Investigating the effects of rare ginsenosides on hyperuricemia and associated sperm damage via nontargeted metabolomics and gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: In ancient times, ginseng was used for hyperuricemia treatment as described in the classic traditional Chinese medical text Shang Han Lun. Recent studies have shown that common ginsenosides and rare ginsenosides (RGS) are the main active compounds in ginseng. RGS have higher activity and are less studied in the treatment of hyperuricemia. AIM OF THE STUDY: To determine whether RGS prevents and ameliorates potassium oxonate(PO)-induced hyperuricemia and concomitant spermatozoa damage in mice and the possible underlying mechanisms. MATERIALS AND METHODS: Potassium oxonate (PO, 300 mg/kg) induced hyperuricemia in mice via the oral administration of RGS (50, 100, or 200 mg/kg) or allopurinol (ALL, 5 mg/kg) for 35 days. Uric acid (UA) and xanthine oxidase (XO) levels were measured to assess the degree of histopathological damage in the liver, kidney, and testis, and renal creatinine (CRE), urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and inflammatory factor (IL-1ß) levels were measured to calculate the sperm density. Mechanisms were also explored based on blood and urine metabolomics and the gut microbiota. RESULTS: In this study, we demonstrated that RGS containing Rg3, Rk1, Rg6, and Rg5 could reduce serum UA levels, inhibit serum and hepatic XO activity, reduce renal CRE and BUN levels, further restore renal SOD and GSH activities, reduce the accumulation of MDA in the kidneys, and attenuate the production of renal IL-1ß. RGS was able to restore sperm density. Metabolomic analysis revealed that RGS improved sphingolipid metabolism, pyrimidine metabolism, and other metabolic pathways. 16S rDNA sequencing revealed that RGS could increase gut microbial diversity, restore the Firmicutes/Bacteroidetes (F/B) ratio, and adjust the intestinal microbial balance. Spearman's correlation analysis revealed a correlation between differentially metabolites and the gut microbiota. Lactobacillus and Akkermansia are the core genera. CONCLUSION: RGS can be a candidate for the prevention and amelioration of hyperuricemia and concomitant sperm damage. Its mechanism of action is closely related to sphingolipid metabolism, pyrimidine metabolism, and the modulation of gut microbiota, such as Lactobacillus and Akkermansia.

Anti-inflammation of LZTFL1 knockdown in OVA-induced asthmatic mice: Through ERK/GATA3 signaling pathway.

Asthma is a common chronic respiratory disease characterized by Th2-type inflammation in the airways. Leucine zip transcription factor-like 1 (LZTFL1) has been implicated in the regulation of Th2-related factors. The knockdown of LZTFL1 resulted in decreased levels of IL-4, IL-5, and IL-13. We hypothesize that LZTFL1 may have an effect on asthma. We established an acute asthmatic mouse model using the Ovalbumin (OVA) sensitization, and we found that LZTFL1 expression was upregulated in OVA-induced CD4 + T cells. Mice challenged with OVA were administered 5 × 107 TU of lentivirus via tail vein injection. LZTFL1 knockdown reversed the frequency of sneezing and nose rubbing in OVA mice. LZTFL1 knockdown reduced inflammatory cell infiltration, reduced goblet cell numbers, and mitigated collagen deposition in lung tissue. LZTFL1 knockdown decreased the levels of OVA-specific IgE, IL-4, IL-5, and IL-13 in alveolar lavage fluid of asthmatic mice. Furthermore, LZTFL1 knockdown inhibited the aberrant activation of MEK/ERK signaling pathway in asthmatic mice. GATA binding protein 3 (GATA3) is an essential transcription factor in Th2 differentiation. Flow cytometry results revealed that LZTFL1 knockdown reduced the number of GATA3 + CD4 + Th2 cells, while it did not affect the stability of GATA3 mRNA. This may be attributed to ERK signaling which stabilized GATA3 by preventing its ubiquitination and subsequent degradation. In conclusion, LZTFL1 knockdown attenuates inflammation and pathological changes in OVA-induced asthmatic mice through ERK/GATA3 signaling pathway.

