ObjectiveTo analyze the correlation between the clinical symptoms， signs， syndrome characteristics and laboratory indicators of cough variant asthma （CVA） and deepen the understanding of the treatment of this disease based on the theory of "Fu Feng". MethodsAn observational study was conducted. A total of 207 CVA patients who visited the respiratory department of the Third Affiliated Hospital of Beijing University of Chinese Medicine from September 2022 to November 2023 were included. The information from the four diagnostic methods and the laboratory test results of patients were collected. Factor analysis was conducted on the information obtained through the four diagnostic methods in TCM， and the nature and location of CVA were extracted. Sample cluster analysis （Q clustering） and the K-means method were used for data clustering analysis to determine the syndrome types of CVA and analyze the syndrome characteristics and differences in laboratory indicators among different syndrome types. ResultsThe main symptom of CVA patients was cough， accompanied by symptoms such as itchy throat， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， chest tightness， hoarseness， bitter mouth， poor appetite， and skin itching. Factor analysis showed that the disease was located in the lung， involving the liver， spleen， and kidney. The pathological factors involved Yin deficiency， Yang deficiency， wind factor， dampness factor， Yin factor， and Qi stagnation. Cluster analysis revealed four syndrome types： Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. Fengfu Yinshang syndrome accounted for the highest proportion， followed by Tanyin Zufei syndrome. There were no significant differences in eosinophil count and percentage， fractional nasal nitric oxide （FnNO） level， and pulmonary function indexes among the four syndromes. The levels of serum total IgE and fractional exhaled nitric oxide （FeNO） in patients with Fengfu Yinshang syndrome were significantly higher than those in patients with Shixie Neiyun syndrome and Tanyin Zufeisyndrome. ConclusionCough is the main symptom of CVA， accompanied by pharyngeal itching， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， and allergic manifestations. The disease involves the lung， liver， spleen， and kidneys. The essence of the pathogenesis lies in a latent dormant pathogen and a disorder of the pivot mechanism. The four common syndrome types are Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. The TCM syndrome types are correlated with laboratory indexes. The serum total IgE and FeNO of patients with Fengfu Yinshang syndrome are worse.

Objective:To evaluate the effect of goal-directed fluid therapy (GDFT) on postoperative acute kidney injury (AKI) in elderly patients undergoing long-time abdominal surgery.Methods:The medical records from elderly patients of both sexes, aged ≥ 65 yr, with a duration of operation ≥ 8 h and American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective first abdominal surgery for gastrointestinal tumors at the Shanxi Provincial People′s Hospital from October 1, 2016 to June 30, 2022, were collected from the electronic medical record database. Patients were divided into conventional fluid therapy group (group C) and GDFT group (group G) according to whether GDFT was employed during operation. In group C, blood pressure was maintained ≥90/60 mmHg or mean arterial pressure≥65 mmHg, and urine output more than 30 ml/h. In group G, the stroke volume variation was maintained ≤13%, and cardiac index ≥2.5 L·min -1·m -2. The patient general characteristics, requirement for fluid, urine output, blood loss, requirement for vasoactive agents and abdominal hyperthermic perfusion, and operation time were recorded during operation. The development of AKI within 72 h after operation and development of other complications (pneumonia, anastomotic leakage, surgical site infection, septic shock, arrhythmia) after operation were recorded. The length of hospital stay and 30-day mortality after operation were recorded. Results:A total of 125 patients were included in this study, with 41 patients in group C and 84 patients in group G. Postoperative AKI occurred in 19 patients, with an incidence of 15.2%. Compared with group C, the requirement for colloid, total volume of fluid infused and urine volume were significantly decreased during operation, the requirement for vasoactive agents was increased during operation ( P<0.05), the risk of postoperative AKI was reduced ( OR=0.23, P<0.05), and no significant change was found in the incidence of other postoperative complications, 30-day mortality, and length of hospital stay in group G ( P>0.05). Conclusions:GDFT can reduce the risk of AKI in the elderly patients undergoing long-time abdominal surgery.

Unplanned readmission is one of the adverse outcomes of patients after left ventricular assist device implantation,which seriously affects the prognosis of patients.This article reviews the incidence,causes,influencing factors and intervention measures of unplanned readmission of patients after left ventricular assist device implantation,in order to improve the attention of nursing staff,early identify high-risk groups of unplanned readmission of patients after left ventricular assist device implantation and provide references for formulating personalized intervention measures.

