OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major chronic respiratory condition with high morbidity and mortality, imposing a serious economic and public health burden. The World Health Organization ranks COPD among the top 4 chronic diseases worldwide. Zangsiwei Qingfei Mixture (ZSWQF), a novel Tibetan herbal formulation independently developed by our research team, has shown therapeutic potential for chronic respiratory diseases. This study aims to evaluate the effects of aerosolized ZSWQF on cigarette smoke-induced COPD in mice and explore its underlying mechanisms. METHODS: Thirty C57 mice were randomly divided into a Control group, a COPD group, and a ZSWQF group. The Control group received saline aerosol inhalation without cigarette smoke exposure; both the COPD group and the ZSWQF group were exposed to cigarette smoke, with the former receiving saline inhalation and the latter treated with ZSWQF aerosol. White blood cell (WBC) count was performed using a fully automatic blood cell analyzer. Serum, alanine transaminase (ALT), and serum creatinine (SCr), as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). BALF cell classification was determined using a hematology analyzer. Lung function was assessed with a small animal pulmonary function system, including airway resistance (RI) and cyclic dynamic compliance (CyDN). Lung tissues were stained with hematoxylin and eosin (HE), and mean linear intercept (MLI) and destruction index (DI) were calculated to evaluate morphological changes. Network pharmacology was applied to identify disease-related and ZSWQF-related targets, followed by intersection and protein-protein interaction (PPI) network analysis, and enrichment analysis of biological functions and pathways. Primary type II alveolar epithelial cell (AEC II) from SD rats were isolated and divided into a Control group, a lipopolysaccharide (LPS) group, a normal serum group, a water extract of ZSWQF (W-ZSWQF) group, a ZSWQF containing serum group, and a MLN-4760 [angiotensin-converting enzyme (ACE) 2 inhibitor]. Western blotting was performed to assess protein expression of ACE, p38 [a mitogen-activated protein kinase (MAPK)], phospho (p)-p38, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, inhibitor of nuclear factor-kappa B alpha (IκBα), p-IκBα, and p-p65 subunit of nuclear factor-kappa B (NF-κBp65). RESULTS: WBC counts were significantly higher in the COPD group than in controls (P<0.01) and decreased following ZSWQF treatment (P<0.05). No significant intergroup differences were found in organ weights, ALT, or SCr (all P>0.05). Serum and BALF levels of IL-6, IL-8, and TNF-α, as well as total BALF cells, neutrophils, and macrophages, were elevated in the COPD group compared with controls and reduced by ZSWQF treatment (P<0.05). COPD mice exhibited increased RI, decreased CyDN, marked alveolar congestion, inflammatory infiltration, thickened septa, and higher MLI and DI values versus controls (P<0.05); ZSWQF treatment significantly reduced MLI and DI (P<0.05). Network pharmacology identified 151 potential therapeutic targets for ZSWQF against COPD, with key nodes including TNF, IL-6, protein kinase B (Akt) 1, albumin (ALB), tumor protein p53 (TP53), non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT) 3, matrix metalloproteinase (MMP)-9, and beta-catenin (CTNNB1). Enrichment analysis indicates involvement of cancer-related, phosphatidylinositol 3-kinase (PI3K)/Akt, hypoxia-inducible factor (HIF)-1, calcium, and MAPK signaling pathways. Western blotting results showed that compared with the LPS group, AEC II treated with ZSWQF-containing serum exhibited decreased expression of ACE, p-p38/p38, p-ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκBα, and p-NF-κBp65, while ACE2 expression was upregulated, consistent with the MAPK/nuclear factor-kappa B (NF-κB) pathway regulation predicted by network pharmacology. CONCLUSIONS Aerosolized ZSWQF provides protective effects in COPD mice by reducing airway inflammation and remodeling.
Animals ; Pulmonary Disease, Chronic Obstructive/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Male ; Network Pharmacology ; Smoke/adverse effects* ; Bronchoalveolar Lavage Fluid ; Administration, Inhalation ; Inflammation/drug therapy* ; Tumor Necrosis Factor-alpha ; Lung/drug effects* ; Interleukin-6/blood*

