Nasal Lavage Fluid Proteomics Reveals Potential Biomarkers of Asthma Associated with Disease Control.

Purpose: Little research has explored the proteomic characteristics of nasal lavage fluid from asthmatic patients. This study aims to investigate whether differentially expressed proteins (DEPs) in nasal lavage fluid can serve as a biomarker to differentiate asthma patients from healthy controls (HCs) and to discern between individuals with well controlled and poorly controlled asthma. Patients and Methods: We enrolled patients with allergic rhinitis (AR), asthma, or both conditions, and HCs in this study. We recorded patients' demographic and medical history data and administered asthma quality of life questionnaire (AQLQ) and asthma control questionnaire (ACQ). Nasal fluid samples were collected, followed by protein measurements, and proteomic analysis utilizing the data-independent acquisition (DIA) method. Results: Twenty-four with asthma, 27 with combined asthma+ AR, 25 with AR, and 12 HCs were enrolled. Four proteins, superoxide dismutase 2 (SOD2), serpin B7 (SERPINB7), kallikrein-13 (KLK13), and bleomycin hydrolase (BLMH) were significantly upregulated in nasal lavage fluid samples of asthma without AR, compared to HCs (Fold change ≥2.0, false-discovery rate [FDR] <0.05). Conversely, 56 proteins including secretoglobin family 2A member 1 (SCGB2A1) were significantly downregulated (fold change ≥2.0, FDR <0.05). Furthermore, 96.49% of DEPs including peptidase inhibitor 3 (PI3) and C-X-C motif chemokine 17 (CXCL17) were upregulated in poorly controlled asthma patients without AR relative those with well- or partly controlled asthma (fold change ≥1.5, FDR <0.05). Search tool for the retrieval of interacting genes/proteins (STRING) analysis showed that PI3, with 18 connections, may be pivotal in asthma control. Conclusion: The study revealed significant alteration in the nasal lavage proteome in asthma without AR patients. Moreover, our results indicated a potential association between the expression of proteome in the upper airway and the level of asthma control. Specifically, PI3 appears to be a key role in the regulation of asthma without AR.

Bone mineral density in adults growth hormone deficiency with different ages of onset: a real-world retrospective study.

PURPOSE: Bone mineral density (BMD) impairment is one of the critical factors for long-term quality of life in adults growth hormone deficiency (AGHD). This study aims to investigate the annual changes in BMD in AGHD patients with different ages of onset and to identify predicting factors that influence BMD. METHODS: AGHD patients (n = 160) with available data for 4 years follow-up from a major tertiary medical center in China were retrospectively included (110 [68.8%] childhood-onset, 119 [74.4%] male). BMD of the axial bone (including total hip, neck of femur, and L1-4) derived from dual X-ray absorptiometry and final height were investigated at the first visit, 12 months, 24 months, 36 months, and 48 months thereafter. Low BMD was defined as Z-score ≤ -2. RESULTS: The prevalence of low BMD was 30.0% at baseline and 12.5% at 4 years of follow-up. The CO AGHD group presented a significantly lower BMD than the AO AGHD group at the baseline (P = 0.009). In contrast, the CO AGHD group had significantly greater median annual BMD change than the AO AGHD group (0.044 vs. -0.0003 g/cm2/year in L1-4, P < 0.001), indicating a significant difference in the overall BMD trend between CO and AO groups. Childhood-onset (odds ratio [OR] 0.326, P = 0.012), low serum testosterone (OR 0.847; P = 0.004) and FT4 (OR 0.595; P = 0.039) level were independent risk factors for BMD loss. CONCLUSION: The annual changes of BMD show a different pattern in AGHD patients with varying ages of onset. Patients with CO AGHD have a lower bone mass, and in general, appropriate replacement therapy is necessary for long-term bone health in AGHD patients.

Comparison of azvudine, molnupiravir, and nirmatrelvir/ritonavir in adult patients with mild-to-moderate COVID-19: a retrospective cohort study.

