Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology* ; Humans ; Airway Remodeling/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; Transforming Growth Factor beta1/metabolism*

OBJECTIVES: To construct a Z-score regression model for coronary artery diameter based on echocardiographic data from children in Sichuan Province and to establish a Z-score calculation formula. METHODS: A total of 744 healthy children who underwent physical examinations at Sichuan Provincial People's Hospital from January 2020 to December 2022 were selected as the modeling group, while 251 children diagnosed with Kawasaki disease at the same hospital from January 2018 to December 2022 were selected as the validation group. Pearson correlation analysis was conducted to analyze the relationships between coronary artery diameter values and age, height, weight, and body surface area. A regression model was constructed using function transformation to identify the optimal regression model and establish the Z-score calculation formula, which was then validated. RESULTS: The Pearson correlation analysis showed that the correlation coefficients for the diameters of the left main coronary artery, left anterior descending artery, left circumflex artery, and right coronary artery with body surface area were 0.815, 0.793, 0.704, and 0.802, respectively (P<0.05). Among the constructed regression models, the power function regression model demonstrated the best performance and was therefore chosen as the optimal model for establishing the Z-score calculation formula. Based on this Z-score calculation formula, the detection rate of coronary artery lesions was found to be 21.5% (54/251), which was higher than the detection rate based on absolute values of coronary artery diameter. Notably, in the left anterior descending and left circumflex arteries, the detection rate of coronary artery lesions using this Z-score calculation formula was higher than that of previous classic Z-score calculation formulas. CONCLUSIONS The Z-score calculation formula established based on the power function regression model has a higher detection rate for coronary artery lesions, providing a strong reference for clinicians, particularly in assessing coronary artery lesions in children with Kawasaki disease.
Humans ; Male ; Female ; Child, Preschool ; Child ; Coronary Artery Disease/diagnostic imaging* ; Infant ; Mucocutaneous Lymph Node Syndrome ; Regression Analysis ; Coronary Vessels/diagnostic imaging* ; Echocardiography ; Adolescent

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

OBJECTIVES: To evaluate the association of GGN repeat polymorphism of androgen receptor (AR) with ovarian reserve and ovarian response in controlled ovarian stimulation (COS). METHODS: This genetic association study was conducted among a total of 361 women aged ≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university-affiliated IVF center. GGN repeat in the AR gene was analyzed with Sanger sequencing. The primary endpoint was the number of antral follicle counts (AFCs), and the secondary endpoints were stimulation days, total dose of gonadotropin (Gn) used, total number of retrieved oocytes, ovarian sensitivity index, and follicular output rate. RESULTS: The GGN repeat in exon 1 of the AR gene ranged from 13 to 24, and the median repeat length was 22. Based on the genotypes (S for GGN repeats <22, L for GGN repeats ≥22), the patients were divided into 3 groups: SS, SL, and LL. Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL (adjusted β=1.8, 95% CI: 0.2-3.4, P=0.024) and group LL (adjusted β=1.5, 95% CI: 0.2-2.7, P=0.021). No significant difference was observed in the number of AFCs between group SL and group LL (P>0.05). Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups, either before or after adjusting for confounding factors (P>0.05). CONCLUSIONS GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women, indicating that AR gene polymorphisms may affect ovarian reserve.
Adult ; Female ; Humans ; Genotype ; Ovarian Follicle/cytology* ; Ovarian Reserve/genetics* ; Ovulation Induction/methods* ; Polymorphism, Genetic ; Receptors, Androgen/genetics* ; East Asian People/genetics*

