Main focus of parents of children with attention deficit hyperactivity disorder and the effectiveness of early clinical screening.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common mental and behavioral disorder among children. AIM: To explore the focus of attention deficit hyperactivity disorder parents and the effectiveness of early clinical screening. METHODS: This study found that the main directions of parents seeking medical help were short attention time for children under 7 years old (16.6%) and poor academic performance for children over 7 years old (12.1%). We employed a two-stage experiment to diagnose ADHD. Among the 5683 children evaluated from 2018 to 2021, 360 met the DSM-5 criteria. Those diagnosed with ADHD underwent assessments for letter, number, and figure attention. Following the exclusion of ADHD-H diagnoses, the detection rate rose to 96.0%, with 310 out of 323 cases identified. RESULTS: This study yielded insights into the primary concerns of parents regarding their children's symptoms and validated the efficacy of a straightforward diagnostic test, offering valuable guidance for directing ADHD treatment, facilitating early detection, and enabling timely intervention. Our research delved into the predominant worries of parents across various age groups. Furthermore, we showcased the precision of the simple exclusion experiment in discerning between ADHD-I and ADHD-C in children. CONCLUSION: Our study will help diagnose and guide future treatment directions for ADHD.

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies.

Among women, breast cancer ranks as the most prevalent form of cancer, and the presence of metastases significantly reduces prognosis and diminishes overall survival rates. Gaining insights into the biological mechanisms governing the conversion of cancer cells, their subsequent spread to other areas of the body, and the immune system's monitoring of tumor growth will contribute to the advancement of more efficient and targeted therapies. MicroRNAs (miRNAs) play a critical role in the interaction between tumor cells and immune cells, facilitating tumor cells' evasion of the immune system and promoting cancer progression. Additionally, miRNAs also influence metastasis formation, including the establishment of metastatic sites and the transformation of tumor cells into migratory phenotypes. Specifically, dysregulated expression of these genes has been associated with abnormal expression of oncogenes and tumor suppressor genes, thereby facilitating tumor development. This study aims to provide a concise overview of the significance and function of miRNAs in breast cancer, focusing on their involvement as tumor suppressors in the antitumor immune response and as oncogenes in metastasis formation. Furthermore, miRNAs hold tremendous potential as targets for gene therapy due to their ability to modulate specific pathways that can either promote or suppress carcinogenesis. This perspective highlights the latest strategies developed for miRNA-based therapies.

Enhancing clinical utility: deep learning-based embryo scoring model for non-invasive aneuploidy prediction.

BACKGROUND: The best method for selecting embryos ploidy is preimplantation genetic testing for aneuploidies (PGT-A). However, it takes more labour, money, and experience. As such, more approachable, non- invasive techniques were still needed. Analyses driven by artificial intelligence have been presented recently to automate and objectify picture assessments. METHODS: In present retrospective study, a total of 3448 biopsied blastocysts from 979 Time-lapse (TL)-PGT cycles were retrospectively analyzed. The "intelligent data analysis (iDA) Score" as a deep learning algorithm was used in TL incubators and assigned each blastocyst with a score between 1.0 and 9.9. RESULTS: Significant differences were observed in iDAScore among blastocysts with different ploidy. Additionally, multivariate logistic regression analysis showed that higher scores were significantly correlated with euploidy (p < 0.001). The Area Under the Curve (AUC) of iDAScore alone for predicting euploidy embryo is 0.612, but rose to 0.688 by adding clinical and embryonic characteristics. CONCLUSIONS: This study provided additional information to strengthen the clinical applicability of iDAScore. This may provide a non-invasive and inexpensive alternative for patients who have no available blastocyst for biopsy or who are economically disadvantaged. However, the accuracy of embryo ploidy is still dependent on the results of next-generation sequencing technology (NGS) analysis.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

[Economic evaluation of Annao Pills combined with antihypertensive drugs in treatment of primary hypertension: a study based on decision tree model].

