[A multicenter study on the accuracy of PAX1/JAM3 dual genes methylation testing for screening cervical cancer].

Objective: To explore the value of cervical cytologic DNA methylation for screening cervical cancer. Methods: This study was a prospective multicenter study conducted from May to October 2022 in Peking Union Medical College Hospital, Zhejiang Provincial People's Hospital, and the Second Affiliated Hospital of Zhejiang University School of Medicine. Women who accepted opportunistic cervical cancer screening in gynecological outpatient clinics were subjected to liquid-based thin-layer cytology testing (TCT), high-risk human papillomavirus (hrHPV) DNA testing and PAX1/JAM3 dual-genes methylation testing (PAX1m/JAM3m). Colposcopy evaluation and biopsy were offered to women according to current guidelines. The accuracies of various testing methods and their combinations were compared based on histological diagnosis. Results: A total of 1 184 samples diagnosed by histopathology were included in this study, consisting of 541 cases (45.7%) of benign cervical tissue or chronic cervicitis, 273 (23.1%) of cervical intraepithelial neoplasia (CIN) 1, 168 (14.2%) of CIN2, 140 (11.8%) of CIN3, and 62 (5.2%) of cervical cancer. The sensitivity and specificity of PAX1m/JAM3m testing for detecting CIN2 or more severe lesions (CIN2+) were 74.1% and 95.9%, respectively. The sensitivity and specificity of PAX1m/JAM3m testing for detecting CIN3+were 87.6% and 86.8%, respectively. Receiver operating characteristic curve analysis showed that, for detecting CIN3+, the area under curve of PAX1m/JAM3m testing (0.872, 95%CI: 0.847-0.897) was significantly superior to TCT testing (0.580, 95%CI: 0.551-0.610) or hrHPV testing (0.503, 95%CI: 0.479-0.515) (all P values<0.05). Conclusions: The PAX1m/JAM3m test in cervical exfoliated cells has excellent accuracy for the diagnosis of both CIN2+and CIN3+, which is superior to traditional screening protocols and screening strategies.

[A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey].

Objective: To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors. Methods: From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions. Results: Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects (χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients (χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications (χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment (R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not (OR=1.83, P<0.001). Conclusions: Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

[Application and exploration of small dose omalizumab in patients with recurrent eosinophilic sinusitis after extended sinus surgery].

Objective: To explore the short-term efficacy of small dose omalizumab in refractory sinusitis with eosinophilia after extended sinus surgery. Methods: A total of 24 patients who met the diagnostic criteria for eosinophilic chronic rhinosinusitis and remained poorly controlled after multiple surgical treatments were included in this study. These patients were admitted to Hunan People's Hospital between January 2020 and June 2022, and comprised 13 males and 11 females with an average age of (46.43±13.74) years. The patients were randomly divided into experimental group (12 cases) and control group (12 cases), both of which underwent extended sinus opening surgery. The experimental group received a small dose of omalizumab (150 mg/month) for 4 months, while no omalizumab was applied in the control group. All patients were followed up monthly, subjective and objective symptom scores were collected and compared between groups, which included visual analogue scale (VAS) score, sino-nasal outcome test (SNOT)-22 score, Lund-Mackay score, and Lund-Kennedy score. Statistical analysis was performed using SPSS 24.0 software. Results: The baseline was set at 1 month after surgery. There was no significant difference in baseline clinical characteristics between the two groups. After 4 months of treatment with omalizumab, the experimental group showed significant improvements in VAS scores for nasal obstruction, rhinorrhea, hyposmia, SNOT-22 score, and Lund-Kennedy score (3.11±1.05 vs 6.44±1.13, 2.00±0.87 vs 6.55±1.33, 2.22±0.67 vs 7.00±1.22, 4.44±0.88 vs 15.22±1.20, 1.67±1.00 vs 7.44±0.88, respectively, all P<0.001). Compared to the control group at 4 months after baseline, the experimental group had significantly lower scores for nasal obstruction, rhinorrhea, hyposmia, SNOT-22, and Lund-Kennedy (3.11±1.05 vs 7.11±1.17, 2.00±0.87 vs 7.67±1.41, 2.22±0.67 vs 7.56±0.88, 4.44±0.88 vs 15.33±2.34, 1.67±1.00 vs 9.00±1.41, respectively, all P<0.001). During a 2-month follow-up period after drug withdrawal, the VAS, SNOT-22, and Lund-Kennedy scores of the experimental group were slightly higher than those before drug withdrawal but showed no significant difference (3.44±1.33 vs 3.11±1.05, 2.22±1.09 vs 2.00±0.86, 2.55±0.88 vs 2.22±0.66, 4.77±0.97 vs 4.44±0.88, 2.11±1.05 vs 1.67±1.00, respectively, all P>0.05). Conclusion: For patients of refractory sinusitis with eosinophilia, a combination of extended sinus surgery and postoperative small dosage of omalizumab can effectively control mucous inflammation, promote mucosal epithelization, and play an important role in the critical early stage of disease recovery.