This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, and molnupiravir in adult patients with mild-to-moderate COVID-19. This retrospective cohort study included patients with mild-to-moderate COVID-19 (asymptomatic, mild, and common types) at the First Hospital of Changsha (Hunan Province, China) between March and November 2022. Eligible patients were classified into the azvudine, nirmatrelvir/ritonavir, or molnupiravir groups according to the antiviral agents they received. The outcomes were the times to nucleic acid negative conversion (NANC). This study included 157 patients treated with azvudine (n = 66), molnupiravir (n = 66), or nirmatrelvir/ritonavir (n = 25). There were no statistically significant differences in the time from diagnosis to NANC among the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups [median, 9 (95% CI 9-11) vs. 11 (95% CI 10-12) vs. 9 (95% CI 8-12) days, P = 0.15], time from administration to NANC [median, 9 (95% CI 8-10) vs. 10 (95% CI 9.48-11) vs. 8.708 (95% CI 7.51-11) days, P = 0.50], or hospital stay [median, 11 (95% CI 11-13) vs. 13 (95% CI 12-14) vs. 12 (95% CI 10-14) days, P = 0.14], even after adjustment for sex, age, COVID-19 type, comorbidities, Ct level, time from diagnosis to antiviral treatment, and number of symptoms. The cumulative NANC rates in the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups were 15.2%/12.3%/16.0% at day 5 (P = 0.858), 34.8%/21.5%/32.0% at day 7 (P = 0.226), 66.7%/52.3%/60.0% at 10 days (P = 0.246), and 86.4%/86.2%/80.0% at day 14 (P = 0.721). No serious adverse events were reported. Azvudine may be comparable to nirmatrelvir/ritonavir and molnupiravir in adult patients with mild-to-moderate COVID-19 regarding time to NANC, hospital stay, and AEs.

Epidemiological and clinical features of COVID-19 inpatients in Changsha, China: A retrospective study from 2020 to 2022.

Objectives: The spread of SARS-Cov-2 remains a global concern along with the emergence of variants. This study aims to characterize the epidemiological and clinical features of hospitalized patients who were dragonized with five different variants of SARS-CoV-2 during the past 3 years. Methods: This retrospective study recruited 432 COVID-19 patients who were hospitalized in the First Hospital of Changsha from January 2020 to August 2022. Clinical records on clinical symptoms, laboratory profiles, and chest CT images was collected. The epidemiological and clinical features were compared between COVID-19 patients infected with either the wild-type, Omicron variant or pre- Omicron variants (e.g., Alpha, Beta, Delta). Results: A total of 432 laboratory-confirmed COVID-19 inpatients were dialogized during three waves, including 247 cases during the wild-type transmission period, 65 cases during the transmission period of pre-Omicron variants, and 119 cases during the transmission period of Omicron variants. The proportion of moderately or severely ill inpatients showed a gradual decline from the wild-type transmission period to the Omicron transmission period. The common symptoms of inpatients infected with SARS-CoV-2 wildtype strains included fever (67.61 %), cough (57.89 %), fatigue (33.60 %), and shortness of breath (12.15 %). In contrast, patients infected with other variants mostly showed upper respiratory symptoms. Based on chest CT images, a lower degree of acute pulmonary infection was observed among inpatients infected with the Omicron variants than those infected with the wild-type strain (31.09 % vs 93.12 %, p-value<0.01). Conclusions: Compared with the wild-type strain, SARS-CoV-2 variants of concern, especially the Omicron variant, mostly caused a lower degree of acute pulmonary infection, indicating the reduced disease severity and mortality among hospitalized COVID-19 patients.

Clinical characteristics and therapeutic outcomes of acromegalic patients with giant growth hormone-secreting pituitary adenomas: a single-center study of 67 cases.

PURPOSE: Acromegalic patients with giant growth hormone-secreting pituitary adenomas (GHPAs) (≥ 40 mm) are relatively rare, and their clinical characteristics and treatment outcome data are limited. This study aims to analyze the clinical practice experience of giant GHPAs. METHODS: Sixty-seven acromegalic patients with giant GHPAs and 67 patients with macro GHPAs (10-39 mm), matched for age and gender from the same hospital during the same period, were retrospectively recruited. The clinical characteristics, treatment, and outcomes were analyzed. RESULTS: Enlargement of the extremities and facial features were the most common symptoms in most patients (92.5%). Compared with the macroadenoma group, more frequent visual impairment (86.6% vs. 25.4%, P < 0.001) and gonadal axis dysfunction (49.3% vs. 34.3%, P = 0.008), higher preoperative fasting GH, nadir GH after OGTT and IGF-1 levels, and a higher proportion of extrasellar tumor invasion were seen in the giant adenoma group. As the adenoma size increases, the total resection rate decreases, and postoperative complications and multimodal treatment strategies increase significantly. Fasting and nadir GH levels remained higher at 1 week postoperatively, and there were more surgical complications and cases of anterior hypopituitarism in the giant group. After a median follow-up of 36 months, 12 patients (36.4%) in the giant GHPA group and 17 (36.2%) in the macro GHPA group achieved biochemical remission. Other factors such as age of onset, age of diagnosis, delayed diagnosis time, metabolic complications, p53 positive rate, and Ki-67 index showed no significant difference between the two groups. CONCLUSIONS: With aggressive multimodal therapy, the biochemical remission rate of acromegalic patients with giant GHPAs is comparable to that of patients with macro adenoma. However, postoperative complications and hypopituitarism need to be closely monitored.