Objective:Chronic obstructive pulmonary disease(COPD)is a significant global public health issue.Modern medical treatments have both benefits and limitations,prompting increasing attention from scholars worldwide on traditional ethnic medicine,and the Zangsiwei Qingfei Mixture is a newly developed formula derived from the effective components of classical Tibetan medicine to treat chronic respiratory diseases.This study aims to investigate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture combined with conventional treatment in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). Methods:Sixty AECOPD patients admitted to the Second Xiangya Hospital of Central South University from May 2021 to May 2023 were enrolled and randomly divided into 2 groups,with 30 patients in each group.The control group received conventional treatment,including bronchodilators,anti-infection agents,expectorants,and oxygen therapy.The experimental group received the Zangsiwei Qingfei Mixture in addition to conventional treatment.The treatment duration was 7 d for both groups.Baseline data such as gender,age,body mass index(BMI),smoking status,Global Initiative for Chronic Obstructive Lung Disease(GOLD)classification,COPD course,and the number of COPD exacerbations in the past year were collected.The primary efficacy indicators were assessed using the modified Medical Research Council(mMRC)dyspnea scale and the modified Borg scale.Secondary indicators included arterial lactic acid(LAC)and serum tumor necrosis factor alpha(TNF-α)levels.Safety indicators included liver and kidney function[alanine transaminase(ALT),aspartate transaminase(AST),serum creatinine(SCr),serum uric acid(SUA)],coagulation function[activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(FIB),and D-dimer].The generalized linear mixed model(GLMM)was used to evaluate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture. Results:Before treatment,there were no statistically significant differences in general baseline data,grading of mMRC dyspnea scale,score of modified Borg scale,arterial LAC,ALT,AST,SCr,SUA,APTT,FIB,and D-dimer between the 2 groups(all P＞0.05).However,serum TNF-α and PT levels in the experimental group were significantly lower than those in the control group(both P＜0.05).GLMM analysis showed that after adjusting for pre-and post-treatment,gender,age,BMI,smoking status,GOLD classification,COPD course,and the number of COPD exacerbations in the past year,the experimental group demonstrated significantly lower grading of mMRC dyspnea scale(coefficient=-0.329,P=0.036),score of modified Borg scale(coefficient=-1.077,P=0.001),serum TNF-α level(coefficient=-14.378,P＜0.001),and arterial LAC level(coefficient=-0.409,P=0.012)compared to the control group.The Zangsiwei Qingfei Mixture had no significant effect on liver,kidney,or coagulation function indicators(all P＞0.05). Conclusion:The Zangsiwei Qingfei Mixture combined with conventional treatment can improve clinical symptoms and promote homeostasis in AECOPD patients,demonstrating safety and reliability.Combining modem medicine with traditional ethnic medicine offers a feasible approach to treating chronic respiratory diseases in the future.

Objective:To explore the relative concentration changes of oxygenated hemoglobin (Oxy Hb) in the prefrontal cortex (PFC) and brain region activation during emotional face recognition tasks in women with perimenopausal depression.Methods:From February to April 2023, forty perimenopausal women were recruited, including 20 women with perimenopausal depression (experimental group) and 20 women with non-perimenopausal depression (control group). All participants were evaluated by the modified Kupperman score, 24-item Hamilton depression scale (HAMD-24), and patient health questionnaire (PHQ-9). Functional near-infrared spectroscopy (fNIRS) equipment was used to measure the relative concentration of Oxy-Hb in the PFC in two groups under the emotional face recognition task. Statistical analysis was performed by SPSS 26.0 software. Data were analyzed by a t-test, rank sum test, and Pearson correlation. Results:There were statistically significant differences in the results of the modified Kupperman score((23.20±3.66), (18.10±1.28)), HAMD-24((15.95±5.47), (3.35±1.84)), and PHQ-9(7.00(5.00, 10.75), 1.50(1.00, 3.00)) scales between the the experimental group and control group ( P<0.05). There was a positive correlation between the modified Kupperman score and the HAMD-24 score in the experimental group ( r=0.685, P=0.01). The reaction time of the experimental group in identifying negative and neutral emotional faces was statistically significant compared to the control group( t=4.01, 4.80, both P<0.05). Compared with identifying neutral emotions, PFC activation was stronger in the experimental group and control group when identifying negative emotions ( P<0.05). The PFC activation in the experimental group was stronger than that in the control group when identifying negative emotions ( P<0.05). There was no statistically significant difference in the activation level between the two groups when identifying neutral emotions ( P>0.05). Conclusion:Women with perimenopausal depression exhibit specificity in emotional processing, with increased PFC activation when identifying negative emotions, impaired emotional processing function of PFC, and dysfunction of aerobic metabolism.