[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].

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.

[The role of DNA methylation in the screening of endometrial cancer in postmenopausal women].

Objective: To explore the application value of cervical exfoliated cell DNA methylation (CDO1m and CELF4m) combined with or without transvaginal sonography (TVS) for screening endometrial cancer in postmenopausal women. Methods: A total of 143 postmenopausal women who underwent hysteroscopy for suspected endometrial lesions in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from May 2020 to October 2021 were enrolled in this study. The cervical exfoliated cells were collected for gene methylation before hysteroscopy. Clinical information, tumor biomarkers, and endometrial thickness of TVS were also collected. With endometrial histopathology as the gold standard, multivariate unconditional logistic regression was applied to analyze the risk factors of endometrial cancer. The role of gene methylation with or without TVS were specifically explored. Results: The 143 patients were divided into an endometrial cancer group (n=56) and a control group (n=87), aged (59.27±6.45) and (61.07±8.26) years, respectively (P=0.051). Multivariate logistic regression analysis showed that, CA125≥35 U/ml, postmenopausal bleeding, endometrial thickness≥5 mm, CDO1m ΔCt≤8.4, and CELF4m ΔCt≤8.8 were the risk factors for endometrial cancer, with OR (95%CI) of 33.23 (2.51-1 335.28), 8.41(1.81-39.05), 14.45 (2.35-88.84), 17.34 (3.34-89.98), and 44.01 (6.79-285.25), respectively (all P values<0.05). The sensitivity and specificity of dual-gene methylation (CDO1 or CELF4) in the screening of endometrial carcinoma were both higher than others factors, reaching 87.5% (95%CI: 75.9%-94.8%) and 90.8% (95%CI: 82.7%-95.9%), respectively. TVS combined with DNA methylation detection further improved the sensitivity to 100.0% (95%CI: 93.6%-100.0%), but could not improve the specificity (59.8%, 95%CI: 48.8%-70.1%). Conclusions: In postmenopausal women with suspected endometrial lesions, the accuracy of cervical cytology DNA methylation is better than other noninvasive clinical indicators for the screening of endometrial cancer. DNA methylation combined with TVS can further improve the sensitivity of screening.

Ear fullness characteristics and prognosis in patients with all-frequency sudden sensorineural hearing loss.

OBJECTIVE: This study investigated the characteristics and prognosis of the feeling of ear fullness in patients with unilateral all-frequency sudden sensorineural hearing loss. METHODS: Our study included 56 patients with a diagnosis of unilateral all-frequency sudden sensorineural hearing loss accompanied by a feeling of ear fullness and 48 patients without a feeling of ear fullness. The condition of these patients was prospectively observed. RESULTS: Positive correlations were observed between grading of feeling of ear fullness and hearing loss in patients with a feeling of ear fullness (r = 0.599, p < 0.001). No significant differences were observed in the total effective rate of hearing recovery between patients with and without a feeling of ear fullness after one month of treatment (Z = -0.641, p = 0.521). Eighty-six per cent of patients (48 out of 56) showed complete recovery from the feeling of ear fullness. There was no correlation between feeling of ear fullness recovery and hearing recovery (r = 0.040, p = 0.769). CONCLUSION: The prognosis of feeling of ear fullness is good. There was no correlation between feeling of ear fullness recovery and hearing recovery for all-frequency sudden sensorineural hearing loss patients.

Influences of different manure N input on soil ammonia-oxidizing archaea and bacterial activity and community structure in a double-cropping rice field.

