OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Cellular mechanical transduction is the process by which cells perceive mechanical signals and transform them into chemical ones.Crucial cellular mechanosensors include PIEZO,TRPV4,and integrins.These sensors can modulate specific pathophysiological processes,such as fibrosis,tumor development,as well as cell proliferation,differentiation,and movement.Recent researches indicate that PIEZO,TRPV4,and integrins play an important role in various types of cancer pain,such as bone cancer pain,by detecting mechanical stimuli,which subsequently activate internal signaling pathways.This review summarizes advancements of PIEZO,TRPV4,and interegrins in cancer pain researches,aiming to lay a foundation for developing new therapeutic drugs that target cellular mechanical transduction for treating cancer pain.

ObjectiveThis paper used the AGREE Ⅱ guideline evaluation tool to evaluate the quality of 14 clinical guidelines for acute myocardial infarction，aiming to provide reference for the formulation and improvement of the guidelines. MethodsClinical guidelines and expert consensus related to acute myocardial infarction were searched by web search. The search period ranges from January 1，2019 to November 1，2024 in CNKI，VIP，Wanfang Data，SinoMed，Web of Science，OVID， the International Guidelines Collaboration Network （GIN），the UK National Institute for Health and Clinical Excellence （NICE），Yimaitong， and other platforms. Three researchers independently screened the literature and used AGREE Ⅱ to score the screening results. After ensuring that the researchers have a consistent understanding of each guideline，the quality of the guidelines was evaluated. After that，the ratings were analyzed by layer according to the issuing agency，category，method of formulation，and funding situation and compared longitudinally by rating time. The clinical guidelines and expert consensus were compared in terms of content and evidence. ResultsA total of 14 guidelines and consensus were included. The results of AGREE Ⅱ in the six areas in descending order were scope and purpose （62.82%±10.43%），rigor （62.40%±12.77%），editorial independence （62.11%±22.26%），participants （61.42%±11.65%），clarity of expression （59.98%±9.62%），and application （52.94%±16.90%） . Eleven of the guidelines were at level B， and three were at level A. In the stratified analysis，the score of the guideline formulated by the Chinese Medical Doctor Association was lower. There was little difference between the scores of Chinese/Western and Western medicine guidelines. The average score of the guidelines was higher than the consensus. Funded guidelines and consensus scores were higher. In the longitudinal comparison，the highest number of guidelines were developed in 2020 and 2021，while those developed in 2023 scored the highest. In the differential comparison analysis，the content of the guidelines was more comprehensive， and the evidence level was higher，while the content of the consensus was more novel， and the evidence was less. ConclusionThe AGREE Ⅱ score of the clinical guidelines for acute myocardial infarction is generally moderate，and there is room for improvement in terms of applicability. At the same time，the content quality of expert consensus should be improved，and more efforts should be made to develop and apply Chinese medicine guidelines for complications such as heart failure and microcirculatory obstruction after acute myocardial infarction.

Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.

Objective To investigate the relationship between plasma dipeptidyl peptidase 4 (DDP4) level and the progression of abdominal aortic aneurysm. Methods Forty-three patients with abdominal aortic aneurysm admitted to Baoji Central Hospital from January 2020 to May 2021 were selected. The follow-up was conducted at least 12 months,the absolute measurement of the maximum anterior-posterior diameters of the aneurysm and the rate of progression were obtained based on the first and last computed tomography angiography data,and the patients were divided into the progression group (with the rate of progression≥0.5 mm/year) and the progression-free group (with the rate of progression<0.5 mm/year) according to the rate of the abdominal aortic aneurysm progression. The clinical characteristics of the two groups were compared. Plasma DDP4 levels were detected by enzyme-linked immunosorbent assay. The correlation between plasma DDP4 and the rate of abdominal aortic aneurysm progression was analyzed by Pearson correlation and multiple linear regression. The predictive performance of plasma DDP4 on abdominal aortic aneurysm progression was analyzed by Logistic regression model and receiver operating characteristic (ROC) curve. Results The thickness of intracavitary thrombus (P=0.046) and the rate of abdominal aortic aneurysm progression (P<0.001) in the progression group were greater/faster than those in the the progression-free group,and the plasma level of DDP was significantly higher than that in the progression-free group (P<0.001). Multivariate Logistic regression analysis showed that plasma DDP4 level was an independent predictor of abdominal aortic aneurysm progression (P<0.05). Pearson correlation analysis showed that plasma DDP4 level was positively correlated with the rate of abdominal aortic aneurysm progression (r=0.517,P<0.001). After adjusting for other confounding factors,multiple linear regression showed that there was still a significantly positive correlation between plasma DDP4 level and abdominal aortic aneurysm progression rate (β=0.312,95％CI:0.002 to 0.484,P=0.048). The area under the curve of baseline plasma DDP4 level for predicting abdominal aortic aneurysm progression was 0.840 (95％CI:0.704 to 0.976),with corresponding cutoff value of 13.89 pg/mL,specificity of 85.7％,and sensitivity of 79.3％. Conclusion Elevated plasma DDP4 levels in patients with abdominal aortic aneurysm are associated with a higher risk of aneurysm progression. Plasma DDP4 is expected to be a predictive biomarker for abdominal aortic aneurysm progression.