Safety of Inactivated SARS-CoV-2 Vaccines Among Adults with Experience of Allergies to Food or Medicines.

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly known as COVID-19, poses significant risk to human health worldwide. The primary strategy for controlling the disease is through vaccination. However, there is an urgent need to establish confidence in the safety of global vaccination efforts, particularly among populations with allergies, as evidence on the adverse effects of SARS-CoV-2 vaccines in this group remains limited. To address this gap, our study aimed to evaluate the safety of inactivated SARS-CoV-2 vaccines in individuals with food and/or drug allergies. The study enrolled a total of 150 participants, who were subjected to a series of questionnaires to evaluate local and systemic reactions within 7 days after each dose. The results revealed that the most prevalent adverse reactions were pain at the injection site (30%) and fatigue (16%) following the initial vaccination. Notably, the incidence of both local and systemic adverse reactions decreased after the second vaccination, which was unexpected. The food allergy and drug allergy subgroups exhibited a similar phenomenon. Furthermore, the incidence of adverse events observed in this study was consistent with the range reported in Phase III clinical trials of inactivated SARS-CoV-2 vaccines. Our findings suggest that individuals with pre-existing food and/or drug allergies have a favorable safety profile when receiving inactivated SARS-CoV-2 vaccination.

Clinical features and therapeutic outcomes of GH/TSH cosecreting pituitary adenomas: experience of a single pituitary center.

Background: Growth hormone (GH)/thyroid stimulating hormone (TSH) cosecreting pituitary adenoma (PA) is an exceedingly rare kind of bihormonal pituitary neuroendocrine tumors (PitNETs). Its clinical characteristics have rarely been reported. Objectives: This study aimed to summarize the clinical characteristics and experience of diagnosis and treatment among patients with mixed GH/TSH PAs from a single center. Methods: We retrospectively reviewed GH/TSH cosecreting PAs from 2063 patients diagnosed with GH-secreting PAs admitted to Peking Union Medical College Hospital between January 1st, 2010, and August 30th, 2022, to investigate the clinical characteristics, hormone detection, imaging findings, treatment patterns and outcomes of follow-up. We further compared these mixed adenomas with age- and sex-matched cases of GH mono-secreting PAs (GHPAs). The data of the included subjects were collected using electronic records from the hospital's information system. Results: Based on the inclusion and exclusion criteria, 21 GH/TSH cosecreting PAs were included. The average age of symptom onset was 41.6 ± 14.9 years old, and delayed diagnosis occurred in 57.1% (12/21) of patients. Thyrotoxicosis was the most common complaint (10/21, 47.6%). The median inhibition rates of GH and TSH in octreotide suppression tests were 79.1% [68.8%, 82.0%] and 94.7% [88.2%, 97.0%], respectively. All these mixed PAs were macroadenomas, and 23.8% (5/21) of them were giant adenomas. Comprehensive treatment strategies comprised of two or more therapy methods were applied in 66.7% (14/21) of patients. Complete remission of both GH and TSH was accomplished in one-third of cases. In the comparison with the matched GHPA subjects, the mixed GH/TSH group presented with a higher maximum diameter of the tumor (24.0 [15.0, 36.0] mm vs. 14.7 [10.8, 23.0] mm, P = 0.005), a greater incidence of cavernous sinus invasion (57.1% vs. 23.8%, P = 0.009) and a greater difficulty of long-term remission (28.6% vs. 71.4%, P <0.001). In addition, higher occurrence rates of arrhythmia (28.6% vs. 2.4%, P = 0.004), heart enlargement (33.3% vs. 4.8%, P = 0.005) and osteopenia/osteoporosis (33.3% vs. 2.4%, P = 0.001) were observed in the mixed PA group. Conclusion: There are great challenges in the treatment and management of GH/TSH cosecreting PA. Early diagnosis, multidisciplinary therapy and careful follow-up are required to improve the prognosis of this bihormonal PA.

