Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

[Effects of rapid and progressive ascent to Tibet plateau on cardiovascular function and stress factors of pre-selected expeditioners for Chinese Antarctic expedition for Kunlun station].

Objective: To explore the different effects of rapid and progressive ascent to Tibet plateau on cardiovascular function and stress factors in pre-selected expeditioners for the 31st, 32nd and 33rd Chinese Antarctic expedition for inland station, to provide a scientific basis for the selection of qualified expeditioners. Methods: A total of 85 pre-selected expeditioners for the 31st, 32nd and 33rd Chinese Antarctic expedition for Kunlun station were enrolled in this study. According to the different manners of entering the plateau, they were divided into the rapid ascent group by aircraft (RAG, n=55) and the progressive ascent group by train (PAG, n=30). Hemodynamics and electrocardiogram were examined at 4 m (Shanghai), areas at altitude of 3 658 m (Lhasa) and 4 300 m(Yangbajain), respectively. Saliva levels of stress factors, including testosterone (T), cortisol (COR) and immunoglobulin A (IgA), were tested by ELISA. Results: The heart rates (HR) were increased significantly, while the SpO2 was decreased significantly in the two groups within 24 hours at altitudes of 3 658 m and 4 300 m (P＜0.05), while there was no significant difference between the two groups at the same altitude. Compared with 4 m, the blood pressure (BP) of the two groups at 3 658 m and 4 300 m was significantly increased (P＜0.05), and some indexes of myocardial contraction and pumping function were significantly reduced (P＜0.05). However, due to the increase of HR, there was no significant change in Cardiac Output (CO). At 4 300 m, the Thoracic Fluid Content (TFC) of the rapid ascent group was significantly higher than that of the progressive ascent group (P＜0.05). Compared with 4m, there was no significant difference in salivary testosterone change between the two groups at 3 658 m above sea level (P＞0.05), while COR and IgA changes in the rapid ascent group were significantly higher than those in another group (P＜0.05). Conclusion: Compared with the progressive ascent by train,expeditioners that rapid ascent to high altitude have significant effects on cardiovascular function and the stress hormones and immunoglobulin levels in saliva. It's suggested that hypoxia adaptation before Antarctic expediting for Kunlun Station could ensure the selected expeditioners' physical and psychological health, so that the mission could be finished smoothly.

[Effects of simulated 5 500 m hypobaric and hypoxia on HPT axis and intestinal flora in rats].

Objective: To investigate the effects of simulated hypoxia environment at an altitude of 5 500 meters on hypothalamic-pituitary-thyroid (HPT) axis and intestinal flora of rats and the correlation between them. Methods: The hypoxia model of adult male SD rats was established by hypobaric chamber with simulated altitude of 5 500 m. The hypoxia groups were set for 1, 3, 7, 14, 21 and 28 days, and the normoxic recovery group were set for 1 and 3 days after hypoxia (8 rats per group, hypoxia time 24h per day). Daily body weight and food intake of rats were recorded. The serum levels of HPT axis hormones were detected by enzyme-linked immunosorbent assay (ELISA). Intestinal flora was analyzed by 16s rDNA sequencing. The correlation between intestinal flora and serum HPT axis hormone was analyzed by Spearman correlation analysis. Results: Compared with the normoxic group, the body weight and food intake were significantly reduced (P＜0.01). In the 1-day and 3-day groups, the levels of thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) were decreased significantly (P＜0.05), the levels of total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4) and free triiodothyronine (FT3) were increased significantly (P＜0.05), and the abundance of Prevotella was decreased significantly (P＜0.05), while those of Parabacteroides, Lactobacillus, Butyricimonas, Bacteroides, Odoribacter and RC4-4 were increased significantly (P＜0.05). In the 14-day, 21-day and 28-day hypoxia groups, the levels of TRH and TSH were decreased significantly (P＜0.05), and the levels of TT4 and TT3 were increased significantly (P＜0.05), and there was no significant difference in other indexes, the abundance of Parabacteroides, Sphaerochaeta, Akkermansia, Elusimicrobium was increased significantly, but that of Lactobacillus and Sutterella was decreased significantly (P＜0.05). Correlation analysis of intestinal flora and HPT axis hormones showed that Butyricimonas, Elusimicrobium and Sutterella were significantly negatively correlated with TRH and TSH (P＜ 0.05), Prevotella, Bacteroides, Odoribacter and Parabacteroides were significantly correlated with TSH, TT4, TT3 and FT4 (P＜ 0.05), respectively. Lactobacillus was significantly correlated with TRH, TSH and FT4 (P＜0.05). Akkermansia was significantly correlated with TRH and FT4 (P＜0.05). RC4-4 was significantly associated with TSH and TT3 (P＜0.05). Conclusion: Hypoxia stress at an altitude simulating 5500 meters significantly changed the composition of the intestinal flora of SD rats. This may be a change in thyroid function adapted to the hypoxia environment, and the degree of change is related to the time of hypoxia stress. The change of intestinal microflora is significantly correlated with the hormone level of HPT axis.

