1. Study on in vitro hypoglycemic effect and mechanism of Polygonum capitatum
Chinese Traditional and Herbal Drugs 2017;48(16):3401-3407
Objective: To investigate the hypoglycemic targets of Polygonum capitatum. Methods: Human liver cancer HepG2 cells were adopted to detect the supernatant culture medium glucose content, and the effect on PPAR-α and GLUT4 gene expression was investigated by qRT-PCR after treatment of P. capitatum extracts (PCB). INS-1 cells similar to islet β cells, divided into drug protection group and repair group, were adopted to determine the cell proliferation activity by MTT; The intracellular SOD and MDA levels were measured by biochemical method; The Cyt C and Caspase-3 protein expression levels were detected by Western blotting. Adopting maltose as substrate of α-glycosidase enzyme inhibition model, the inhibitory efficiency of PCB on glycosidic enzyme was determined. Results: PCB group significantly promoted the absorption of HepG2 cells to supernatant glucose and increased the expression of PPAR-α and GLUT4 genes significantly. Aim at protection and repair of INS-1 cells, PCB group significantly increased cell vitality and SOD level, reduced MDA level compared with model group, and at the same time significantly reduced Cyt C and Caspase-3 protein expression levels. PCB had inhibitory activity to α-glycosidase enzymes, with IC50 of 11.53 mg/mL. Conclusion: PCB could significantly increase the PPAR-α and GLUT4 genes expression to promote the absorption of HepG2 cells to supernatant glucose by blocking the Cyt C-Caspase-3 pathways to reduce apoptosis of islet cells which were damaged by STZ and by raising SOD and declining MDA to improve INS-1 cell oxidative stress; What’s more it has inhibitory activity to α-glycosidase enzymes.
2.Expert consensus on marsupialization of cystic lesions of the jaw
TAO Qian ; HE Yue ; LIU Bing ; HOU Jinsong ; NAN Xinrong ; ZHANG Bin ; ZHANG Leitao ; QIAO Bin
Journal of Prevention and Treatment for Stomatological Diseases 2020;28(2):69-72
Marsupialization is effective in the treatment of cystic lesions of the jaw. It is a simple operation that can result in minimal trauma, the reduction of postoperative recurrence, and maximum preservation of the surrounding tissue structure and function. However, there is a certain failure rate in clinical treatment due to the improper grasp of indications and nonstandard operation. The highest failure rate reported in the literature is 32.6%. To further standardize the clinical application of marsupialization and improve the success rate of treatment, we put forward an expert consensus of marsupialization in the treatment of jaw cystic lesions by reviewing the domestic and foreign literature and summarizing the experience in marsupialization from some famous domestic experts. In this consensus, we propose three elements of marsupialization: the establishment of the opening, the maintenance of cyst plugs and regular washing. The scope of application of marsupialization includes jaw cysts and cystic ameloblastomas. It is necessary to standardize the position of the opening, the size of the opening and the manufacture of the cyst plug, and a panoramic film or cone beam computed tomography(CBCT) should be used to observe the changes in the cystic cavity before and after operation. A second-stage operation should be performed when the lesion is significantly reduced by more than 50% or at least 5 mm from important structures; furthermore, the teeth of focus should be treated according to the relationship between the lesion and tooth and the type of tooth.
3.Combination of Tumor Volume and Epstein-Barr Virus DNA Improved Prognostic Stratification of Stage II Nasopharyngeal Carcinoma in the Intensity Modulated Radiotherapy Era: A Large-Scale Cohort Study.
Qiu Yan CHEN ; Shao Yan GUO ; Lin Quan TANG ; Tong Yu LU ; Bo Lin CHEN ; Qi Yu ZHONG ; Meng Sha ZOU ; Qing Nan TANG ; Wen Hui CHEN ; Shan Shan GUO ; Li Ting LIU ; Yang LI ; Ling GUO ; Hao Yuan MO ; Rui SUN ; Dong Hua LUO ; Chong ZHAO ; Ka Jia CAO ; Chao Nan QIAN ; Xiang GUO ; Mu Sheng ZENG ; Hai Qiang MAI
Cancer Research and Treatment 2018;50(3):861-871
PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.
