Chronic obstructive pulmonary disease （COPD） is a common clinical chronic airway disease with high morbidity， high mortality， a heavy disease burden， and complex mechanisms that have not been fully elucidated. Clinical problems promote the continuous progress of basic research. The establishment and evaluation of animal models is an important way to delve into the pathogenesis and treatment strategies of COPD. On the basis of the etiology， pathogenesis， diagnostic criteria， and syndrome differentiation of COPD in traditional Chinese medicine （TCM） and Western medicine， this paper summarizes the establishment methods and characteristics of existing animal models of COPD and analyzes the fitting degree of the models with the disease characteristics in Western medicine and syndrome characteristics in TCM. The results showed that the animal models of COPD in Western medicine were mainly induced by single factors and compound factors， and the model with the highest fitting degree was established by cigarette smoke combined with lipopolysaccharide and hormone. The model showed a fitting degree of 84% with the disease characteristics in Western medicine and 70% with the syndrome characteristics in TCM， being consistent with the clinical characteristics of COPD induced by multiple factors. Most of the animal models of COPD in TCM were established on the basis of disease models and combined with TCM etiology and pathogenesis characteristics， and prepared by syndrome differentiation. Among them， the model of accumulation of cold and water retention in lung had the highest fitting degree of 92% with the TCM diagnostic criteria. The models of phlegm-heat obstructing lung and phlegm-stasis obstructing lung had the fitting degree of 94% with clinical manifestations in Western medicine and the highest fitting degree with the diagnostic criteria in Western medicine. Different animal models of COPD have their own advantages and disadvantages， and most of them simply replicate the manifestations of COPD at a certain stage， failing to reflect the multiple causes and the dynamic changes of TCM etiology and pathogenesis. Moreover， the syndromes of these models fail to match the clinical syndromes in TCM. Therefore， establishing the animal models reflecting clinical characteristics of COPD in TCM and Western medicine and improving the model evaluation criteria are important contents to promote the overall development of integrated traditional Chinese and western medicine for COPD.

Objective To study the correlation between traditional Chinese medicine(TCM)constitution and pathogenic factors in patients with ankylosing spondylitis(AS).Methods One hundred patients of AS and their family members who had medical consultation in the Fifth Hospital of Xi'an(i.e.,Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine)in August 2019 and September 2020 were selected as the study subjects.The guidelines of Classification and Determination of Traditional Chinese Medicine Constitution issued by the China Association of Chinese Medicine were adopted to determine the traditional Chinese medicine(TCM)constitution types of the study subjects.The sociodemographic information,living habits,clinical symptoms,and TCM constitution types of the AS patients and their family members were collected by means of questionnaires and clinical investigations,and then the pathogenic factors of the patients with AS were investigated.The binomial Logistic regression model was used to analyze the correlation between TCM constitution types and pathogenic factors in patients with AS.Results(1)Among the 100 AS patients,the majority of them had the biased constitutions,and the biased constitutions with the occurrence frequency in descending order were yang deficiency constitution,qi deficiency constitution,and damp-heat constitution,which accounted for 33.00%,14.00%,and 18.00%,respectively.(2)The prevalence rates of AS in the first-,second-,and third-degree relatives of AS patients were 56.25%,40.00%and 25.00%,respectively.For the positive rates of human leukocyte antigen B27(HLA-B27)in AS patients and their family members,HLA-B27 in AS patients was all positive,while the positive rates of HLA-B27 in the first-,second-,and third-degree relatives of AS patients were 44.31%,30.67%and 15.63%,respectively.(3)The results of regression analysis showed that the disease duration of AS patients was significantly correlated with qi deficiency constitution,the grading of sacroiliac arthritis was correlated with qi stagnation constitution,and age was correlated with blood stasis constitution(P＜0.05 or P＜0.01).The results indicated that disease duration and age were the important factors affecting the constitution types of AS patients,and disease duration was closely related to qi deficiency while age was closely related to blood stasis.Conclusion AS is a highly hereditary autoimmune disease,and its onset is associated with HLA-B27.Yang deficiency is the basic constitution type of AS,and damp-heat constitution is the main constitution type in the progression of AS(especially in the active stage of the disease).The prolongation of the disease will exacerbate the illness condition of AS and then the manifestations of qi deficiency will be more obvious.