Hyperuricemia and clustering of cardiovascular risk factors in the Chinese adult population.

Hyperuricemia is common in China and the relevance of hyperuricemia and cardiovascular disease (CVD) risk has been highlighted, but to date there has been rarely nation-wide study in China. Here, we aim to estimate the current prevalence of hyperuricemia and evaluate the associations between hyperuricemia and cardiovascular risk factors (CRFs) clustering in a large sample of China adults including a plurality of ethnic minorities. Generally, a nationally representative sample of 22983 adults aged ≥18 years was recruited from 2007 to 2011. Questionnaire data and information on anthropometric characteristics, and laboratory measurements were collected. We define hyperuricemia as SUA ≥416 mmol/L for men and SUA ≥357 mmol/L for women. We found that the prevalence of hyperuricemia was 13.0% (18.5% in men and 8.0% in women). To our estimation, hyperuricemic subjects had higher prevalence rates of CRFs clustering than non-hyperuricemic subjects. Furthermore, there was a dose-response association between the number of CVD risk factors clustering and hyperuricemia. Our study revealed a high prevalence of hyperuricemia and CVD risk factors clustering among Chinese adults, and hyperuricemia was significantly associated with coexistence of more CVD risk factors. Therefore, guidance and effective lifestyle intervention are required to prevent hyperuricemia and CVD risk factors in China.

[Effect of HIF-1alpha on sex hormone levels and germ cell apoptosis of mice].

OBJECTIVE: To study the effect of hypoxia on hypothalamus-adenohypophysis-testis axis hormone levels, germ cell apoptosis and hypoxia-inducible factor-1alpha (HIF-1alpha) expression in testis of adolescent mice, and explore HIF-1alpha regulation on the reproductive function of male mice. METHODS: Eighty SPF grade adolescent C57BL/6 mice were randomly divided into normoxia group, hypoxia 3, 7, 14 and 28 d groups. The level of serum testosterone (T), free testosterone (FT), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) was analyzed by ELISA. Detected the sperm count, motility rate and abnormal sperm rate of epididymal sperm suspension. The apoptosis cells in testis were determined using TUNEL method. The expression of HIF-1alpha was analyzed using Western blot. RESULTS: Compared with corresponding normoxia group, serum T, FT, FSH and LH concentrations in hypoxia 3 d group were significantly higher (P < 0.05); T and LH concentrations in hypoxia 14 d group were significantly lower (P < 0.05). Sperm count and motility rate in hypoxia 7 and 14 d groups significantly declined (P < 0.05); abnormal sperm rate in all hypoxia groups significantly increased (P < 0.05). The apoptosis index (AI) of germ cells in hypoxia 7, 14 and 28 d groups significantly increased (P < 0.05), and the levels of HIF-1alpha protein expression were significantly higher (P < 0.05). CONCLUSION: HIF-1alpha protein highly expressed in mice testis could induce germ cell apoptosis increased in chronic hypoxia environment.

[Effects of different altitudes on cardiac hemodynamics and electrocardiogram of healthy male adults].

