Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

Objective To investigate the genetic differences among different populations based on 13 autosomal STR loci in CODIS core.Methods Data of 13 autosomal STR loci(CSF1PO,FGA,THO1,TPOX,vWA,D3S1358,D5S818,D7S820,D8S1179,D13S317,D16S539,D18S51,D21S11)were collected from 95 populations in scientific journals between 1999 and 2021,soursed from the PubMed database,which had been published.Allele frequencies of loci were sorted out and forensic genetic parameters including gene differentiation coefficient(Gst),total heterozygosity(Ht),subpopula-tion heterozygosity(Hs)values,and Nei's DA genetic distance were calculated.Principal component analysis,phylogenetic tree,and multidimensional scale analysis were conducted to assess population ge-netic structure.Results A total of 265 alleles were detected at the 13 STR loci in these 95 popula-tions.The mean values of Gst,Ht,and Hs were 0.023 247,0.797 915 and 0.779 365.Population genetic analyses reflected significant differences among populations from Asia,Africa and Europe.In Asian populations,there was a certain degree of distinction between mainland and island populations;the Han population showed a certain degree of distinction with surrounding populations in mainland;while within the Han population,there were two distinct clusters formed by the northern Han and the south-ern Han.Conclusion The 13 autosomal STR loci in CODIS core demonstrate potential value for popu-lation identification across different groups,and may be used for the differentiation of ethnic groups,among different continental populations.

This paper aims to study the effect of p-cymene on mice with deficiency-cold syndrome induced by hydrocortisone and deficiency-heat syndrome induced by dexamethasone and explore the medicinal properties and mechanism of p-cymene with mild and warm nature based on the dominant characteristics of the two-way applicable conditions of mild drugs. A total of 80 KM mice were randomly divided into blank group, deficiency-cold syndrome model group, deficiency-cold syndrome + ginseng group, and deficiency-cold syndrome + low-dose and high-dose p-cymene groups, as well as blank group, deficiency-heat syndrome model group, deficiency-heat syndrome + American ginseng group, and deficiency-heat syndrome + low-dose and high-dose p-cymene groups. Hydrocortisone and dexamethasone solution were intragastrically administered for 14 consecutive days to prepare deficiency-cold syndrome and deficiency-heat syndrome models. Except for the blank group and the model group intragastrically administered with normal saline, the other groups were intragastrically administrated with drugs for 14 days. The levels of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), triiodothyronine(T3), thyroxine(T4), total cholesterol(TC), triglyceride(TG), immunoglobin G(IgG), and immunoglobin M(IgM) in serum, as well as the activity of Na~+-K~+-ATPase in liver tissue were detected. The expression of transient receptor potential melastatin 8(TRPM8), transient receptor potential vanilloid 1(TRPV1), and uncoupling protein 1(UCP1) in brown adipose tissue of deficiency-cold syndrome model after intervention with p-cymene was studied. The results showed that p-cymene could effectively improve the levels of cAMP, cAMP/cGMP, TC, IgM, and IgG in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and reduce the content of cGMP. The effects on T3, T4, and TG were not statistically significant. At the same time, p-cymene could reduce the levels of cAMP, cAMP/cGMP, and T4 in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and increase the levels of cGMP, IgM, and IgG, and it had no effect on T3, TC, and TG. In addition, p-cymene could up-regulate the expression of TRPV1 and UCP1 in brown fat of mice with deficiency-cold syndrome and down-regulate the expression of TRPM8. In summary, p-cymene could significantly regulate the syndrome indexes of mice with deficiency-cold syndrome, and some indexes of mice with deficiency-heat syndrome could be improved, but the effects on lipid metabolism and energy metabolism indexes were not obvious, indicating that the regulation effect of p-cymene on deficiency-cold syndrome model was more prominent and that the medicinal properties of p-cymene were mild and warm. The regulation of TRPV1/TRPM8/UCP1 channel expression may be the molecular biological mechanism of p-cymene with mild and warm nature affecting the energy metabolism of the body.
Animals ; Cymenes ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Disease Models, Animal ; Humans ; Cyclic AMP/metabolism* ; Monoterpenes/administration & dosage* ; Liver/metabolism* ; Cyclic GMP/metabolism* ; TRPV Cation Channels/genetics* ; Uncoupling Protein 1/genetics*

This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias. We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between October 2012 and October 2022. In total, 31 patients underwent the conventional Byars procedure (conventional group), and 45 patients underwent the modified Byars staged procedure (modified group). Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage. Notably, there were no statistically significant differences in the preoperative baseline characteristics, duration of surgery, amount of blood loss, or occurrence of postoperative complications, including urethral fistula, stricture and diverticulum, or penile curvature, between the conventional and modified groups. However, there was a significantly lower incidence of coronal sulcus fistula (0 vs 16.1%, P = 0.02) and glans dehiscence (0 vs 12.9%, P = 0.02) in the surgical group than that in the conventional group. In addition, the modified group exhibited a notably greater rate of normotopic urethral opening (100.0% vs 83.9%, P = 0.01) and a higher mean score on the Hypospadias Objective Penile Evaluation (HOPE; mean ± standard error of mean: 8.6 ± 0.2 vs 7.9 ± 0.3, P = 0.02) than did the conventional group. In conclusion, the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula. Consequently, it offers a promising approach for achieving favorable penile esthetics, thereby providing a reliable therapeutic option for severe hypospadias.
Humans ; Hypospadias/surgery* ; Male ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Child, Preschool ; Child ; Postoperative Complications/etiology* ; Urethra/surgery* ; Plastic Surgery Procedures/methods* ; Surgical Flaps ; Penis/surgery* ; Treatment Outcome ; Infant