Nerolidol attenuates airway inflammation and airway remodeling and alters gut microbes in ovalbumin-induced asthmatic mice.

Asthma is a common respiratory disease associated with airway inflammation. Nerolidol is an acyclic sesquiterpenoid with anti-inflammatory properties. BALB/C mice were sensitized with ovalbumin (OVA) to induce asthma symptoms and given different doses of Nerolidol. We found that Nerolidol reduced OVA-induced inflammatory cell infiltration, the number of goblet cells and collagen deposition in lung tissue. Nerolidol reduced the OVA-specific IgE levels in serum and alveolar lavage fluid in an asthma model. Immunohistochemical staining of α-SMA (the marker of airway smooth muscle) showed that Nerolidol caused bronchial basement membrane thinning in asthmatic mice. The hyperplasia of airway smooth muscle cells (ASMCs) is an important feature of airway remodeling in asthma. ASMCs were treated with 10 ng/mL TGF-ß to simulate the pathological environment of asthma in vitro and then treated with different doses of Nerolidol. Nerolidol inhibited the activity of TGF-ß/Smad signaling pathway both in the lung tissue of OVA-induced mouse and TGF-ß-stimulated ASMCs. 16s rRNA sequencing was performed on feces of normal mice, the changes of intestinal flora in OVA-induced asthmatic mice and Nerolidol-treated asthmatic mice were studied. The results showed that Nerolidol reversed the reduced gut microbial alpha diversity in asthmatic mice. Nerolidol changed the relative abundance of gut bacteria at different taxonomic levels. At the phylum level, the dominant bacteria were Bacteroidota, Firmicutes, and Proteobacteria. At the genus level, the dominant bacteria were Lactobacillus, Muribaculaceae, Bacteroides, and Lachnospiraceae. We conclude that Nerolidol attenuates OVA-induced airway inflammation and alters gut microbes in mice with asthma via TGF-ß/Smad signaling.

Efficacy and safety of macrolides in the treatment of children with bronchiectasis: a meta-analysis.

BACKGROUND: This study summarized the available randomized controlled trials (RCTs) to assess the efficacy and safety of macrolides on pathogens, lung function, laboratory parameters, and safety in children with bronchiectasis. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for available papers published up to June 2021. The outcomes were the pathogens, adverse events (AEs), and the forced expiratory volume in one second (FEV1%) predicted. RESULTS: Seven RCTs (633 participants) were included. The long-term use of macrolides reduced the risk of the presence of Moraxella catarrhalis (RR = 0.67, 95% CI: 0.30-1.50, P = 0.001; I2 = 0.0%, Pheterogeneity = 0.433), but not Haemophilus influenza (RR = 0.19, 95% CI: 0.08-0.49, P = 0.333; I2 = 57.0%, Pheterogeneity = 0.040), Streptococcus pneumonia (RR = 0.91, 95% CI: 0.61-1.35, P = 0.635; I2 = 0.0%, Pheterogeneity = 0.515), Staphylococcus aureus (RR = 1.01, 95% CI: 0.36-2.84, P = 0.986; I2 = 61.9%, Pheterogeneity = 0.033), and any pathogens present (RR = 0.61, 95% CI: 0.29-1.29, P = 0.195; I2 = 80.3%, Pheterogeneity = 0.006). Long-term macrolides had no effect on FEV1% predicted (WMD = 2.61, 95% CI: -1.31, 6.53, P = 0.192; I2 = 0.0%, Pheterogeneity = 0.896). Long-term macrolides did not increase the risk of AEs or serious AEs. CONCLUSION: Macrolides do not significantly reduce the risk of pathogens present (except for Moraxella catarrhalis) or increase FEV1% predicted among children with bronchiectasis. Moreover, macrolides were not associated with AEs. Considering the limitations of the meta-analysis, further larger-scale RCTs are needed to confirm the findings. IMPACT: Macrolides do not significantly reduce the risk of pathogens present (except for Moraxella catarrhalis) among children with bronchiectasis. Macrolides do not significantly increase FEV1% predicted among children with bronchiectasis. This meta-analysis reports on the efficacy and safety of macrolides in the treatment of children with bronchiectasis, providing evidence for the management of children with bronchiectasis. This meta-analysis does not support the use of macrolides in the management of children with bronchiectasis unless the presence of Moraxella catarrhalis is provenor suspected.

