Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

In vaccination,traditional vaccines are administered intramuscularly or subcutaneously,mainly inducing humoral immunity,with weak induction of mucosal immunity and insufficient protection against respiratory and gastrointestinal viruses.Current research has found that immuni-zation vaccines can effectively induce mucosal immunity through oral or nasal administration,but there is a lack of effective mucosal adjuvants,and there is an urgent need for the development of safe and effective new mucosal adjuvants.With the advancement of nano-adjuvant research,novel nanoparticles have attracted widespread attention due to their good mucosal adhesion,efficient an-tigen-loading ability,biocompatibility,and advantages in immune-enhancement,nano-size effect,tissue-targeting,and slow release of antigens,etc.,and are expected to be used as novel mucosal ad-juvants in the prevention and treatment of animal diseases.To date,significant progress has been made in research targeting mucosal adjuvants such as polymeric nanoparticles,inorganic nanoparti-cles,and liposomes.This paper reviews the application of nanomucosal adjuvants in animal vaccines and their mechanisms of action at home and abroad,and analyzes the physicochemical factors af-fecting the immune-enhancing effect of nanoparticle adjuvants,with a view to providing a reference for the development of novel mucosal adjuvants.

Objective: To investigate the occupational health status of medical radiation workers in Hangzhou City, so as to provide the basis for their occupational health risk assessment. Methods: Data on medical radiological workers who underwent occupational health examinations from 2021 to 2022 were collected through the Physical Examination Information Management System of the Hangzhou Occupational Disease Prevention and Control Hospital. The physical examination data including blood routine, eye lens, thyroid ultrasound, thyroid function, liver function, renal function and blood lipid were collected, and the abnormal rates of occupational health examinations among workers with different genders, working years and occupational exposure types were analyzed. Results: A total of 3 968 medical radiation workers were investigated, including 2 310 males (58.22%) and 1 658 females (41.78%). There were 2 039 (51.39%), 821 (20.69%) and 1 108 (27.92%) workers with 1-<6, 6-<10 years and 10 years and above of work, respectively. Diagnostic radiology was the predomenant type of exposure, with 2 240 workers accounting for 56.45%. The abnormal rates of thyroid ultrasound and blood lipid were 47.73% and 45.21%, respectively, which were relatively higher than other items. The abnormal rates of micronucleus rate, thyroid ultrasound, thyroid function and renal function were higher in females than in males, while the abnormal rates of lymphocyte count, liver function and blood lipid in males were higher in males than in females (all P<0.05). With the increase of working years, the abnormal rates of micronucleus rate and blood lipid showed upward trends (both P<0.05). There were statistically significant differences in the abnormal rates of thyroid ultrasound, liver function and blood lipid among different occupational exposure types (all P<0.05). Conclusion Long-term low-dose ionizing radiation environment affects the thyroid, micronucleus rate and blood lipid of medical radiation workers in Hangzhou City, with differences observed among workers with different genders and occupational exposure types.

Objective To explore the correlation between the pulmonary artery diameter(PAD),PAD/aortic diameter(AOD),right ventricular diameter(RVD),RVD/left ventricular diameter(LVD)measured on pulmonary artery CT angiography(CTPA)cross-sectional images and the degree of embolism,cardiac biomarkers in patients with medium-to-high risk acute pulmonary embolism(APE).Methods The clinical data of 53 patients with medium-to-high risk APE,who received interventional treatment at the Putian Municipal First Hospital of China From January 2021 to December 2023,were retrospectively analyzed.The PAD,PAD/AOD,RVD,and RVD/LVD were measured on CTPA cross-sectional images.The correlations of the above indexes with CT embolism index(CTEI),N terminal pro B type natriuretic peptide(NT-proBNP),and cardiac troponin Ⅰ(cTnⅠ)were analyzed.Results A weak-moderate positive correlation existed between PAD,RVD,RVD/LVD and CTEI(r=0.506,r=0.310,r=0.452 respectively,P＜0.001,P=0.024,P=0.001 respectively),while no correlation existed between PAD/AOD and CTEI(r=0.247,P=0.075).Compared with the NT-proBNP negative group,in the NT-proBNP positive group the values of PAD,PAD/AOD and RVD/LVD were higher(all P＜0.05),and there was no statistically significant difference in RVD value between the two groups(P＞0.05).A weak-moderate positive correlation existed between NT-proBNP and PAD,PAD/AOD,RVD,RVD/LVD(r=0.454,r=0.326,r=0.302,r=0.405 respectively,P=0.001,P=0.017,P=0.028,P=0.003 respectively).There were no statistically significant differences in PAD,PAD/AOD,RVD and RVD/LVD values between the cTnⅠ negative group and the cTnI positive group(all P＞0.05).No correlation existed between cTnⅠ and PAD,PAD/AOD,RVD,RVD/LVD(r=0.188,r=0.042,r=-0.021,r=0.139 respectively,and P=0.195,P=0.772,P=0.884,P=0.342 respectively).Conclusion CTPA cross-sectional quantitative indicators are helpful in evaluating the embolism degree of APE and right heart function,but it cannot be used to assess myocardial injury.