OBJECTIVE: To detect the changes of cardiovascular system at different altitudes, so as to prevent and predict the susceptibility to acute mountain sickness. METHODS: The test was performed with noninvasive cardiovascular monitor and electrocardiogram in healthy male Chinese members of the 25th and 26th expeditions to the antarctic kunlun station at different altitudes (40 m, 3 650 m and 4 300 m). RESULTS: Compared with 40 m, from 3 650 m to 4 300 m, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI) significantly increased (P < 0.05); cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke index (SI), velocity index (VI), acceleration index (ACI), left ventricular ejection time (LVET) significantly decreased (P < 0.05) and pre-ejection period(PEP) decreased with no significance (P > 0.05). CONCLUSION: SVR significantly increased but contractile and blood-pumping function of left ventricular decreased inversely associated with the Q-Tc interval, as the altitude is increasing.

High prevalence of coexisting prehypertension and prediabetes among healthy adults in northern and northeastern China.

BACKGROUND: Prehypertension and prediabetes are major risk factors of cardiovascular disease, and their combined presence may result in more serious cardiovascular outcomes than expected with either prehypertension or prediabetes alone. The aim of the present study was to evaluate the prevalence of coexisting prehypertension and prediabetes, and the associated risk profiles in a Chinese population. METHODS: A cross-sectional survey in a representative sample of 3,595 men and 4,593 women aged 18 years and older was performed between 2008 and 2010. Prehypertension and prediabetes were diagnosed using the guidelines from the Seventh Report of the Joint National Committee on prevention, detection, and treatment of high blood pressure and American Diabetes Association, respectively. Prehypertension was defined as a systolic blood pressure of 120-139 mmHg and/or diastolic blood pressure of 80-89 mmHg, and prediabetes was defined as a fasting blood glucose of 5.6-6.9 mmol/L. RESULTS: The prevalence of coexisting prehypertension and prediabetes was 11.0%. Men had a higher prevalence of coexisting prehypertension and prediabetes than women (14.2% vs. 8.4%; P < 0.0001). This prevalence increased with age and body mass index, and was the lowest among Mongolian-Chinese (5.1%). A multivariate analysis showed that γ-glutamyltransferase and uric acid were significantly and positively correlated with body mass index, waist circumference, blood pressure, triglycerides, and total cholesterol, and negatively correlated with high density lipoprotein cholesterol in subjects with prehypertension and prediabetes. CONCLUSIONS: There is a large proportion of Chinese adults with coexisting prehypertension and prediabetes. Thus, there is a need for more efforts that implement public health programs that target the earlier stages of hypertension and diabetes.

[Impact of draining mode of enlarged maxillary ostium on mucociliary transportation system].

OBJECTIVE: The purpose of this study was to investigate the proper site for enlarging maxillary natural ostium during ESS, and to compare the draining mode of mucociliary transportation system. METHODS: Three groups were designed to observe the differences of tracer agent transported from maxillary sinus to nasal cavity. Normal control group: 30 cases; Trial group A:30 cases, the maxillary natural ostium were radically enlarged by all sides; Trial group B: 30 cases, the maxillary natural ostium were enlarged by reservation of whole inferior edge and cut away anterior and/or posterior edge. The patients in two trial groups were after nasal endoscopic sinus surgery for more than 12 months and the maxillary ostium were well open. RESULTS: Tracer agent was drained from maxillary sinus to nasal cavity by inferior edge (s) of natural ostium in control group. The core area was posterior part of inferior edge. In trial group A, tracer agent was drained out by inferior edge in 4 cases (13.3%), tracer agent drained out by posterior and/or superior edge(s) and then dispersed to ethmoid sinus in 17 cases (56.7%),tracer agent stacked and/or circularly flowed in the maxillary sinus, and could not be transported out in 9 cases (30.0%). In trial group B,tracer agent drained out by inferior edge to middle meatal in all subjects (30/30,100%), and there was no redirection of the mucociliary transportation. CONCLUSIONS: The inferior edge of natural ostium is the main passage of mucociliary transportation system of maxillary sinus. If the inferior edge of maxillary natural ostium reserved, the post-operative drainage of maxillary sinus would be the same as normal ones. Radical removal of all edges of maxillary natural ostium could lead to redirection of mucociliary transportation, only few cases could drain out by inferior edge, most cases drained out by posterior and/or superior edge and then dispersed to ethmoid sinus. In some cases, tracer agent often stacked in the maxillary sinus and could not be drained out. When there was a need to enlarge the maxillary natural ostium in ESS, it should be done in the anterior and/or posterior edge of natural ostium, the inferior edge should not be damaged so as not to interfere the passage of mucociliary transportation system of the maxillary sinus.