Objective:To investigate the effects of single intermittent theta-burst stimulation on functional connectivity in patients with mild cognitive impairment(MCI).Methods:From July to November 2020, forty MCI patients were selected and randomly divided into iTBS true stimulation group and iTBS sham-stimulation group, with 20 patients in each group.iTBS targeted the left dorsolateral prefrontal cortex (DLPFC). Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), activity of daily living scale(ADL), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were evaluated at baseline.The resting state electroencephalography (rsEEG) was collected for 5 minutes before and after iTBS in the two groups.The phase lag index(PLI) of EEG functional connectivity was calculated, and the functional connectivity matrix diagram was drawn.SPSS 26.0 software was used for statistical analysis.Data were statistically analyzed by χ2 test, Wilcoxon rank sum test and independent sample t-test. Results:There were no significant differences in scores of MoCA, ADL, HAMD and HAMA between the two groups(all P>0.05). In the iTBS true stimulation group, compared with that before iTBS treatment(0.140(0.133, 0.144)), the PLI of β band increased significantly after iTBS treatment(0.146(0.136, 0.167))( P<0.05). The region of increased PLI was mainly concentrated in the central region(C3/C4-T7/T8). Compared with that before iTBS treatment(0.251(0.232, 0.299)), the PLI of α band increased after iTBS treatment(0.286(0.241, 0.359)), but the difference was not statistically significant( P>0.05). Conclusion:Single iTBS treatment can significantly increase the EEG functional connectivity in patients with MCI, indicating that iTBS targeting the left DLPFC can effectively regulate the EEG functional connectivity in patients with MCI, which may reveal the mechanism of iTBS in improving cognitive function in patients with MCI.

IgG4-related disease (IgG4-RD) is a rare autoimmune fibrosis disease characterized by elevated serum IgG4 and tissues as well as organs infiltrated with IgG4-positive cells, resulting in swelling and damage.It is currently treated as first-line treatment with glucocorticoids. Autoimmune hemolytic anemia (AIHA) is also a relatively rare disease that caused by autoreactive erythrocyte antibodies. Although both are autoimmune-related diseases, they rarely overlap. The relationship between them is not clear. A case of IgG4-RD combined with AIHA is reported. The patient has shortness of breath, cough, and sputum after physical activity. Physical examination showed appearance of anemia, yellow staining of skin and sclera, palpable neck and multiple swollen lymph nodes. Laboratory examination, bone marrow biopsy, and lymph node biopsy confirmed the diagnosis. Therefore, clinicians should develop ideas and raise awareness of such diseases.
Anemia, Hemolytic, Autoimmune ; diagnosis ; drug therapy ; Autoimmune Diseases ; complications ; Biopsy ; Humans ; Immunoglobulin G ; Immunoglobulin G4-Related Disease ; complications ; diagnosis

The new model of evidence-based medicine (EBM) that appeared in last century has experienced the global development of nearly 30 years, which praise and question all have.How to develop this medical model scientifically.? This article will talk about personal thinking about this from three aspects.Ⅰ.Looking back and relearning evidence-based medicine;Ⅱ.What is the current misunderstanding of evidence-based medicine? Ⅲ.Medical ethics to be reaffirmed in evidence-based medical practice.

Objective:To investigate the demographic characteristics and the causes for pulmonary hypertension (PH) in adult patients.Methods:A total of 2 508 adult patients diagnosed as PH,who came from the Second Xiangya Hospital of Central South University from January 2010 to December 2014,were retrospectively investigated.All subjects underwent the clinical diagnosis,or the echocardiographic diagnosis,or thetraditional hemodynamic criteria by right heart catheterization (RHC).The patient's data including hospital numbers,gender,ages,primary diseases,etc,are collected and analyzed.Results:In this study,the number of patients diagnosed as PH was increased year by year.The median age of 2 508 patients was 47 (18-93) years old,and there were 933 males (37.2％),the ratio of male to female was 1:1.69 (P＜0.05).Female was more common in Class Ⅰ PH (pulmonary arterial hypertension) and Class Ⅱ PH (pulmonary hypertension due to left heart disease)(＞70％),but there were more male patients (74.5％) in Class Ⅲ PH (pulmonary hypertension due to lung diseases and/or hypoxia).In our study,896 cases (35.73％) were the Class Ⅰ PH,1 163 cases was the Class Ⅱ PH (46.37％),411 cases was the Class Ⅲ PH (16.39％),and the Class Ⅳ PH (chronic thromboembolic pulmonary hypertension) and the Class Ⅴ PH (PH with unclear and/ or multifactorial mechanisms) were diagnosed in 32(1.27％) and 6 patients (0.24％),respectively.The diseases with largest number of patients for the top 7 primary PH were rheumatic heart disease (1 090,43.48％),congenital heart disease (692,27.60％),chronic obstructive pulmonary disease (358,14.28％),connective tissue related disease(156,6.22％),valvular heart disease (66,2.63％),idiopathic PH (46,1.83％) and pulmonary embolism (27,1.08％).Conclusion:Adult PH patients' peak incidence age is 41-50 years old.This disease is more common among women,and the Class Ⅰ/Ⅱ PH are common in women while the Class Ⅲ is more common in men.Rheumatic heart disease and congenital heart disease may be the most common cause for pulmonary hypertension in China,and chronic obstructive pulmonary disease is the most common cause for the Class Ⅲ PH,in which the patients are old.