Objective To evaluate the safety and efficacy of profunda femoral vein thrombosis clearance in endovascular treatment of acute lower extremity deep venous thrombosis (DVT). Methods From January 2022 to September 2023, clinical data of acute lower extremity DVT patients who underwent percutaneous mechanical thrombectomy (PMT) for profunda femoral vein thrombosis were retrospectively analyzed. The 12-month primary patency rate of iliofemoral vein and incidence of post-thrombotic syndrome(PTS) were analyzed. Results Twenty-two patients were included in the study, and all patients underwent PMT for profunda femoral vein thrombosis. Five patients were treated through the contralateral common femoral vein via crossover approach, and 17 patients were treated through the contralateral common femoral vein combined with the ipsilateral deep vein approach. The 12-month primary patency rate of iliofemoral vein was 90.9% (20/22), and the incidence of PTS was 9.1% (2/22). Conclusions For patients with acute lower extremity DVT undergoing endovascular treatment, PMT for profunda femoral vein thrombosis is safe and effective, achieving good primary patency of iliofemoral vein and low incidence of PTS.

OBJECTIVE: To explore whether hydrocortisone can improve the prognosis of patients with severe community-acquired pneumonia (sCAP) by Meta-analysis. METHODS: Randomized controlled trial (RCT) on hydrocortisone in the treatment of sCAP were extracted from the database including PubMed, Cochrane library, Web of Science, and Embase, and the search time was up to April 29, 2023. The patients in the standard treatment group received standard treatment such as antibiotics and supportive care, while those in the hydrocortisone group received hydrocortisone treatment on the basis of standard treatment. Meta-analysis was used to compare the mortality, duration of mechanical ventilation, mechanical ventilation rate and incidence of adverse reactions (hyperglycemia, gastrointestinal bleeding, secondary infection) between the two groups. The risk of literature bias was assessed. The studies that might have publication bias were corrected by the subtraction and complementation method. At the same time, trial sequential analysis (TSA) was conducted. RESULTS: A total of 5 RCTs involving 1 031 patients were finally enrolled, including 494 patients in the standard treatment group and 537 patients in the hydrocortisone group. Among the 5 studies, the research site of 2 studies was in the mixed ward. Considering the inclusion characteristics of the study population, there was doubt whether its research object was sCAP patients, which might have a certain impact on the results and introduce potential bias. Meta-analysis showed that the mortality in the hydrocortisone group was significantly lower than that in the standard treatment group [6.0% vs. 14.0%; odds ratio (OR) = 0.38, 95% confidence interval (95%CI) was 0.25-0.59, P < 0.01; I² = 9%]. The studies that were asymmetric were corrected by the reduction and supplementation method. Even after filling the missing studies, hydrocortisone could still reduce the death risk of the patient (OR = 0.49, 95%CI was 0.32-0.73, P < 0.01; I² = 31%). TSA showed that the average mortality of the standard treatment group was about 14.0%, and that of the hydrocortisone group was about 6.0%, with a relative risk reduction (RRR) = 57%. The calculated sample size was 699 cases, and the actual sample size was 1 031 cases. The actual sample size exceeded the required sample size, and the Z-curve crossed the O'Brien-Fleming boundary and the curve corresponding to P = 0.05, it meant that hydrocortisone could effectively reduce the mortality of sCAP. Compared with the standard treatment group, no statistical difference in the duration of mechanical ventilation was found in the hydrocortisone group [mean difference (MD) = -3.26, 95%CI was -6.72-0.21, P = 0.07; I² = 0%], but the 8-day mechanical ventilation rate was significantly lowered (19.5% vs. 55.4%; OR = 0.24, 95%CI was 0.12-0.45, P < 0.01; I² = 0%), and also no significantly difference was found in the incidence of hyperglycemia (54.3% vs. 44.6%, OR = 1.26, 95%CI was 0.56-2.84, P = 0.58; I² = 61%), gastrointestinal bleeding (2.5% vs. 3.6%; OR = 0.70, 95%CI was 0.34-1.46, P = 0.34; I² = 0%) and secondary infection (9.2% vs. 11.5%; OR = 0.46, 95%CI was 0.06-3.35, P = 0.45; I² = 53%). CONCLUSION Hydrocortisone can reduce the mortality rate of sCAP patients, decrease their need for mechanical ventilation, and does not increase the risk of hyperglycemia, gastrointestinal bleeding, or secondary infections.
Humans ; Hydrocortisone/therapeutic use* ; Community-Acquired Infections/drug therapy* ; Pneumonia/drug therapy* ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; Community-Acquired Pneumonia