Efficacy and safety of Chinese herbal medicine children's Zibei Xuanfei syrup in treating acute trachea-bronchitis with wind-heat invading lung syndrome: A randomized, double-blind, multicentre, controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Children's Zibei Xuanfei syrup is an herbal preparation from a lifetime professor, famous old Chinese doctor, and postgraduate supervisor of medical doctor of Shandong University of Traditional Chinese Medicine. This herbal preparation promotes lung health, relieves cough, reduces phlegm, and benefits pharynx. AIM OF THE STUDY: To verify the clinical efficacy and safety of Zibei Xuanfei syrup for children in treatment of acute trachea bronchitis with wind-heat invading lung syndrome. MATERIALS AND METHODS: This was an age-stratified, block randomized, double-blind, extremely low dose parallel control, multi-center clinical trial. A total of 453 pediatric patients diagnosed with acute tracheal bronchitis in Western medicine and cough due to exogenous factors with wind-heat invading lung syndrome in Chinese medicine were enrolled. They were divided into three subgroups based on age 1∼3, 4-7, and 8-14 years old, and randomly assigned to children's Zibei Xuanfei syrup and extremely low doses of children's Zibei Xuanfei syrup (control) in a 3:1 ratio. The primary outcome was the decreased values of cough Visual Analogue Scale (VAS) score after 7 days of administration. Secondary outcomes included a decrease in cough VAS score after 3 and 5 days of the administration, and the total score of Traditional Chinese Medicine(TCM) syndrome after 3, 5, and 7 days of treatment. The chest X-ray and blood C-reactive protein were examined during screening. The safety assessment included blood urine, and stool routine, liver and kidney function of laboratory tests, and an electrocardiogram at the screening and the last visit. RESULTS: The subjects of two groups had high administration adherence (completion over 80%) (299/323, 92.6% in children's Zibei Xuanfei syrup group vs 103/107, 96.3% in the control group; p > 0.05). The children's Zibei Xuanfei syrup group was significantly better than the control group in the decreased values of cough VAS score after 7 days of administration(6.35 ± 3.45 vs 3.73 ± 3.98, p < 0.001). The subgroup analysis of the decreased value of cough VAS scores aged 1-3 years old were 5.80 ± 3.43 vs 3.75 ± 4.38 (P = 0.003), 4-7 years old was 6.30 ± 3.69 vs 2.73 ± 3.65 (P < 0.001), and 8-14 years old were 6.91 ± 3.12 vs 4.69 ± 3.75(P = 0.001)respectively. The secondary outcomes decrease values of cough VAS score of children's Zibei Xuanfei syrup group vs control group after 5 days of administration were 5.88 ± 2.90 vs 3.55 ± 3.41(P < 0.001), after 3 days of administration were 3.61 ± 2.53 vs 2.43 ± 2.56 (P < 0.001). The effective rate of the TCM symptom total score of children's Zibei Xuanfei syrup group vs control group was 91.38% vs 54.95%after 7 days of the administration, 86.93% vs 50.94% after 5 days of the administration, and 64.78% vs 40.19% after 3 days administration(each p < 0.001). There was no significant difference in Adverse Event between the two groups (59/331, 17.82% vs 15/111, 13.51%, P > 0.05). The children's Zibei Xuanfei syrup group had 5 Serious Adverse Events (incidence rate 1.21%), all of which were unrelated to the trial drug. CONCLUSION: Children's Zibei Xuanfei syrup appears to be extremely effective and safe in the treatment of acute trachea bronchitis with wind-heat invading lung syndrome. Future studies with large sample sizes will need to collect more safety data use for children.

2-Undecanone alleviates asthma by inhibiting NF-κB pathway.

