OBJECTIVES: To explore the mechanism of Pingchuanning Formula (PCN) for inhibiting airway inflammation in rats with asthmatic cold syndrome. METHODS: A total of 105 SD rats were randomized equally into 7 groups, including a control group, an asthmatic cold syndrome model group, 3 PCN treatment groups at high, medium and low doses, a Guilong Kechuanning (GLCKN) treatment group, and a dexamethasone (DEX) treatment group. In all but the control rats, asthma cold syndrome models were established and daily gavage of saline, PCN, GLCKN or DEX was administered 29 days after the start of modeling. The changes in general condition, lung function and lung histopathology of the rats were observed, and inflammatory factors in the alveolar lavage fluid (BALF), oxidative stress, lung tissue ultrastructure, cytokine levels, and expressions of the genes related to the HMGB1/Beclin-1 axis and autophagy were analyzed. RESULTS: The rat models had obvious manifestations of asthmatic cold syndrome with significantly decreased body mass, food intake, and water intake, reduced FEV_0.3, FVC, and FEV_0.3/FVC, obvious inflammatory cell infiltration in the lung tissue, and increased alveolar inflammation score and counts of neutrophils, eosinophils, lymphocytes, macrophages, and leukocytes in the BALF. The rat models also had significantly increased MDA level and decreased SOD level and exhibited obvious ultrastructural changes in the lung tissues, where the expressions of HMGB1, Beclin-1, ATG5, TNF-α, IL-6,IL-1β, and IL-13 and the LC3II/I ratio were increased, while the levels of Bcl-2 and IFN-γ were decreased. PCN treatment significantly improved these pathological changes in the rat models, and its therapeutic effect was better than that of GLKCN and similar to that of DEX. CONCLUSIONS PCN can effectively alleviate airway inflammation in rat models of asthmatic cold syndrome possibly by modulating the HMGB1/Beclin-1 signaling axis to suppress cell autophagy, thereby attenuating airway inflammatory damages.
Animals ; Rats ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Asthma/pathology* ; Beclin-1 ; HMGB1 Protein/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Male ; Lung/pathology* ; Inflammation

Objective To study the syndrome-drug association rule and the medication law of cough medical cases treated by Xin'an doctors using the data mining method;To provide reference for the treatment of cough.Methods The medical records of Xin'an doctors were collected and summarized.The frequency analysis,topology analysis and Louvain clustering analysis were used to conduct data mining research on syndrome types and prescriptions,and the relationship between syndrome types and prescriptions in cough treatment medical records and the law of drug composition in prescriptions were discussed.Results A total of 525 medical cases were included,and 26 kinds of syndromes were obtained,such as wind-heat invading lung,phlegm-dampness holding lung,lung qi deficiency.There were 243 kinds of Chinese materia medica involved,and 18 kinds of Chinese materia medica were with more than 70 times in frequency.The main properties were cold,warm and mild,and the main tastes were sweet,bitter and pungent,mainly in lung meridian,or the main properties were mild and warm and the main taste was sweet,mainly in spleen and stomach meridian.There were 25 categories in efficacy,which were mainly tonics and heat-clearing medicine.30 core medicines and core medicinal networks were obtained,such as Glycyrrhizae Radix et Rhizoma,Poria and Armeniacae Semen Amarum.The core drug combination of main syndromes of exogenous cough and excess syndrome and deficient syndrome of endogenous cough were obtained by syndrome-drug clustering analysis.Conclusion Xin'an doctors have distinctive characteristics in the diagnosis and treatment of cough diseases,and pay attention to the use of the methods of"strengthening the basic and promoting original qi","nourishing yin and protecting yin","cultivating the soil and promoting gold"and the inheritance of the prescriptions on the basis of cough relieving,phlegm resolving,and syndrome-based treatment.

Objective To investigate the effects of Shenqi Tiaoshen Formula(SQTSF)for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease(COPD)and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.Methods Forty-eight SD rats were randomly divided into control group,model group,low-,medium-,and high-dose SQTSF groups,and aminophylline(APL)group.In all but the control group,rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline,SQTSF or APL via daily gavage as indicated(starting from day 30).The rats were observed for changes in body weight,grip strength,lung function,lung pathology,inflammatory cytokines in bronchoalveolar lavage fluid(BALF),oxidative stress levels,iron ion metabolism,cellular and mitochondrial ultrastructural changes in the lung tissue,and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.Results The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight,grip strength,and lung function parameters.Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial,perivascular,and alveolar inflammation and alveolar destruction,significantly increased IL-1β,TNF-α,IL-6,and IL-13 levels in BALF,and elevated pulmonary oxidative stress levels and Fe2+and total iron ion concentrations.The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2,GPX4,and SLC7A11 and increased ACSL4 expressions in the lung tissue.Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.Conclusion SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.