Premature ovarian insufficiency(POI)is a disease that seriously affects the health and life of women,which is also one of the main causes of female infertility.The incidence of POI is increasing in recent years.The diagnostic criteria of POI are not uniform,and different diagnostic criteria have inconsistent thresholds for various indicators.Strict diagnostic criteria are more conducive to early detection and treatment of POI.At present,complementary and alternative therapies such as traditional Chinese medicine,acupuncture and moxibustion are widely used in the treatment of POI.This article reviewed the recent studies on the complementary and alternative therapy of traditional Chinese medicine in the treatment of POI,and finds that the dialectical treatment of traditional Chinese medicine is based on the perspective of traditional Chinese medicine theory and puts forward corresponding treatment plans for different dialectical types.For example,treatment from the kidney,tonifying kidney filling essence,regulating chongren;Treatment from the liver,soothing the liver,regulating qi,nourishing blood and softening the liver;Treatment from the heart and spleen,nourishing Yangming,tonifying the spleen and nourishing the heart.In terms of acupuncture treatment,regulating menstruation and promoting pregnancy and regulating the conception vessel and toning the governor vessel and toning the kidney are often used to treat POI.In addition,moxibustion regulates body function by stimulating the bladder meridian and conception vessel and governor vessel acupoints.Other methods,such as ear acupoint bean-pressing,acupoint thread-embedding and acupoint injection,have also shown potential in the treatment of POI.This article summarizes the role and characteristics of traditional Chinese medicine in the treatment of POI,in order to provide ideas and basis for clinical treatment of POI.

Cellular mechanical transduction is the process by which cells perceive mechanical signals and transform them into chemical ones.Crucial cellular mechanosensors include PIEZO,TRPV4,and integrins.These sensors can modulate specific pathophysiological processes,such as fibrosis,tumor development,as well as cell proliferation,differentiation,and movement.Recent researches indicate that PIEZO,TRPV4,and integrins play an important role in various types of cancer pain,such as bone cancer pain,by detecting mechanical stimuli,which subsequently activate internal signaling pathways.This review summarizes advancements of PIEZO,TRPV4,and interegrins in cancer pain researches,aiming to lay a foundation for developing new therapeutic drugs that target cellular mechanical transduction for treating cancer pain.

Objective To investigate the relationship between plasma dipeptidyl peptidase 4 (DDP4) level and the progression of abdominal aortic aneurysm. Methods Forty-three patients with abdominal aortic aneurysm admitted to Baoji Central Hospital from January 2020 to May 2021 were selected. The follow-up was conducted at least 12 months,the absolute measurement of the maximum anterior-posterior diameters of the aneurysm and the rate of progression were obtained based on the first and last computed tomography angiography data,and the patients were divided into the progression group (with the rate of progression≥0.5 mm/year) and the progression-free group (with the rate of progression<0.5 mm/year) according to the rate of the abdominal aortic aneurysm progression. The clinical characteristics of the two groups were compared. Plasma DDP4 levels were detected by enzyme-linked immunosorbent assay. The correlation between plasma DDP4 and the rate of abdominal aortic aneurysm progression was analyzed by Pearson correlation and multiple linear regression. The predictive performance of plasma DDP4 on abdominal aortic aneurysm progression was analyzed by Logistic regression model and receiver operating characteristic (ROC) curve. Results The thickness of intracavitary thrombus (P=0.046) and the rate of abdominal aortic aneurysm progression (P<0.001) in the progression group were greater/faster than those in the the progression-free group,and the plasma level of DDP was significantly higher than that in the progression-free group (P<0.001). Multivariate Logistic regression analysis showed that plasma DDP4 level was an independent predictor of abdominal aortic aneurysm progression (P<0.05). Pearson correlation analysis showed that plasma DDP4 level was positively correlated with the rate of abdominal aortic aneurysm progression (r=0.517,P<0.001). After adjusting for other confounding factors,multiple linear regression showed that there was still a significantly positive correlation between plasma DDP4 level and abdominal aortic aneurysm progression rate (β=0.312,95％CI:0.002 to 0.484,P=0.048). The area under the curve of baseline plasma DDP4 level for predicting abdominal aortic aneurysm progression was 0.840 (95％CI:0.704 to 0.976),with corresponding cutoff value of 13.89 pg/mL,specificity of 85.7％,and sensitivity of 79.3％. Conclusion Elevated plasma DDP4 levels in patients with abdominal aortic aneurysm are associated with a higher risk of aneurysm progression. Plasma DDP4 is expected to be a predictive biomarker for abdominal aortic aneurysm progression.

Premature ovarian insufficiency(POI)is a disease that seriously affects the health and life of women,which is also one of the main causes of female infertility.The incidence of POI is increasing in recent years.The diagnostic criteria of POI are not uniform,and different diagnostic criteria have inconsistent thresholds for various indicators.Strict diagnostic criteria are more conducive to early detection and treatment of POI.At present,complementary and alternative therapies such as traditional Chinese medicine,acupuncture and moxibustion are widely used in the treatment of POI.This article reviewed the recent studies on the complementary and alternative therapy of traditional Chinese medicine in the treatment of POI,and finds that the dialectical treatment of traditional Chinese medicine is based on the perspective of traditional Chinese medicine theory and puts forward corresponding treatment plans for different dialectical types.For example,treatment from the kidney,tonifying kidney filling essence,regulating chongren;Treatment from the liver,soothing the liver,regulating qi,nourishing blood and softening the liver;Treatment from the heart and spleen,nourishing Yangming,tonifying the spleen and nourishing the heart.In terms of acupuncture treatment,regulating menstruation and promoting pregnancy and regulating the conception vessel and toning the governor vessel and toning the kidney are often used to treat POI.In addition,moxibustion regulates body function by stimulating the bladder meridian and conception vessel and governor vessel acupoints.Other methods,such as ear acupoint bean-pressing,acupoint thread-embedding and acupoint injection,have also shown potential in the treatment of POI.This article summarizes the role and characteristics of traditional Chinese medicine in the treatment of POI,in order to provide ideas and basis for clinical treatment of POI.