Biomarkers
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Cohort Studies*
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DNA*
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Herpesvirus 4, Human*
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Humans
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Lymph Nodes
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Nasopharynx
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Plasma
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Prognosis
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Radiotherapy*
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Tumor Burden*
4.Osteosarcoma Cells Derived Exosome Activate Inflammatory Signaling Pathways in Lung Fibroblast Cells
Xian-biao XIE ; Li-li WEN ; Dong-ming LV ; Hong-bo LI ; Wei-hai LIU ; Yu-tong ZOU ; Hao YAO ; Jing-nan SHEN
Journal of Sun Yat-sen University(Medical Sciences) 2020;41(4):509-514
【Objective】 To investigate the function and molecular mechanism of osteosarcoma cells derived exosome on microenvironment of target organs. 【Methods】 The osteosarcoma derived exosomes were extracted and injected into nude mice through tail vein after PKH26 fluorescence staining. The liver, spleen, lung, kidney and brain tissues were extracted 24 hours later and then the amount of red fluorescence in different fields was counted under fluorescence microscope. The uptake of exosomes in different types of cells was detected by immunofluorescence. 143B derived exosomes were co-cultured with human lung fibroblasts, and the uptake was detected by fluorescence microscopy. The expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α were detected by RT-qPCR, while the changes of p-p65 in inflammatory signaling pathway of NF- κB and p-ERK, p-p38 in MAPK signaling were detected by western blotting. 【Results】 TSG101, Flotillin-1, CD63 and CD9 were expressed in 143B derived exosomes, and Calnexin expression was absent(P<0.05). The exosomes presented a saucer-like structure under electron microscope. The size of the exosomes is(141.92± 52.85) nm. The exosomes distributed more in lung tissue than liver, kidney, spleen and brain after injection through the tail vein of nude mice(P<0.05). The mRNA levels of inflammatory cytokines IL-1β, IL-6and TNF-α were significantly increased in human lung fibroblast cells after incubation with 143B exosomes(P<0.05). p-p65, p-ERK and p-p38MAPK were significantly up-regulated(P<0.05) . 【Conclusions】 Osteosarcoma cells derived exosomes could activate inflammatory signaling pathway NF-κB and MAPK, and up-regulate the expression of the inflammatory cytokines IL-1β, IL-6 and TNF-α in lung fibroblast cells.
5.Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.
Yuan Yue ZHU ; Rui Zhi ZHENG ; Gui Xia WANG ; Li CHEN ; Li Xin SHI ; Qing SU ; Min XU ; Yu XU ; Yu Hong CHEN ; Xue Feng YU ; Li YAN ; Tian Ge WANG ; Zhi Yun ZHAO ; Gui Jun QIN ; Qin WAN ; Gang CHEN ; Zheng Nan GAO ; Fei Xia SHEN ; Zuo Jie LUO ; Ying Fen QIN ; Ya Nan HUO ; Qiang LI ; Zhen YE ; Yin Fei ZHANG ; Chao LIU ; You Min WANG ; Sheng Li WU ; Tao YANG ; Hua Cong DENG ; Jia Jun ZHAO ; Lu Lu CHEN ; Yi Ming MU ; Xu Lei TANG ; Ru Ying HU ; Wei Qing WANG ; Guang NING ; Mian LI ; Jie Li LU ; Yu Fang BI
Biomedical and Environmental Sciences 2021;34(1):9-18
Objective:
The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.
Methods:
The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.
Results:
A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).
Conclusion
An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged
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Asian Continental Ancestry Group
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Blood Glucose/analysis*
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China/epidemiology*
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Cohort Studies
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Diabetes Mellitus/blood*
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Female
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Glucose Tolerance Test
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Glycated Hemoglobin A/analysis*
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Glycemic Index
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Humans
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Male
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Middle Aged
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Uric Acid/blood*
6.Overactive bladder symptom score to evaluate efficacy of solifenacin for the treatment of overactive bladder symptoms.
Ming LIU ; Jianye WANG ; Yong YANG ; Ruihua AN ; Jianguo WEN ; Zhichen GUAN ; Shaobin ZHENG ; Dongwen WANG ; Bo SONG ; Limin LIAO ; Hongqian GUO ; Jiaquan XIAO ; Yinghao SUN ; Zhoujun SHEN ; Chuize KONG ; Dalin HE ; Yiran HUANG ; Xiaofeng WANG ; Xu ZHANG ; Hanzhong LI ; Jian HUANG ; Xiaokun ZHAO ; Puqing ZENG ; Xishuang SONG ; Zhangqun YE
Chinese Medical Journal 2014;127(2):261-265
BACKGROUNDOveractive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB.
METHODSThis was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated.
RESULTSAt baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy.
CONCLUSIONSWe showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Muscarinic Antagonists ; therapeutic use ; Prospective Studies ; Quality of Life ; Quinuclidines ; therapeutic use ; Solifenacin Succinate ; Tetrahydroisoquinolines ; therapeutic use ; Treatment Outcome ; Urinary Bladder, Overactive ; drug therapy
7. Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin in Asian adult patients with chronic HCV genotype 1b infection and compensated cirrhosis
Lai WEI ; Guiqiang WANG ; Kopecky-Bromberg SARAH ; Jun CHENG ; Qing XIE ; Maorong WANG ; Min XU ; Zhongping DUAN ; Jinlin HOU ; Mingxiang ZHANG ; Yuexin ZHANG ; Hong TANG ; Wei ZHAO ; Shumei LIN ; Zhansheng JIA ; Junqi NIU ; Zhiliang GAO ; Hong YUAN ; Minghua LIN ; Xinmin ZHOU ; Yan LUO ; Fredrick LINDA ; Mobashery NILOUFAR ; Ye WANG ; Jidong JIA
Chinese Journal of Hepatology 2018;26(5):353-358
Objective:
To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis.