The purpose of this study was to evaluate the economics of Annao Pills combined with antihypertensive drugs in the treatment of primary hypertension in the Chinese medical setting. TreeAge pro 2018 was used for cost-effect analysis and sensitivity analysis of the two treatment regimens. The intervention time of the simulation model was 2 weeks. The cost parameters were derived from Yaozhi.com, and the effect parameters were based on Meta-analysis of randomized controlled trial(RCT) involving Annao Pills. The experimental group was treated with Annao Pills combined with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets), and the control group was treated with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets). The basic analysis showed that the incremental cost-effect ratio(ICER) of the two groups was 2 678.67 yuan, which was less than 7.26% of the per capita disposable income in 2022. That is, compared with anti-hypertensive drugs alone, Annao Pills combined with antihypertensive drugs cost 2 678.67 yuan more for each additional patient with primary hypertension. The results of sensitivity analysis verified the robustness of the basic analysis results. The probability sensitivity results showed that when the patient's personal willingness to pay the price was higher than 2 650 yuan, the probability of the regimen in the experimental group was higher, which was consistent with the results of the basic analysis. In conclusion, when the price was higher than 2 650 yuan, Annao Pills combined with anti-hypertensive drugs was more economical than anti-hypertensive drugs alone in terms of improving the response rate of the patients with primary hypertension.

[Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines].

Due to the lack of specialized guidance, the post-marketing research on clinical effectiveness of Chinese patent medicines demonstrates varied quality and lacks high-quality evidence, failing to meet the demands of policy-making, clinical decision-making, and industrial decision-making. To address this issue, this project gathered experts in clinical medicine, clinical pharmacy, evidence-based medicine, drug epidemiology, medical ethics, and policy and regulation in China. They referred to the model of international post-marketing research on medicines and developed Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines under the framework of relevant laws and regulations and technical guidance documents in China. The guidelines were developed with consideration to the characteristics of Chinese patent medicines, China's national conditions, and all the stakeholders including marketing authorization holders, clinical researchers, drug administration, and users. The development of the guidelines followed the requirements for developing group standards set by the China Association of Chinese Medicine. The guidelines fully implement the concept of full life-cycle research, emphasizing the combination of traditional Chinese medicine(TCM) theory, human use experience, and clinical trials and pay attention to the compliance, scientificity, and ethics of research. The guidelines clarify the topic selection and decision-making path of the post-marketing research on effectiveness of Chinese patent medicines through six steps: determining research purpose, analyzing drug characteristics, evaluating research basis, proposing clinical orientation, clarifying research purpose, and implementing classified research. The general principles of research design and implementation were clarified from eight aspects: research type, research objects, sample size, efficacy indicators, bias, missing data, evidence level, and practicality. It focuses on the research on the TCM syndrome-based efficacy evaluation, clinical value-oriented mechanism of action, and the effectiveness of Chinese patent medicines with different routes of administration. The guidelines provide a universal methodological basis for the post-marketing research on clinical effectiveness of Chinese patent medicines.

[Guidelines for economic evaluation of post-marketing Chinese patent medicine].

With the premise of drug safety and effectiveness, pharmacoeconomic evaluation can provide optimal solutions for diversified decision-making application scenarios from different research perspectives while maximizing the rational utilization of existing healthcare resources. Chinese patent medicine is an essential component of pharmaceutical utilization in China and a significant part of healthcare expenditure in China. However, the economic evaluation of post-marketing Chinese patent medicine is lacking. These evaluations often lack standardization, exhibit varying quality, and are unable to effectively support healthcare decisions, indicating a need for improvement in overall quality. Given this situation, this project has gathered leading experts from China and has strictly adhered to the requirements of the group standards set by the China Association of Traditional Chinese Medicine in developing Guidelines for economic evaluation of post-marketing Chinese patent medicine, aiming to provide methodological guidance for the post-market pharmacoeconomic evaluation of Chinese patent medicine, enhancing the standardization of pharmacoeconomic evaluations of Chinese patent medicine and the scientific validity of research results, and thereby elevating the overall quality of pharmacoeconomic evaluations for post-marketing Chinese patent medicine. The guidelines adhere to the framework provided by relevant laws and regulations in China and technical guidance documents. It is based on guidance from traditional Chinese medicine(TCM) theories, focusing on the unique characteristics of TCM. It covers various aspects of pharmacoeconomic evaluation, including fundamental principles, research topic selection, research question definition, study design type selection, cost identification and measurement, health outcomes, and evaluation methods. The guidelines offer methodological recommendations and decision guidance to address common issues and challenges in the pharmacoeconomic evaluation of post-marketing Chinese patent medicine.

Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation.

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.

Constricted posterior fourchette deformities: Definition, classification and surgical treatment.

BACKGROUND: Labiaplasty is one of the top cosmetic procedures patients are seeking in the past two years. However, treatment of disease in posterior fourchette caused by various etiological factors was less investigated and neglected. METHODS: Three types of posterior fourchette deformity were proposed: (1) Redundant posterior fourchette, (2) Relaxed posterior fourchette, and (3) Constricted posterior fourchette. Local flap transfer technique was applied. Y-V-plasty and 5-Z-Flap-plasty were used to treat web type and tight type of the constricted posterior fourchette, respectively. Follow-ups were arranged on the Internet or at the outpatient clinic. Visual analogue scale (VAS) was utilized to evaluate sexual discomfort in the satisfaction questionnaires during follow-up. RESULTS: A total of 48 patients with constricted posterior fourchette deformity from May 2022 to May 2023 were reviewed in the study. Y-V-plasty could decrease VAS in patients with web-type deformity by 4.13 ± 1.46 (p＜0.001). 5-Z-Flap-plasty could decrease VAS in patients with tight-type deformity by 3.76 ± 1.53 (p＜0.05). Satisfaction rates of the web type and tight type were 93.1% (27/29) and 86.7% (13/15) respectively. Complications include two cases of hematoma, one case of persistent pain and two cases of dehiscence. CONCLUSION: Constricted posterior fourchette seriously affects the quality of life. Y-V-plasty and 5-Z-Flap-plasty can be utilized to treat the two subtypes of constricted posterior fourchette, which can effectively reduce the pain score of patients with high satisfaction and few long-term complications.

Two new megastigmane glycosides from the leaves of Nicotiana tabacum and their anti-inflammatory activities.

Two new megastigmane glycosides, (6 R,7E,9R)-3-oxo-α-ionyl-9-O-α-L-rhamnopyranosyl-(1''→4')-ß-D-glucopyranoside (1) and (6 R,7E,9R)-3-oxo-α-ionyl-9-O-ß-D-glucopyranosyl-(1''→6')-ß-D-glucopyranoside (2), together with six known analogues (3-8) were isolated from the leaves of Nicotiana tabacum. The structures of all metabolites were determined by comprehensive analysis of NMR and MS spectroscopic data as well as by comparison with those of previously reported. The in vitro anti-inflammatory activity of all isolates was evaluated using a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model, and the compounds 1, 3, 7, and 8 exhibited inhibition of LPS-induced NO production in RAW264.7 macrophage cells with IC50 values of 42.3-61.7 µM (positive control, dexamethasone, IC50 = 21.3 ± 1.2 µM).

Anisotropic Magnetic Polymeric Particles with a Controllable Structure via Seeded Emulsion Polymerization.

Magnetic polymer composites have been widely utilized in potential applications in material science, such as reduction of dyes, immunodiagnostics, biomedicals, and magnetically controllable photonic crystals owing to large surface areas, fast separation, and recyclable performance. In this work, anisotropic magnetic particles were prepared by seeded emulsion polymerization, with morphologies of "Fe3O4-shell", "hemisphere-like", "raspberry-like", "multiple lobes-like", and "sandwich-like". Poly(styrene/divinylbenzene/mono-2-(methacryloxy)ethyl succinate)@ Fe3O4 (P(St/DVB/MMES)@Fe3O4) were the seed microspheres, and P(St/DVB/MMES)@Fe3O4@polymer particles are achieved by seeded emulsion polymerizations. The morphology of the particles depends on polymerization conditions (monomer ratios and surfactant), particle properties, and so on. Then, the minimum surface free energy change principles were used to predict the equilibrium morphologies of the magnetic polymer composites. Through theory, the model gives the correct tendency and good agreement with the equilibrium morphology which was in tandem with TEM results. Lastly, after in situ surface deposition of Ag nanoparticles, magnetic composite particles with sandwich-like morphology were applied for the catalytic degradation of 4-nitrophenol (4-NP) reacting with NaBH4. The apparent rate coefficient is 0.0069 s-1, and it can keep mainly about 80% efficiency in catalysis after five cycles.

DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

Effects of fertilizer application on the growth of Stranvaesia davidiana D. seedlings.

Wild plants represent a potential source of urban landscape trees. Stranvaesia davidiana Dcne. is a member of the Stranvaesia Lindl. Genus, which belongs to family Rosaceae Juss. It has great ornamental value. It can contribute to urban color foliage and fruit species. However, the most effective fertilizer application strategy required for its cultivation is unknown. Therefore, we conducted an orthogonal experiment to investigate the fertilizer type and level (pure nitrogen) using ten experimental groups, including an untreated control group. Pot experiments were used to determine the growth indices of seedlings, including plant height, basal diameter, and chlorophyll content post-fertilizer treatment. This study explored the most appropriate fertiler application model for the growth of S. davidiana seedlings. The results revealed that enhanced seedling growth depended on the type and amount of fertilizer used, and their interaction. Fertilizer application increased the plant height by 2.67 cm to 12.26 cm, basal diameter by 0.39 cm to 0.75 cm, and chlorophyll content by 5.66 to 19.86. Among the different types of fertilizer, organic fertilizer increased the plant height by 0.42 cm to 9.59 cm and basal diameter by 0.01 cm to 0.05 cm, compared with the control group. Organic fertilizer had the maximum effect on seedling growth, especially at medium levels. The total growth of basal diameter and chlorophyll content was 1.58 ± 0.04 cm and 39.53 ± 2.37, respectively. Basal diameter is the most critical index in seedling reproduction . The study results suggest that the application of 4.06 g of organic fertilizer per plant was the most effective, and served as a basis for further field trials.

Comprehensive aesthetic corrections of gynecomastia using the reproducible safe and minimally invasive surgical strategy.

BACKGROUND: Minimally invasive access and fast recovery are trends of gynecomastia surgery. We placed great importance on liposuction and modified original pull-through technique. The purpose of this study was to present a refined surgical strategy for gynecomastia in grade I and II. METHODS: The refined strategy embraced enhanced liposuction to remove the intraglandular fat sufficiently, followed by open resection of gland using the pull-through and bottom-up technique with adjuvant liposuction in the end. Surgical data were recorded and satisfactory questionnaires with 5-point scales were administered during follow-up. RESULTS: Between January 2017 and May 2022, 165 patients underwent enhanced liposuction combined with the pull-through and bottom-up technique for gland excision. Age ranged from 12 to 56 years. The median length of surgery was 100 min. A median of 300 ml of fat was aspirated and a median of 20.8 g of gland was excised. Seventy-seven patients (46.7%) responded the questionnaires at least 6 months postoperatively, and the average overall satisfaction was 4.68 ± 0.52 points. Thirteen sides of breasts developed complications with a rate of 4.0%. CONCLUSION: Enhanced liposuction combined with pull-through and bottom-up technique proved effective to treat grade I and II gynecomastia with minimal scarring and high satisfaction. The refined strategy was simple and safe, and would obtain optimal outcomes even for inexperienced surgeons.

Fingerprinting and characterization of the polysaccharides from Polygonatum odoratum and the in vitro fermented effects on Lactobacillus johnsonii.

Polygonatum odoratum (Yu-Zhu) can be utilized to treat the digestive and respiratory illness. Previous studies have revealed that the underlying therapeutic mechanism of P. odoratum polysaccharides (POPs) is associated with remodeling the gut microbiota. However, POPs in terms of the chemical composition and fermentation activities have been understudied. Here we developed the three-level fingerprinting approaches to characterize the structures of POPs and probed into the beneficial effects on promoting the growth and fermentation of Lactobacillus johnsonii. POPs were prepared by water decoction followed by alcohol sedimentation, while trifluoroacetic acid under different conditions to prepare the hydrolyzed oligosaccharides and monosaccharides. POPs exhibited three main molecular distribution of 601-620 kDa, 4.12-6.09 kDa, and 3.57-6.02 kDa. Hydrolyzed oligosaccharides with degree of polymerization (DP) 2-13 got primarily characterized by analyzing the rich fragmentation information obtained by hydrophilic interaction chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (HILIC/IM-QTOF-MS). Amongst them, the DP5 oligosaccharide was characterized as 1,6,6-kestopentaose. The molecular ratio of Fru: Ara: Glc: Gal: Xyl was 87.72: 0.30: 11.56: 0.19: 0.23. In vitro fermentation demonstrated that 4.5 mg/mL of POPs could significantly promote the growth of L. johnsonii. Co-cultivated with 4.5 mg/mL of POPs, L. johnsonii exhibited stronger antimicrobial activity against Klebsiella pneumoniae. The concentrations of short-chain fatty acids in the POPs-lactobacilli fermented products, including acetic acid, isobutyric acid, and isovaleric acid, were increased. Conclusively, POPs represent the promising prebiotic candidate to facilitate lactobacilli, which is associated with exerting the health benefits.

