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 value of contrast-enhanced ultrasound(CEUS)guided fine needle aspiration(FNA)in diagnosing the nature of type 4 thyroid nodules by thyroid imaging re-porting and data system(TI-RADS).Methods A total of 120 patients with TI-RADS type 4 thyroid nodules were selected as subjects.Sixty patients underwent CEUS-guided FNA(CEUS group),while the other 60 patients underwent conventional ultrasound-guided FNA(conventional ultrasound group).Using pathological results as the gold standard,Kappa consistency tests were used to analyze the diagnostic consistency of conventional ultrasound-guided FNA and CEUS-guided FNA for TI-RADS type 4 thyroid nodules.Results Among 120 patients with TI-RADS type 4 thyroid nodules(138 nodules),85 malignant nodules and 53 benign nodules were confirmed by pathology.In the CEUS group,there were 28 benign nodules and 42 malignant nodules(40 papillary thyroid carcino-mas and 2 medullary carcinomas).In the conventional ultrasound group,there were 25 benign nod-ules and 43 malignant nodules(39 papillary thyroid carcinomas and 4 medullary carcinomas).The false positive rate and false negative rate of conventional ultrasound-guided FNA for diagnosing malignant TI-RADS type 4 thyroid nodules were 3.62％and 5.07％,respectively.For CEUS-guided FNA,the rates were 2.17％and 2.90％,respectively.The sensitivity,specificity and accuracy of con-ventional ultrasound-guided FNA for diagnosing the nature of TI-RADS type 4 thyroid nodules were 83.72％,80.00％and 82.35％,respectively,with Kappa value of 0.627.For CEUS-guided FNA,these values were 90.48％,89.29％and 90.00％,respectively,with Kappa value of 0.793.Based on pathological examination,the diagnostic agreement rates for malignant TI-RADS type 4 thyroid nodules were 79.07％for conventional ultrasound-guided FNA and 83.33％for CEUS-guided FNA,with Kappa values of 0.719 and 0.786,respectively.Conclusion CEUS-guided FNA can provide high-resolution,real-time dynamic imaging information,thereby improving the sensitivity and specificity of diagnosing the nature of TI-RADS type 4 thyroid nodules.

ObjectiveTo observe the effect of Buyang Huanwutang in treating diabetic peripheral neuropathy （DPN） by inhibiting pyroptosis through AMP-activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1） mitophagy pathway. MethodSixty male SPF SD rats （6-7 weeks old） were used in animal experiments and numbered according to their body mass. They were then randomly divided into four groups by computer： normal group， model group， α-lipoic acid group（60 mg·kg^-1）， and Buyang Huanwutang group（15 g·kg^-1）， with 15 rats in each group. The diabetic model was established by injection of streptozocin （STZ）. After successful modeling， the α-lipoic acid group and the Buyang Huanwutang group were given corresponding drugs， and the normal group and the model group were given normal saline. Sensory nerve conduction velocity （SNCV） and paw withdrawal threshold （PWT） were measured at the end of administration for 12 weeks. Immunohistochemistry and Western blot were used to detect the expression of phosphorylated AMP activated protein kinase （p-AMPK）， phosphorylated UNC-51-like kinase 1 （p-ULK1）， protein involved in microtubule-associated protein 1 light chain 3 （LC3）， selective autophagy receptors （p62/SQSTM1）， Beclin1， NOD receptor protein structure domain-related proteins 3 （NLRP3）， Caspase-1 （Caspase-1）， and interleukin-1 beta （IL-1β） in dorsal root ganglia （DRG）. Immunofluorescence was used to detect the expression of the N-terminal gasdermin D （N-GSDMD）. ResultCompared with those in the normal group， rats in the model group had increased fasting blood glucose （P<0.01） and significantly reduced SNCV， PWT （P<0.01）， LC3Ⅱ/LC3Ⅰ， Beclin1， p-AMPK/AMPK， and p-ULK1/ULK1 （P<0.01）. In addition， p62， NLRP3， N-GSDMD/GSDMD， IL-1β， and cleaved Caspase-1/Caspase-1 were significantly increased （P<0.01）. Compared with those in the model group， SNCV and PWT were increased （P<0.01） in each administration group， and LC3Ⅱ/LC3Ⅰ， Beclin1， p-AMPK/AMPK， and p-ULK1/ULK1 were significantly increased （P<0.05， P<0.01）. p62， N-GSDMD/GSDMD， cleaved Caspase-1/Caspase-1， NLRP3， and IL-1β decreased （P<0.05， P<0.01）. Compared with the α-lipoic acid group， the Buyang Huanwutang group had significantly increased SNCV， PWT （P<0.05）， LC3Ⅱ/LC3Ⅰ， and p-ULK1/ULK1 （P<0.05） and significantly decreased NLRP3 and N-GSDMD/GSDMD （P<0.05）. ConclusionBuyang Huanwutang regulates mitophagy and inhibits pyroptosis through the AMPK/ULK1 pathway to prevent and treat DPN， and its therapeutic effect may be better than α-lipoic acid.

