positive. This suggests that it is possible to form vacancy clusters in the CoCrFeMnNi HEA when high-energy ion or neutron irradiation causes cascade damage.

The invasion status of lymphovascular space and lymph nodes in cervical cancer assessed by mono-exponential and bi-exponential DWI-related parameters.

AIM: To investigate whether mono-exponential and bi-exponential diffusion-weighted imaging (DWI)-related parameters of the primary tumour can evaluate the status of lymphovascular space invasion (LVSI) and lymph node metastasis (LNM) in patients with cervical carcinoma preoperatively. MATERIALS AND METHODS: Eighty patients with cervical carcinoma were enrolled, who underwent preoperative multi b-value DWI and radical hysterectomy. They were classified into LVSI(+) versus LVSI(-) and LNM(+) versus LNM(-) according to postoperative pathology. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D∗), and perfusion fraction (f) were calculated from the whole tumour (_whole) and tumour margin (_margin). All parameters were compared between LVSI(+) and LVSI(-) and between LNM(+) and LNM(-). Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the diagnostic performance of these parameters. RESULTS: f_margin and D∗_whole showed significant differences in differentiating LVSI(+) from LVSI(-) tumours (p=0.002, 0.008, respectively), while LNM(+) tumours presented with significantly higher ADC_margin than that of LNM(-) tumours (p=0.009). The other parameters were not independent related factors with the status of LVSI or LNM according to logistic regression analysis (p>0.05). The area under the ROC curve of f_margin combined with D∗_whole in discriminating LVSI(+) from LVSI(-) was 0.826 (95% confidence interval [CI]: 0.691-0.961), while ADC_margin in differentiating LNM(+) from LNM(-) was 0.788 (95% CI: 0.648-0.928). CONCLUSIONS: The parameters generated from mono-exponential and bi-exponential DWI of the primary cervical carcinoma could help discriminate its status regarding LVSI (f_margin and D∗_whole) and LNM (ADC_margin).

Circular RNA hsa_circ_103809 promotes cell migration and invasion of gastric cancer cells by binding to microRNA-101-3p.

OBJECTIVE: Studies have found that hsa_circ_103809, a newly discovered circRNA in recent years, can serve as an oncogene involved in the progression of hepatocellular carcinoma. However, its role in gastric cancer (GCa) remains elusive. The aim of this study was to reveal the molecular mechanism of hsa_circ_103809 affecting the process of GCa, thus providing new ideas for its treatment. PATIENTS AND METHODS: Hsa_circ_103809 expression in GCa and adjacent tissues specimens were studied by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis, and its effect on the prognosis of GCa patients was analyzed. In GCa cells lines, hsa_circ_103809 was knocked down by small interfering RNA, and GCa cell metastasis ability was detected by cell wound healing test and transwell assay. Finally, the potential target gene of hsa_circ_103809 was predicted through bioinformatics website and verified by Luciferase assay. RESULTS: Hsa_circ_103809 showed an increased expression both in GCa tissues and cell lines, predicting a poor prognosis of GCa patients. Meanwhile, the invasive and migration capacities of GCa cells were remarkably reduced after the knockdown of hsa_circ_103809. Bioinformatics website predicted that there existed binding sites of hsa_circ_103809 on microRNA-101-3p, and Luciferase assay verified that hsa_circ_103809 can adsorb microRNA-101-3p. In GCa tissues, qPCR detected a significantly reduced expression of microRNA-101-3p, which was negatively correlated with that of hsa_circ_103809. In addition, the knockdown of hsa_circ_103809 enhanced microRNA-101-3p expression in GCa cell lines. Subsequent in vitro experiments further detected that the overexpression of hsa_circ_103809 partially reversed the inhibitory effect of microRNA-101-3p overexpression on GCa cell migration ability and invasiveness. CONCLUSIONS: Hsa_circ_103809, highly expressed in GCa, may promote the migration capacity of GCa cells by adsorbing microRNA-101-3p and thus become a new therapeutic target for GCa.

[Diagnostic performance of pathology, culture and ROSE of lung biopsy for suspected pulmonary infectious diseases].