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

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the intestinal flora in rats with chronic obstructive pulmonary disease (COPD) and explore its possible mechanism based on the gut-lung axis theory. METHODS: A total of 30 male SD rats of SPF grade were randomly divided into a normal control (NC) group, a model group and an EA group, 10 rats in each one. In the model group and the EA group, COPD model was established by intratracheal instillation of lipopolysaccharide combined with cigarette fumigation. In the EA group, EA was applied at bilateral "Feishu" (BL13) and "Zusanli" (ST36), with disperse-dense waves, in frequency of 4 Hz/20 Hz, current of 1-3 mA, 20 min a time, once a day for 14 days continuously. Before and after modeling, as well as after intervention, body weight was observed; after intervention, the lung function indexes (forced expiratory volume in 0.1 second [FEV_0.1], FEV_0.1/forced vital capacity [FVC]%, forced expiratory volume in 0.3 second [FEV_0.3] and FEV_0.3/FVC%) were measured, serum levels of inflammatory factors (tumor necrosis factor-α[TNF-α], interleukin-6[IL-6], interleukin-1β[IL-1β] and interleukin-10[IL-10]) were detected by ELISA, histopathology of lung and colon tissues was observed by HE staining, the intestinal flora were analyzed by 16S rRNA, and the correlations between lung function and intestinal flora were analyzed. RESULTS: Compared with the NC group, in the COPD group, the body weight and lung function indexes were reduced (P<0.01); the lung and colon tissues were damaged, the mean linear intercept (MLI) of alveolus and inflammatory cell numbers of 100 μm² in lung tissue were increased (P<0.01); the serum levels of TNF-α, IL-6 and IL-1β were increased (P<0.01, P<0.05), and the serum level of IL-10 was decreased (P<0.01); α-diversity indexes of intestinal flora were increased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was increased (P<0.01), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was decreased (P<0.01, P<0.05); 31 different expressed metabolic pathways were identified between the two groups. Compared with the COPD group, in the EA group, the body weight and lung function indexes were increased (P<0.01); the damage of lung and colon tissues was improved, the MLI of alveolus was decreased (P<0.05); the serum levels of TNF-α, IL-6 and IL-1β were decreased (P<0.05), and the serum level of IL-10 was increased (P<0.05); α-diversity indexes of intestinal flora were decreased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was decreased (P<0.01, P<0.05), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was increased (P<0.01); 35 different expressed metabolic pathways were identified between the two groups. The lung function was positive related with Actinobacteria, Tenericutes, TM7 and YRC22, and was negative related with Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus. CONCLUSION EA may ameliorate lung function and tissue injury of COPD by regulating intestinal flora dysbiosis and inflammatory response, suggesting an anti-inflammatory effect mediated via "gut-lung" axis.
Animals ; Pulmonary Disease, Chronic Obstructive/genetics* ; Male ; Electroacupuncture ; Rats ; Rats, Sprague-Dawley ; Lung/metabolism* ; Gastrointestinal Microbiome ; Humans ; Interleukin-6/immunology* ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/microbiology* ; Interleukin-10/immunology*

OBJECTIVES: To explore the application of the colloidal gold method and chemiluminescence method in detecting gonadotropin (Gn) in morning urine for assessing pubertal development status in children. METHODS: A total of 132 children diagnosed with central precocious puberty (CPP), early and fast puberty (EFP), and premature thelarche (PT) at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2021 to December 2022 were included, along with 685 healthy children who underwent routine health examinations at the hospital's pediatric health care department during the same period. All 132 patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test. Both patients and healthy children had their urinary Gn levels measured using the colloidal gold method and chemiluminescence method, including levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The correlation between serum Gn and urinary Gn detected by the two methods, as well as the correlation between Tanner stages of healthy children and urinary Gn, was analyzed. RESULTS: Urine Gn levels detected by both the colloidal gold method and chemiluminescence method showed a positive correlation with serum LH baseline values, LH peak values, baseline LH/FSH ratios, and peak LH/FSH ratios (P<0.05). In healthy children, urinary LH levels detected by the chemiluminescence method gradually increased from Tanner stage Ⅰ to Ⅳ (P<0.05), while urinary FSH levels were lower in Tanner stage I than in stages Ⅱ, Ⅲ, and IV (P<0.05). Urinary LH levels detected by the colloidal gold method were lower in Tanner stage I compared to stages Ⅱ, Ⅲ, and IV, with the highest levels observed in Tanner stage Ⅳ (P<0.05). Additionally, urinary FSH levels in Tanner stage Ⅲ were higher than in stages Ⅰ and Ⅱ (P<0.05). The area under the receiver operating characteristic curve for evaluating Tanner stages I and II in healthy children using urinary LH and FSH levels by the chemiluminescence method and urinary LH levels by the colloidal gold method were 0.730, 0.699, and 0.783, respectively. CONCLUSIONS The colloidal gold method and chemiluminescence method for detecting Gn in morning urine show good correlation with serum Gn levels. As a non-invasive and convenient detection method, the colloidal gold method can serve as a useful tool for screening the onset of pubertal development in children.
Humans ; Child ; Male ; Female ; Gold Colloid ; Luminescent Measurements/methods* ; Gonadotropins/urine* ; Puberty ; Luteinizing Hormone/urine* ; Child, Preschool ; Adolescent ; Follicle Stimulating Hormone/urine*