ObjectiveTo investigate the mechanism of Buyang Huanwutang in treating diabetic peripheral neuropathy （DPN） via mitochondrial transport. MethodDiabetes in SD rats was induced by a high-carbohydrate/high-fat diet and intraperitoneal injection of streptozotocin （STZ）. The 45 diabetic rats were randomly assigned into a DPN group， an alpha-lipoic acid （60 mg·kg^-1·d^-1） group， and a Buyang Huanwutang （15 g·kg^-1·d^-1） group， with 15 rats in each group. Fifteen normal SD rats were fed with the standard diet and set as the control group. The rats were administrated with corresponding drugs by gavage for 12 weeks. The paw withdraw threshold （PWT） and motor nerve conduction velocity （MNCV） were measured at the end of medication， and the sciatic nerve and the bilateral dorsal root ganglia of L4-5 were collected. The injury model of NSC34 cells was established by treating with 50 mmol·L^-1 glucose and 250 μmol·L^-1 sodium palmitate. The NSC34 cells were then randomly assigned into a blank （10% blank serum） group， a DPN （10% blank serum） group， an apha-lipoic acid （10% apha-lipoic acid-containing serum） group， a Buyang Huanwutang （10% Buyang Huanwutang-containing serum） group， and a Buyang Huanwutang + Compound C （CC） （10% Buyang Huanwutang-containing serum + 10 μmol·L^-1 CC） group. The cell intervention lasted for 24 h. The immunofluorescence method， immunohistochemistry， and Western blot were employed to determine the expression levels of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， phosphorylated cAMP-response element binding protein （p-CREB）， kinesin family member 5A （KIF5A）， and dynein cytoplasmic 1 intermediate chain 2 （DYNC1I2）. ResultCompared with the control group， the DPN group of rats showed increased fasting blood glucose （P<0.01）， decreased MNCV and PWT （P<0.01）， down-regulated expression of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.01）， and up-regulated expression of DYNC1I2 （P<0.01）. Compared with the DPN group， drug intervention groups showed increased MNCV and PWT （P<0.01）， up-regulated expression of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.05， P<0.01）， and down-regulated expression of DYNC1I2 （P<0.05， P<0.01）. The Buyang Huanwutang group had higher levels of MNCV and KIF5A （P<0.05） and lower level of DYNC1I2 （P<0.01） than the apha-lipoic acid group. Compared with the blank group， the DPN group of NSC34 cells showed decreased levels of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.01） and increased level of DYNC1I2 （P<0.01）. The apha-lipoic acid group and Buyang Huanwutang group had higher levels of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.05， P<0.01） and lower level of DYNC1I2 （P<0.01） in NSC34 cells than the DPN group. Buyang Huanwutang group had higher KIF5A level （P<0.05） in NSC34 cells than the apha-lipoic acid group. Moreover， the Buyang Huanwutang + CC group had lower levels of KIF5A， DYNC1I2， p-AMPK/AMPK， and p-CREB/CREB （P<0.01） in NSC34 cells than the Buyang Huanwutang group. ConclusionBuyang Huanwutang may regulate mitochondrial anterograde transport via the AMPK/CREB pathway to prevent and treat DPN.