Asthma is characterized by airway inflammation and remodeling. 2-Undecanone (methyl nonyl ketone), a volatile organic compound originating from Houttuynia cordata, has the potential to ameliorate inflammatory diseases. This study aimed to explore potential benefits of 2-undecanone in asthma. 2-Undecanone (100, 200, or 400 mg/kg) was administered intragastrically to ovalbumin (OVA)-challenged BALB/c mice. Lung tissues were collected to observe histopathological changes, and bronchoalveolar lavage fluid (BALF) was collected for the detection of inflammatory cells and cytokine production. The results showed that 2-undecanone ameliorated OVA-induced pathologic changes of lungs, including reducing inflammatory cell infiltration, goblet cell hyperplasia, and airway smooth muscle thickness. The number of inflammatory cells and the levels of IL-4, IL-5, IL-13, and IgE in BALF were decreased by 2-undecanone in asthmatic mice. Furthermore, abnormal activation of NF-κB pathway in lung tissues of asthmatic mice was impeded by 2-undecanone. In vitro, 2-undecanone (12.5, 25, or 50 µM) suppressed platelet-derived growth factor-BB-induced proliferation and migration of primary airway smooth muscle cells (ASMCs), and inhibited the switching of ASMCs from contractile phenotype to synthetic phenotype. Consistently, 2-undecanone blocked NF-κB activation in ASMCs. Collectively, 2-undecanone relieves asthma through alleviating airway inflammation and remodeling, and this beneficial effect is achieved by inhibiting NF-κB pathway.

Environmental and sensitization variations among asthma and/or rhinitis patients between 2008 and 2018 in China.

BACKGROUND: Little is known about the changes in allergen sensitization in China secondary to the environmental variations over the past decade. We aimed at investigating the variations in sensitization among asthma and/or rhinitis patients in China between 2008 and 2018. METHODS: This study analyzed cross-sectional data from national surveys conducted in China in 2008 and 2018. After finishing the questionnaire, participants underwent serum specific IgE measurements. A total of 2322 and 2798 patients were enrolled in 2008 and 2018, respectively. The significance of differences in sensitization rates among four regions of China were assessed. Correlation analysis was used to identify the associations of sensitization with climate change and planting of Artemisia desertorum between the two surveys. RESULTS: Compared with 2008, the general sensitization rate to mites significantly increased in 2018, which ranked highest among all tested allergens. Sensitization to pollens, especially Artemisia vulgaris, showed the greatest increase in the north. The annual mean temperature, rainfall and relative humidity in all four regions, and the Artemisia desertorum coverage in the northeastern area, increased significantly in 2018 as compared with 2008. From 2008 to 2018, an increase in Dermatophagoides pteronyssinus sensitization was significantly associated with an increase in relative humidity (r = 0.54, p = 0.037). The increase in A. vulgaris sensitization was significantly associated with the increase in the A. desertorum planting area (r = 0.67, p = 0.006) and with a decrease in rainfall (r = -0.59, p = 0.021). CONCLUSIONS: House dust mites remain the most important allergen in Chinese individuals with asthma and/or rhinitis. Pollen sensitization dramatically increased in northern China. Increases in sensitization to dust mites and Artemisia were related to the increases in humidity and planting area of A. desertorum.