OBJECTIVE: To explore the relationship between main pulmonary artery diameter and process of chronic pulmonary disease.
 METHODS: We retrospectively reviewed 9 cases without pulmonary diseases (control group) and 100 cases with chronic pulmonary diseases, which were divided into 3 groups: the simple chronic pulmonary disease (A group, 37 cases), the compensatory period of chronic cor pulmonale (B group, 20 cases) and the decompensatory period of chronic cor pulmonale (C group, 43 cases). Main pulmonary artery diameter (MPAD) was measured by chest CT. The differences of MPAD among these 4 groups were analyzed.
 RESULTS: There was a strong positive correlation between pulmonary artery diameter and process of chronic pulmonary disease. Mean MPAD in the group C was higher than that in the group B (P<0.05), and mean MPAD in the group B was higher than that in the group A (P<0.05). Mean MPAD in control group was the smallest one among all groups (P<0.05).
 CONCLUSION Main pulmonary artery diameter could reflect the process of chronic pulmonary disease.
Case-Control Studies ; Chronic Disease ; Humans ; Hypertension, Pulmonary ; physiopathology ; Pulmonary Artery ; pathology ; Retrospective Studies ; Tomography, X-Ray Computed

BACKGROUNDHypoxic pulmonary hypertension (HPH) contributes to the pathogenesis of cardiopulmonary diseases. Several lines of evidence indicate that the Rho A/Rho-kinase pathway play an important role in the progress of pulmonary hypertension. Stains have been shown exert numerous biological effects that are independent of their cholesterol-lowering property. We hypothesized that the Rho A/Rho-kinase pathway is involved in the pathogenesis of HPH, and that atorvastatin would attenuate involvement of the Rho A/Rho-kinase pathway in a HPH rat model.

METHODSThirty-two Wistar rats were randomly divided into four groups: control group, hypoxic group, atovastatin group, and normal saline group. The control group was kept in a normoxia environment. The other groups were exposed to hypoxia for three weeks. Atovastatin was administered daily via a gastric gavage in the atovastatin group. We measured the mean pulmonary arterial pressure (mPAP), the ratio of the right ventricular weight to the sum of the weights of the left heart ventricle and septum (RV/(LV+S)), arteriole wall thickness/vascular external diameter (WT%), vascular area/total vascular area (WA%), expression of RhoA and phos-MYPT-1 protein in lung tissue, and NF-κB activation in pulmonary vascular smooth muscle cells.

RESULTSCompared with the control group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were increased in the hypoxic and normal saline groups (P < 0.05). Compared with the hypoxic group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were decreased in the atovastatin group (P < 0.05). Correlations between phos-MPTY-1 and mPAP, WA%, WT%, and NF-κB activation were all positive.

CONCLUSIONSThe Rho A/Rho-kinase pathway plays an important role in the development of HPH. Atorvastatin reversed HPH by inhibiting the activity of Rho A/Rho-kinase and NF-κB.

Animals ; Atorvastatin Calcium ; Blotting, Western ; Heptanoic Acids ; therapeutic use ; Hypertension, Pulmonary ; drug therapy ; enzymology ; Hypoxia ; metabolism ; Male ; NF-kappa B ; metabolism ; Pyrroles ; therapeutic use ; Random Allocation ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; rho-Associated Kinases ; metabolism ; rhoA GTP-Binding Protein ; metabolism

OBJECTIVE: To determine the levels of Rho-kinase and CD4+CD25+ regulatory T cells in patients with asthma, and the relationship between Rho-kinase and CD4+CD25+ regulatory T cells. METHODS: We included 16 patients with moderate to severe asthma in the research group and 14 healthy people as the control group. The levels of Rho-kinase in the 2 groups were measured by ELISA. The level of CD4+CD25+ regulatory T cells in the 2 groups was measured by flow cytometry. The pulmonary function was measured by spirometer. RESULTS: The level of Rho-kinase in the research group was higher than that in the healthy controls (P<0.05). The level of CD4+CD25+ regulatory T cells in the healthy controls was higher than that of the research group (P<0.05). There was no correlation between the level of Rho-kinase in the peripheral blood of the 2 groups and forced expiratiory volume at the first second/ forced vital capacity (FEV1%) (r=-0.491, P>0.05). The level of CD4+CD25+ regulatory T cells in the peripheral blood of the 2 groups showed a positive correlation with FEV1% (r=0.380, P=0.038). There was no correlation between the level of Rho-kinase and the level of CD4+CD25+ regulatory T cells in the peripheral blood of the 2 groups (r=-0.438, P>0.05). CONCLUSION Rho-kinase and CD4+CD25+ regulatory T cells may play a key role in the pathogenesis of asthma.
Asthma ; blood ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Forced Expiratory Volume ; Humans ; T-Lymphocytes, Regulatory ; cytology ; Vital Capacity ; rho-Associated Kinases ; blood