Recent advances in enzymatic and chemoenzymatic synthesis of N- and O-glycans.

Glycosylation is one of the most common post-translational modifications of proteins, which plays essential roles in regulating the biological functions of proteins. Efficient and versatile methods for the synthesis of homogeneous and well-defined N- and O-glycans remain an urgent need for biological studies and biomedical applications. Despite their structural complexity, tremendous progress has been made in the synthesis of N- and O-glycans in recent years. This review discusses some recent advances in the enzymatic and chemoenzymatic synthesis of N- and O-glycans.

[Meta-analysis and trial sequential analysis of Chaihuang Granules in treatment of upper respiratory tract infection in children].

This study aimed to evaluate the efficacy and safety of Chaihuang Granules in the treatment of upper respiratory tract infection in children. The databases such as CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched for randomized controlled trial(RCT) of Chaihuang Granules for the treatment of upper respiratory tract infection in children, and supplemented by manual searching of gray literature. Two investigators independently screened the literature, extracted data, and assessed the methodological quality. Meta-analysis was performed using RevMan 5.4 software, trial sequential analysis was conducted using TSA 0.9.5.10 Beta software, and evidence quality evaluation was carried out using GRADE profiler 3.6.1 software. Eighteen RCTs involving 2 459 patients(1 262 in the treatment group and 1 197 in the control group) were included. Meta-analysis showed that compared with conventional therapy alone, Chaihuang Granules significantly improved the total effective rate(RR=1.18, 95%CI[1.15, 1.22], P<0.000 01), reduced the disappearance time of symptoms/signs(MD=-1.39, 95%CI[-1.66,-1.12], P<0.000 01), improved cytokine levels(MD=-2.40, 95%CI[-3.80,-1.00], P=0.000 8), improved humoral immune levels(MD=0.75, 95%CI[0.60, 0.90], P<0.000 01), and reduced the recurrence rate(MD=-2.11, 95%CI[-2.98,-1.25], P<0.000 01). However, the incidence of adverse reactions was not increased(RR=0.94, 95%CI[0.59, 1.49], P=0.78). Subgroup analysis showed that:(1) both Chaihuang Granules used alone(RR=1.19, 95%CI[1.11, 1.27], P<0.000 01) and in combination with other therapies(RR=1.18, 95%CI[1.14, 1.22], P<0.000 01) effectively improved the total effective rate.(2) In terms of symptoms/signs disappearance time, Chaihuang Granules effectively reduced the duration of fever(MD=-1.18, 95%CI[-1.78,-0.58], P=0.000 1), cough with sputum(MD=-1.82, 95%CI[-2.38,-1.25], P<0.000 01), cough(MD=-1.31, 95%CI[-1.89,-0.74], P<0.000 01), sore throat(MD=-1.57, 95%CI[-2.25,-0.89], P<0.000 01), and lung rales(MD=-1.49, 95%CI[-2.06,-0.92], P<0.000 01).(3) Regarding cytokine levels, Chaihuang Gra-nules effectively improved the levels of interleukin(IL)-2(MD=-0.94, 95%CI[-1.16,-0.72], P<0.000 01), IL-6(MD=-4.71, 95%CI[-6.39,-3.03], P<0.000 01), and tumor necrosis factor-α(TNF-α)(MD=-2.07, 95%CI[-2.43,-1.71], P<0.000 01).(4) In terms of cellular immune levels, Chaihuang Granules effectively improved the levels of CD3~+(MD=4.11, 95%CI[1.53, 6.69], P=0.002), CD4~+(MD=4.21, 95%CI[1.69, 6.73], P=0.001), CD8~+(MD=-2.65, 95%CI[-3.93,-1.37], P<0.000 1), and CD4~+/CD8~+(MD=0.25, 95%CI[0.14, 0.37], P<0.000 1).(5) In terms of humoral immune levels, Chaihuang Granules effectively improved the levels of IgA(MD=0.44, 95%CI[0.23, 0.64], P<0.000 1), IgM(MD=0.31, 95%CI[0.15, 0.46], P=0.000 1), and IgG(MD=2.02, 95%CI[1.60, 2.43], P<0.000 01). Trial sequential analysis showed that the cumulative Z-curve of the total effective rate crossed the boundary value, further confirming its clinical efficacy. The GRADE evidence quality evaluation showed that the evidence quality of the above outcome indicators was low or very low, and the recommendation strength was weak. Compared to conventional therapy alone, Chaihuang Granules can effectively improve the total effective rate of treatment, alle-viate symptoms and signs of upper respiratory tract infection in children, improve inflammatory conditions, enhance immune function, and reduce the recurrence rate. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