Objective:To investigate the risk factors for periprosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) and construct a nomogram model for prediction of such risks.Methods:In this retrospective study, we enrolled 69 patients with PJI after primary TKA (the infection group, n=69) who had been admitted to Department of Orthopedics, Nanjing Jinling Hospital, The First School of Clinical Medicine, Southern Medical University from January 2010 to December 2019. The non-infection group included the patients of the same kind but without postoperative infection during the same period who were matched according to time of admission, age, and gender in a ratio of 1∶3 ( n=207). The data on body mass index, anesthesia method, operation time, preoperative C-reactive protein, preoperative albumin, and comorbid medical conditions were collected from both groups to screen the risk factors for postoperative development of PJI using univariate and multivariate conditional logistic regression analyses. After a nomogram of the risk factors was plotted using R software, the consistency index (C-index) was calculated. The receiver operating characteristic curve, calibration curve, and clinical decision curve were drawn. Results:Multivariate conditional logistic regression analysis showed that preoperative albumin <35 g/L ( OR=7.166, 95% CI: 3.427 to 14.983, P<0.001), operation time >90 min ( OR=3.163, 95% CI: 1.476 to 6.779, P=0.003), diabetes mellitus ( OR=3.966, 95% CI: 1.833 to 8.578, P<0.001), rheumatic diseases ( OR=3.531, 95% CI: 1.362 to 9.156, P=0.009), and chronic lung diseases ( OR=4.734, 95% CI: 1.790 to 12.521, P=0.002) were risk factors for development of PJI after primary TKA. The nomogram constructed with R software visualized the model. The C-index of the nomogram was 0.809 (95% CI: 0.751 to 0.867), indicating a good predictive capability of the model. The calibration curves of the model showed that the nomogram was in good agreement with the actual observations. The decision curves showed that the threshold probabilities of the model ranged from 0.08 to 0.75, providing a good net clinical benefit. Conclusions:Preoperative low albumin, prolonged operation time, diabetes, rheumatic diseases, and chronic lung diseases may be the risk factors for PJI after primary TKA. The nomogram prediction model based on these factors can provide a reference for clinicians to prevent PJI.

Objective This study investigated the impact of occupational mercury(Hg)exposure on human gene transcription and expression,and its potential biological mechanisms. Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA. Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10 μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels. Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective To explore the efficacy and safety of modified meibomian gland massage combined with ultrasonic atomization and drug therapy for dry eye in high-altitude military personnel.Methods A total of 180 patients(360 eyes)with dry eye who were diagnosed and treated by the medical team of General Hospital of Central Theater Command of Chinese PLA from July to October 2022 in Linzhi,Tibet(average altitude of 3100 meters)were selected as the research subjects.Patients were divided into four block groups based on the course of the disease:＜1 month,1-3 months,3-6 months,and≥6 months,and each block group was randomly assigned to control group,traditional group and modified group by random number table method,with 60 cases in each group.Control group received routine treatment(artificial tear drops and atomization fumigation);on the basis of routine treatment,traditional group underwent traditional meibomian gland massage,and modified group underwent modified meibomian gland massage.After 3 months of treatment,the scores of symptoms and signs,total effective rate,duration of treatment and incidence of adverse events were compared among the 3 groups.Results In the intra-group comparison before and after treatment,except for control group's symptom scores difference which was not statistically significant(P＞0.05),all other scores decreased significantly(P＜0.05).In the inter-group