Clinical and Proteomic-Based Molecular Characterizations of Invasive and Noninvasive Somatotroph PitNETs.

INTRODUCTION: Somatotroph pituitary neuroendocrine tumours (PitNETs) are characterized by complex and variable biological behaviours with unpredictable patterns of growth and invasiveness. The molecular mechanisms and reliable predictors of biological markers of invasiveness remain unknown. METHODS: Seventy-two acromegaly patients were consecutively enrolled. Data-independent acquisition-based proteomics and ingenuity pathway analysis were conducted between invasive and noninvasive somatotroph PitNETs. The expression of selected biomarkers was verified in PitNET tissue, and its correlation with various clinical indicators and outcomes of these tumours was assessed. The invasive phenotypes of GH3 cells were validated in vitro. RESULTS: Patients with invasive somatotroph PitNETs were significantly younger at onset and diagnosis, with significantly higher secretion and faster growth and a lower long-term biochemical response rate than patients with noninvasive somatotroph PitNETs. Proteomic data were evaluated in a consecutively collected sample of 19 (10 invasive and 9 noninvasive somatotroph PitNETs) tumours and indicated a distinct proteomic pattern. The enriched and important pathways included IL-4, PDGF, PTEN, VEGF, PI3K/AKT, FAK, and other pathways that were significantly associated with tumour proliferation, migration, and invasion. High cathepsin Z (CTSZ) expression was found in invasive somatotroph PitNETs and significantly positively correlated with parameters of tumour invasion and growth. In Ctsz-overexpressing GH3 cells, cell proliferation, invasion, and migration were consequently increased. CONCLUSION: It is more difficult for patients with invasive somatotroph PitNETs to achieve remission than those with noninvasive somatotroph PitNETs, and proteomic data analysis has revealed the high expression of CTSZ as a contributing factor to invasive transformation and poor prognosis in somatotroph PitNETs for the first time.

The role of GICT and environmental regulation in affecting ecological footprint.

Research studies have recently diverted attention towards the determinant of ecological footprints, but related issues have not provided consistent results. Based on the IPAT model (environmental impact (I) is decomposed into three elements: population (P), affluence (A, economic growth), and technology level (T)), this paper empirically explores the validity of the green information and communication technology (GICT)-induced environmental Kuznets curve (EKC) hypothesis. The research applies a quantile regression (QR) that tests over 95 countries' panel data for the period 2000-2017 by using six types of ecological footprint (EF) as environmental degradation indicators and environmental regulations (ERs) as interaction variables. We confirm the vital role that GICT plays in lessening cropland, forest area, and grazing land, while increasing its impact on built-up land. Additionally, the findings partially support the existence of an inverted U-shaped GICT-induced environmental EKC hypothesis for a decreasing impact on cropland, forest area, and grazing land via consideration of non-market-based ER as the interaction term. GICT does not notably reduce carbon-absorption land usage; however, improvements of GICT and non-market-based ER in those nations have been accompanied by lower environmental degradation.

High-Performance Liquid Chromatography-Mass Spectrometry-based Metabolic Profiling of Adult Growth Hormone Deficiency.

CONTEXT: Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Metabolic profiles in AGHD patients have been insufficiently evaluated. OBJECTIVE: This work aims to explore serum metabolite profiles by metabolomics analysis and assess potential metabolites associated with recombinant human growth hormone (rhGH) treatment. METHODS: Thirty-one AGHD patients and 31 healthy controls were enrolled. Untargeted ultra-performance liquid chromatography-coupled mass spectroscopy was conducted in all patients and controls at baseline and during 12 months of rhGH treatment in 11 AGHD patients. Data were processed by principal component analysis, variable importance in projection scoring, orthogonal partial least squares-discriminant analysis, and MetaboAnalyst 5.0. We further explored the associations between metabolites and clinical parameters. RESULTS: Metabolomics indicated a distinct metabolic pattern between AGHD patients and healthy controls. The perturbed pathways mainly include the biosynthesis of unsaturated fatty acids, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid elongation, degradation, and biosynthesis. rhGH treatment increased the levels of specific glycerophospholipids compounds and reduced fatty acid ester compounds. Significant correlations existed between the 40 identified metabolites and insulin-like growth factor-1 SD score (IGF-1 SDS), body composition, and glucose and lipid metabolism plasma markers. During rhGH treatment, there was a statistically significant negative correlation between deoxycholic acid glycine conjugate and waist-to-hip ratio, while a statistically significant positive correlation existed between decanoylcarnitine and serum low-density lipoprotein levels. CONCLUSION: AGHD patients have unique metabolomic profiles. rhGH treatment alters the serum levels of several fatty acid compounds/amino acids, which may contribute to the improvement of metabolic status in AGHD patients.