Effect of Jiuwei Zhuhuang Powder on Cough Resolution in Children with Upper Respiratory Tract Infections: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of Jiuwei Zhuhuang Powder (JWZH), a Tibetan patent medicine in treating upper respiratory tract infection (URTI) associated cough in children. METHODS: The study was a multicenter, randomized, open-label, controlled trial. A total of 142 children aged 2 to 14 years old, with URTI-associated cough within 48 h of onset, were randomly assigned to two groups at a 1:1 ratio by computer-generated randomization sequence. Children were treated with JWZH (1 to 1.5 g, twice to thrice daily) in the treatment group or conventional treatment (Pediatric Paracetamol, Artificial Cow-bezoar and Chlorphenamine Maleate Granules, 0.25 to 1 g, thrice daily) in the control group for 5 days. The primary endpoints were the time to cough resolution and 4-day cough resolution rate. The secondary endpoints were the daily improvement in symptom scores and cough resolution rate during the study period. RESULTS: A total of 138 children were included in the intention-to-treat analysis, with 71 cases in the treatment group and 67 cases in the control group. Compared with the conventional treatment, the children receiving JWZH had a shorter time to cough resolution [hazard ratio, 2.10; 95% confidence interval (CI), 1.29-3.40; P=0.003]. The median time to cough resolution for children receiving JWZH was shorter than that of the conventional treatment (2 days vs. 3 days; P<0.001). The 4-day cough resolution rate in the JWZH group was higher than that of the control group (94.4% vs. 74.6%; risk difference: 19.8%, 95% CI: 8.1%-31.5%; relative risk: 1.265, 95% CI: 1.088-1.470; P=0.001). There were no statistically significant differences in the improvement of other symptoms caused by URTI (P>0.05). Adverse events was reported in 5.6% (4/71) and 4.5% (3/67) in participants of JWZH and PPACCM groups (P>0.05), respectively, which were all mild and resolved without treatment. CONCLUSION: JWZH seemed to be a safe and effective therapy for URTI-associated cough in children. (Trial registration No. ChiCTR2000039421).

Chrysophanol attenuates airway inflammation and remodeling through nuclear factor-kappa B signaling pathway in asthma.

Chrysophanol (CHR), a purified active constituent extracted from Rheum palmatum L., possesses anti-inflammatory activity. This study aimed to evaluate its effects on asthma-associated airway inflammation and remodeling. BALB/c mice were sensitized and challenged by ovalbumin (OVA) and administrated with different doses of CHR. We found that CHR decreased OVA-induced pulmonary inflammation: the levels of interleukin (IL)-4, IL-5, and IL-13, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase were downregulated. CHR also attenuated airway remodeling induced by OVA challenge-CHR inhibited pulmonary α-smooth muscle actin expression. Moreover, both the nuclear translocation and activity of NF-κB p65 were inhibited by CHR in the asthmatic lung. Enhanced autophagy was initiated in the lung by OVA challenge as evidenced by upregulated light chain 3 beta, autophagy-related protein 5, and Beclin 1. CHR suppressed OVA-induced alterations in these autophagy-related molecules. In vitro, CHR (2 or 20 µM) was used to treat human pulmonary epithelial BEAS-2B cells in the presence of 10 ng/ml recombinant TNF-α. CHR not only exhibited the antiproliferation effect but also inhibited the activation of nuclear factor-kappa B (NF-kB) signaling pathway in TNF-α-treated BEAS-2B cells. In conclusion, our study indicates that CHR has the potential to ameliorate asthma.

Regulatory Effect of Xiaoqinglong Decoction on Thymic Stromal Lymphopoietin (TSLP) Inflammation Promoter in Mice with Cold Asthma.

Allergic asthma is a complex and chronic inflammatory airway disease. The thymic stromal lymphopoietin (TSLP) signaling pathway plays an important role in asthma. Xiaoqinglong Decoction (XQL) is the first choice to treat cold asthma in clinical settings. In this study, the role of the TSLP pathway in the onset of asthma and the protective mechanism of XQL were investigated. A total of 50 female mice were randomly divided into the following groups: the blank group (A), the model group (B), the XQL group (C), the dexamethasone group (D), and the XQL + dexamethasone group (E). Asthma was induced with ovalbumin, and corresponding drug intervention was carried out for 7 days, after which serum and lung tissue end points were analyzed. Serum interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), nuclear factor κB (NF-κB), and TSLP levels were higher in group B than in group A (p<0.05). However these levels were lower in group C and D than in group B (p<0.05), and there was no significant difference between groups C and D (p>0.05). Interestingly, these end points were significantly lower in group E than in groups C and D (p<0.05). Regarding pathologic changes, the inflammatory infiltrate in the lungs of groups C, D, and E was lower than that of group B, especially in group E. We conclude that the TSLP pathway plays an important role in the course of asthma, and can be used as an important target for asthma treatment; XQL may play a role in reducing inflammation and relieving asthma by regulating the TSLP signaling pathway.

Effect of Hospital to Home nutrition management model on postoperative clinical outcomes of patients with laryngeal carcinoma.