Reference data for quantitative ultrasound values of calcaneus in 2927 healthy Chinese men.

Quantitative ultrasound (QUS) is a bone densitometry technique that is rapidly gaining popularity for the assessment of bone status. However, few QUS data are available for men, especially in China. In the present study, a random stratified sample of 2927 Chinese men (10-90 years) was recruited, and bone status was established using measurements by Achilles ultrasonometer. The peak stiffness index (SI) value for Chinese men was 103.0 +/- 20.8, which presented in the age group of 20-24 years. Pearson correlation analysis showed that there was significant correlation between SI and age (P < 0.001), and multivariate regression analysis indicated that weight was also an important factor for SI. In addition, in comparison with the normal data of Italian and Japanese males, the SI value for Chinese males in each age group was lower than those of Italians but higher than Japanese, except for the 20-29 years age group. The descending velocity of curves for Chinese men was lower than that of Italian and Japanese men. In conclusion, QUS values of the calcaneus provided by the present study may be used as normal reference values for Chinese men.

[Ultrasonic bone mineral density of calcaneus in 1 816 healthy subjects in Guangxi autonomous region].

OBJECTIVE: To study the relationship between ultrasonic bone mineral density (BMD) of calcaneus and age, height, and body weight, and to establish the normal reference value for stiffness index (SI) of healthy subjects in Guangxi autonomous region and provide scientific foundation for the diagnosis and prevention of osteoporosis. METHODS: SI of calcaneus in 1 816 healthy adults aged 11-90 years (775 men, 1 041 women) were measured with quantitative ultrasound. According to their ages, all the men and women were divided into 13 groups by 5-year age group. RESULTS: SI reached peak values in 21-25 year group in men (range: 111.45 +/- 21.19) and in 16-20 year group in women (range: 101.26 +/- 17.51). Then the SI value began to decline with aging. The SI featured by a typical dual-peak curve in women and the decrease rate of SI was faster in women than in men over 61 years. Multivariate linear regression analysis showed significantly negative correlation between SI and age (P < 0.001), positive correlation between SI and body weight (P < 0.05 for men; P < 0.01 for women), and positive correlation between SI and height in women (P < 0.01). CONCLUSION: SI correlates with age, height, and weight. The acquired SI value may provide a reference for the diagnosis of osteoporosis.

[Bone density of calcaneus of 2769 healthy persons in Zhejiang province].

OBJECTIVE: To provide a scientific basis for the diagnosis and prevention of osteoporosis in Chinese populations. METHODS: The stiffness index (STI) of the calcaneus was measured with the Achilles Express ultrasound apparatus made in USA among 2769 healthy persons, 1262 males and 1507 females, aged 10 to over 60, in Zhejiang province. The relationships between the STI and sex and age were analyzed. RESULTS: The peak STI appeared in the age 20 - 24 among the males, and appeared in the age 15 - 19 among the females. Beyond these age periods the STI decreased along with the age. The STI values of the males aged over 54 were significantly higher than those of the females the same age. The speed of STI decrease of the females aged over 55 was higher than the males of the same age (P < 0.01). The prevalence of osteoporosis was higher in the females than in the males. The STI was negatively correlated with age, and positively correlated with height and body weight in both sexes. The practically measured T values were mostly significantly lower than the instrument' T values (with young adult Japanese as reference population). CONCLUSION: There are significant relationships between STI and age, height, and body weight in both males and females. The distribution of bone mineral density of the reference population for the imported instrument does not completely accord with that of Chinese. It is necessary to establish a standard adaptable to the specific condition of Chinese.