Objective:To investigate the accuracy of next-generation sequencing technology(NGS)in detecting the polymorphisms of HLA-DRB1,DQB1,DQA1,DRB3,DRB4,DRB5,DPA1 and DPB1 alleles in randomly-selected unrelated healthy individuals from Shenzhen Han population,investigate the potential reason for HLA-DRB1 allele dropout in routine NGS,and establish an internal quality control system.Methods:NGS-based HLA class Ⅱ genotyping was performed on 1 012 samples using the MiSeqDxTM platform.The suspected missed alleles indicated by the quality control software and HLA-DRB1 homozygotes were confirmed by PCR-SSOP or PCR-SBT methods.Results:A total of 139 alleles were detected,including HLA-DRB1(45),DRB3(7),DRB4(5),DRB5(7),DQA1(17),DQB1(21),DPA1(10)and DPB1(27).HLA-DRB 1*09:01(17.09％),15:01(10.72％);DRB3*02:02(25.99％),03:01(10.18％);DRB4*01:03(36.46％);DRB5*01:01(15.42％);DQA1*01:02(20.01％),03:02(17.19％);DQB1*03:01(19.47％),03:03(17.98％),05:02(11.66％),06:01(10.67％);DPA1*02:02(54.45％),01:03(31.18％)and DPB1*05:01(39.13％),02:01(16.90％)alleles were the most common alleles in Shenzhen Han population(frequencies＞10％).There was no statistical difference between the gene frequencies of HLA-DRB1 and DQB1 loci in our study.The HLA Common and Well-Documented Alleles in China(CWD2.4)(x2=12.68,P＞0.05).94 cases of HLA-DRB1 homozygous samples detected by NGS were retested by PCR-SSOP or SBT method,and one case of allele dropout at HLA-DRB1 locus was found.SBT method confirmed that the allele of DRB1*04:03 was missed.The laboratory internal quality control system was established.Two cases of new alleles were detected and named by WHO Nomenclature Committee for Factors of the HLA System.Conclusion:The HLA genotyping results based on NGS showed a significantly lower ambiguity rate.The HLA class Ⅱ alleles exhibit genetic polymorphism in the Han population of unrelated healthy individuals in Shenzhen.The independent method based on NGS in clinical histocompatibility testing has limitations and requires internal quality control strategies to avoid allele-dropout events.

Separation and determination of chiral and achiral impurities in glimepiride tablets by supercritical fluid chromatography. Chiral and achiral impurities were separated on a ACQUITY UPC² Trefoil^TM CEL1 column (150 mm × 3.0 mm, 2.5 μm) maintained at 30 ℃ with the mobile phase containing a mixture of CO₂ and methanol-isopropanol (1∶1) at 1 mL·min^-1, and the detection wavelength was set at 228 nm. The back pressure was set at 13.8 MPa. The injection volume was 5 μL. In the chromatogram of the system suitability solution, the peaks elute in the following order: impurity Ⅳ, impurity Ⅴ, glimepiride, impurity Ⅲ, impurity Ⅰ and impurity Ⅱ. The six substances were separated successfully in 6 min using the proposed method with a resolution factor of 2.9, 1.6, 3.0, 2.0, 6.4. The impurity Ⅰ-Ⅴ detection limit (S/N = 3) was 0.17, 0.10, 0.06, 0.15, 0.10 μg·mL^-1, respectively. Good linear relationship was established between the peak response and the concentration in the range of 0.48-51.30 μg·mL^-1 for all impurities. The spiked recovery of impurity Ⅰ-Ⅴ was found to be acceptable for 99.9%, 98.9%, 102.1%, 100.1%, 96.3% (n = 9), respectively. The related substance and assay results of 11 sample batches are consistent with the results obtained using the HPLC method in the Chinese Pharmacopoeia. Compared to the two HPLC methods in the Chinese Pharmacopoeia, the established supercritical fluid chromatography method can simultaneously separate glimepiride and its 5 impurities in a single run, and it has the following advantages: simplified sample preparation, greatly reducing the volumes of organic solvents, environmentally friendly, high accuracy and good reproducibility. It can be employed for the quality control of the chiral and achiral impurities in glimepiride tablets.

Objective To investigate the environmental contamination related to first patient with carbapenem-re-sistant Acinetobacter baumannii(CRAB)infection and the infection status of relevant patients in a newly established intensive care unit(ICU)of a hospital in Tibetan area,and analyze the transmission risk.Methods From the ad-mission in ICU of a patients who was first detected CRAB on November 15,2021 to the 60th day of hospitalization,all patients who stayed in ICU for＞48 hours were performed active screening on CRAB.On the 30th day and 60th day of the admission to the ICU of the first CRAB-infected patient,environment specimens were taken respectively 2 hours after high-frequency diagnostic and therapeutic activities but before disinfection,and after disinfection but before medical activities.CRAB was cultured with chromogenic culture medium.Results Among the 13 patients who were actively screened,1 case was CRAB positive,he was transferred from the ICU of a tertiary hospital to the ICU of this hospital on November 19th.On the 40th day of admission to the ICU,he had fever,increased frequency for sputum suction,and CRAB was detected.The drug sensitivity spectrum was similar to that of the first case,and he also stayed in the adjacent bed of the first case.64 environmental specimens were taken,and 9 were positive for CRAB,with a positive rate of 14.06％,8 sampling points such as the washbasin,door handle and bed rail were positive for CRAB after high-frequency diagnostic and therapeutic activities.After routine disinfection,CRAB was detected from the sink of the washbasin.Conclusion For the prevention and control of CRAB in the basic-level ICU in ethnic areas,it is feasible to conduct risk assessment on admitted patients and adopt bundled prevention and con-trol measures for high-risk patients upon admission.Attention should be paid to the contaminated areas(such as washbasin,door handle,and bed rail)as well as the effectiveness of disinfection of sink of washbasin.

