C0818, a novel curcumin derivative, induces ROS-dependent cytotoxicity in human hepatocellular carcinoma cells in vitro via disruption of Hsp90 function.

Heat shock protein 90 (Hsp90) is the most common molecular chaperone that controls the maturation of many oncoproteins critical in tumor development. Hsp90 has been considered as a promising target for cancer treatment, but the clinical significance of Hsp90 and the mechanisms of Hsp90 regulating the tumor-promoting effects in hepatocellular carcinoma (HCC) remain obscure. Previous studies have shown that curcumin, a polyphenol derived from the plant turmeric (Curcuma longa), inhibits tumor growth, which may provide an effective alternative therapy for HCC. Compared to curcumin, a novel derivative of curcumin, 3,5-(E)-Bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride (C0818) that is more potent in Hsp90 inhibition and antitumor activity. In this study, we investigated the effect of C0818 on HCC cells in vitro and its relation to Hsp90 inhibition. We showed that C0818 concentration-dependently inhibited the proliferation, the colony formation and induced apoptosis in HepG2 and Sk-Hep-1 cells. C0818 concentration-dependently inhibited DNA synthesis and induced G2/M phase arrest in HepG2 and Sk-Hep-1 cells. We further demonstrated that C0818 induced ROS- and caspase-dependent apoptosis in HCC cells through the mitochondrial-mediated pathway. C0818 induced the degradation of Hsp90 client proteins as RAS, C-Raf, P-C-Raf, Erk, P-ERK, MEK, P-MEK, Akt and P-Akt, which led to subsequent inhibition of the RAS/RAF/MEK/ERK and PI3K/AKT pathways. We revealed that C0818 could inhibit the binding of Hsp90 with its clients without affecting their transcription, which subsequently induced the degradation of Hsp90 clients by the proteasome rather than the lysosome. These results are of potential importance for elucidating a novel Hsp90 inhibitor targeting HCC.

Study on the Clinical Features and Prognosis of Penicilliosis marneffei Without Human Immunodeficiency Virus Infection.

OBJECTIVE: To improve the diagnosis and treatment of Penicilliosis marneffei without human immunodeficiency virus infection. METHODS: Analyze and review the clinical features, diagnosis and treatment of six cases of P. marneffei without human immunodeficiency virus infection at The First Affiliated Hospital of Fujian Medical University. RESULTS: Two cases were diagnosed in the ENT Department, three cases in the respiratory department and one case in the dermatological department. Penicillium marneffei infection was confirmed by sputum culture, blood culture and tissue biopsy. After definite diagnosis, one refused further treatment, and others showed significant improvement. CONCLUSION: Penicilliosis marneffei is insidious onset and easy to be escaped and misdiagnosed. To achieve early diagnosis and appropriate treatment, doubtful cases should be alerted for the diagnoses as P. marneffei.

Overexpression of YKL40,IL-6, IL-8, TNF-α in tonsils and the role of YKL40 in childhood with obstructive sleep apnea syndrome.

To evaluate the levels of YKL40, IL-6(interleukin-6), IL-8(interleukin-8), IL-10(interleukin-10), TNF-α (tumor necrosis factor-α) in OSAS (obstructive sleep apnea syndrome)children and explore the mechanism of YKL40 promoting inflammatory factors overexpression in tonsils. qPCR and ELISA were used to identify the expression of YKL40, IL-6, IL-8, IL-10, and TNF-α in the tonsils of OSAS children. Primary tonsil lymphocytes (PTLCs) were cultured and recombinant human YKL40(rhYKL40)was used to stimulate PTLCs in different concentrations and at different time points. The activation of NF-κB in PTLCs was screened by western blotting. Relative mRNA of YKL40, IL-6, IL-8, TNF-α was over expressed in OSAS-derived tonsil tissue and the levels of YKL40, IL-6, IL-8, and TNF-α was increased in OSAS-derived protein supernatant of tonsil tissue.The relative mRNA expression of IL-6, IL-8 and TNF-α increased under the treatment of YKL40 (100 ng/mmol for 24 h). The phosphorylation of p65 in NF-κB pathway was stimulated in the process. The levels of YKL40, IL-6, IL-8, and TNF-α increases in OSAS children, and YKL40 promotes the overexpression of IL-6, IL-8 and TNF-α in PTLCs via NF-κB pathway. The result implements that inflammation may play an important role in the pathogenesis of OSAS in children.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

A nationwide survey of otolaryngologists' compliance with Chinese guidelines for diagnosis and treatment of allergic rhinitis.

BACKGROUND: A higher compliance with clinical guidelines helps improve treatment outcomes. But the clinical practice of otolaryngologists is not always consistent with guidelines. OBJECTIVE: To describe otolaryngologists' compliance with guidelines about allergic rhinitis (AR) management and identify factors responsible for the discordance between clinical practice and guideline recommendations in China. METHODS: A cross-sectional nationwide survey was designed and conducted via an online platform. Recruitment was done by emailing otolaryngologists registered in the Chinese Society of Otorhinolaryngology-Head and Neck Surgery or by inviting otolaryngologists to scan a Quick Respond (QR) code that linked to the questionnaire at various academic meetings. RESULTS: A total of 2142 otolaryngologists were eligible and completed the survey. Of them, 64.7% had over 10 years work experience and 97.4% had a bachelor's degree or higher. About 18.3% of the participants strictly copied the guideline in clinical practice, while 73.7% used the guideline that had been adjusted according to their clinical experience. Otolaryngologists were most concerned about the efficacy, safety, and minimum age of AR medications, and least concerned about patient preferences. Regarding the use of intranasal steroids (INS), leukotriene receptor antagonists (LTRA), and H1-antihistamines, 86.8%, 55.7% and 51.2% of otolaryngologists complied with the guideline recommendations, respectively. Educational background was a factor affecting the compliance with guidelines and acceptance of INS. CONCLUSION: A vast majority of Chinese otolaryngologists complied with the current Chinese AR guidelines. A difference still existed between the otolaryngologists' real-world and guideline-recommended management. The otolaryngologists should pay more attention to patient preferences. A higher education could improve otolaryngologists' adherence to the guidelines.