Epidemiological characteristics of 17 imported patients infected with SARS-CoV-2 Omicron variant. / 17ä¾‹æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªå¢ƒå¤–è¾“å ¥æ„ŸæŸ“è€ çš„æµè¡Œç— å­¦ç‰¹å¾.

OBJECTIVES: With the continuous generation of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pressure of epidemic prevention and control continues to increase in China. Omicron with stronger infectiousness, immune escape ability and repeated infection ability spread to many countries and regions around the world in a short period of time. China has also successively reported cases of imported Omicron infections. This study aims to understand the epidemiological characteristics of Omicron variant via analyzing the epidemiological characteristics of imported patients with Omicron in Hunan Province, and to provide reference for preventing and controlling the imported epidemics. METHODS: The clinical data of imported patients with coronavirus disease 2019 admitted to Hunan Province from December 16 to December 31, 2021 were retrospectively collected. The epidemiological information, general information, clinical classification, clinical symptoms, vaccination status, and lung CT were analyzed. Nasopharyngeal swabs and blood samples were collected. Virus nucleic acid was detected by magnetic beads method using SARS-CoV-2 detection kit. Ct values of ORF1ab gene and N gene were compared between asymptomatic infected patients and confirmed patients. The specific IgM and IgG antibodies were detected by chemiluminescence assay using SARS-CoV-2 IgM test kit and SARS-CoV-2 IgG test kit, respectively. Ct values of IgM and IgG antibodies were compared between asymptomatic infected patients and confirmed patients. RESULTS: Seventeen patients with Omicron variant infection were treated in Hunan, including 15 confirmed patients (5 common type and 10 mild type) and 2 asymptomatic infection patients. The 17 patients were all Chinese, they were generally young, and 16 were male. There were 9 patients with diseases. Of them 3 patients had respiratory diseases. All 17 patients had completed the whole process of vaccination, but only one person received a booster shot of SARS-CoV-2 vaccine. The clinical manifestations of the patients were mild, mainly including dry/painful/itchy throat, cough, and fatigue. The total protein and creatine in the asymptomatic infection and confirmed cases infected with Omicron variant were all within the normal range, but other biochemical indicators were abnormal. There were the significant differences in C-reactive protein and fibrinogen between asymptomatic infection and confirmed patients (both P<0.05). There were more patients with elevated C-reactive protein in confirmed patients than without confirmed ones. The detection rate of specific IgM and IgG antibodies on admission was 100%, and there was no significant difference in the specific antibody levels between asymptomatic infection and confirmed patients (P>0.05). There were no significant differences in Ct values of ORF1ab gene and N gene (21.35 and 18.39 vs 19.22 and 15.67) between the asymptomatic infection and the confirmed patients (both P>0.05). Only 3 patients had abnormal lung CT, showing a small amount of patchy and cord-like shadows. One of them had no abnormality on admission but had pulmonary lesions and migratory phenomenon after admission. CONCLUSIONS: The patients with Omicron variant tend to be young people and have milder clinical symptoms, but the viral load is high and the infectiveness is strong. Therefore, the timely identification and effective isolation and control for asymptomatic infections and confirmed patients with mild symptoms are extremely important. In terms of epidemic prevention and control, the government still needs to strengthen the risk control of overseas input, adhere to normalized epidemic prevention and control measures, to effectively control the source of infection, cut off the route of transmission, and protect vulnerable people.

Corrigendum: Clinical Characteristics of Short-Stature Patients With Collagen Gene Mutation and the Therapeutic Response to rhGH.

[This corrects the article DOI: 10.3389/fendo.2022.820001.].

The side effects of dopamine receptor agonist drugs in Chinese prolactinoma patients: a cross sectional study.

