Objective To investigate the protective effect and mechanism of astragaloside Ⅳ(AS-Ⅳ)on the pulmonary arterial hypertension(PAH)model induced by monocrotaline(MCT)/monocrotaline pyrrole(MCTP)in SD rats/human pulmonary artery endothelial cell(HPAEC).Methods In vivo experiment,60 male SD rats were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(20 mg/kg)group,AS-Ⅳ medium-dose(40 mg/kg)group,AS-Ⅳ high-dose(80 mg/kg)group,or sildenafil(Sil,100 mg/kg)group,with 10 rats in each group;except for the control group,PAH rat models were established by single intraperitoneal injection of MCT(60 mg/kg)in other groups.In vitro experiment,HPAECs were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(10 μmol/L)group,AS-Ⅳ medium-dose(20 μmol/L)group,MCTP+AS-Ⅳ high-dose(40 μmnol/L)group,or p38 mitogen-activated protein kinase(MAPK)signaling pathway inhibitor(SB203580,5 μmol/L)group;except for the control group,in vitro PAH cell models were established by MCTP(60 μg/mL)induction for 24 h in other groups.In vivo experiments,after 4 weeks of drug intervention,the right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)of rats were measured by hemodynamic methods,the right ventricle hypertrophy index was measured by weighing methods,the percentage of pulmonary arteriole wall thickness to outer diameter(WT％)and percentage of the wall area to total vascular area(WA％)were observed by hematoxylin-eosin staining,the expression of cysteine aspartic acid specific protease 3(caspase 3)protein in lung tissue was observed by immunohistochemistry(IHC),and the apoptosis of lung tissue cells was detected by TUNEL assay.In vitro experiments,JC-1 staining was used to detect the mitochondrial membrane potential in cells,and immunofluorescence was used to detect caspase 3 protein expression.In vitro and in vivo experiments,Western blotting was used to detect the expression of caspase 3,B-cell lymphoma gene 2(Bcl-2),Bcl-2 associated X protein(Bax),p38 MAPK,and phosphorylated p38 MAPK proteins in lung tissue and HPAECs.Results In vivo experiments,the RVSP,mPAP,and right ventricle hypertrophy index were decreased in the Sil group and each dose group of AS-Ⅳ(all P＜0.01);the WA％and WT％of each dose group of AS-Ⅳ were decreased(all P＜0.01),the expression of caspase 3 protein in lung tissue was decreased(all P＜0.01),and the apoptosis of lung tissue cells was decreased(all P＜0.01).In vitro experiments showed that after intervention with each dose of AS-Ⅳ and SB203580,the mitochondrial membrane potential of HPAEC was increased(all P＜0.01)and the expression of caspase 3 was decreased(all P＜0.01).In vivo and in vitro experiments,each dose of AS-Ⅳand SB203580 reduced the expression of Bax and phosphorylated p38 MAPK proteins,and increased the expression of Bcl-2 protein(all P＜0.01).Conclusion AS-Ⅳ reduces apoptosis by inhibiting p38 MAPK signaling pathway,improving PAH in SD rats.

Objective:To establish a predictive model of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer based on magnetic resonance imaging (MRI) parameters and multimodal ultrasound.Methods:The medical records of 279 patients with HER2 positive breast cancer admitted to Linyi People’s Hospital, Tai’an Central Hospital Affiliated to Qingdao University and Shandong First Medical University affiliated Provincial Hospital from Mar. 2021 to Nov. 2023 were retrospectively analyzed, and randomly divided into a training set ( n=223) and a validation set ( n=56) according to the 8∶2 law. All patients received neoadjuvant chemotherapy combined with targeted therapy and were divided into non-pathologic complete response (NpCR) and pathologic complete response (pCR) groups according to chemotherapy effect. By comparing MRI parameters and multimodal ultrasound parameters of the two groups, and the pCR risk model after neoadjuvant chemotherapy for HER2 positive breast cancer patients was constructed and verified. Results:After 3 cycles of chemotherapy, the incidence of pCR in 223 patients in the training set was 42.15%. Among 56 patients in the validation set, the incidence of pCR was 42.86%. The apparent diffusion coefficient (ADC) of pCR group was higher than NpCR group ( P<0.05). The peak systolic flow velocity (PSV), resistance index (RI), maximum radial change rate, area under the curve (AUC) and peak intensity (PI) in pCR group were higher than NpCR group ( P<0.05), and the ultrasound elastic score in pCR group was lower than NpCR group ( P<0.05). ΔADC ( OR=4.141, 95% CI: 1.820-9.421), maximum diameter change rate ( OR=5.212, 95% CI: 2.291-11.857), PI ( OR=4.802, 95% CI: 2.111-10.923) and ultrasonic elasticity score ( OR=6.629, 95% CI: 1.595-8.256) were the influencing factors of pCR after neoadjuvant chemotherapy for HER2 positive breast cancer ( P<0.05). The sensitivity and specificity of pCR predicted by the training set model after neoadjuvant chemotherapy for HER2 positive breast cancer were 90.43% (95% CI: 82.15%-95.26%), 91.47% (95% CI: 84.91%-95.45%), and the AUC was 0.904 (95% CI: 0.834-0.968). Validation set model predicted the pCR sensitivity after neoadjuvant chemotherapy for HER2 positive breast cancer was 87.50% (95% CI: 66.54%-96.71), specificity was 90.63% (95% CI: 73.83%-97.55%), and AUC was 0.897 (95% CI: 0.821-0.954) . Conclusion:The histogram model based on ΔADC, maximum radial rate of lesion change, PI and ultrasonic elasticity score can be used to evaluate the risk of pCR after neoadjuvant chemotherapy for HER2 positive breast cancer.