Study on the correlation between OSAS and thoracic deformity in children: A retrospective single-center study in China.

OBJECTIVE: To evaluate the correlation between obstructive sleep apnea syndrome (OSAS) and the development of thoracic deformity in Children. METHODS: A retrospective analysis was performed with the medical records of 39 pediatric OSAS patients with thoracic deformity and matching 39 without thoracic deformity as control group between January 2015 and June 2019. The contrast was performed with age, gender, height, weight, body mass index (BMI), apnea/hypopnea index (AHI), the lowest oxyhemoglobin saturation (loSpO2)at night, tonsil and adenoid size, Alkaline phosphatase (ALP)and trace elements and metals between two groups. RESULTS: BMI, AHI, the lowest SpO2, Phosphorus and Zinc were the risk factors of thoracic deformity. Age, gender, disease history, the size of tonsil and adenoid, ALP and other trace elements were no significant difference occurred between two groups. CONCLUSION: OSAS characterized by apnea and hypoxia which are caused by narrow upper airway may be one cause of thoracic deformity in children. Pediatricians, thoracic and otolaryngologic surgeons should be alert to OSAS when thoracic deformities are diagnosed in children.

FM807, a curcumin analogue, shows potent antitumor effects in nasopharyngeal carcinoma cells by heat shock protein 90 inhibition.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy usually associated with overexpression of both epidermal growth factor receptor (EGFR) and ß-catenin. FM807 is a novel curcumin analogue with antitumor activity against both poorly and well-differentiated NPC cell lines as well as good selectivity for tumor cells. FM807 actions were shown to include inhibition of cell growth, induction of necrotic/late apoptotic cell death, and G1 arrest in NPC cells. Crucially, it exhibited potent antitumor effects both in vitro and in vivo. Binding of FM807 to the N-terminus of Hsp90 disrupted Hsp90/client complexes, resulting in degradation of the Hsp90 client protein EGFR and inhibition of the downstream Raf/MEK/ERK and PI3K/AKT pathway. FM807 also depleted levels of the intranuclear transcription factors ß-catenin, Cyclin D1 and c-Myc levels by inhibiting Hsp90 chaperoned nuclear transport. In conjunction with its low toxicity in NPC xenograft mice, these results provide a sound preclinical basis for further development of FM807 as a novel therapeutic agent in the treatment of NPC.

[Multi-center study of clinical treatment on the flat type of sudden hearing loss].

OBJECTIVE: To investigate the effect of different treatment options for the flat type of sudden hearing loss. METHODS: Prospective, multi-center clinical study was carried out using internationally used standardized clinical research method. Patients with the flat type of sudden hearing loss between 18 and 65 years old, within two weeks duration, and without any medical treatment were recruited. Treatment options were randomly selected according to the designed random table. RESULTS: From August 2007 to October 2011, 402 patients with the flat type of sudden hearing loss who met the criteria (account for 39.26% of the total number of patients) from the 33 hospitals were collected; the total effective rate was 82.59%, and no significant difference was detected between different treatments, (χ(2) = 10.95, P = 0.28). In the 402 cases, 139 were cured (34.58%); 118 were markedly improved (29.35%); 75 were effective (18.66%); 70 were invalid (17.41%). CONCLUSIONS: The therapeutic efficacy of flat type of sudden hearing loss overall is good; the treatment of improving the inner ear blood rheology and/or reducing blood fibrinogen has clinical significance; the therapeutic efficacy of using glucocorticoid systemically is good as well; there is no obvious difference between combination and single medication.

[Test-retest reliability of Mandarin monosyllable lists: a multi-center study in Chinese dialectal regions].

OBJECTIVE: To develop 22 Chinese Mandarin monosyllable lists with good psychometrical equivalence. This study was to evaluate the test-retest reliability of these lists when it was used in speech recognition test in normal hearing dialectal speakers. METHODS: Seven cities including Dalian, Shanghai, Hangzhou, Wuhan, Guangzhou, Fuzhou and Xiamen were selected as testing centers which contain 6 typical Chinese dialectal regions including north of China, East of China, north of Fujian, south of Fujian, Guangdong and mid-south of China. At each center, 22 local normal hearing people were selected to join this study. Every participant was tested by each recognition test of all 22 lists twice in two sessions and same test order respectively. The second run of testing was carried out within 10 days-1 month since first run of testing. RESULTS: There was a significant correlations between scores obtained at the two sessions (r = 0.682, P < 0.01). Paired student-t test had shown that a gross score of all dialectal participants was significantly higher than that of initial test to retest (P < 0.01). The mean increment of score was (2.7 +/- 10.1)%. A significant difference of test-retest score in 7 sites was 19.8% and it was equal to 5 test items. A one way ANOVA analysis had indicated that there were statistically significant difference between the score improvement of 7 test sites (P < 0.01). Another analysis had shown that there was no significant correlation between test-retest score improvement and intra-session intervals (P = 0.947). CONCLUSIONS: Mandarin monosyllabic recognition test seems to be more stable, and the present study has indicated a systematic differences in Chinese Mandarin monosyllable recognition scores between test and retest. Monosyllable recognition test is not susceptible to memory effect. Pearson's correction analysis is not suitable to evaluation for test-retest reliability.