BACKGROUND: Recently, side effects from Dopamine Receptor Agonist Drugs (DAs) in treating pituitary prolactinoma have raised widespread concern. This study explores the incidence and influencing factors of DAs-related side effects in Chinese prolactinoma patients. METHODS: A cross-sectional study was conducted. 51 prolactinoma patients treated with DAs, 12 prolactinoma or pituitary microadenoma patients without DAs treatment, and 33 healthy controls were included. The Barratt impulsivity scale-11, Patient Health Questionnaire 9, and the ICD screening questionnaire were all used to evaluate the psychological and physical side effects of DAs. Clinical data of all subjects were collected from their electronic medical records. RESULTS: The incidence of ICDs in the treated group, the untreated group, and control group was 9.8% (5/51), 16.7% (2/12), and 9.1% (3/33), respectively. In the treated group in particular, there were 1 patient (2%, 1/51), 2 patients (3.9%, 2/51), and 2 patients (3.9%, 2/51) with positive screening for punding, compulsive shopping, and hypersexuality, respectively. In terms of depression, the incidence of "minimal", "mild" and "moderate" depression in the treated group was 62.8% (32/51), 25.5% (13/51), and 5.9% (3/51), respectively. The incidence of physical symptoms was 51.0% (26/51) in the treated group and gastrointestinal symptoms were the most common symptoms (33.3%, 17/51). In addition, we found that the various parameters of DAs treatment had no association with the occurrence of physical symptoms or ICDs (all P > 0.05). CONCLUSIONS: Chinese prolactinoma patients treated with DAs had a lower incidence of ICDs (9.8%), while gastrointestinal symptoms were common. In this way, more attention should be paid to side effects, especially physical symptoms, in Chinese prolactinoma patients with DAs therapy during follow-up regardless of dose.

Clinical Characteristics of Short-Stature Patients With Collagen Gene Mutation and the Therapeutic Response to rhGH.

CONTEXT: Clinical genetic evaluation has been demonstrated as an important tool to elucidate the causes of growth disorders. Genetic defects of collagen formation (the collagenopathies) have been reported to be associated with short stature and skeletal dysplasias. Etiological diagnosis of skeletal abnormality-related short stature is challenging, and less is known about recombinant human growth hormone (rhGH) therapy. OBJECTIVE: This is a single-center cohort study which aims at exploring the genetic architecture of short-stature children with skeletal abnormalities and evaluating the frequency of collagenopathies to determine their phenotype, including the rhGH treatment response. PATIENTS AND METHODS: One hundred and six children with short stature and skeletal abnormalities were enrolled who were evaluated by next-generation sequencing (NGS) to detect variants in the skeletal collagen genes including COL1A1, COL1A2, COL2A1, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, and COL11A2. The results were evaluated using American College of Medical Genetics and Genomics (ACMG) guidelines. Clinical characteristics and rhGH treatment response were summarized. RESULTS: Twenty-four pathogenic or likely pathogenic variants of collagen genes were found in 26 of 106 (24.5%) short-stature patients with skeletal abnormalities, of which COL2A1 mutations were the most common, accounting for about 57.7%. Other frequent mutations associated with skeletal development include FGFR3, ACAN, NPR2, COMP, and FBN1 in 12.2%, 0.9%, 0.8%, 0.4%, and 0.4%, respectively, resulting in significantly different degrees of short stature. An overview of clinical features of collagenopathies showed growth retardation, skeletal abnormalities, and heterogeneous syndromic abnormalities involving facial, eye, hearing, and cardiac abnormalities. The average height of 9 patients who received rhGH treatment improved from a median of -3.2 ± 0.9 SDS to -2.2 ± 1.3 SDS after 2.8 ± 2.1 years. The most significant height improvement of 2.3 SDS and 1.7 SDS was also seen in two patients who had been treated for more than 6 years. CONCLUSIONS: A proband-based NGS revealed that distinct genetic architecture underlies short stature in varying degrees and clinical features. Skeletal abnormality-related short stature involving multiple systems should be tested for skeletal collagen gene mutation. Limited rhGH treatment data indicate an improved growth rate and height, and close monitoring of adverse reactions such as scoliosis is required.

Clinical features and nasal inflammation in asthma and allergic rhinitis.

