ObjectiveTo establish an animal model of atrial fibrillation（AF） that accurately reflects the phlegm-heat and blood stasis（TRYZ） pathogenesis in traditional Chinese medicine. MethodsForty SPF-grade SD rats were randomly assigned using a random number table to the following groups：the control group， the TRYZ+AF group，the AF group and the TRYZ group， with ten rats in each group. The TRYZ+AF and TRYZ groups underwent a high-fat diet combined with intraperitoneal lipopolysaccharide（LPS） injection to simulate the pathological alterations of TRYZ syndrome. Groups TRYZ+AF and AF were induced with acetylcholine-calcium chloride（Ach-CaCl₂） via caudal vein injection to induce AF. The control group received no intervention and was maintained under normal conditions. The modeling period lasted 3 weeks. Electrocardiography was used to assess AF episodes and duration， echocardiography evaluated left atrial dimensions and cardiac function， fully automated biochemical analyzer measured the levels of total cholesterol（TC）， triglycerides（TG）， high-density lipoprotein cholesterol（HDL-C） and low-density lipoprotein cholesterol（LDL-C）， hemoreometer analyzed the whole blood viscosity， plasma viscosity， and whole blood reduced viscosity， a coagulation analyzer assessed prothrombin time（PT）， activated partial thromboplastin time（APTT）， thrombin time（TT）， and fibrinogen（FIB）， enzyme-linked immunosorbent assay（ELISA） was used to determine the levels of C-reactive protein（CRP）， interleukin（IL）-1β， IL-6， IL-17， tumour necrosis factor（TNF）-α， matrix metalloproteinase-9（MMP-9）， galectin-3（Gal-3）， Collagen Ⅰ， and α-smooth muscle actin（α-SMA）. Hematoxylin-eosin（HE） staining and Masson's trichrome staining were used to analyze pathological changes in atrial myocardium， Western blot was employed to detect MMP-9， Collagen Ⅰ and α-SMA protein expression in myocardial tissue， real-time quantitative polymerase chain reaction（Real-time PCR） evaluated fibrous factor gene expression levels. Changes in the TRYZ syndrome were assessed via body weight， tongue color［red（R）， green（G）， and blue（B）］， and rectal temperature. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to detect differential metabolites between the control group and the TRYZ+AF group. ResultsFollowing three weeks of sustained modeling， compared with the control group， rats in the TRYZ+AF and the TRYZ groups exhibited reduced body weight， dry faeces， elevated rectal temperature， dark red tongue， decreased RGB values on the tongue surface， and markedly elevated TC and LDL-C levels（P<0.05， P<0.01）. The TRYZ+AF， TRYZ， and AF groups exhibited significantly decreased TT， APTT and PT， along with markedly elevated whole blood viscosity and FIB（P<0.05， P<0.01）. Rats in the TRYZ+AF and AF groups exhibited AF rhythm， markedly decreased heart rate， prolonged RR intervals， enlarged left atrium， and significantly reduced ejection fraction and shortening fraction（P<0.05， P<0.01）. Serum levels of CRP， IL-1β， IL-6， IL-17， TNF-α， MMP-9， Gal-3， Collagen Ⅰ， and α-SMA were elevated in rats from the TRYZ+AF， TRYZ， and AF groups compared to the control group， with the most pronounced increase observed in the TRYZ+AF group（P<0.05， P<0.01）. Histopathology revealed that the collagen fiber deposition in the atrial of rats in the TRYZ+AF， TRYZ and AF groups was higher than that in the control group（P<0.05， P<0.01）. Western blot and Real-time PCR results further demonstrated that the protein and mRNA expression levels of MMP-9， Collagen Ⅰ and α-SMA in the myocardial tissue of the TRYZ+AF group were higher than those in the other three groups（P<0.05， P<0.01）. Metabolomic analysis revealed 173 differentially expressed metabolites in the TRYZ+AF group and the control group， primarily enriched in pathways such as glycerophospholipid metabolism and glycolysis/gluconeogenesis. ConclusionThis study successfully establishes a rat model of AF integrated with the TRYZ syndrome， demonstrating the pathological process where the interactions of phlegm， heat and stasis jointly trigger tremor， this provides a reliable experimental tool for in-depth research into the biological basis of this disease syndrome.

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Objective To investigate the clinical characteristics of pulmonary hypertension(PH) in patients with chronic obstructive pulmonary disease (COPD) and study the related risk factors.Methods Patients with stable COPD enrolled in this study,undergoing examinations including full pulmonary function tests (PFT),6-minute walk distance (6MWD),Exercise Oxyhemoglobin,Saint.George's respiratory questionnaire (SGRQ) and transthoracic echocardiography.Pulmonary artery systolic pressure (sPAP) ≥ 36 mmHg(1 mmHg =0.133 kPa) was defined as PH.Results A total of 251 patients were finally evaluable in this study.The frequency of PH was 55.4％ (139/251) in patients with stable COPD.Significant differences were seen between patients with PH and without PH respectively in the following factors (mean P ＜0.05):proportion of age ≥ 60 years (69.8％ vs 57.1％),forced expiratory volume in one second (FEV1)(％ predicted) [(47.5±8.2)％ vs(61.2±10.2)％ and(49.8±7.9)％ vs(66.4±11.3)％],sPAP [(41.9 ± 9.1) mmHg vs (28.2 ± 3.2) mmHg],exercise oxyhemoglobin desaturation [(-5.5 ± 3.2) ％ vs(-2.2 ± 1.2) ％],6MWD [(316.0 ± 55.2) m vs(390.0 ±75.2) m].The following variables were negatively correlated with sPAP:6MWD (r =-0.330,P =0.003),FEV1 (％ predicted) (r =-0.210,P =0.024 and r =-0.130,P =0.012,respectively).The following variables were positively correlated with sPAP:age(r =0.560,P =0.031),exercise oxyhemoglobin desaturation ＞ 3％ (r =0.540,P =0.001).Logistic regression test has showed that age≥ 60 years,exercise oxygen desaturation ＞ 3％,FEV1 (％ predicted) ＜ 50％,6MWD ＜ 350 m were risk factors for PH in COPD.Conclusion The incidence of PH in COPD increases with age,yet the performance of lung function and the activity of endurance decrease in elder patients.Sixty years or older,exercise oxygen desaturation ＞ 3％,FEV1 (％ predicted) ＜ 50％,6MWD ＜ 350 m are risk factors of PH in COPD.Echocardiography or right heart catheterization when needed should be considered to confirm the diagnosis.

Objective To explore the effect of the self-designed cotton-padded covering for a modified lithotomy position on preventing complications in the lower limbs in patients undergoing gynecological laparscopic surgery.Methods A total of 320 patients undergoing radical hysterectomy or deep invasive endometriosis were selected and randomly divided into an observation group(n=160) and a control group(n=160).The patients in the control group were placed on the routine lithotomy position,the lower extremity and popliteal space protected with oasis outline cushion in the control group,while the patients in the observation group were placed on the same pads,the lower extremity and popliteal space protected with the self-designed cotton-padded coverings.Results The average temperature of the lower limbs of patients after operation in the observation group was significantly higher than that in the control group (P<0.01).The incidences of complications in the observation group were significantly lower than those in the control group(all P<0.05). Conclusion The self-designed cotton-padded covering for modified lithotomy position can effectively prevent the complications of the lower limbs and improve the comfort of patients.

A group of SARS-Iike coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64% amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γ and IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.