Objective To investigate the role and mechanism of NLRP3/Caspase-1/IL-1 β inflammasome pathway in the formation of aortic dissection in mice.Methods Fifty male C57BL/6 mice(3 weeks old,body weight 10～13 g)were divided into control group(n =10,normal diet),β-aminopropionitrile(BAPN)group[n =20,drink water containing 1 g/(kg·d)BAPN],and BAPN+MCC950 group[n=20,drink water containing 1 g/(kg·d)BAPN and intraperitoneal injection of 20 mg/(kg·d)NLRP3 inhibitor,MCC950]by random sampling.Water intake,body weight,incidence of aortic dissection and aortic dissection-related mortality were recorded.The inflammatory infiltration in the aorta was observed with HE staining,elastic fiber breakage was observed by elastic Van Gieson(EVG)staining,average fluorescence intensity of NLRP3,IL-1β,α-SMA and OPN was detected by immunofluorescence assay,and protein expression levels of NLRP3,Caspase-1,ASC,IL-1β,α-SMA and OPN were measured with Western blotting.Results No aortic dissection or death was observed in the control group.The BAPN group had an incidence of aortic dissection of 80％,aortic dissection-related mortality of 35％,and obvious broken elastic fibers and inflammatory infiltrate in the aortic wall,and increased expression levels of NLRP3,Caspase-1,ASC and IL-1 β,decreased contractile α-SMA and increased synthetic protein OPN when compared with the control group(P<0.05).While MCC950 treatment decreased the incidence of aortic dissection(80％vs 35％,P=0.004)and aortic dissection-related mortality(35％vs 15％,P=0.144),alleviated the broken elastic fibers and inflammatory infiltrate in the aortic wall,and down-regulated the expression of NLRP3,Caspase-1,ASC and IL-1β,enhanced contractile α-SMA and decreased the synthetic protein when compared with the BAPN group(P<0.05).Conclusion The occurrence of aortic dissection in mice is associated with activation of NLRP3/Caspase-1/IL-1 β inflammasome pathway.NLRP3 inhibitor,MCC950,can reduce the occurrence of aortic dissection and show a protective effect on blood vessels.

Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.

Objective:To study the distribution and changes of dopamine transporter (DAT) in guinea pig eyes under different light patterns.Methods:Thirty-six 3-week-old white ordinary-grade guinea pigs were randomly selected and divided into groups of 10 000 lx, 5 000 lx, and 500 lx, with 12 guinea pigs in each group exposed to strong light, medium strong light, and normal light, respectively.Each group was randomly divided into 3 subgroups, with 4 guinea pigs in each subgroup.The 3 subgroups of 500 lx group received light exposure for 5, 20, and 40 minutes, respectively.The 3 subgroups of 5 000 lx group received light exposure for 2, 4, and 40 minutes, respectively.The 3 subgroups of 10 000 lx group received light exposure for 2, 5, and 20 minutes, respectively.After light treatment, each group of guinea pigs was injected with 99mTc-TRODAT-1 for SPECT DAT imaging, and image data were collected by Micro-SPECT.The region of interest (ROI) of guinea pig retinas was analyzed using Micro-CT software.The counts of ROI were expressed as Sum, which reflected the relative distribution or density of DAT.The DAT density between experimental and control eyes of guinea pigs after light exposure, the differences in DAT density between guinea pig eyes under different light intensities, the differences in DAT density between guinea pig eyes after different light durations, and the cumulative and interactive effects of light intensity and light duration on DAT aggregation in guinea pigs were compared.Another 3 guinea pigs were selected, and after light exposure, the 3 guinea pigs' eyes underwent continuous image acquisition for 6 hours at 20-minute intervals, and 18 images per guinea pig were acquired to analyze the trend of DAT density in guinea pig eyes over time.This study was approved by the Ethics Committee of Shanghai General Hospital (No.2020SQ196). Results:The DAT density (Sum value) of experimental eyes at 500, 5 000, and 10 000 lx were 5 598.97±3 159.38, 8 636.78±2 503.16, and 7 407.39±2 053.41, respectively, significantly higher than 4 388.89±2 902.90, 5 981.92±3 057.44, and 5 091.32±2 039.36 of control eyes ( t=5.31, 4.69, 11.80; all at P<0.001). At 500 lx, there was a statistically significant difference in DAT density between the experimental and control eyes of guinea pigs at different light exposure durations ( F=14.01, P<0.01), while no significant difference was found at other light intensities at different light exposure durations (both at P>0.05). When the light exposure time was 5 minutes, the difference in DAT density between the experimental and control eyes of guinea pigs was significantly greater in the 10 000 lx group than in the 500 lx group ( t=-13.22, P<0.001). There was no statistically significant difference between different groups at other light exposure durations (all at P>0.05). No cumulative or interactive effects of light intensity and light duration were found on the differences in DAT density (all at P>0.05). Continuous scanning after illumination showed that DAT density in guinea pig retinas first increased to a peak over time and then gradually returned to normal values. Conclusions:Light, even under moderate or normal light levels, can cause an increase in the secretion of DAT in the retina and stimulate the production of DAT.Light intensity and duration have no cumulative or interactive effects on the distribution and density of retinal DAT.