Asthma and allergic rhinitis (AR) are widely considered to be the most common chronic inflammatory disorders. This study was performed to investigate the clinical features, disease severity, and upper airway inflammation among patients with asthma, AR, and asthma comorbid AR. Blood and nasal lavage fluid samples were collected from patients with isolated asthma (n = 23), isolated AR (n = 22), and asthma comorbid AR (n = 22). Demographic data, symptom evaluation, and spirometry were obtained from all subjects. The levels of interleukin (IL)-4, IL-5, IL-13, IL-17, IL-25, IL-33, and S100 proteins were measured in the nasal lavage fluid. Compared with isolated asthma, patients with asthma comorbid AR showed a lower quality of life according to the asthma quality-of-life questionnaire (AQLQ) score (6.11 ± 0.47 vs. 6.45 ± 0.35, P = 0.007). Additionally, no significant difference in the levels of IL-4 (P = 0.116), IL-25 (P = 0.235), and S100A12 (P = 0.392) was observed in nasal lavage fluid among three groups. However, miniscule levels of IL-5, IL-17, IL-13, IL-33, S100A8, and S100A9 were detected in nasal lavage fluid in all three groups. Patients with asthma comorbid AR showed an increased level of systemic cytokine in plasma than that of patients with isolated AR or asthma alone. The finding from our study may help clinicians to better understand the airway inflammation among asthma patients with or without AR.

Nasal Bacterial Microbiome Differs Between Healthy Controls and Those With Asthma and Allergic Rhinitis.

Perturbation of the microbiome has numerous associations with the phenotypes and progression in chronic airways disease. However, the differences in the nasal microbiome in asthma and allergic rhinitis (AR) have not been defined. We examined whether the nasal microbiome would vary among different comorbidities in asthma and AR and that those differences may be associated with the severity of asthma. Nasal lavage fluid was collected from 110 participants, including 20 healthy controls, 30 subjects with AR, 30 subjects with asthma and 30 subjects with combined asthma + AR. The Asthma Control Questionnaire (ACQ-7) was used to evaluate asthma control status. Using 16S rRNA bacterial gene sequencing, we analyzed nasal microbiome in patients with asthma, AR, combined asthma + AR, and healthy controls. Bacterial diversity was analyzed in corresponding with α diversity indices (Chao and Shannon index). Compared with healthy controls, the Chao index tended to be lower in subjects with AR (P = 0.001), asthma (P = 0.001), and combined asthma + AR (P = 0.001) when compared with healthy controls. Furthermore, the Shannon index was significantly lower in subjects with asthma (P = 0.013) and comorbid asthma with AR (P = 0.004) than the control subjects. Disparity in the structure and composition of nasal bacteria were also observed among the four groups. Furthermore, patients with combined asthma + AR and isolated asthma were divided into two groups according to the level of disease control: partially or well-controlled and uncontrolled asthma. The mean relative abundance observed in the groups mentioned the genera of Pseudoflavonifractor were dominated in patients with well and partially controlled disease, in both isolated asthma and combined asthma + AR. In subjects with uncontrolled asthma and combined asthma + AR, a lower evenness and richness (Shannon index, P = 0.040) was observed in nasal microbiome composition. Importantly, lower evenness and richness in the nasal microbiome may be associated with poor disease control in combined asthma + AR. This study showed the upper airway microbiome is associated with airway inflammation disorders and the level of asthma control.

The criticality of tourism development, economic complexity, and country security on ecological footprint.

What kinds of countries are likely to be prosperous and have a sustainable environment at the same time? How might countries reorient their policy setting to be more capable of suppressing environmental degradation? To explore these questions, this research examines data from 99 countries for 2006-2017, takes the six major forms of ecological footprint (EF) as indicators of environmental quality, and probes the environmental Kuznets curve (EKC) hypothesis via quantile regression approach. We find that tourism development leads to greater environmental degradation, with tourism development particularly corresponding to more usage of carbon absorption land and cropland. The lower the country security is, the better is the environmental quality. Economic complexity also worsens environmental quality. However, country security weakens the negative influence of tourism development and economic complexity on environmental quality, specifying that better country security stalls the negative impact of tourism and economic complexity on environmental quality. Results mostly support the tourism- and country security-induced EKC hypotheses in fishing footprint, whereas economic complexity-induced EKC is generally validated in cropland footprint. Finally, we present that tourism arrivals, economic complexity, and country security have varying impacts across diverse ecological footprint quantiles.

Fish Intake, Dietary Polyunsaturated Fatty Acids, and Lung Cancer: Systematic Review and Dose-Response Meta-Analysis of 1.7 Million Men and Women.