Objective:To investigate the clinical characteristics of sepsis-induced myocardial injury and microbial distribution.Methods:It was a retrospective observational study conducted from Jan 2023 to Dec 2023 in the Department of Emergency Intensive Care Medicine, Changshu Hospital Affiliated to Soochow University. Patients meeting the sepsis 3.0 criteria were included, excluding those with underlying cardiovascular diseases or incomplete data. Patients were categorized into myocardial injury (SIMI) and non-myocardial injury (Non-SIMI) groups based on troponin levels. General patient information, laboratory results, microbial findings, and prognostic indicators were collected. Differences in clinical parameters between the two groups were compared. Factors showing statistical differences in univariate analysis were further analyzed using multivariable logistic regression to identify risk factors for SIMI. Conduct propensity score matching among Pulmonary infection patients who underwent bronchoalveolar lavage high-throughput sequencing to compare microbial distribution between groups. Bracken was used to estimate species-level abundance from Kraken2 results, and α and β diversity analyses were conducted on the metagenomic samples.Results:A total of 179 patients were included in the study, with 98 (54.4%) in the Non-SIMI group and 81 (45.5%) in the SIMI group. There were 69 deaths overall (38.5%), with 23 (23.7%) in the Non-SIMI group and 46 (56.8%) in the SIMI group (χ 2=20.347, P<0.01). The 28-day survival curve indicated survival rates in the SIMI group were significantly lower compared to the Non-SIMI group (Log Rank χ 2=21.270, P<0.01). Univariate analysis revealed that fungal infection rate ( P=0.007), C-reactive protein ( P=0.021), procalcitonin, blood urea nitrogen, creatinine, alanine transaminase, and lactate levels were higher in the SIMI group compared to the Non-SIMI group (all P<0.01), prothrombin time was prolonger ( P<0.01) and APACHEⅡ scores were higher ( P<0.01), while serum albumin, base excess, and platelet levels were lower (all P<0.01). Multivariable logistic regression analysis indicated that fungal infection ( OR=3.441, P=0.015) was a risk factor for SIMI, whereas base excess and platelets were protective factors ( OR=0.845, 0.988, both P<0.01). Comparison of bronchoalveolar lavage high-throughput sequencing results in the pulmonary infection subgroup showed the relative abundance of Haemophilus paraininfluenzae in Non-SIMI group was higher than SIMI group among the top 20 species ( P=0.013). There were no statistically significant differences in microbial αand β-diversity between the two groups. Conclusions:The incidence of SIMI is relatively highamong sepsis patients and it affects their prognosis. Risk factors for SIMI include fungal infection, decreased platelet count, and reduced base excess levels. Among patients with pulmonary infections, there is a lower risk of SIMI associated with Haemophilus influenzae infection.

Tenecteplase is a third-generation thrombolytic drug.Compared with alteplase,it has the advantages of longer half-life and higher fibrin specificity.The effectiveness and safety of tenecteplase in the treatment of acute ischemic stroke have been extensively studied in clinical research.The article summarized the research progress of tenecteplase in the treatment of acute ischemic stroke based on completed randomized controlled studies and related Meta-analyses,and explored the pharmacological characteristics,effectiveness,and safety of tenecteplase,as well as current guideline recommendations,aiming to offer a reference for choosing more appropriate diagnostic and therapeutic methods for patients with acute ischemic stroke.

Esophageal cancer cases in China account for more than 50% of the world, among which approximately 90% are histological subtypes of esophageal squamous cell carcinoma. Over 50% of esophageal cancer patients are initially diagnosed at locally advanced or advanced stages. The R0 resection rate with surgical treatment alone is relatively low, and local recurrence and distant metastasis are prone to occur, resulting in a low 5-year survival rate. Recent research has focused on neoadjuvant therapy for esophageal cancer, but the most effective form of such therapy remains undetermined. Immunotherapy is currently the most active research field in tumor treatment. Further exploration of the treatment model combing immunotherapy with neoadjuvant chemotherapy or chemoradiotherapy is expected to improve the therapeutic effect and survival benefit in patients with locally advanced resectable esophageal squamous cell carcinoma.