Peripheral artery disease(PAD),commonly encountered in vascular surgery,predominantly affects the lower limbs and presents with ischemic symptoms resulting from atherosclerosis.It carries risks of adverse limb events and cardiovascular events.Antithrombotic therapy remains a cornerstone in the management of PAD.This article reviews the evidence and research progress regarding dual-pathway antithrombotic therapy for PAD.Multiple clinical trials have demonstrated that,compared to single antiplatelet therapy,dual-pathway antithrombotic therapy significantly reduces the risks of major adverse limb events and major adverse cardiovascular events without a significant increase in bleeding risk.For high-risk patients,such as those with advanced age,multivessel disease,comorbid coronary artery disease,or those undergoing endovascular revascularization,the benefits of dual-pathway antithrombotic therapy are particularly pronounced.Current clinical guidelines have incorporated dual-pathway antithrombotic therapy into their recommendations,standardized criteria for identifying the most appropriate patient populations remain lacking.Despite its advantages in reducing adverse events,its long-term safety profile and optimal target populations warrant further investigation.

Objective:To compare the clinical characteristics of severe Mycoplasma pneumoniae pneumonia（SMPP）with bronchiolitis and consolidation to raise awareness.Methods:Retrospective analysis was conducted on children hospitalized at the first affiliated hospital of Xiamen University diagnosed with（SMPP）from February 2023 to January 2024.The children were divided into bronchiolitis group and large consolidation group based on their high-resolution CT imaging findings.Data on basic information，clinical features，auxiliary examination results，and bronchoscopy findings were analyzed.Results:This study included 415 pediatric patients，including 203 with bronchiolitis and 212 with large consolidation.The proportion of males，atopy rate，and first-degree relative atopy rate in the bronchiolitis group were higher，and the age of the bronchiolitis group was younger（ P<0.05）.The fever peak，incidence of fever，and low breath sound in the bronchiolitis group were lower，and the incidence of hypoxemia，wheezing，shortness of breath，inspiratory tri-concave signs，moist rales were higher than those in the consolidation group（ P<0.05）.The white blood cell counts，platelet counts，and lactate dehydrogenase were higher and the percentage of neutrophils，C-reactive protein，ferritin，D-dimer，and fibrinogen degradation products were lower in the bronchiolitis group than those in the consolidation group（ P<0.05）.The rate of 2 or more bronchoscopy procedures，and the proportion of longitudinal plica，mucus plug，and plastic in the consolidation group were higher than those in the bronchiolitis group（ P<0.05）.After three months of follow-up，there were 8 cases of bronchiolitis obliterans，including 7 cases in the bronchiolitis group and 1 case in the large consolidation group. Conclusion:If atopy，wheezing，and dyspnea are present in young children and preschool children with confirmed SMPP，they should be closely monitored for signs of bronchiolitis SMPP.Children with significant consolidation on imaging should have the possibility of various intrapulmonary and extrapulmonary problems taken into account.Appropriate treatment options should be implemented during the acute phase based on the imaging findings.

Objective:This study aims to explore the intervention effects of five different intelligent rehabilitation technologies, namely immersive virtual reality (imVR), non-fully immersive virtual reality (Nf-imVR), augmented reality, brain-computer interface (BCI), and rehabilitation robot (RT), on the upper limb function and activities of daily living of stroke patients with upper limb dysfunction.Methods:A computer-based search was conducted in PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Databases for randomized controlled trials (RCT) on the intervention effects of different intelligent rehabilitation technologies on stroke patients with upper limb dysfunction. Manual search and other retrieval methods were also supplemented. The retrieval time limit was from the establishment of the databases to May 31, 2024. Data were extracted and the methodological quality was evaluated, and a network Meta-analysis was performed using Stata 17.0 software.Results:A total of 34 articals were included, involving 1 926 patients, and the studies included five intelligent rehabilitation technologies. The control groups all received dose-matched conventional physical training. The results of the network Meta-analysis showed that, compared with the dose-matched conventional physical training, in terms of improving upper limb function, the BCI had the best effect, followed by imVR, RT, Nf-imVR, and augmented reality in sequence; in terms of improving activities of daily living, the BCI still had the best effect, followed by imVR, RT, augmented reality, and Nf-imVR in sequence. The clustering ranking of upper limb function and activities of daily living was BCI >imVR > RT > Nf-imVR > augmented reality in turn.Conclusions:Intelligent rehabilitation technologies have advantages in improving the upper limb function and activities of daily living of stroke patients with upper limb dysfunction, and the BCI has obvious advantages.