Objective To explore the analgesic effect of different doses of dezocine combined with ropivacaine for thoracic paravertebral block(TPVB)on patients undergoing thoracoscopic radical resection of lung cancer and the influence on hemodynamics and immune function of patients.Methods Patients with lung cancer who underwent thoracoscopic radical resection were divided into low-dose group and high-dose group according to random number table method.Both groups of patients were given total intravenous anesthesia to complete the surgery.At 15 min before general anesthesia induction,the low-dose group was given TPBV with 0.1 mg·kg-1 dezocine+0.375％ropivacaine for a total of 20 mL,and the high-dose group was given TPBV with 0.15 mg·kg-1 dezocine+0.375％ropivacaine for a total of 20 mL.Comparisons were performed on both groups in terms of analgesic effect,hemodynamic parameters,immune function and occurrence of adverse drug reactions.Results There were 48 cases in low-dose group and 46 cases in high-dose group.In low-dose group,the heart rate values before TPVB,before skin incision,at 5 min after sectioning and at the end of surgery were(78.52±6.54),(70.79±7.07),(74.48±6.68)and(76.69±7.29)beat·min-1,the mean arterial pressure values were(93.16±5.72),(86.38±7.51),(92.15±6.36)and(91.14±6.13)mmHg.In high-dose group,the heart rate values at the above time points were(79.36±7.11),(71.68±6.49),(74.76±7.06)and(76.57±6.52)beat·min-1;the mean arterial pressure values were(93.89±7.18),(85.27±7.41),(90.34±6.52)and(92.43±6.34)mmHg,there were no statistical differences between the two groups(all P＞0.05).The resting state scores at 2,6 and 12 h after surgery were(1.38±0.19),(1.54±0.21)and(1.72±0.16)points,the pain scores at motion state were(1.88±0.15),(2.36±0.37)and(3.26±0.38)points in low-dose group;in high-dose group,the resting state scores were(1.32±0.17),(1.58±0.22)and(1.81±0.18)points,the pain scores at motion state were(1.81±0.13),(2.11±0.31)and(3.03±0.36)points,respectively,there were no statistical differences between the two groups(all P＞0.05).The number of analgesic pump compressions at 24 h after surgery and the number of cases with analgesic remedy were(5.12±1.26)times and 15 cases in low-dose group and were(4.74±1.03)times and 10 cases in high-dose group,with no statistical differences between the groups(all P＞0.05).The percentages of CD3+cells in low-dose group at the end of surgery and at 12 h and 24 h after surgery were(68.51±6.76)％,(54.22±5.43)％and(51.47±6.58)％,the percentages of CD4+cells were(40.29±5.02)％,(34.94±4.79)％and(30.48±5.11)％,CD4+/CD8+ratios were 1.54±0.34,1.36±0.28 and 1.16±0.23;the percentages of CD3+cells in high-dose group were(67.92±7.11)％,(56.58±6.36)％and(54.47±6.89)％,percentages of CD4+cells were(41.33±5.75)％,(35.86±5.21)％and(32.27±4.78)％,the CD4+/CD8+were 1.53±0.35,1.40±0.30 and 1.22±0.26,all with no significant difference(all P＞0.05).The incidence of postoperative adverse drug reactions in high-dose group and low-dose group were 32.61％and 14.58％,with significant difference(P＜0.05).Conclusion When TPVB regimen of dezocine combined with ropivacaine is used in thoracoscopic radical resection of lung cancer,the analgesic effect of low-dose dezocine is comparable to that of high-dose dezocine,with lower risk of adverse drug reactions.