Objective:To compare the motivated forgetting ability between adolescents with depression and normal adolescents and to explore the relationship of this ability with childhood trauma and symptoms of depression.Methods:Totally 141 adolescents diagnosed with depression according to the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),and 42 normal controls participated in the study.The directed forgetting(DF)task was employed,using emotional images as memory stimuli,to compare the recognition per-formance between the two groups.The presence of the DF effect was identified when the recognition score under the"to-be-remembered"condition was significantly higher than the"to-be-forgotten"condition.The Childhood Trauma Questionnaire Short Form(CTQ-SF)and Beck Depression Inventory-Ⅱ(BDI-Ⅱ)were utilized to assess the severi-ty of participants'childhood trauma and depression symptoms.Results:Unlike the control group,the adolescents with depression only exhibited the DF effect with positive stimuli(P＜0.001).In the depression group,the DF effect value for negative stimuli partially mediated the relationship between CTQ-SF scores and BDI-Ⅱ scores(effect size=0.10,95％confidence interval 0.05-0.17,accounting for 21.3％of the total effect).Conclusion:The motivated forgetting ability is partially impaired in adolescents with depression.The ability,especially regarding negative memories,plays a partial mediating role between childhood trauma and depressive symptoms in adolescents with depression.

【Objective】 To investigate the effects of recombinant human coagulation factor Ⅶa combined with Bakri balloon compression on oxidative stress and coagulation in patients with refractory postpartum hemorrhage. 【Methods】 Prospectively, 80 patients with refractory postpartum hemorrhage in Chengdu Fifth People′s Hospital from June 2019 to June 2022 were selected and grouped according to the random number table method. The control group (n=40) was treated with Bakri balloon compression, and the observation group (n=40) was treated with recombinant human coagulation factor Ⅶa combined with Bakri balloon compression. The bleeding-related indexes and adverse effects were observed in both groups, and the prenatal and 24 h postpartum oxidative stress, coagulation function and inflammatory factors were compared between the two groups. 【Results】 The blood loss in the observation group and the control group was (683.96±146.52) vs(796.63±152.41)mL during operation, (812.46±161.53) vs(965.39±166.22)mL in 2 h after delivery, (899.53±178.74) vs(1 084.31±203.67)mL in 24 h after delivery, and the transfusion volume was (512.31±104.76) vs(683.25±113.52)mL, and the onset time of hemostasis was (14.63±3.18) vs (21.72±5.29) min (P<0.05); the difference in the incidence of adverse reactions between the two groups was not significant (P>0.05). At 24 h postpartum, NE, Cor, SOD and MDA were higher than those before delivery in both groups, but the observation group was lower than the control group (P<0.05); TT, APTT and PT were longer and Fib was lower in both groups than before delivery, but TT, APTT and PT were shorter and Fib was higher in the observation group than in the control group (P<0.05); CRP, IL-8 and TNF-α were higher in both groups than before delivery, but the observation group was lower than in the control group (P<0.05). 【Conclusion】 Hemostasis in patients with refractory postpartum hemorrhage treated with recombinant human coagulation factor Ⅶa combined with Bakri balloon compression was effective, which can improve coagulation, reduce transfusion, decrease oxidative stress injury and inflammatory response without increasing adverse effects.

Bibenzyls, a kind of important plant polyphenols, have attracted growing attention for their broad and remarkable pharmacological activities. However, due to the low abundance in nature, uncontrollable and environmentally unfriendly chemical synthesis processes, these compounds are not readily accessible. Herein, one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes. Three types of efficiently post-modifying modular strains were engineered by employing methyltransferases, prenyltransferase, and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules. Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes. Especially, a prenylated bibenzyl derivative ( 12) was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke. RNA-seq, quantitative RT-PCR, and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor, mitochondria associated 3 (Aifm3), suggesting that Aifm3 might be a new target in ischemic stroke therapy. This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.

Phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) is a key factor in pulmonary vascular remodeling. Inhibiting or reversing phenotypic transformation can inhibit pulmonary vascular remodeling and control the progression of hypoxic pulmonary hypertension. Recent studies have shown that hypoxia causes intracellular peroxide metabolism to induce oxidative stress, induces multi-pathway signal transduction, including those related to autophagy, endoplasmic reticulum stress and mitochondrial dysfunction, and also induces non-coding RNA regulation of cell marker protein expression, resulting in PASMCs phenotypic transformation. This article reviews recent research progress on mechanisms of hypoxia-induced phenotypic transformation of PASMCs, which may be helpful for finding targets to inhibit phenotypic transformation and to improve pulmonary vascular remodeling diseases such as hypoxia-induced pulmonary hypertension.
Humans ; Pulmonary Artery ; Hypertension, Pulmonary ; Vascular Remodeling/genetics* ; Hypoxia/genetics* ; Myocytes, Smooth Muscle ; Cell Proliferation/physiology* ; Cells, Cultured ; Cell Hypoxia/genetics*