AIMS: The short-term effects of different organic manure nitrogen (N) input on soil ammonia-oxidizing archaea (AOA) and bacterial (AOB) activity and community structure at maturity stages of early rice and late rice were investigated in the present paper, in a double-cropping rice system in southern China. METHODS AND RESULTS: A field experiment was done by applying five different organic and inorganic N input treatments: (i) 100% N of chemical fertilizer (M0), (ii) 30% N of organic manure and 70% N of chemical fertilizer (M30), (iii) 50% N of organic manure and 50% N of chemical fertilizer (M50), (iv) 100% N of organic manure (M100) and (v) without N fertilizer input as control (CK). Microbial community changes were assessed using fatty acid methyl esters, and ammonia oxidizer (AO) changes were followed using quantitative PCR. The results showed that AOA were higher than that of AOB based upon amoA gene copy at maturity stages of early rice and late rice. Also, the abundance of AOB and AOA with M30, M50 and M100 treatments was significantly higher than that of CK treatment. Manure N input treatments had significant effect on AOB and AOA abundance, and a higher correlation between AOB and manure N input was observed. AOB correlated moderately with soil organic carbon content, and AOA correlated moderately with water-filled pore space. CONCLUSIONS: This study found that abundance of AOB and AOA was increased under the given organic N conditions, and the soil AOB and AOA community and diversity were changed by different short-term organic manure N input treatments. SIGNIFICANCE AND IMPACT OF THE STUDY: Soil microbial community and specific N-utilizing microbial groups were affected by organic manure N input practices.

[Characteristics and prognosis of ear fullness feeling in patients with all-frequency sudden deafness].

Objective: The characteristics and prognosis of ear fullness feeling in patients with all-frequency sudden deafness were explored. Method: 104 patients (104 ears) with unilateral all-frequency sudden deafness were collected in study from June 2015 to March 2019, including 50 males and 54 females, the mean age ranged from 23-65 years, and the disease duration ranged from 1-9 days. Of those, 56 patients accompanied with the feeling of ear fullness (FEF) were enrolled into'the ear fullness group', and 48 patients without FEF were included in'the without ear fullness group'. Patients' treatment strategy followed the Chinese Medical Association Guidelines for the diagnosis and treatment of sudden deafness (2015). Moreover, VAS scale scores and subjective grading of FEF were acquired in patients with FEF. We analyzed the clinical characteristics and prognosis of FEF with SPSS 23.0 software. Results: There were no differences between the two groups in terms of age, gender, duration of disease, the side of deaf ear, degree of hearing loss, and auditory brainstem evoked potential results (age,t=1.566; gender,χ(2)=0.001; duration, t=0.057; side,χ(2)=0.033; degree of hearing loss Z=-0.180; ABR,χ(2)=0.001;all P>0.05) . There was a positive correlation between the subjective grading of FEF and the degree of hearing loss in patients with FEF (r=0.599, P<0.001) . The total rate of hearing improvement following one month of treatments in patients with FEF vs with no FEF was 35/56(62.5%) vs 28/48(58.3%) (Z=-0.641, P=0.521). After one month of treatment, the total effective rate of FEF was 94.6%(53/56), and the improvement of FEF had nothing to improvement of hearing (r=0.040, P=0.769) . Conclusions: The degree of hearing loss is positively correlated with the degree of FEF in patients with all-frequency sudden deafness. Hearing recovery is not related to FEF. The recovery effect of FEF is good, and has no correlation with hearing recovery.

[Diagnostic value of serum miRNA let-7a for laryngeal carcinoma and effects of let-7a on proliferation and apoptosis of laryngeal carcinoma cells].