Objective To investigate the effects of Shenqi Tiaoshen Formula(SQTSF)for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease(COPD)and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.Methods Forty-eight SD rats were randomly divided into control group,model group,low-,medium-,and high-dose SQTSF groups,and aminophylline(APL)group.In all but the control group,rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline,SQTSF or APL via daily gavage as indicated(starting from day 30).The rats were observed for changes in body weight,grip strength,lung function,lung pathology,inflammatory cytokines in bronchoalveolar lavage fluid(BALF),oxidative stress levels,iron ion metabolism,cellular and mitochondrial ultrastructural changes in the lung tissue,and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.Results The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight,grip strength,and lung function parameters.Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial,perivascular,and alveolar inflammation and alveolar destruction,significantly increased IL-1β,TNF-α,IL-6,and IL-13 levels in BALF,and elevated pulmonary oxidative stress levels and Fe2+and total iron ion concentrations.The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2,GPX4,and SLC7A11 and increased ACSL4 expressions in the lung tissue.Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.Conclusion SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.

Objective To detect the expression level of hsa_circ_0082002 in serum of patients with primary hepatocellular carcinoma(HCC)and explore its auxiliary diagnostic value.Methods A total of 70 HCC pa-tients treated in this hospital from January 2020 to December 2022 were selected as the HCC group,55 pa-tients with liver cirrhosis(LC)were selected as the LC group,55 patients with chronic hepatitis B(CHB)were selected as the CHB group,and 50 healthy people were selected as the control group.The relative expres-sion level of hsa_circ_0082002 in serum of each group was detected by real-time fluorescent quantitative PCR,and the level of serum alpha-fetoprotein(AFP)was detected by electrochemiluminescence.The receiver oper-ating characteristic(ROC)curve was used to evaluate the differential diagnostic efficacy of hsa_circ_0082002 and AFP for HCC.Results The relative expression levels of serum hsa_circ_0082002 in HCC group,LC group,CHB group and control group were 2.750(1.925,4.393),2.199(1.416,2.850),1.591(0.925,2.107)and 1.035(0.666,1.680),respectively.The relative expression level of serum hsa_circ_0082002 in the HCC group was higher than those in the LC group,CHB group and HC group,and the differences were statistically signifi-cant(all P＜0.05).The results of ROC curve showed that the area under the curve(AUC)of hsa_circ_0082002 and AFP in the differential diagnosis of HCC were 0.813 and 0.779,respectively.The AUC of combined detection of hsa_circ_0082002 and AFP was 0.871,with a sensitivity of 75.71％and specificity of 83.13％.Conclusion Serum hsa_circ_0082002 may be a biomarker for the diagnosis of HCC.

In order to standardize the postoperative pain management in adults in China, the Chinese Society of Anesthesiology formulated the "Clinical practice guidelines for postoperative pain management in adults (2024 edition)" according to the methods and steps of the "Principles for Formulation/Revision of Clinical Diagnosis and Treatment Guidelines in China (2022 Edition)". This protocol mainly introduced the purpose of guideline formulation, the formation and responsibilities of the working group, the collection and selection of clinical questions, the evaluation and synthesis of evidence, the formation of recommendations and other processes.