The purpose of this investigation was to determine the effectiveness of a Hospital to Home (H2H) nutrition management model on the postoperative clinical outcomes of patients with laryngeal carcinoma. Eighty-six patients with laryngeal carcinoma were randomly divided into an observation (H2H nutrition management) or control group (routine nutrition management). The ratios of urine lactulose to mannitol (L/M) in serum orexin-A levels of patients in both groups on the 1st postoperative day were significantly higher than before surgery; these levels decreased from the 7th and 14th postoperative day, but remained higher than before surgery (p<0.05). There was no statistical difference in the L/M and orexin-A levels between the two groups before surgery and on the 1st postoperative day; those indexes were statistically decreased in the observation as compared to the control group on the 7th and 14th postoperative days. The nutritional status grades were evaluated using a Patient-Generated Subjective Global Assessment (PG-SGA) quantitative scoring at 3 months after surgery and showed that malnutrition rates were significantly lower in the observation as compared to the control group. Serum levels of hemoglobin (Hb), albumin (Alb), prealbumin (PAB) and transferrin (TRF), 3 months after surgery showed significantly lower Hb and Alb and significantly higher PAB and TRF levels in the observation compared to the control group. After one year follow-up, there were no significant differences in hospitalization time and cost between the two groups, but the postoperative complication, readmission and mortality rates in the observation group were significantly lower than that the control group. Each dimension score of quality of life in the observation group was significantly higher than the control group. In conclusion, the H2H nutrition management model can effectively improve the postoperative nutritional level of patients with laryngeal carcinoma, resulting in a lower rate of complication, readmission and mortality resulting in an improved patient's quality of life.

[Epidemiological survey and risk factor analysis of asthma in children in urban districts of Zhengzhou, China].

OBJECTIVE: To study the epidemiological features, treatment status, and risk factors for asthma in children in Zhengzhou, China. METHODS: Questionnaires for primary screening were issued using the method of multi-stage stratified sampling. Suspected asthmatic children were given a second questionnaire, physical examination, medical history review, and auxiliary examination to confirm the diagnosis. Age- and sex-matched non-asthmatic children were randomly recruited to the control group. RESULTS: The number of valid questionnaires was 10 616 (5 444 males and 5 172 females). There were 308 confirmed asthma cases and the overall prevalence was 2.90%. The prevalence in boys was higher than that in girls (3.4% vs 2.4%). The prevalence in children under 3 years of age was 10.2%, which was higher than that in other age groups. The top three triggers for asthma attack in children were respiratory infection (94.2%), weather changes (89.0%), and exercise (35.1%). The most common asthma attack was moderate (71.8%), followed by mild (22.7%). Inhaled corticosteroids, systemic corticosteroids, and antibiotics were applied to 94.8% (292 cases), 74.7% (230 cases), and 90.9% (280 cases) of all patients, respectively. Multivariate logistic regression analysis indicated the following major risk factors for asthma: history of allergic rhinitis (OR=150.285, 95% CI: 31.934-707.264), history of eczema (OR=10.600, 95% CI: 1.054-106.624), history of atopic dermatitis (OR=31.368, 95% CI: 3.339-294.683), food allergies (OR=27.373, 95% CI: 2.670-280.621), method of birth (OR=2.853, 95% CI: 1.311-6.208), age of first antibiotic use (OR=0.384, 95% CI: 0.172-0.857), frequency of antibiotic use within 1 year of age (OR=9.940, 95% CI: 6.246-15.820), use of wall decorating materials (OR=2.108, 95% CI: 1.464-3.036), and use of heat supply in winter (OR=6.046, 95% CI: 1.034-35.362). CONCLUSIONS: The prevalence of childhood asthma is associated with age and gender in Zhengzhou. Most asthma attacks are moderate, often triggered by respiratory infection. Treatment of asthma has been standardized, but still needs further improvement. History of allergic rhinitis, eczema, atopic dermatitis and food allergies, cesarean delivery, frequent use of antibiotics within 1 year of age, use of decorating materials on the wall, and use of heating in winter may increase risk for asthma, and use of antibiotics in older age is a protective factor against asthma in children.