Tuberculosis (TB) is still a major public health issue today. A novel TB vaccine is a key approach to reaching the targets of WHO's End-TB Strategy. In recent years, significant progress has been made in the research and development of TB vaccines both in China and abroad. A breakthrough has been made in both application scenarios and technological routes, and several vaccine candidates have entered phase Ⅲ clinical trials. This review summarizes information from clinical trials involving key TB vaccine candidates under development in China and abroad. It highlights six candidates that are most promising for marketing or inspiring future research and development, analyzes the current difficulties in the research and development of novel TB vaccines, and provides an outlook for the future.

Objective:To establish a predictive model of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer based on magnetic resonance imaging (MRI) parameters and multimodal ultrasound.Methods:The medical records of 279 patients with HER2 positive breast cancer admitted to Linyi People’s Hospital, Tai’an Central Hospital Affiliated to Qingdao University and Shandong First Medical University affiliated Provincial Hospital from Mar. 2021 to Nov. 2023 were retrospectively analyzed, and randomly divided into a training set ( n=223) and a validation set ( n=56) according to the 8∶2 law. All patients received neoadjuvant chemotherapy combined with targeted therapy and were divided into non-pathologic complete response (NpCR) and pathologic complete response (pCR) groups according to chemotherapy effect. By comparing MRI parameters and multimodal ultrasound parameters of the two groups, and the pCR risk model after neoadjuvant chemotherapy for HER2 positive breast cancer patients was constructed and verified. Results:After 3 cycles of chemotherapy, the incidence of pCR in 223 patients in the training set was 42.15%. Among 56 patients in the validation set, the incidence of pCR was 42.86%. The apparent diffusion coefficient (ADC) of pCR group was higher than NpCR group ( P<0.05). The peak systolic flow velocity (PSV), resistance index (RI), maximum radial change rate, area under the curve (AUC) and peak intensity (PI) in pCR group were higher than NpCR group ( P<0.05), and the ultrasound elastic score in pCR group was lower than NpCR group ( P<0.05). ΔADC ( OR=4.141, 95% CI: 1.820-9.421), maximum diameter change rate ( OR=5.212, 95% CI: 2.291-11.857), PI ( OR=4.802, 95% CI: 2.111-10.923) and ultrasonic elasticity score ( OR=6.629, 95% CI: 1.595-8.256) were the influencing factors of pCR after neoadjuvant chemotherapy for HER2 positive breast cancer ( P<0.05). The sensitivity and specificity of pCR predicted by the training set model after neoadjuvant chemotherapy for HER2 positive breast cancer were 90.43% (95% CI: 82.15%-95.26%), 91.47% (95% CI: 84.91%-95.45%), and the AUC was 0.904 (95% CI: 0.834-0.968). Validation set model predicted the pCR sensitivity after neoadjuvant chemotherapy for HER2 positive breast cancer was 87.50% (95% CI: 66.54%-96.71), specificity was 90.63% (95% CI: 73.83%-97.55%), and AUC was 0.897 (95% CI: 0.821-0.954) . Conclusion:The histogram model based on ΔADC, maximum radial rate of lesion change, PI and ultrasonic elasticity score can be used to evaluate the risk of pCR after neoadjuvant chemotherapy for HER2 positive breast cancer.

Tuberculosis (TB) is still a major public health issue today. A novel TB vaccine is a key approach to reaching the targets of WHO's End-TB Strategy. In recent years, significant progress has been made in the research and development of TB vaccines both in China and abroad. A breakthrough has been made in both application scenarios and technological routes, and several vaccine candidates have entered phase Ⅲ clinical trials. This review summarizes information from clinical trials involving key TB vaccine candidates under development in China and abroad. It highlights six candidates that are most promising for marketing or inspiring future research and development, analyzes the current difficulties in the research and development of novel TB vaccines, and provides an outlook for the future.

Tenecteplase is a third-generation thrombolytic drug.Compared with alteplase,it has the advantages of longer half-life and higher fibrin specificity.The effectiveness and safety of tenecteplase in the treatment of acute ischemic stroke have been extensively studied in clinical research.The article summarized the research progress of tenecteplase in the treatment of acute ischemic stroke based on completed randomized controlled studies and related Meta-analyses,and explored the pharmacological characteristics,effectiveness,and safety of tenecteplase,as well as current guideline recommendations,aiming to offer a reference for choosing more appropriate diagnostic and therapeutic methods for patients with acute ischemic stroke.

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.