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.

Objective:To evaluate the role of orphan nuclear receptor Nur77 in tunicamycin(TM)-induced injury to hippocampal neurons and the relationship with endoplasmic reticulum stress in mice.Methods:Mouse HT22 cells were divided into 4 groups ( n=10 each) using a random number table method: control group (C group), Nur77 specific agonist Csn-B group (Csn-B group), endoplasmic reticulum stress inducer TM group (TM group), and TM+ Csn-B group. Cells in C group were cultured for 24 h under normal condition. In Csn-B group, Csn-B at a final concentration of 10 μg/ml was added to the culture medium, and the cells were incubated for 24 h. In TM group, TM at a final concentration of 200 ng/ml was added to the culture medium and the cells were incubated for 24 h to induce cell endoplasmic reticulum stress injury. Cells in TM+ Csn-B group were pretreated with Csn-B at a final concentration of 10 μg/ml for 15 min, then TM at a final concentration of 200 ng/ml was added, and the cells were co-incubated for 24 h. The cell viability was examined by CCK-8 assay kit after treatment in each group. The expression of endoplasmic reticulum stress-related protein CCAAT/enhancer-binding protein homologous protein (CHOP), glucose regulated protein 78 (GRP78)and apoptosis-associated protein Bcl-2, Bax, caspase-3 and cleaved-caspase-3 was detected by Western blot. Results:Compared with C group, the cell viability was significantly decreased, and the expression of CHOP, GRP78, Bax and cleaved-caspase-3 was up-regulated, and the expression of Bcl-2 and caspase-3 was down-regulated in TM group ( P<0.05 or 0.01). Compared with TM group, the cell viability was significantly increased, the expression of CHOP, GRP78, Bax and cleaved-caspase-3 was down-regulated, and the expression of Bcl-2 and caspase-3 was up-regulated in TM+ Csn-B group ( P<0.05 or 0.01). Conclusions:Orphan nuclear receptor Nur77 is involved in TM-induced injury to hippocampal neurons, which is related to activation of the endoplasmic reticulum stress in mice.

Objective:To introduce a novel method to repair bottoming-out and double-bubble deformity after augmentation mammaplasty with a hammock-shaped capsular flap, and to evaluate its clinical effect of the related complications.Methods:From 2015 to 2019, a total of 16 patients (aged range from 23 to years, with average age of 33.4 years) were treated in the Department of Plastic Surgery, Shanghai Mylike Cosmetic Hospital. We performed a novel hammock-shaped capsular flap with periareolar incision. First of all, the periprosthetic capsule was widely separated from the lower pole of the breasts. Then the inframammary folds were anchored to the chest wall to eliminate the excess the cavity. Finally, the capsular flaps were raised up from both anterior and posterior leaf and resutured by fold tile shaped suture, in order to elevate the inframammary folds in aesthetic revision.Results:Only one case showed mild hematoma and healed after treatment. After 6 months follow-up, all the inframammary folds were elevated to the ideal position, and the double-bubble deformity was corrected with concealed scars and satisfactory shape and symmetry. Meanwhile, recurrent cases and capsule contraction were not observed.Conclusions:For patients with bottoming-out and double-bubble complications after augmentation mammaplasty, the use of hammock-shaped capsular flap can effectively revise the deformation. This technical refinement seems to afford stable outcomes with convenient operation and minor injury and produce satisfactorily clinical effects with fewer complications.