Objective: To explore the diagnostic performance of CT guided percutaneous lung biopsy (PTLB) with pathology, culture and rapid on-site evaluation (ROSE) in patients with pulmonary infectious diseases. Methods: From January 2016 to June 2018, a retrospective study was implemented in the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University. Patients who received PTLB, suspected with lung infection were included. The basic information, clinical symptoms, imaging findings, diagnostic methods, complications, and changes in treatment of cases were collected. The diagnostic sensitivity of histopathology, microbial culture, and ROSE were evaluated at the same time. Results: A total of 529 cases were enrolled, including 354 males and 175 females, (59±14) years old in average. Tuberculosis was identified in 197 cases, non-tuberculosis mycobacteria (NTM) pulmonary disease in 8, cryptococcosis in 95, pulmonary aspergillosis in 27, filamentous fungal pneumonia in 3, talaromyces marneffei pulmonary infection in 3 and pulmonary candidiasis in 1, bacterial pneumonia in 39, and pathogen were unknown in 156 cases. A total of 417 cases were submitted for histopathology and microbial culture at the same time, the diagnostic value of pathology and microbial culture were 35.0% (146/417) and 45.6% (190/417), respectively. Combined pathology with microbial culture, the diagnostic value increased to 62.8% (262/417). The diagnostic accuracy of ROSE was 51.8% (71/137). The most common complication of PTLB was pneumothorax 26.1% (138/529). 56.1% (297/529) of the patients received targeted treatment after the diagnosis was confirmed, and 43.9% (232/529) maintained the original treatment. Conclusion: The pathology, microbial culture, and ROSE of PTLB have relative high diagnostic value for pulmonary infectious diseases.

[High serum cholesterol: a novel risk factor for thyroid associated ophthalmopathy?]

This study was aimed to investigate the association between dyslipidemia and thyroid associated ophthalmopathy (TAO). We evaluated the relationship between dyslipidemia and TAO in 218 patients with Graves' disease (GD) and found that the serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in the GD subjects with TAO (n=110) were significantly increased [(5.32±1.39) mmol/L vs. (3.18±2.12) mmol/L, (2.98±0.75) mmol/L vs. (1.25±0.98) mmol/L] than those in the GD subjects without TAO (n=108). TC and LDL-C were positively correlated with the Clinical disease activity score (CAS) [TC (r=0.7, P=0.03),LDL-C (r=0.82, P=0.03)], and the levels of TC (OR=2.56, P=0.02) and LDL-C(OR=2.01, P=0.015) were positively associated with TAO. These suggested that high serum cholesterol level is a novel risk factor for TAO, and management of blood lipids should be included in the treatment of TAO.

Chlorhexidine-based decolonization to reduce healthcare-associated infections and multidrug-resistant organisms (MDROs): who, what, where, when, and why?

Body surface decolonization with chlorhexidine bathing and nasal mupirocin has become a simple solution for prevention of healthcare-associated infections. The clinical trial evidence for this practice will be reviewed to understand who benefits from this practice, for what reasons, and at what times. The method of bathing and nasal decolonization will also be discussed as proper application is needed for maximal effectiveness. Finally, the conflict between current effectiveness and future potential for fueling resistance is considered.

[Case report and diagnosis of Noonan syndrome with multiple lentigines with deafness as its main clinical feature].

Summary Noonan syndrome with multiple lentigines（NSML） is a disorder with syndromic hearing loss. Abnormalities of other systems in NSML have received increasing attention, but hearing loss is rarely concerned. And due to the incomplete phenotype, some patients with NSML maybe missed or maybe confused with other syndromic deafness such as Waardenburg syndrome. Our study will familiarize more otolaryngologists with Leopard syndrome. A 5-year-old boy with bilateral sensorineural hearing loss and numerous symmetrically distributed dark brown macules that had good effect of cochlear implantation was collected in this study. And his father had bilateral sensorineural hearing loss and numerous symmetrically distributed dark brown macules. Waardenburg syndrome was initially diagnosed by clinical phenotype and its molecular etiology was confirmed by gene diagnosis. Waardenburg syndrome-related deafness genes and 131 known deafness genes were not identified by second-generation sequencing. Whole-exon sequencing was performed for 4 individuals in the family and the results were confirmed by Sanger sequencing. This study confirmed the diagnosis by identifying a disease-causing mutation in the PTPN11 gene, which was a heterozygous missense mutation at p. Tyr279Cys（c. 836A>G）. The mutation co-segregated with hearing loss in the family. Our results demonstrated that hearing loss in this family was caused by heterozygous mutations in PTPN11. These cases will familiarize more otolaryngologists with NSML, and they emphasize the importance of considering NSML as a possible cause of hearing problems.