comparison after treatment,the scores of both traditional group and modified group were significantly better than those of control group(P＜0.05),but no significant difference was observed in symptom and sign scores between traditional and modified groups(P＞0.05).Compared with control group,the total effective rates of traditional group and modified group both significantly increased(P＜0.01),but there was no significant difference in total effective rate between traditional and modified groups(P＞0.05).The treatment time in modified group was significantly longer than that in control group(P＜0.05),but significantly shorter than that in traditional group(P＜0.05).The incidence of adverse events was significantly lower in modified group than that in traditional group(P＜0.001).Conclusion In high-altitude areas,modified meibomian gland massage combined with ultrasonic atomization and local drug therapy for dry eye is safe and effective,non-invasiveness and easy to perform,and suitable for promoting and application in military field training.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

OBJECTIVE To investigate the modulating effect of neotropics on form deprivation myopia(FDM)in guinea pigs.METHODS Tricolour guinea pigs were randomly divided into normal control group,FDM model group,FDM+saline group,FDM+atropine group,and FDM+neotropine group,with eight animals in each group.Except for the normal control group,the right eyes of the guinea pigs were covered for 14 d to establish a guinea pig FDM model.The drug administration groups were injected with 10 μL of saline,1%atropine,or 1%neotropine into the vitreous cavity once every other day.The changes in the refractive error and axial length of both eyes were recorded for 1 d before the intervention and for 14 d after the intervention.Then,the eyeballs of guinea pigs were taken from the right eyes.HE staining was used to evaluate the histopathological structure of the sclera while sirius red staining was used to detect the collagen protein content in the sclera.RT-qPCR was used to detect the mRNA expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase(MMP-2)and tissue inhibitor of metalloproteinase(TIMP-2)in guinea pigs'sclera.The protein expression levels of collagen type Ⅰ(Col-Ⅰ)and TGF-β1 in guinea pig sclera were detected by Western blotting while those of MMP-2,TIMP-2 and Ki-67 were detected by immunohistochemical staining.RESULTS Compared with the nor-mal control group,eyes of guinea pig in the FDM model group showed a significantly lower refractive error(P<0.01),significant elongation of the ocular axis(P<0.01),scattered distribution of scleral fibre bundles,sparse collagen cells,reduced scleral thickness(P<0.01),and a significantly lower collagen protein content(P<0.01).The mRNA and protein expressions of TIMP-2 and TGF-β1 were lower(P<0.05,P<0.01),and MMP-2 was higher(P<0.01)in scleral tissue.The protein expression level of Col-Ⅰwas lower(P<0.05)while that of Ki-67 was elevated(P<0.01)in scleral tissue.Compared with the FDM model group,there were no significant changes in any of the indexes in the FDM+saline group.The refractive error of the right eyes of guinea pigs in the FDM+neotropium group and the FDM+atropium group were significantly higher(P<0.05),the length of the ocular axis was significantly shorter(P<0.05),the collagen fibres were arranged more tightly,the fibre bundles were distributed more orderly,the distribution of the collagen cells was more uniform,and the thickness of the sclera was significantly increased(P<0.01).Collagen protein contents were significantly higher(P<0.05,P<0.01),the mRNA and protein expressions of TIMP-2 and TGF-β1 were significantly higher(P<0.01),MMP-2 mRNA and protein expressions were significantly lower(P<0.05,P<0.01).The protein expression level of Col-Ⅰwas higher(P<0.05,P<0.01),and that of Ki-67 was lower(P<0.05,P<0.01)in scleral tissue.CONCLU-SION The muscarinic antagonist neotropine inhibits the development of myopia in guinea pigs in the FDM model by reversing both the down-regulation of TGF-β1 and the up-regulation of MMP-2 in scleral tissues and inhibiting the remodeling of the scleral extracellular matrix.