Hypothyroidism reduces the risk of lung cancer through oxidative stress response and the PI3K/Akt signaling pathway: An RNA-seq and Mendelian randomization study.

Hypothyroidism has been suggested to play a role in tumor progression. However, the causal association between hypothyroidism and lung cancer remains unknow. To elucidate the potential association between hypothyroidism and lung cancer risk, we employ a Mendelian randomization (MR) approach. MR was performed to analyze pooled data from the International Lung Cancer Consortium (11,348 cases and 15,861 controls; European ancestry) to determine the causal relationship between hypothyroidism and lung cancer. We used 36, 83, and 14 single nucleotide polymorphisms as instrumental variables for hypothyroidism/myxoedema, hypothyroidism, and exercise, respectively. We further investigated the mechanisms involved in transcriptome analysis using data from The Cancer Genome Atlas and Genotype-Tissue Expression database. We conducted an initial validation of intermediary factor using a two-step MR analysis. Genetically predicted hypothyroidism was significantly related to the risk of overall lung cancer, specifically the risk of lung squamous cell cancer (LSCC) but not with the risk of lung adenocarcinoma (LUAD) as assessed using the inverse-variance weighted (IVM) method. A similar causal association was found between hypothyroidism/myxoedema and the risk of lung cancer, LSCC, and LUAD. Transcriptome analysis showed that genes associated with hypothyroidism, lung cancer, and LSCC were enriched in the PI3K/Akt signaling pathway and oxidative stress response. However, genes related to hypothyroidism and LUAD did not exhibit enrichment in these pathways. Hypothyroidism was significantly associated with strenuous sports or other exercises. Moreover, genetically predicted exercise was significantly related to the risk of overall lung cancer, and LSCC, but not LUAD. We detected no horizontal pleiotropy using the MR-PRESSO and MR Egger regression intercept. Hypothyroidism was causally associated with a lower risk of lung cancer, and these effects might be mediated by the oxidative stress response and the PI3K/Akt signaling pathway. Therefore, our study suggests that the potential factors and viable etiologies of hypothyroidism that contributed to lung cancer risk deserve further investigation.

Polygonatum odoratum polysaccharide attenuates lipopolysaccharide-induced lung injury in mice by regulating gut microbiota.

Polygonatum odoratum is appreciated for its edible and medicinal benefits especially for lung protection. However, the contained active components have been understudied, and further research is required to fully exploit its potential application. We aimed to probe into the beneficial effects of Polygonatum odoratum polysaccharide (POP) in lipopolysaccharide-induced lung inflammatory injury mice. POP treatment could ameliorate the survival rate, pulmonary function, lung pathological lesions, and immune inflammatory response. POP treatment could repair intestinal barrier, and modulate the composition of gut microbiota, especially reducing the abundance of Klebsiella, which were closely associated with the therapeutic effects of POP. Investigation of the underlying anti-inflammatory mechanism showed that POP suppressed the generation of pro-inflammatory molecules in lung by inhibiting iNOS+ M1 macrophages. Collectively, POP is a promising multi-target microecological regulator to prevent and treat the immuno-inflammation and lung injury by modulating gut microbiota.