[Distribution of systemic vascular resistance disorders and its related factors in Hebei province].

OBJECTIVE: To analyze the distribution features of systemic vascular resistance (SVR) disorder in healthy subjects in Hebei province. METHODS: SVR and systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), heart rate (HR), cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke index (SI), left ventricular ejection time (LVET), left cardiac work (LCW) and cardiovascular function were determined with Bioz. com Cardio Dynamics. Total cholesterol (TC), triglyceride (TG) and influencing factor were tested by automated hematology analyzer in 999 healthy subjects living in Hebei province. RESULTS: SVR disorder gradually increased with the ageing in healthy subjects and the prevalences of SVR disorders was higher among females than among males (P < 0.001). SVR was positively correlated with SBP, DBP, MAP, PP, LVET, body mass index (BMI), TC, and TG, and was inversely associated with HR, CO, CI, SV, SI, LCW, and arterial compliance (AC). CO and MAP were independent influencing factors with SVR. CONCLUSION: SVR disorder is associated with age, sex, and blood pressure in populations in Hebei province and may be a marker of vascular injury.

[Analysis of the levels of serum total calcium and inorganic phosphate of 2,342 children in Beijing].

OBJECTIVE: To study the changes of serum total calcium (Ca) and inorganic phosphate (P) levels during children growth and related factors. METHODS: Using a stratified-multi-steps-cluster sampling method, we selected 2,342 healthy children aged 10-18 years from urban and suburban areas of Beijing from September 2001 to December 2001 to test the levels of serum Ca and P. Their meal status was also surveyed to analyse the correlation of the leves of serum Ca and P with sex, age, height, weight, and diet on statistic basis. RESULTS: The Ca levels of Beijing children were (2.39 +/- 0.12) mmol/L, which had a positive correlation with age, height, and weight (P < 0.01). The Ca levels of female children were somewhat higher than those of male [male, (2.38 +/- 0.12) mmol/L; female, (2.39 +/- 0.12) mmol/L; P < 0.05]. The Ca levels of urban children were significantly higher than those of suburban children [urban, (2.40 +/- 0.13) mmol/L; suburban, (2.37 +/- 0.10) mmol/L; P < 0.001]. The P levels of Beijing children were (1.39 +/- 0.18) mmol/L, which had a negative correlation with age, height, and weight (P < 0.01). The P levels of male children were significantly higher than those of female [male, (1.43 +/- 0.18) mmol/L; female, (1.36 +/- 0.17) mmol/L; P < 0.001]. The P levels of urban children were significant higher than those of suburban children [urban, (1.41 +/- 0.19) mmol/L; suburban, (1.38 +/- 0.16) mmol/L; P < 0.001]. The Ca levels of Beijing children had a negative correlation with P levels (r=-0.141, P < 0.01). [Ca] x [P] (mmol/L) of Beijing children were 3.32 +/- 0.44. The value of [Ca] x [P] reached peak by 3.45 +/- 0.46 when Beijing children were of 13-14 years old, and then the value declined with increasing age. CONCLUSION: The levels of serum Ca and P correlates with sex, age, growth, and diet. The level of serum Ca goes up while P goes down during the children growth.

The physiology constant database of teen-agers in Beijing.

Physiology constants of adolescents are important to understand growing living systems and are a useful reference in clinical and epidemiological research. Until recently, physiology constants were not available in China and therefore most physiologists, physicians, and nutritionists had to use data from abroad for reference. However, the very difference between the Eastern and Western races casts doubt on the usefulness of overseas data. We have therefore created a database system to provide a repository for the storage of physiology constants of teen-agers in Beijing. The several thousands of pieces of data are now divided into hematological biochemistry, lung function, and cardiac function with all data manually checked before being transferred into the database. The database was accomplished through the development of a web interface, scripts, and a relational database. The physiology data were integrated into the relational database system to provide flexible facilities by using combinations of various terms and parameters. A web browser interface was designed for the users to facilitate their searching. The database is available on the web. The statistical table, scatter diagram, and histogram of the data are available for both anonym and user according to queries, while only the user can achieve detail, including download data and advanced search.