To investigate the protective effect of hirudin on kidneys of diabetic rats and its molecular mechanism.

To investigate the protective effect of hirudin on kidneys of diabetic rats and its molecular mechanism.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

Three-dimensional graphene hydrogel(3DGH)was successfully prepared through a hydrothermal method,followed by its composition with gold nanoparticles(AuNPs)to construct a highly sensitive Au/3DGH graphene electrochemical transistor(GECT)dopamine(DA)sensor.AuNPs are efficient electrocatalytic materials.However,their tendency to aggregate during electrodeposition hinds the practical application.The porous and interconnected network structure of 3DGH provided abundant attachment sites,effectively preventing AuNPs aggregation.By modifying the sensor's gate with Au/3DGH,the excellent electrocatalytic performance of Au/3DGH towards DA and the high sensitivity of GECT were utilized to achieve highly sensitive detection of DA.The sensor exhibited a low detection limit of 20 nmol/L and a linear range of 20 nmol/L to 2.5 mmol/L.Remarkably,the sensor showed high sensitivity,excellent selectivity and strong stability,and hold great potnetial in highly sensitive portable detection of DA in disease prevention and clinical monitoring.

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 investigate the distribution of traditional Chinese medicine(TCM)constitution in chronic hepatitis B(CHB)patients complicated with metabolism associated fatty liver disease(MAFLD),and to explore the correlation of the complication of MAFLD with TCM constitution and body composition,thus to determine their predictive values for the complication of MAFLD in CHB patients.Methods A retrospective study was adopted.The study started from the collection of the clinical data of 235 outpatients who attended the Department of Hepatology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to December 2023,and was diagnosed as CHB following the diagnostic criteria.According to the controlled attenuation parameter(CAP)value,134 cases of CHB patients were allocated to the non-MAFLD group(CAP＜238 dB/m)and 101 cases were allocated to the MAFLD group(CAP≥238 dB/m).And then the distribution of TCM constitution in the two groups was observed.In addition,according to the body mass index(BMI)value,the patients were divided into the non-obese group(141 cases,BMI＜24.0 kg/m2)and the overweight/obese group(94 cases,BMI≥24.0 kg/m2).And then the logistic regression was used to analyze the independent risk factors for the complication of MAFLD in CHB patients,multivariate logistic regression was used to analyze the influencing factors,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of the influencing factors for the complication of MAFLD in CHB patients and to determine their optimal cut-off values.Results(1)The constitutions of CHB patients in the MAFLD group were predominated by balanced constitution(36.6%),damp-heat constitution(20.8%),and phlegm-damp constitution(14.9%),which accounted for 72.3%in total.(2)In CHB patients complicated with MAFLD,the overweight/obese group had higher levels of γ-glutamyl-transpeptidase(γ-GT),BMI,total body fat mass(TBFM),total muscle mass(TMM),total body water(TBW),interacel1ular water(ICW),extracellular water(ECW),body fat ratio(BFR),visceral fat area(VFA),basal metabolism(BM),and trunk fat mass(TFM)than the non-obese group,and the differences were statistically significant(P＜0.05 or P＜0.01).(3)The results of multivariate logistic regression analysis showed that the white blood cell(WBC)count,blood uric acid(UA),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and VFA were the influencing factors for the complication of MAFLD in the CHB patients in clinic.(4)The results of ROC curve analysis showed that in CHB patients,the areas under the ROC curve(AUC)for age,TG,UA,and VFA were 0.532,0.680,0.738,and 0.859 respectively;the optimal cut-off values of VFA in CHB patients,non-obese CHB patients,and overweight/obese CHB patients were 74.98,66.5 and 112.2 cm2 respectively,and the optimal cut-off values of VFA in patients with balanced constitution,phlegm-damp constitution,and damp-heat constitution were 85.50,66.50,and 74.98 cm2 respectively.The AUC values of VFA in various populations were significantly higher than those of age,TG,and UA,and the combined prediction by multivariate analysis has higher predictive value than that by univariate analysis.Conclusion The AUC value of VFA for predicting the risk of MAFLD is the highest in patients with CHB,and the possibility of the complication of MAFLD increased with the increase of the cut-off point level of VFA.The optimal cut-off values of VFA varies in non-obese group and overweight/obese group of CHB patients and in CHB patients with different TCM constitution.