The current treatment of glioma is facing drug resistance,which limits the efficacy of traditional chemotherapy drugs.This study aims to explore the potential mechanisms of the trifluoromethylquinazoline compound(KZL204)against glioma.Through the Cell Counting Kit-8(CCK-8)assay,we found that KZL204 significantly inhibits the growth of drug-resistant cancer cells,with a 48-hour half-maximal inhibitory concentration(IC50)of 3.63±0.38 μmol/L,which is significantly better than the positive control drug temozolomide(TMZ)(IC50 value of 81.67±5.49 μmol/L).Additionally,flow cytometry analysis showed that KZL204 treatment significantly increased the apoptosis rate of drug-resistant tumor cells and arrested the cell cycle at the G2/M phase.At the same time,the Transwell assay confirmed the inhibitory effect of KZL204 on the migration and invasion of drug-resistant cancer cells.Transcriptome analysis revealed 2 435 differentially expressed genes in drug-resistant cancer cells treated with KZL204,of which 1 320 were upregulated,and 1 115 were downregulated.KEGG and GO enrichment analysis showed that these differential genes were significantly enriched in apoptosis-related signaling pathways.Further bioinformatics prediction and Venn diagram analysis identified 35 potential core targets,with the PI3K-AKT signaling pathway being the most significant among the differentially expressed genes.Quantitative real-time PCR(RT-qPCR)experiments confirmed the downregulating effects of KZL204 on genes such as CREB3L1,CSF1,CXCL5,BCL3,and the upregulating effects on genes like FOS,LT A,PTGS2,MAP2K3.Immunoblotting experiments at the protein level also confirmed the impact of KZL204 on the expression of apoptotic proteins,including the upregulation of Bax,cleaved Caspase-3 protein,and the downregulation ofAKT,Bcl-2,Caspase-3,and Caspase-8 protein expression.In summary,KZL204 significantly inhibits the growth and metastasis of drug-resistant glioblastoma and induces apoptosis and cell cycle arrest by regulating the PI3K-AKT and apoptosis-related signaling pathways,demonstrating its potential as a candidate drug against drug-resistant glioma.

Objective To evaluate the intraoperative identification of ectopic parathyroid tissue in the central neck region using autofluorescence point-spectral analysis(AFPSA)combined with immune colloidal gold technique(ICGT),for guiding total parathyroidectomy(TPTX)or clean parathyroidectomy(CPTX)in the management of secondary hyperparathyroidism(SHPT).Methods Retrospectively collected and compared the clinical data of 64 patients with SHPT from October 2019 to June 2023.In the observation group,TPTX was performed as the initial procedure in 36 cases,followed by sampling of suspicious targets using AFPSA in the central neck area and subsequent detection through ICGT.CPTX was then conducted if a positive result was obtained.On the other hand,the control group consisted of 28 cases where only TPTX was performed without any additional tests during surgery.The surgical data,parathyroid hormone(PTH)levels,blood calcium levels,blood phosphorus levels,alkaline phosphatase(ALP)levels,regression of clinical symptoms,changes in parathyroid function and occurrence of hypocalcemia were compared between these two groups.Results In the observation group,there were 9 cases of AFPSA-ICGT positivity,including 2 left-sided cases,4 right-sided cases,and 3 thymic cases;among these posi-tive cases,there were a total of 10 locations with mildly hyperplastic or nonhyperplastic microscopic parathyroid tissue.The difference in the number of total parathyroid glands removed(including ectopic)between the two groups was statistically significant(P<0.05).At both 3 and 6 months postoperatively,ALP levels in the observation group were significantly lower than those in the control group(P<0.01 and P<0.001 respectively);at 6 months postoperatively,differences in PTH and blood phosphorus levels between the two groups were also statistically significant(P<0.05 and P<0.001 respectively).Joint bone pain and skin itching recurred in some patients within the control group at six months after surgery(P<0.05),whereas recurrence of SHPT was less frequent within the observation group compared to controls(P<0.05);however,no statistically significant differences were observed regarding postoperative hypoparathyroidism or hyperparathyroidism as well as hypocalcemia between either groups.Conclusion The AFPSA-ICGT intraoperative test can be utilized to guide surgery for SHPT,enabling accurate and efficient identification as well as safe targeting of parathyroid tissues that may not exhibit obvious hyperplasia in the central cervical region.