Methods:
An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs.
Results:
A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal.
Conclusion
Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.
8. Efficacy and safety of paritaprevir/ritonavir/ombitasvir combined with dasabuvir in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection: a randomized, double-blind, placebo-controlled study - China data
Lai WEI ; Jun CHENG ; Yan LUO ; Jun LI ; Zhongping DUAN ; Jinlin HOU ; Jidong JIA ; Mingxiang ZHANG ; Yan HUANG ; Qing XIE ; Guiqiang WANG ; Dongliang YANG ; Wei ZHAO ; Caiyan ZHAO ; Hong TANG ; Shumei LIN ; Guozhong GONG ; Junqi NIU ; Zhiliang GAO ; Kopecky-Bromberg SARAH ; Fredrick LINDA ; Mobashery NILOUFAR ; Ye WANG ; Jiefei WANG
Chinese Journal of Hepatology 2018;26(5):359-364
Objective:
To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily combined with dasabuvir 250mg, twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection.
Methods:
A randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial was conducted in mainland China, Korea, and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated (interferon alpha /pegylated interferon alpha) and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection. Patients randomly received OBV/PTV/r plus DSV for 12 weeks (Group A), or placebo for 12 weeks (Group B) followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks. Sustained response (SVR12) rate obtained at 12 weeks and (SVR24) 24 weeks after discontinuation of treatment, and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed.
Results:
A total of 410 cases of Chinese patients were included and randomly assigned to group A and B (with 205 cases in each group) in a 1:1 ratio. The rates of SVR12 and SVR24 were 99% (95%
9.Expert consensus on the prevention and treatment of adverse reactions in subcutaneous immunotherapy(2023, Chongqing).
Yu Cheng YANG ; Yang SHEN ; Xiang Dong WANG ; Yan JIANG ; Qian Hui QIU ; Jian LI ; Shao Qing YU ; Xia KE ; Feng LIU ; Yuan Teng XU ; Hong Fei LOU ; Hong Tian WANG ; Guo Dong YU ; Rui XU ; Juan MENG ; Cui Da MENG ; Na SUN ; Jian Jun CHEN ; Ming ZENG ; Zhi Hai XIE ; Yue Qi SUN ; Jun TANG ; Ke Qing ZHAO ; Wei Tian ZHANG ; Zhao Hui SHI ; Cheng Li XU ; Yan Li YANG ; Mei Ping LU ; Hui Ping YE ; Xin WEI ; Bin SUN ; Yun Fang AN ; Ya Nan SUN ; Yu Rong GU ; Tian Hong ZHANG ; Luo BA ; Qin Tai YANG ; Jing YE ; Yu XU ; Hua Bin LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(7):643-656
10.Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population.
Meng Fan LIU ; Rui Xia MA ; Xian Bao CAO ; Hua ZHANG ; Shui Hong ZHOU ; Wei Hong JIANG ; Yan JIANG ; Jing Wu SUN ; Qin Tai YANG ; Xue Zhong LI ; Ya Nan SUN ; Li SHI ; Min WANG ; Xi Cheng SONG ; Fu Quan CHEN ; Xiao Shu ZHANG ; Hong Quan WEI ; Shao Qing YU ; Dong Dong ZHU ; Luo BA ; Zhi Wei CAO ; Xu Ping XIAO ; Xin WEI ; Zhi Hong LIN ; Feng Hong CHEN ; Chun Guang SHAN ; Guang Ke WANG ; Jing YE ; Shen Hong QU ; Chang Qing ZHAO ; Zhen Lin WANG ; Hua Bin LI ; Feng LIU ; Xiao Bo CUI ; Sheng Nan YE ; Zheng LIU ; Yu XU ; Xiao CAI ; Wei HANG ; Ru Xin ZHANG ; Yu Lin ZHAO ; Guo Dong YU ; Guang Gang SHI ; Mei Ping LU ; Yang SHEN ; Yu Tong ZHAO ; Jia Hong PEI ; Shao Bing XIE ; Long Gang YU ; Ye Hai LIU ; Shao wei GU ; Yu Cheng YANG ; Lei CHENG ; Jian Feng LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(6):579-588
Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female
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Humans
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Adolescent
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SARS-CoV-2
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Smell
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COVID-19/complications*
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Cross-Sectional Studies
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COVID-19 Vaccines
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Incidence
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Olfaction Disorders/etiology*
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Taste Disorders/etiology*
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Prognosis