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

Background Macrophages are essential components of the natural immune system. They play a significant role in resisting foreign bodies in the respiratory tract and maintaining the homeostasis of the internal environment of lung tissue. Objective To investigate the mechanism of macrophage pyroptosis induced by silica dust with different particle sizes. Methods The modified murine macrophage cell line, RAW-ASC cells, was cultured and divided into a blank control group, a lipopolysaccharide (LPS) group (1 μg·mL⁻¹ LPS), a nano-SiO₂ group (1 μg·mL⁻¹ LPS+100 μg·mL⁻¹ nano-SiO₂), a micro-SiO₂ group (1 μg·mL⁻¹ LPS+750 μg·mL⁻¹ micro-SiO₂), and a positive control group [1 μg·mL⁻¹ LPS+3 mmol·L⁻¹ adenosine triphosphate (ATP)]. Apart from the blank control group, cells in other groups were pretreated with LPS for 6 h, and then exposed to SiO₂ or ATP for 4 h. According to the molecular target NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and reactive oxygen species (ROS), we applied MCC950 (NLRP3 inhibitor) and N-acetyl cysteine (NAC, ROS scavenger) to macrophages. CCK-8 assay was used to detect cell viability; 5-ethynyl-2'-deoxyuridine (EdU) staining was used to detect cell proliferation; lactate dehydrogenase (LDH) assay kit was used to detect LDH in supernatant; calcein AM/PI fluorescent double-staining was applied to evaluate cell rupture; 2',7'-dichlorofluorescin diacetate (DCFH-DA) fluorescent probe was used to measure the content of ROS; Western blotting was used to measure the expressions of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1, gasdermin D (GSDMD), and interleukin-1β (IL-1β). Results Compared with the blank group, 100 μg·mL^-1nano-SiO₂ and 750 μg·mL^-1micro-SiO₂ dust exposure reduced the cell viability to 40% and 68% (P<0.05), and the cell proliferation rate to 30% and 33% (P<0.01), respectively; they also induced cell lysis and ROS release, upregulated NLRP3, ASC, Caspase-1, GSDMD, and IL-1β at protein level (P<0.05), and induced macrophage pyroptosis. After intervening with MCC950 (10 μmol·L^-1) and NAC (10 mmol·L^-1), the expressions of NLRP3, ASC, Caspase-1, and IL-1β decreased (P<0.05), and, specifically, NAC effectively reduced ROS levels (P<0.05). Conclusion Both nano- and micro-SiO₂ dust have cytotoxicity, can upregulate ROS level, activate NLRP3 inflammasome, and promote the release of cytokines, leading to pyroptosis. These results are helpful to reveal the molecular mechanism of macrophage pyroptosis induced by SiO₂ dust.

Objective: To investigate the relationship between the expression of p-Stat3 and Survivin in gastric cancer and the clinical characteristics and prognosis of patients, and to establish the prediction model of postoperative survival of patients combined with alanine aminotransferase(ALT) and aspartate aminotransferase(AST). Methods: Data of 133 patients undergoing gastric tumor resection were collected and followed up. The expression of p-STAT3 and Survivin in gastric cancer and precancerous tissues were detected by immunohistochemical method. Kaplan-Meier method was used to draw the survival curve. Logistic regression model combined with receiver operating characteristic curve(ROC) curve was used to describe the predictive value of multi-index combined detection on postoperative survival status of patients. The prediction model of the histogram was established using Survival and RMS packages in R Studio software. Results: The expressions of p-Stat3 and Survivin in gastric cancer tissues were higher than those in precancerous tissues. The expression of p-Stat3 in gastric cancer tissues was positively correlated with the depth of invasion and TNM stage, while the expression of Survivin in gastric cancer tissues was positively correlated with the degree of differentiation and the depth of invasion. The higher the expression levels of p-Stat3 and Survivin, the worse the prognosis. The lower the ALT level, the worse the prognosis. Survivin, ALT and AST were the optimal combination for predicting postoperative survival in patients with gastric cancer. Conclusion The expression of p-Stat3 and Survivin plays an auxiliary role in the diagnosis of gastric cancer. P-Stat3, Survivin and ALT are correlated with the prognosis of patients with gastric cancer and have predictive value. Survivin, ALT and AST combined model has a big value to predict the postoperative survival prognosis of gastric cancer patients, which can provide a reference for clinical practice.