To determine the association between fish intake and dietary polyunsaturated fatty acids (PUFA) and incidence of lung cancer. We systematically reviewed and meta-analyzed all available studies to quantify the associations of fish and PUFA consumption with risk of lung cancer. Relative risk (RR) with 95% confidence interval (CI) was calculated. 13 population-based prospective cohort studies involving 1,785,000 participants and two randomized control trials were included. Our study demonstrated that dietary PUFA significant reduced risk of lung cancer for men (RR 0.99, 95%CI 0.98 to 1.00) and the U.S. population (RR 0.99, 95%CI 0.98 to 1.00). Dose-response analysis indicated that a 5 g/day increment of dietary PUFA was associated with 5% lower risk of lung cancer (RR 0.95, 95%CI 0.91 to 0.99). In addition, PUFA supplementation is significant improved overall survival in patients with lung cancer (RR 1.98, 95%CI 1.09 to 3.59). Our study showed an inverse association between dietary PUFA and risk of lung cancer in males and among the U.S. population. Although smoking cessation is the single biggest factor associated with lung cancer risk reduction, this study adds to a growing body of evidence that diet may have a role in modestly reducing lung cancer risk.

SARS-CoV-2 Omicron BA.5 infection recurrence after Paxlovid treatment: The first case report in Hunan Province. / 湖南省首例Paxlovidæ²»ç–—æ–°åž‹å† çŠ¶ç— æ¯’å¥¥å¯†å ‹æˆŽBA.5å˜å¼‚æ ªå¤é˜³ç— ä¾‹æŠ¥é“.

We report a case of coronavirus disease 2019 (COVID-19) patient who was cured by oral administration of nirmatrelvir/ritonavir (Paxlovid). The patient was treated with Paxlovid after being first infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5 variant. On the 11th day after SARS-CoV-2 nucleic acid test turned negative, SARS-CoV-2 nucleic acid test was positive again, and the threshold of nucleic acid cycle number was equivalent to that of the first infection. The results of two whole gene sequencing showed that it was the same virus strain infection, suggesting that the case was re-positive. Without specific treatment, SARS-CoV-2 nucleic acid detection in nasopharyngeal swab turned negative. It is not uncommon for Paxlovid to recover after treating COVID-19, and most of the patients can recover without specific treatment. However, it is necessary to further study the mechanism that may lead to the recovery of SARS-CoV-2.

Clinical Characteristics and Long-Term Recombinant Human Growth Hormone Treatment of 18q- Syndrome: A Case Report and Literature Review.

Background: 18q- syndrome is a rare chromosomal disease caused by the deletion of the long arm of chromosome 18. Some cases with 18q- syndrome can be combined with growth hormone deficiency (GHD), but data on the efficacy of recombinant human growth hormone (rhGH) treatment in 18q- syndrome are limited. Methods: Here, we report one case of 18q- syndrome successfully treated with long-term rhGH supplement. Previously reported cases in the literature are also reviewed to investigate the karyotype-phenotype relationship and their therapeutic response to rhGH. Results: A 7.9-year-old girl was referred for evaluation for short stature. Physical exam revealed proportionally short stature with a height of 111.10 cm (-3.02 SD score (SDS)), low-set ears, a high-arched palate, a small jaw, webbed neck, widely spaced nipples, long and tapering fingers, and cubitus valgus. Thyroid function test indicated subclinical hypothyroidism. The peak value of growth hormone was 10.26 ng/ml in the levodopa provocation test. Insulin-like growth factor 1 (IGF-1) was 126 ng/ml (57-316 ng/ml). Other laboratory investigations, including complete blood cell count, liver and kidney function, gonadal function, serum adrenocorticotropin levels, and serum cortisol levels, were all within normal ranges. Karyotype analysis showed 46, XX, del (18) (q21). L-Thyroxine replacement and rhGH treatment were initiated and maintained in the following 7 years. At the age of 14.8, her height has reached 159.5 cm with a height SDS increase of 2.82 SDS (from -3.02 SDS to -0.20 SDS). No significant side effects were found during the treatment. The literature review indicated the average rhGH treatment duration of 16 patients was 5.9 ± 3.3 years, and the average height SDS significantly increased from -3.12 ± 0.94 SDS to -1.38 ± 1.29 SDS after the rhGH treatment (p < 0.0001). Conclusion: The main clinical manifestations of 18q- syndrome include characteristic appearance, intellectual disability, and abnormal genital development. The literature review suggested a significant height benefit for short stature with 18q- syndrome from long-term rhGH treatment.