Objective: To investigate the diagnostic value of serum miRNAlet-7a in laryngeal carcinoma and the effect of let-7a on proliferation and apoptosis of laryngeal carcinoma cells. Methods: Real-time quantitative PCR was used to determine the expression level of serum miRNAlet-7a. The miRNA let-7a mimetic was synthesized and transiently transfected into the laryngeal carcinoma Hep-2 cell line by cationic liposome method. The effects of up-regulation of let-7a expression on laryngeal cancer Hep-2 cells were detected by FCM and MTT assays,respectively. The association of let-7a levels with laryngeal cancer and the diagnostic value for laryngeal cancer were analyzed. Measurement data were taken by t test or analysis of variance; Counting data were analyzed by χ(2) test and Fisher exact probability method. The receiver operating characteristic curve was used to analyze the diagnostic value of let-7a for laryngeal cancer. Results: The relative expression of serum let-7a in healthy subjects was significantly higher than that in patients with laryngeal cancer (0.931±0.094) vs (0.380±0.113) (t=26.507,P<0.01). The relative expressions of serum let-7a in patients with laryngeal cancer before and after surgery were (0.380±0.113) vs(0.493±0.164),with significant difference (t=3.848,P<0.01).The relative expression of serum let-7a was related to lymph node metastasis (t=2.946, P<0.01). There was a positive correlation between the relative expression of let-7a in laryngeal carcinoma and that in serum (r=0.466,P=0.003). After transfection of let-7a mimics, Hep-2 cells showed an increased significant increase in the expression of let-7a (P<0.01), proliferation (P<0.01) and apoptosis (P<0.01). ROC curve analysis showed that the best critical value for relative expression of let-7a in the diagnosis of laryngeal carcinoma was 0.557 with a sensitivity of 0.794,a specificity of 0.727,an area under curve(AUC) of 0.859,and a 95%CI of 0.773-0.926. Conclusions: miRNA let-7a can inhibit the proliferation of laryngeal carcinoma Hep-2 cells and promote apoptosis. Serum let-7a is down-regulated in patients with laryngeal cancer and the level of let-7a is related to lymph node metastasis,which would help early diagnosis and postoperative disease monitoring of laryngeal cancer,but further research is needed.

[Hyper-IgE syndromes].

A hyper-IgE syndrome is a rare immunodeficiesncy disease, often accompanied by high serum IgE. It often characterized by facial features, repeated skin infections, eczema and pulmonary infection, including autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES). AR-HIES is caused by mutations in STAT3, which is presented as connective tissue, bone, vascular disease, and high brain white matter signal. AD-HIES is mainly caused by mutations in DOCK8 and TYK2, which is presented as severe viral infection and poor prognosis. The treatment for Hyper-IgE syndromes is mainly to control infection, skin care and other symptomatic treatment, if necessary, should be done as early as possible hematopoietic stem cell transplantation. This article reviews the clinical manifestations, pathogenesis and treatment of high IgE syndrome.

[Synovial sarcoma of infratemporal fossa and pterygopalatine involving maxillary sinus 1 case and the literature review].

We report a case which involves the maxillary sinus by original of synovial sarcoma of infratemporal fossa and pterygopalatine. A 40-years-old man presented with a history of tumor under the earlobe. It is derived from the synovial sarcoma under temporal fossa after tumor excision. The patient is limited to open his mouth and nasal obstruction. The nasal pathologic examination consider synovial sarcoma.We report the case to improve doctors' comprehension of its pathogenesis,clinical manifestations,teeatment and prognosis.

Expression and fast preparation of biologically active recombinant human coagulation factor VII in CHO-K1 cells.

Human coagulation factor VII (FVII) plays an important role in the blood coagulation process and exists in micro amounts in human plasma; therefore, any attempt at the large-scale production of FVII in significant quantities is challenging. The purpose of this study was to express and obtain biologically active recombinant FVII (rFVII) from Chinese hamster ovary K1 (CHO-K1) cells. The full-length FVII cDNA was isolated from a HepG2 cell line and then subcloned in pcDNA3.1 to construct an expression vector, pcDNA-FVII. CHO-K1 cells were transfected with 1 µg pcDNA-FVII. The cell line that stably expressed secretory FVII was screened using 900 µg/mL G418. The FVII copy number in CHO-K1 cells was detected by quantitative polymerase chain reaction (qPCR). The rFVII was purified in ligand affinity chromatography medium. The purified protein was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. The biological activity of the purified FVII protein was determined by a prothrombin time assay. Three cell lines that permanently expressed rFVII were screened. The qPCR results demonstrated that each CHO-K1 cell harbored two FVII DNA copies. The SDS-PAGE and Western blot analysis showed that the purified protein was about 50 kDa. The purity of the target protein was 95%. The prothrombin time assay indicated that the FVII-specific activity of rFVII was 2573 ± 75 IU/mg. This method enabled the fast preparation of high-purity rFVII from CHO-K1 cells, and the purified protein had good biological activity.