Objective:To investigate the changes of inflammatory indicators in patients with chronic obstructive pulmonary disease (COPD) and to analyze the related factors.Methods:From January 2018 to January 2019, 500 patients with COPD in the Sixth People's Hospital of Zhuji were selected.According to whether the infection was occurred, the patients were divided into observation group and control group.The observation group was 286 COPD patients (57.20%) complicated with pulmonary infection, and the control group was 214 patients (42.80%) without infection.The inflammation indicators of the two groups[serum interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10), tumor necrosis factor (TNF-α, TNF-β) and interferon (IFN-α, IFN-γ)]were detected and analyzed, and the relevant factors that caused infection were analyzed.Results:The serum interleukins (IL-1β, IL-2, IL-4, IL-6 and IL-10) in the observation group were significantly higher than those in the control group, and IL-8 level in the observation group was lower than that in the control group[(4.77±0.78)ng/L vs.(26.57±3.87)ng/L], the differences were statistically significant ( t=7.059, 67.098, 17.886, 17.259, 92.807, 17.181, all P<0.05). The levels of TNF-α, TNF-β and IFN-α in the observation group were higher than those in the control group[(48.81±11.53)μg/L vs.(33.91±10.84)μg/L, (95.36±17.87)ng/L vs.(46.12±12.18)ng/L, (26.81±4.45)ng/L vs.(7.78±3.54)ng/L], IFN-γ level in the observation group was lower than those in the control group[(46.25±10.09)pg/L vs.(55.67±14.23)pg/L], the differences were statistically significant ( t=14.666, 34.719, 51.532, 8.658, all P<0.001). The age≥60 years old (75.52% vs.49.07%), hospitalization time[(25.63±6.76)d vs.(20.53±5.87)d], antibiotic use time[(21.54±3.87)d vs.(13.50±4.21)d], diabetes history(77.27% vs.53.74%), mechanical ventilation(69.23% vs.10.28%), application of glucocorticoids(44.75% vs.69.16%) between the two groups had statistically significant differences (χ 2=37.285, t=8.824, 22.133, 30.759, χ 2=172.640, 29.478, all P<0.05). Logistic regression analysis showed that age≥60 years, diabetes history, antibiotic use time, mechanical ventilation, and application of glucocorticoid were the influencing factors of pulmonary infection in patients with COPD ( OR=1.527, 6.386, 2.801, 2.632, 2.084, all P<0.05). Conclusion:The detection of inflammatory factors (especially IL-8, IL-2) in COPD patients with pulmonary infection has clinical significance in the diagnosis and treatment of pulmonary infection.Long-term application of antibiotics, mechanical ventilation, and the application of glucocorticoids can easily lead to pulmonary infection in COPD patients.Therefore, preventive measures can be taken according to relevant factors in the clinic.

Objective To investigate the clinical features and surgical treatment of cerebral amyloid angiopathy hemorrhage (CAAH) caused by cerebral vascular amyloidosis.Methods The clinical data,radiological diagnoses,pathology results and treatment efficacies of 76 patients with CAAH,admitted to and performed surgery in our hospital from August 2010 to September 2015,were retrospectively analyzed.Results The first preoperative CT indicated that prompt hematomas were located in the cerebral hemisphere brain cortex,forming lobulated or irregular shape;2 or more lesions of recurrent hemorrhage were noted in 14 (18.4％);34 (44.7％) were with subarachnoid hemorrhage,16 (21.1％) were with intraventricular hemorrhage.Histopathological examination supported the diagnosis.Sixteen patients (21.1％) underwent second operation during hospitalization due to large amount of bleeding.During hospitalization,18 (23.7％) died,and 20 (26.3％) had long-term coma.During the follow-up period,23 patients (30.3％) had recurrent intracranial hemorrhage,of which,6 patients (7.9％) underwent surgical treatment,and 17 patients (22.4％) died.Conclusion The bleeding sites of CAAH mainly locate in the lobes of the brain surface,with lobulated or irregular shape,which is easily complicated with subarachnoid hemorrhage or intraventricular hemorrhage,with multiple features;diagnostic rate of CAAH can be improved by pathological examination of brain tissues and blood vessels;CAAH after surgery has high relapse rate and poor surgical results.