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.

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 explore the effects of methimazole on endocrine function in patients with hyperthyroidism at different neuregulin 4(NRG4)levels.Methods A total of 60 patients with hyperthyroidism admitted to Huzhou First People's Hospital from January 2022 to January 2023 were selected.According to the level of NRG4,they were divided into case Ⅰ group(NRG4<80ng/ml,28 cases),case Ⅱ group(NRG4 80-120ng/ml,18 cases)and case Ⅲ group(NRG4>120ng/ml,14 cases).The clinical efficacy,thyroid hormone levels,glucose and lipid metabolism indexes and adverse reactions of three groups were compared.Results The difference of total effective rate among three groups was statistically significant(χ2=10.836,P<0.001).There were statistically significant differences in thyroid-stimulating hormone(TSH),free triiodothyronine(FT3),free thyroxine(FT4)between groups,time points and interactions among three groups(P<0.05).TSH levels increased and FT3 and FT4 levels decreased in all three groups after treatment(P<0.05).One month after treatment,the levels of fasting blood glucose,2h postprandial blood glucose,glycated hemoglobin,total cholesterol and low density lipoprotein cholesterol in three groups were significantly lower than before treatment(P<0.05),and the differences in above indicators among the three groups were statistically significant(P<0.05).There was no significant difference in total incidence of adverse reactions among three groups(χ2=5.349,P=0.069).After treatment,NRG4 levels in three groups decreased significantly over time(P<0.05).There were significant differences in NRG4 levels among the three groups at different time points(P<0.05),and case Ⅰ group

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.

Attempts have been made to modulate motor sequence learning (MSL) through repetitive transcranial magnetic stimulation, targeting different sites within the sensorimotor network. However, the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified. This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper (SMAp) in modulating MSL across different complexity levels and for both hands, as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation. Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL, which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions, particularly in interhemispheric connections. These findings may have important clinical implications, particularly for motor rehabilitation in populations such as post-stroke patients.
Humans ; Transcranial Magnetic Stimulation ; Motor Cortex/physiology* ; Male ; Electroencephalography ; Neuronal Plasticity/physiology* ; Female ; Adult ; Evoked Potentials, Motor/physiology* ; Young Adult ; Learning/physiology*

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 explore the effects of methimazole on endocrine function in patients with hyperthyroidism at different neuregulin 4(NRG4)levels.Methods A total of 60 patients with hyperthyroidism admitted to Huzhou First People's Hospital from January 2022 to January 2023 were selected.According to the level of NRG4,they were divided into case Ⅰ group(NRG4<80ng/ml,28 cases),case Ⅱ group(NRG4 80-120ng/ml,18 cases)and case Ⅲ group(NRG4>120ng/ml,14 cases).The clinical efficacy,thyroid hormone levels,glucose and lipid metabolism indexes and adverse reactions of three groups were compared.Results The difference of total effective rate among three groups was statistically significant(χ2=10.836,P<0.001).There were statistically significant differences in thyroid-stimulating hormone(TSH),free triiodothyronine(FT3),free thyroxine(FT4)between groups,time points and interactions among three groups(P<0.05).TSH levels increased and FT3 and FT4 levels decreased in all three groups after treatment(P<0.05).One month after treatment,the levels of fasting blood glucose,2h postprandial blood glucose,glycated hemoglobin,total cholesterol and low density lipoprotein cholesterol in three groups were significantly lower than before treatment(P<0.05),and the differences in above indicators among the three groups were statistically significant(P<0.05).There was no significant difference in total incidence of adverse reactions among three groups(χ2=5.349,P=0.069).After treatment,NRG4 levels in three groups decreased significantly over time(P<0.05).There were significant differences in NRG4 levels among the three groups at different time points(P<0.05),and case Ⅰ group