Objective:To evaluate the effects of sugammadex on the quality of recovery after laparoscopic bariatric surgery in severely obese patients.Methods:One hundred and eighty patients, aged 18-65 yr, with body mass index ≥ 40 kg/m 2, undergoing elective laparoscopic bariatric surgery, of American Society of Anesthesiologists physical status Ⅲ, were enrolled and divided into 2 groups ( n=90 each) by the random number table method: sugammadex group (S group) and neostigmine group (N group). Before anesthesia, bilateral T 6 and T 9 paravertebral nerve blocks were performed, and 0.33% ropivacaine 15 ml was injected on each side.When the reappearance of T 2 was monitored under train-of-four (TOF) stimulation after the end of surgery, and sugammadex 2 mg/kg was intravenously injected in S group, and neostigmine 0.04 mg/kg and atropine 0.02 mg/kg were intravenously injected in N group.After the patient was transferred to the general ward, flurbiprofen axetil 50 mg was injected intravenously every 12 h, and oxycodone and flurbiprofen axetil were used for patient-controlled intravenous analgesia at the same time.When the numerical rating scale (NRS) score ≥4 and the analgesic pump was ineffective, bilateral T 7 paravertebral nerve block was performed for rescue analgesia, and 0.33% ropivacaine 15 ml was injected on each side.The postoperative quality of recovery was assessed by the 15-item Quality-of-Recovery scale before operation and at 24 h after operation.The TOF ratio ≥ 0.9 and extubation time were recorded.The SpO 2 at the time of transfer to post-anesthesia care unit (PACU), the lowest SpO 2 and occurrence of SpO 2 < 92% during PACU were recorded.The occurrence of residual muscle relaxation and Ramsay sedation score were recorded at 30 min after entering PACU.The time of PACU stay, time to the first off-bed activity and length of hospital stay were recorded.The cumulative consumption of oxycodone, requirement for rescue analgesia, dizziness, nausea and vomiting, hypoxemia, and pulmonary complications were recorded within 48 h after operation. Results:There were no significant differences in the total score of 15-item Quality-of-Recovery scale before surgery and at 24 h after surgery, cumulative consumption of oxycodone within 48 h after surgery, rate of rescue analgesia, and incidence of dizziness, nausea and vomiting, hypoxemia and pulmonary complications between the two groups ( P>0.05). Compared with N group, the scores of the three recovery indicators (feel energized with enough rest, engagement in work or family activities, and tension and anxiety) were significanatly increased, time to TOF ratio ≥ 0.9, extubation time, time of PACU stay, time to the first off-bed activity and length of hospital stay were shortened, and the incidence of residual muscle relaxation was decreased in S group ( P<0.05). Conclusions:Antagonizing residual muscle relaxation with sugammadex is helpful for the recovery of severely obese patients after laparoscopic bariatric surgery.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable malignancy, with an only 6% 5-year relative survival rate. The dismal therapeutic effect is attributed to the chemotherapy resistance and unique pathophysiology with abundant inflammatory cytokines and abnormal hyperplasia of extracellular matrix (ECM). Based on the theory that bone marrow mesenchymal stem cells (BM-MSCs) can influence the tumorous microenvironment and malignant growth of PDAC, we employed exosomes (Exos) derived from BM-MSCs as PDAC-homing vehicles to surpass the restrictions of pathological ECM and increase the accumulation of therapeutics in tumor site. To overcome chemoresistance of PDAC, paclitaxel (PTX) and gemcitabine monophosphate (GEMP)-an intermediate product of gemcitabine metabolism-were loaded in/on the purified Exos. In this work, the Exo delivery platform showed superiorities in homing and penetrating abilities, which were performed on tumor spheroids and PDAC orthotopic models. Meanwhile, the favorable anti-tumor efficacy and , plus relatively mild systemic toxicity, was found. Loading GEMP and PTX, benefitting from the naturally PDAC selectivity, the Exo platform we constructed performs combined functions on excellent penetrating, anti-matrix and overcoming chemoresistance (Scheme 1). Worth expectantly, the Exo platform may provide a prospective approach for targeted therapies of PDAC.

Objective    To evaluate the efficacy and safety of modified maze Ⅳ (Cox-maze Ⅳ) in hypertrophic obstructive cardiomyopathy (HOCM) patients. Methods    From June 2016 to June 2019, 30 HOCM and persistent atrial fibrillation (pAF) patients received Cox-maze Ⅳ operation with modified extended Morrow operation, including 21 males and 9 females. The average age was 51.36±10.27 years and the average weight was 72.48±11.29 kg. All patients underwent left atrial appendectomy. Recurrence of AF, improvement of symptoms, cardiac function (NYHA) were assessed during follow-up. Results    There was no death during the perioperative period. Postoperative left ventricular outflow tract gradient was significantly decreased compared with that before operation (P<0.01), and all systolic anterior motion (SAM) signs disappeared after operation. Thirty patients were all effectively followed up for 3-40 (16.24±8.26) months. During the follow-up period, there was no death, and the cardiac function (NYHA) of all patients recovered to gradeⅠ-Ⅱ. At the end of follow-up, twenty-four patients (80.00%) maintained sinus rhythm, and twenty-seven patients (90.00%) maintained sinus rhythm after amiodarone conversion. Univariate analysis showed that the smoking history (P=0.04), left atrial diameter≥55 mm before operation (P=0.03), left atrial diameter≥50 mm after operation (P=0.02), postoperative tricuspid regurgitation (P=0.02) were closely related to postoperative AF recurrence. The increase of left atrial diameter after operation was an independent risk factor for AF recurrence (P=0.02). Conclusion    Morrow/Cox-maze Ⅳ procedure is safe and effective in treatment of patients with HOCM complicated with pAF, which helps to maintain postoperative sinus rhythm, and to improve the cardiac function. The increase of left atrial diameter after operation is an independent risk factor for AF recurrence.