Objective:To study the clinical value of serum microRNA-34a (miR-34a) and aryl hydrocarbon receptor nuclear transcript-like protein 1 (BMAL1) in cervical cancer and their relationship with high-risk human papillomavirus (HR-HPV) infection.Methods:The clinical data of 76 patients with cervical cancer and 50 patients with benign cervical diseases in the Affiliated Hospital of Jining Medical University from January to December 2022 were retrospectively analyzed. The expression levels of serum miR-34a and BMAL1 were detected by real-time fluorescence quantitative polymerase chain reaction, and HR-HPV infection was detected by flow fluorescent hybridization. The patients were followed up until December 2023, and the death and poor prognosis (death, tumor recurrence and progression and severe complications at 1-year of follow-up) were recorded. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of miR-34a, BMAL1 and related indexes in evaluating the poor prognosis in patients with cervical cancer at 1-year. Multivariate Cox regression analysis was used to analyze the independent risk factors for death in patients with cervical cancer. The Kaplan-Meier survival curve was used to analyze the relationship between miR-34a, BMAL1 expression and survival period, and the log-rank test was used for comparison.Results:The expression level of serum miR-34a in patients with cervical cancer was significantly lower than that in patients with benign cervical lesions (0.46 ± 0.08 vs. 0.67 ± 0.11), the expression level of serum BMAL1 was significantly higher than that in patients with benign cervical lesions (0.58 ± 0.07 vs. 0.41 ± 0.07), and there were statistical differences ( t= 12.40 and 13.34, P<0.01). The expression levels of serum miR-34a and BMAL1 in patients with cervical cancer were associated with tumor differentiation, myometrial invasion depth, lymph node metastasis, distant metastasis and International Federation of Gynecology and Obstetrics (FIGO) stage, and there were statistical differences ( P<0.05 or<0.01); they were not associated with age, menopause and pathological type, and there were no statistical differences ( P>0.05). In patients with cervical cancer, the expression level of miR-34a in patients with HR-HPV positive infection (60 cases) was significantly lower than that in patients with HR-HPV negative infection (16 cases): 0.41 ± 0.07 vs. 0.49 ± 0.08, the expression level of BMAL1 was significantly higher than that in patients with HR-HPV negative infection: 0.65 ± 0.09 vs. 0.53 ± 0.06, and there were statistical differences ( t = 3.68 and 4.24, P<0.05 or<0.01). In patients with benign cervical diseases, there were no statistical differences in the expression levels of miR-34a and BMAL1 between patients with HR-HPV positive infection (7 cases) and patients with HR-HPV negative infection (43 cases) ( P>0.05). ROC curve analysis result showed that miR-34a combined with BMAL1 had the highest sensitivity (90.4%), specificity (89.9%) and area under curve (0.911) in assessing the 1-year poor prognosis in patients with cervical cancer ( P<0.01), and the optimal cutoff values of miR-34a and BMAL1 expression level were ≤0.39 and ≥0.64. Multivariate Cox regression analysis result showed that poor differentiation, myometrial invasion depth ≥1/2, lymph node metastasis, distant metastasis, FIGO stage Ⅲ+Ⅳ, miR-34a expression level ≤0.46 and BMAL1 expression level ≥0.58 were independent risk factors for death in patients with cervical cancer ( OR = 1.857, 2.125, 2.337, 2.751, 2.457, 3.885 and 3.666; 95% CI 0.845 to 5.788, 0.726 to 5.924, 0.709 to 5.631, 0.693 to 5.727, 0.801 to 5.936, 1.244 to 6.423 and 1.031 to 5.612; P<0.01). Kaplan-Meier survival curve analysis result showed that the median survival time in cervical cancer patients with miR-34a expression level ≤0.39 and BMAL1 expression level ≥0.64 (21 cases) was significantly lower than that in the other cervical cancer patients (miR-34a expression level>0.39 or BMAL1 expression level<0.64, 55 cases): (26.4 ± 4.2) months vs. (34.2 ± 5.6) months, log-rank χ2 = 17.12, P<0.05. Conclusions:The expression level of serum miR-34a in patients with cervical cancer is significantly reduced and the expression level of BMAL1 is significantly increased, which is related to the condition, prognosis and HR-HPV infection. It can be used as a marker for the assessment of the condition and prognosis of cervical cancer. The combined detection of the two can significantly improve the sensitivity and specificity in predicting poor prognosis of cervical cancer.

Objective To explore the selection strategy of diagnostic and therapeutic regimens and assess the efficacy for postoperative infection following internal fixation of patellar fractures. Methods A retrospective analysis was conducted on the clinical data of 12 patients with postoperative infection after internal fixation of patellar fractures. Results A total of 6 patients underwent complete removal of the internal fixation devices during debridement and were subsequently fixed with knee braces, while the other 6 had their original internal fixation devices removed and replaced with Kirschner wire fixation. Three patients developed septic arthritis and underwent knee arthroscopic lavage treatment. All 12 patients underwent bacterial culture and metagenomic next-generation sequencing (mNGS) testing, and the key pathogenic bacteria were successfully identified by mNGS. All wounds achieved primary healing within 2 weeks after closure. At the final follow-up, all patients exhibited good fracture healing, with Böstman patellar fracture function scores ranging from 24 to 29 (mean score of 26.58), and the outcomes were evaluated as excellent in 7 cases and good in 5, resulting in an excellent and good rate of 100.0%. Conclusion For patients with early and delayed postoperative infections following internal fixation of patellar fractures, removal of the internal fixation devices can help reduce the risk of infection recurrence. For patients with concurrent septic arthritis, early diagnosis and timely implementation of arthroscopic joint debridement and irrigation and drainage are crucial.